71 results on '"CARDIAC-FUNCTION"'
Search Results
2. Single and Combined Aluminium and Cadmium Exposure during Pregnancy Mediate Changes in Cardio Metabolic Indices in Mice
- Author
-
O. P. Onavwose, P. C. Ichipi-Ifukor, and S. O. Asagba
- Subjects
Aluminium ,Cadmium ,in-utero exposure ,cardiac-function ,oxidative-stress ,Science - Abstract
The potential risk of Aluminium and Cadmium co-exposure is high owing to evidence of their co-contamination of several food products. Therefore, the present study investigated effect of single and combined exposures of aluminium and cadmium during pregnancy on cardio metabolic changes in mice. Following delivery and at the end of 78 days postnatal development, it was observed that exposure to Al and Cd during pregnancy altered indices of cardiac function via pathways related to angiotensin, cardiac troponin and oxidative stress signalling which may have impacted directly on the histoarchitectural features of the heart. Comparatively, prenatal exposure to Cd alone impacted more negatively to the heart in relation to exposure to either Al only or co-exposure to Al and Cd.
- Published
- 2024
- Full Text
- View/download PDF
3. Lipidomics Reveals Myocardial Lipid Composition in a Murine Model of Insulin Resistance Induced by a High-Fat Diet
- Author
-
Universitat Rovira i Virgili, Girona, J; Soler, O; Samino, S; Junza, A; Martínez-Micaelo, N; García-Altares, M; Ràfols, P; Esteban, Y; Yanes, O; Correig, X; Masana, L; Rodríguez-Calvo, R, Universitat Rovira i Virgili, and Girona, J; Soler, O; Samino, S; Junza, A; Martínez-Micaelo, N; García-Altares, M; Ràfols, P; Esteban, Y; Yanes, O; Correig, X; Masana, L; Rodríguez-Calvo, R
- Abstract
Ectopic fat accumulation in non-adipose tissues is closely related to diabetes-related myocardial dysfunction. Nevertheless, the complete picture of the lipid metabolites involved in the metabolic-related myocardial alterations is not fully characterized. The aim of this study was to characterize the specific lipid profile in hearts in an animal model of obesity/insulin resistance induced by a high-fat diet (HFD). The cardiac lipidome profiles were assessed via liquid chromatography-mass spectrometry (LC-MS)/MS-MS and laser desorption/ionization-mass spectrometry (LDI-MS) tissue imaging in hearts from C57BL/6J mice fed with an HFD or standard-diet (STD) for 12 weeks. Targeted lipidome analysis identified a total of 63 lipids (i.e., 48 triacylglycerols (TG), 5 diacylglycerols (DG), 1 sphingomyelin (SM), 3 phosphatidylcholines (PC), 1 DihydroPC, and 5 carnitines) modified in hearts from HFD-fed mice compared to animals fed with STD. Whereas most of the TG were up-regulated in hearts from animals fed with an HFD, most of the carnitines were down-regulated, thereby suggesting a reduction in the mitochondrial beta-oxidation. Roughly 30% of the identified metabolites were oxidated, pointing to an increase in lipid peroxidation. Cardiac lipidome was associated with a specific biochemical profile and a specific liver TG pattern. Overall, our study reveals a specific cardiac lipid fingerprint associated with metabolic alterations induced by HFD.
- Published
- 2024
4. Comparative efficacy of finger versus forehead Plethysmographic Variability Index monitoring in pediatric surgical patients
- Author
-
Seyfullah Fidan, Seniyye Ülgen Zengin, Meliha Orhon, Tümay Umuroğlu, and Fidan S., ZENGİN S. Ü. , ORHON ERGÜN M., UMUROĞLU T.
- Subjects
Anesteziyoloji ve Ağrı Tıbbı ,PI ,CHILDREN ,Sağlık Bilimleri ,Pediatrics ,Clinical Medicine (MED) ,Çocuk Sağlığı ve Hastalıkları ,Child Health and Diseases ,CARDIAC-FUNCTION ,Anesthesiology ,Surgery Medicine Sciences ,Health Sciences ,fluid responsiveness ,USCOM ,Klinik Tıp (MED) ,Pediatri, Perinatoloji ve Çocuk Sağlığı ,Internal Medicine Sciences ,Klinik Tıp ,ANESTEZİYOLOJİ ,SITE ,PREDICT FLUID RESPONSIVENESS ,Dahili Tıp Bilimleri ,CLINICAL MEDICINE ,ARTERIAL ,Tıp ,pediatric ,Anesthesiology and Pain Medicine ,Anesteziyoloji ,Pediatri ,Cerrahi Tıp Bilimleri ,Pediatrics, Perinatology and Child Health ,Medicine ,PEDİATRİ ,WAVE-FORM ,PVI - Abstract
Introduction The Plethysmographic Variability Index can be measured by both finger and forehead probes. Vasoconstriction may jeopardize the reliability of finger PVI measurements in pediatric patients undergoing surgery. However, forehead vasculature exhibits more marked resistance to alterations in the vasomotor tonus. Objective Our aim was to compare the Plethysmographic Variability Index measured via finger or forehead probes in mechanically ventilated pediatric surgery patients in terms of their ability to predict fluid responsiveness as well as to determine the best cut-off values for these two measurements. Materials and Methods A total of 50 pediatric patients undergoing minor elective surgery were included after provision of parental consent and ethics committee approval. Perfusion index measured at the finger or forehead and Plethysmographic Variability Index monitoring comprised the primary assessments. Hemodynamic parameters monitored included perfusion index, Plethysmographic Variability Index, and cardiac output. A >= 15% increase in cardiac output following passive leg raise maneuver was considered to show fluid responsiveness. Two groups were defined based on fluid responsiveness: Group R (responsive) and Group NR (non-responsive). Student\"s t-test, Mann-Whitney U test, DeLong test, and ROC were used for statistical analysis. Results The area under curve for finger and forehead Plethysmographic Variability Index prior to passive leg raise maneuver were 0.699 (p = .011) and 0.847 (p < .001), respectively. The sensitivity for finger and forehead measurements at a cut-off value of
- Published
- 2022
5. The erythropoietin receptor expressed in skeletal muscle is essential for mitochondrial biogenesis and physiological exercise
- Author
-
Alexander H. Maass, Kirsten T Nijholt, Willem P. T. Ruifrok, B. Daan Westenbrink, Belend Mahmoud, Herman H W Silljé, Salva R. Yurista, Rudolf A. de Boer, Dirk J. van Veldhuisen, Mario G. Pavez-Giani, Wiek H. van Gilst, L. M. G. Meems, Anouk H G Wolters, and Cardiovascular Centre (CVC)
- Subjects
Male ,Cardiac function curve ,medicine.medical_specialty ,Muscle Physiology ,Physiology ,PGC-1-ALPHA ,Clinical Biochemistry ,PROTEIN ,Exercise-induced physiological adaptation ,Neovascularization, Physiologic ,Erythropoietin receptor ,CAPACITY ,CARDIAC-FUNCTION ,Mitochondrial biogenesis ,Physical Conditioning, Animal ,Physiology (medical) ,Internal medicine ,Mitophagy ,Receptors, Erythropoietin ,medicine ,Animals ,Myocyte ,Cardiomegaly, Exercise-Induced ,Muscle, Skeletal ,Mice, Knockout ,Organelle Biogenesis ,business.industry ,Myocardium ,food and beverages ,Skeletal muscle ,RECOMBINANT-HUMAN-ERYTHROPOIETIN ,Exercise performance ,Cardiac and skeletal muscle ,Adaptation, Physiological ,ISCHEMIA ,MICE ,DIFFERENTIATION ,Endocrinology ,medicine.anatomical_structure ,Erythropoietin ,VOLUME ,embryonic structures ,HEART-FAILURE ,Erythropoiesis ,business ,medicine.drug - Abstract
Erythropoietin (EPO) is a haematopoietic hormone that regulates erythropoiesis, but the EPO-receptor (EpoR) is also expressed in non-haematopoietic tissues. Stimulation of the EpoR in cardiac and skeletal muscle provides protection from various forms of pathological stress, but its relevance for normal muscle physiology remains unclear. We aimed to determine the contribution of the tissue-specific EpoR to exercise-induced remodelling of cardiac and skeletal muscle. Baseline phenotyping was performed on left ventricle and m. gastrocnemius of mice that only express the EpoR in haematopoietic tissues (EpoR-tKO). Subsequently, mice were caged in the presence or absence of a running wheel for 4 weeks and exercise performance, cardiac function and histological and molecular markers for physiological adaptation were assessed. While gross morphology of both muscles was normal in EpoR-tKO mice, mitochondrial content in skeletal muscle was decreased by 50%, associated with similar reductions in mitochondrial biogenesis, while mitophagy was unaltered. When subjected to exercise, EpoR-tKO mice ran slower and covered less distance than wild-type (WT) mice (5.5 ± 0.6 vs. 8.0 ± 0.4 km/day, p
- Published
- 2021
6. Therapeutic approaches in heart failure with preserved ejection fraction
- Subjects
RENAL SYMPATHETIC DENERVATION ,PULMONARY-ARTERY PRESSURE ,Heart failure ,Preserved ejection fraction ,Pharmacotherapy in HFpEF ,CARDIOVASCULAR OUTCOMES ,EXERCISE CAPACITY ,Device therapy ,DIASTOLIC FUNCTION ,RESISTANT HYPERTENSION ,SYSTOLIC FUNCTION ,CARDIAC-FUNCTION ,ATRIAL-FIBRILLATION ,LCZ696 ,VENTRICULAR MECHANICAL DYSSYNCHRONY - Abstract
In contrast to the wealth of proven therapies for heart failure with reduced ejection fraction (HFrEF), therapeutic efforts in the past have failed to improve outcomes in heart failure with preserved ejection fraction (HFpEF). Moreover, to this day, diagnosis of HFpEF remains controversial. However, there is growing appreciation that HFpEF represents a heterogeneous syndrome with various phenotypes and comorbidities which are hardly to differentiate solely by LVEF and might benefit from individually tailored approaches. These hypotheses are supported by the recently presented PARAGON-HF trial. Although treatment with LCZ696 did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among HFpEF patients, subanalyses suggest beneficial effects in female patients and those with an LVEF between 45 and 57%. In the future, prospective randomized trials should focus on dedicated, well-defined subgroups based on various information such as clinical characteristics, biomarker levels, and imaging modalities. These could clarify the role of LCZ696 in selected individuals. Furthermore, sodium-glucose cotransporter-2 inhibitors have just proven efficient in HFrEF patients and are currently also studied in large prospective clinical trials enrolling HFpEF patients. In addition, several novel disease-modifying drugs that pursue different strategies such as targeting cardiac inflammation and fibrosis have delivered preliminary optimistic results and are subject of further research. Moreover, innovative device therapies may enhance management of HFpEF, but need prospective adequately powered clinical trials to confirm safety and efficacy regarding clinical outcomes. This review highlights the past, present, and future therapeutic approaches in HFpEF.
- Published
- 2020
7. Therapeutic approaches in heart failure with preserved ejection fraction: past, present, and future
- Author
-
Stefan D. Anker, Carsten Tschöpe, Michael Böhm, Christian Werner, Jan Wintrich, Christoph Maack, Ingrid Kindermann, Christian Ukena, Simina Selejan, Carolyn S.P. Lam, Ulrich Laufs, and Adriaan A. Voors
- Subjects
medicine.medical_specialty ,RENAL SYMPATHETIC DENERVATION ,Heart failure ,Review ,CARDIOVASCULAR OUTCOMES ,EXERCISE CAPACITY ,law.invention ,RESISTANT HYPERTENSION ,SYSTOLIC FUNCTION ,Angiotensin Receptor Antagonists ,CARDIAC-FUNCTION ,Randomized controlled trial ,law ,Internal medicine ,medicine ,VENTRICULAR MECHANICAL DYSSYNCHRONY ,Animals ,Humans ,LCZ696 ,Randomized Controlled Trials as Topic ,Ejection fraction ,business.industry ,Aminobutyrates ,PULMONARY-ARTERY PRESSURE ,Biphenyl Compounds ,Stroke Volume ,Atrial fibrillation ,General Medicine ,Preserved ejection fraction ,medicine.disease ,Pharmacotherapy in HFpEF ,DIASTOLIC FUNCTION ,Hospitalization ,Device therapy ,Clinical trial ,Drug Combinations ,Renal sympathetic denervation ,ATRIAL-FIBRILLATION ,Cardiology ,Valsartan ,Biomarker (medicine) ,Cardiology and Cardiovascular Medicine ,business ,Heart failure with preserved ejection fraction - Abstract
In contrast to the wealth of proven therapies for heart failure with reduced ejection fraction (HFrEF), therapeutic efforts in the past have failed to improve outcomes in heart failure with preserved ejection fraction (HFpEF). Moreover, to this day, diagnosis of HFpEF remains controversial. However, there is growing appreciation that HFpEF represents a heterogeneous syndrome with various phenotypes and comorbidities which are hardly to differentiate solely by LVEF and might benefit from individually tailored approaches. These hypotheses are supported by the recently presented PARAGON-HF trial. Although treatment with LCZ696 did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among HFpEF patients, subanalyses suggest beneficial effects in female patients and those with an LVEF between 45 and 57%. In the future, prospective randomized trials should focus on dedicated, well-defined subgroups based on various information such as clinical characteristics, biomarker levels, and imaging modalities. These could clarify the role of LCZ696 in selected individuals. Furthermore, sodium-glucose cotransporter-2 inhibitors have just proven efficient in HFrEF patients and are currently also studied in large prospective clinical trials enrolling HFpEF patients. In addition, several novel disease-modifying drugs that pursue different strategies such as targeting cardiac inflammation and fibrosis have delivered preliminary optimistic results and are subject of further research. Moreover, innovative device therapies may enhance management of HFpEF, but need prospective adequately powered clinical trials to confirm safety and efficacy regarding clinical outcomes. This review highlights the past, present, and future therapeutic approaches in HFpEF.
- Published
- 2020
8. Predictors of left ventricular remodelling in patients with dilated cardiomyopathy – a cardiovascular magnetic resonance study
- Author
-
Upasana Tayal, Amrit Lota, John G.F. Cleland, Amal Muthumala, Michael P. Frenneaux, John Gregson, Sanjay K Prasad, Suzan Hatipoglu, Ramasamy Manivarmane, Ravi Assomull, Stuart A. Cook, Ricardo Wage, James S. Ware, Cemil Izgi, Andrew D Scott, Dudley J. Pennell, Jason Dungu, Brian P Halliday, Simon Newsome, Wellcome Trust, British Heart Foundation, and Medical Research Council (MRC)
- Subjects
Male ,Cardiac & Cardiovascular Systems ,Magnetic Resonance Spectroscopy ,Dilated cardiomyopathy ,Contrast Media ,Gadolinium ,030204 cardiovascular system & hematology ,Ventricular Function, Left ,Ventricular Dysfunction, Left ,0302 clinical medicine ,Recovery ,PROGNOSTIC-SIGNIFICANCE ,Extracellular fluid ,Prospective Studies ,Prospective cohort study ,DOBUTAMINE STRESS ECHOCARDIOGRAPHY ,1102 Cardiorespiratory Medicine and Haematology ,Dobutamine stress ,BETA-BLOCKADE ,Ejection fraction ,Ventricular Remodeling ,medicine.diagnostic_test ,ASSOCIATION ,Myocardial remodelling ,PREVALENCE ,cardiovascular system ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,Life Sciences & Biomedicine ,Cardiomyopathy, Dilated ,Cardiac function curve ,medicine.medical_specialty ,IMPROVEMENT ,EJECTION FRACTION ,03 medical and health sciences ,CARDIAC-FUNCTION ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,Heart Failure ,Science & Technology ,MYOCARDIAL CONTRACTILE RESERVE ,business.industry ,Stroke Volume ,Magnetic resonance imaging ,medicine.disease ,Myocardial Contraction ,Cardiovascular System & Hematology ,Heart failure ,Cardiovascular System & Cardiology ,Myocardial fibrosis ,business ,SYSTOLIC HEART-FAILURE - Abstract
Aims:\ud There is an important need for better biomarkers to predict left ventricular (LV) remodelling in dilated cardiomyopathy (DCM). We undertook a comprehensive assessment of cardiac structure and myocardial composition to determine predictors of remodelling.\ud \ud Methods and results:\ud Prospective study of patients with recent‐onset DCM with cardiovascular magnetic resonance (CMR) assessment of ventricular structure and function, extracellular volume (T1 mapping), myocardial strain, myocardial scar (late gadolinium enhancement) and contractile reserve (dobutamine stress). Regression analyses were used to evaluate predictors of change in LV ejection fraction (LVEF) over 12 months. We evaluated 56 participants (34 DCM patients, median LVEF 43%; 22 controls). Absolute LV contractile reserve predicted change in LVEF (1% increase associated with 0.4% increase in LVEF at 12 months, P = 0.02). Baseline myocardial strain (P = 0.39 global longitudinal strain), interstitial myocardial fibrosis (P = 0.41), replacement myocardial fibrosis (P = 0.25), and right ventricular contractile reserve (P = 0.17) were not associated with LV reverse remodelling. There was a poor correlation between contractile reserve and either LV extracellular volume fraction (r = −0.22, P = 0.23) or baseline LVEF (r = 0.07, P = 0.62). Men were more likely to experience adverse LV remodelling (P = 0.01) but age (P = 0.88) and disease‐modifying heart failure medication (beta‐blocker, P = 0.28; angiotensin‐converting enzyme inhibitor, P = 0.92) did not predict follow‐up LVEF.\ud \ud Conclusions:\ud Substantial recovery of LV function occurs within 12 months in most patients with recent‐onset DCM. Women had the greatest improvement in LVEF. A low LV contractile reserve measured by dobutamine stress CMR appears to identify patients whose LVEF is less likely to recover.
- Published
- 2020
9. Emerging roles of extracellular vesicle-associated non-coding RNAs in hypoxia: Insights from cancer, myocardial infarction and ischemic stroke
- Author
-
Hermann, Dirk M., Xin, Wenqiang, Baehr, Mathias, Giebel, Bernd, and Doeppner, Thorsten R.
- Subjects
Inhibit Cardiomyocyte Apoptosis ,Promotes Angiogenesis ,Ischemia/Reperfusion Injury ,Cardiac-Function ,Cell Lung-Cancer ,Stromal Cells - Abstract
Hypoxia is a central pathophysiological component in cancer, myocardial infarction and ischemic stroke, which represent the most common medical conditions resulting in long-term disability and death. Recent evidence suggests common signaling pathways in these diverse settings mediated by non-coding RNAs (ncRNAs), which are packaged in extracellular vesicles (EVs) protecting ncRNAs from degradation. EVs are a heterogeneous group of lipid bilayer-covered vesicles released from virtually all cells, which have important roles in intercellular communication. Recent studies pointed out that ncRNAs including long non-coding RNAs (IncRNAs) and microRNAs (miRNAs) are selectively sorted into EVs, modulating specific aspects of cancer development, namely cell proliferation, migration, invasion, angiogenesis, immune tolerance or drug resistance, under conditions of hypoxia in recipient cells. In myocardial infarction and stroke, ncRNAs shuttled via EVs have been shown to control tissue survival and remodeling post-hypoxia by regulating cell injury, inflammatory responses, angiogenesis, neurogenesis or neuronal plasticity. This review discusses recent evidence on EV-associated ncRNAs in hypoxic cancer, myocardial infarction and stroke, discussing their cellular origin, biological function and disease significance. The emerging concept of IncRNA-circular RNA/ miRNA/ mRNA networks is outlined, upon which ncRNAs synergistically respond to hypoxia in order to modify disease responses. Particular notion is given to ncRNAs participating in at least two of the three conditions, which revealed a large degree of overlaps across pathophysiological conditions. Possible roles of EV-ncRNAs as therapeutic products or theranostic markers are defined.
- Published
- 2022
10. Left ventricular systolic ejection time is an independent predictor of all-cause mortality in heart failure with reduced ejection fraction
- Author
-
Alhakak, Alia S., Sengelov, Morten, Jørgensen, Peter G., Bruun, Niels E., Johnsen, Cecilie, Abildgaard, Ulrik, Iversen, Allan Z., Hansen, Thomas F., Teerlink, John R., Malik, Fady I., Solomon, Scott D., Gislason, Gunnar, Biering-Sorensen, Tor, Alhakak, Alia S., Sengelov, Morten, Jørgensen, Peter G., Bruun, Niels E., Johnsen, Cecilie, Abildgaard, Ulrik, Iversen, Allan Z., Hansen, Thomas F., Teerlink, John R., Malik, Fady I., Solomon, Scott D., Gislason, Gunnar, and Biering-Sorensen, Tor
- Abstract
Aims Colour tissue Doppler imaging (TDI) M-mode through the mitral leaflet is an easy and precise method to obtain cardiac time intervals including isovolumic contraction time (IVCT), isovolumic relaxation time (IVRT) and systolic ejection time (SET). The myocardial performance index (MPI) is defined as [(IVCT + IVRT)/SET]. Whether cardiac time intervals obtained by the TDI M-mode method can be used to predict outcome in patients with heart failure with reduced ejection fraction (HFrEF) remains unknown.Methods and results A total of 997 patients with HFrEF (mean age 67 +/- 11 years, 74% male) underwent an echocardiographic examination including TDI. During a median follow-up of 3.4 years (interquartile range 1.9-4.8 years), 165 (17%) patients died. The risk of mortality increased by 9% per 10 ms decrease in SET [per 10 ms decrease: hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.06-1.13; P <0.001]. The association remained significant even after multivariable adjustment for clinical and echocardiographic parameters (per 10 ms decrease: HR 1.06, 95% CI 1.01-1.11; P = 0.030). The MPI was a significant predictor in an unadjusted model (per 0.1 increase: HR 3.06, 95% CI 1.16-8.06; P = 0.023). However, the association did not remain significant after multivariable adjustment. No significant associations between IVCT or IVRT and mortality were found in unadjusted nor adjusted models. Additionally, SET provided incremental prognostic information with regard to predicting mortality when added to established clinical predictors of mortality in patients with HFrEF.Conclusion In patients with HFrEF, SET provides independent and incremental prognostic information regarding all-cause mortality.
- Published
- 2021
11. Sitagliptin does not reduce the risk of cardiovascular death or hospitalization for heart failure following myocardial infarction in patients with diabetes: observations from TECOS
- Author
-
Timo E. Strandberg, Michael A. Nauck, Tuncay Delibasi, Russell S. Scott, Harvey D. White, Rury R. Holman, Eric D. Peterson, Karen S. Pieper, Yuliya Lokhnygina, Darren K. McGuire, Axel Riefflin, HUS Internal Medicine and Rehabilitation, Timo Strandberg / Principal Investigator, Department of Medicine, Helsinki University Hospital Area, and Clinicum
- Subjects
Male ,lcsh:Diseases of the circulatory (Cardiovascular) system ,Time Factors ,Endocrinology, Diabetes and Metabolism ,Myocardial Infarction ,Type 2 diabetes ,030204 cardiovascular system & hematology ,MELLITUS ,0302 clinical medicine ,Risk Factors ,Case fatality rate ,IMPROVES ,REPERFUSION ,Myocardial infarction ,Original Investigation ,OUTCOMES ,GLUCAGON-LIKE PEPTIDE-1 ,Incidence ,Middle Aged ,ISCHEMIA ,3. Good health ,Hospitalization ,Treatment Outcome ,Sitagliptin ,Female ,Cardiology and Cardiovascular Medicine ,medicine.drug ,medicine.medical_specialty ,Cardiovascular outcomes ,030209 endocrinology & metabolism ,Acute myocardial infarction ,Placebo ,Risk Assessment ,03 medical and health sciences ,CARDIAC-FUNCTION ,Double-Blind Method ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Aged ,Heart Failure ,Dipeptidyl-Peptidase IV Inhibitors ,Proportional hazards model ,business.industry ,Sitagliptin Phosphate ,medicine.disease ,RECEPTOR AGONISTS ,SIZE ,Diabetes Mellitus, Type 2 ,lcsh:RC666-701 ,LIRAGLUTIDE ,3121 General medicine, internal medicine and other clinical medicine ,Heart failure ,business - Abstract
Background To examine the effects of the DPP-4i sitagliptin on CV outcomes during and after incident MI in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Methods TECOS randomized 14,671 participants with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) to sitagliptin or placebo, in addition to usual care. For those who had a within-trial MI, we analyzed case fatality, and for those with a nonfatal MI, we examined a composite cardiovascular (CV) outcome (CV death or hospitalization for heart failure [hHF]) by treatment group, using Cox proportional hazards models left-censored at the time of the first within-trial MI, without and with adjustment for potential confounders, in intention-to-treat analyses. Results During TECOS, 616 participants had ≥ 1 MI (sitagliptin group 300, placebo group 316, HR 0.95, 95% CI 0.81–1.11, P = 0.49), of which 25 were fatal [11 and 14, respectively]). Of the 591 patients with a nonfatal MI, 87 (15%) died subsequently, with 66 (11%) being CV deaths, and 57 (10%) experiencing hHF. The composite outcome occurred in 58 (20.1%; 13.9 per 100 person-years) sitagliptin group participants and 50 (16.6%; 11.7 per 100 person-years) placebo group participants (HR 1.21, 95% CI 0.83–1.77, P = 0.32, adjusted HR 1.23, 95% CI 0.83–1.82, P = 0.31). On-treatment sensitivity analyses also showed no significant between-group differences in post-MI outcomes. Conclusions In patients with type 2 diabetes and ASCVD experiencing an MI, sitagliptin did not reduce subsequent risk of CV death or hHF, contrary to expectations derived from preclinical animal models. Trial registration clinicaltrials.gov no. NCT00790205
- Published
- 2019
12. Fetal myocardial deformation measured with two-dimensional speckle-tracking echocardiography
- Author
-
N. H. M. van Oostrum, S.G. Oei, Sally-Ann B. Clur, J. O. E. H. van Laar, D. A. A. van der Woude, C. M. de Vet, E. R. van den Heuvel, Paediatric Cardiology, ACS - Amsterdam Cardiovascular Sciences, Eindhoven MedTech Innovation Center, and Signal Processing Systems
- Subjects
Male ,Left ,Speckle tracking echocardiography ,Heart Ventricles/diagnostic imaging ,Ventricular Function, Left ,Pregnancy ,REPRODUCIBILITY ,Medicine and Health Sciences ,Ventricular Function ,Prenatal ,Prospective Studies ,Longitudinal Studies ,Prospective cohort study ,Ultrasonography ,ARCHITECTURE ,Radiological and Ultrasound Technology ,two-dimensional speckle tracking ,Obstetrics and Gynecology ,Gestational age ,General Medicine ,Fetal Heart/diagnostic imaging ,VENTRICULAR STRAIN MECHANICS ,medicine.anatomical_structure ,Echocardiography ,Cardiology ,HEART ,Female ,pregnancy ,fetal strain ,Cardiac function curve ,medicine.medical_specialty ,Heart Ventricles ,Echocardiography/methods ,Ultrasonography, Prenatal ,deformation values ,Fetal Heart ,CARDIAC-FUNCTION ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Fetus ,strain rate ,business.industry ,Reproducibility of Results ,DIABETES-MELLITUS ,Bayes Theorem ,VELOCITY ,PERFORMANCE ,QUANTIFICATION ,medicine.disease ,PEAK SYSTOLIC STRAIN ,Reproductive Medicine ,Ventricle ,Reference values ,business - Abstract
Objectives: Two-dimensional speckle-tracking echocardiography (2D-STE) is a promising technique which allows assessment of fetal cardiac function, and can be used in the evaluation of cardiac and non-cardiac diseases in pregnancy. However, reliable fetal reference values for deformation parameters measured using 2D-STE are needed before it can be introduced into clinical practice. This study aimed to obtain reference values for fetal global longitudinal strain (GLS) and GLS rate (GLSR) measured using 2D-STE and compare right and left ventricular values. Methods: This was a prospective longitudinal cohort study of uncomplicated pregnancies that underwent echocardiography every 4 weeks from inclusion at 18–21 weeks until delivery to obtain four-chamber loops of the fetal heart. Left and right ventricular GLS and GLSR were measured using 2D-STE at each examination. Using Bayesian mixed-effects models, reference values with lower and upper 5% prediction limits were calculated according to gestational age. Right and left ventricular GLS values according to gestational age were compared using the Wilcoxon signed-rank test. Results: A total of 592 left ventricular and 566 right ventricular GLS and GLSR measurements were obtained from 124 women with uncomplicated pregnancy and non-anomalous, appropriately grown fetuses. Reference values were obtained for both fetal ventricles according to gestational week. GLS and GLSR values of both ventricles increased (i.e. became less negative) significantly during pregnancy. Right ventricular GLS values were significantly higher (i.e. less negative) than the respective left ventricular values at every gestational week. Conclusions: Reference values were obtained for fetal GLS and GLSR measured using 2D-STE. GLS and GLSR values increased significantly for both ventricles from the second trimester until delivery. GLS values were significantly higher for the right ventricle compared with the left ventricle. Future studies are needed to assess whether the obtained reference values are helpful in clinical practice in the assessment of pregnancy complications, such as fetal growth restriction or cardiac anomaly. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
- Published
- 2021
13. Effects of dispersant treated oil upon exploratory behaviour in juvenile European sea bass (Dicentrarchus labrax)
- Author
-
Christophe Lebigre, Nicolas Le Bayon, Cassandre Aimon, Guy Claireaux, Stéphane Le Floch, Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de documentation de recherche et d'expérimentations sur les pollutions accidentelles des eaux (Cedre), Cedre, Unité de recherche Sciences et Technologies Halieutiques (STH), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Institut Français de Recherche pour l'Exploitation de la Mer - Brest (IFREMER Centre de Bretagne), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Sciences et Technologies Halieutiques (STH)
- Subjects
Health, Toxicology and Mutagenesis ,0211 other engineering and technologies ,02 engineering and technology ,010501 environmental sciences ,environmental-pollutants ,01 natural sciences ,Environmental pollution ,chemistry.chemical_compound ,GE1-350 ,Petroleum Pollution ,media_common ,polycyclic aromatic-hydrocarbons ,Aquatic ecosystem ,General Medicine ,Pollution ,fish embryos ,petroleum-hydrocarbons ,Petroleum ,TD172-193.5 ,Dicentrarchus ,Exploration ,media_common.quotation_subject ,Zoology ,panorama ,Biology ,Dispersant ,Animals ,Juvenile ,Behaviour ,14. Life underwater ,Sea bass ,European sea bass ,Ecosystem ,0105 earth and related environmental sciences ,021110 strategic, defence & security studies ,cardiac-function ,Public Health, Environmental and Occupational Health ,Oil spill ,biology.organism_classification ,Hydrocarbons ,Environmental sciences ,danio-rerio ,Open field test ,chemistry ,13. Climate action ,swimming performance ,exposure ,horizon crude-oil ,Exploratory Behavior ,locomotor-activity ,Bass ,[SDE.BE]Environmental Sciences/Biodiversity and Ecology ,Teleost fish ,Water Pollutants, Chemical - Abstract
WOS:000604141800013; International audience; Accidental spills are pervasive pollution in aquatic ecosystems. Resorting to chemical dispersant is one of the most implemented strategies in response to oil spills, but it results in an increase in the bio-availability of oil compounds known to disturb fish neurosensory capacities and hence fish habitat use. While it has become well established that acute oil exposure can cause a range of physiological defects, sub-lethal consequences on animal behaviour have only received recent attention. Here we investigated the effect of an exposure to a 62 h-dispersant treated oil on the exploration tendency (exploratory activity, and avoidance of unfamiliar open areas) of juvenile European sea bass. Three different concentrations of chemically dispersed oil were tested, low and medium conditions bracketing the range of likely situations that fish encounter following an oil spill, the high dose representing a more severe condition. Fish recovery capacities were also evaluated during 2 weeks post-exposure. Our results suggest a dose-response relationship; the low dose (0.048 +/- 0.007 g L-1 of total petroleum hydrocarbons ([TPH])) had no effect on sea bass behavioural response to a novel environment while medium (0.243 +/- 0.012 g L-1 [TPH]) and high (0.902 +/- 0.031 g L-1 [TPH]) doses altered fish exploratory activity and their typical avoidance of unfamiliar open areas. Our experiment also suggest signs of recovery capacities in the first 10 days following oil exposure even if fish might need more time to fully recover from observed alterations. We discuss the possibility that observed alterations may result from a neurosensory or physiological known defects of oil exposure, causing anaesthetic-like sedative behaviours. Altogether, this study shows that juvenile sea bass exposed to oil spill exhibit transient behavioural impairments that may have major population-level consequences given the high mortality experienced by juveniles.
- Published
- 2021
14. Left and right ventricular functions may be impaired in children diagnosed with subclinical hypothyroidism
- Author
-
Alper Akın, Mehmet Türe, Ruken Yıldırım, Edip Unal, Hasan Balık, Yusuf Kenan Haspolat, Dicle Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Çocuk Sağlığı ve Hastalıkları Ana Bilim Dalı, Akın, Alper, Ünal, Edip, Yıldırım, Ruken, Türe, Mehmet, Balık, Hasan, and Haspolat, Yusuf Kenan
- Subjects
Male ,Performance ,Ventricular Dysfunction, Right ,Doppler-echocardiograhy ,lcsh:Medicine ,Cardiac-function ,030204 cardiovascular system & hematology ,Adolescents ,Doppler imaging ,Ventricular Dysfunction, Left ,0302 clinical medicine ,Disease ,Myocardial Performance Index ,Patient group ,lcsh:Science ,Child ,L-Thyroxine therapy ,Subclinical infection ,Multidisciplinary ,Ventricular function ,Echocardiography, Doppler ,Child, Preschool ,Cardiology ,cardiovascular system ,Female ,Thyroid-hormone ,Risk ,Cardiac function curve ,medicine.medical_specialty ,congenital, hereditary, and neonatal diseases and abnormalities ,Adolescent ,Diastole ,030209 endocrinology & metabolism ,Article ,03 medical and health sciences ,Diastolic-function ,Hypothyroidism ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,Normal range ,business.industry ,lcsh:R ,Cardiovascular biology ,Thyroid diseases ,Thyroxine ,Dysfunction ,Case-Control Studies ,lcsh:Q ,business - Abstract
Subclinical hypothyroidism (SH) may influence both ventricular functions. The aim of this study was to evaluation the findings of Tissue Doppler Imaging (TDI) and other echocardiography modalities in children with SH. We compared left ventricular mass index (LVMI) and TDI parameters of patients with SH and children with euthyroidism. Subclinical hypothyroidism was diagnosed when thyroid stimulating hormone level was higher than the reference value of the laboratory (> 4.2 mIU/L) and free thyroxine level was in normal range. The study included a group of 35 patients with SH and a control group of 38 children with euthyroidism (mean age was 7.6 ± 3.5 years and 9.0 ± 2.4 years, respectively). LVMI was significantly higher in the patient group (p = 0.005). TDI parameters including mitral septal ejection time was lower (p = 0.003) and mitral septal myocardial performance index was higher (p = 0.009) in the patient group. Right ventricular TDI revealed that tricuspid lateral E/Ea and tricuspid septal E/Ea were higher (p = 0.015 and p = 0.024, respectively) and tricuspid septal Ea/Aa and ejection time were lower (p = 0.018 and p = 0.017, respectively) in the patient group. SH may lead to increase LVMI. Left ventricular systolic and diastolic TDI parameters (lower mitral septal ejection time, higher mitral septal myocardial performance index) as well as right ventricular systolic (lower tricuspid septal ejection time) and diastolic (higher tricuspid septal and lateral E/Ea, lower tricuspid septal Ea/Ea) functions may be also impaired in children with subclinical hypothyroidism. TDI is a useful method used for the assessment of the effect of SH on cardiac functions.
- Published
- 2020
15. The Interaction of the Endogenous Hydrogen Sulfide and Oxytocin Systems in Fluid Regulation and the Cardiovascular System
- Author
-
Christiane Waller, Tamara Merz, Peter Radermacher, Sarah Ecker, Nicole Denoix, Oscar McCook, and Rui Wang
- Subjects
0301 basic medicine ,DOWN-REGULATION ,DDC 540 / Chemistry & allied sciences ,Biological correlates ,Physiology ,Clinical Biochemistry ,hydrogen sulfide ,Endogeny ,Biochemistry ,0302 clinical medicine ,DDC 570 / Life sciences ,INDUCED CARDIOPROTECTION ,Atrial natriuretic peptides ,Psychosomatische Störung ,Hydrogen sulfide ,cardiovascular ,DDC 600 / Technology (Applied sciences) ,Stickstoffoxidsynthase ,Cardiovascular system ,psychosomatic medicine ,ddc:540 ,PORCINE MODEL ,Perspective ,Blood pressure ,H2S DONORS ,medicine.drug ,Psychological trauma ,medicine.medical_specialty ,Cystathionine gamma-lyase ,Blutdruck ,Stress ,Physical trauma ,03 medical and health sciences ,CARDIAC-FUNCTION ,ddc:570 ,medicine ,Molecular Biology ,Fluid regulation ,cystathionine γ-lyase ,Cystathioninlyase (Cystathionin-gamma-lyase) ,business.industry ,lcsh:RM1-950 ,Psychosomatic medicine ,Nitric oxide ,Cell Biology ,Medicine, Psychosomatic ,medicine.disease ,equipment and supplies ,Oxytocin receptor ,oxytocin receptor ,030104 developmental biology ,lcsh:Therapeutics. Pharmacology ,Oxytocin ,fluid regulation ,business ,Schwefelwasserstoff ,Neuroscience ,ddc:600 ,030217 neurology & neurosurgery - Abstract
The purpose of this review is to explore the parallel roles and interaction of hydrogen sulfide (H2S) and oxytocin (OT) in cardiovascular regulation and fluid homeostasis. Their interaction has been recently reported to be relevant during physical and psychological trauma. However, literature reports on H2S in physical trauma and OT in psychological trauma are abundant, whereas available information regarding H2S in psychological trauma and OT in physical trauma is much more limited. This review summarizes recent direct and indirect evidence of the interaction of the two systems and their convergence in downstream nitric oxide-dependent signaling pathways during various types of trauma, in an effort to better understand biological correlates of psychosomatic interdependencies., publishedVersion
- Published
- 2020
16. Reduced right ventricular function on cardiovascular magnetic resonance imaging is associated with uteroplacental impairment in tetralogy of Fallot
- Author
-
Michael G. Dickinson, Gertjan T. Sieswerda, Anne S. Siegmund, Tineke P. Willems, Berto J. Bouma, Monique R.M. Jongbloed, Arie P.J. van Dijk, Jolien W. Roos-Hesselink, Thomas M. Gorter, Petronella G. Pieper, Dirk J. van Veldhuisen, Caterina M. Bilardo, Cardiovascular Centre (CVC), Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Cardiology, ACS - Heart failure & arrhythmias, and ACS - Pulmonary hypertension & thrombosis
- Subjects
lcsh:Diseases of the circulatory (Cardiovascular) system ,Heart disease ,Ventricular Dysfunction, Right ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,030204 cardiovascular system & hematology ,Umbilical Arteries ,030218 nuclear medicine & medical imaging ,0302 clinical medicine ,Risk Factors ,Prenatal Diagnosis ,Tetralogy of Fallot ,Ejection fraction ,Radiological and Ultrasound Technology ,WOMEN ,REFERENCE RANGES ,CONGENITAL HEART-DISEASE ,Uterine Artery ,PREGNANCY ,Uteroplacental Circulation ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,Blood Flow Velocity ,Adult ,Cardiac function curve ,VENOUS CONGESTION ,medicine.medical_specialty ,RENAL-FUNCTION ,Magnetic Resonance Imaging, Cine ,EJECTION FRACTION ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,CARDIAC-FUNCTION ,Predictive Value of Tests ,Internal medicine ,medicine.artery ,medicine ,Humans ,Placental Circulation ,Radiology, Nuclear Medicine and imaging ,Cardiac Surgical Procedures ,Retrospective Studies ,Angiology ,Congenital heart disease ,Pregnancy ,BLOOD-FLOW ,business.industry ,Research ,Ultrasonography, Doppler ,Umbilical artery ,medicine.disease ,Right ventricular function ,DOPPLER FLOW ,lcsh:RC666-701 ,Ventricular Function, Right ,Uteroplacental circulation ,business - Abstract
Background Maternal right ventricular (RV) dysfunction (measured by echocardiography) is associated with impaired uteroplacental circulation, however echocardiography has important limitations in the assessment of RV function. We therefore aimed to investigate the association of pre-pregnancy RV and left ventricular (LV) function measured by cardiovascular magnetic resonance with uteroplacental Doppler flow parameters in pregnant women with repaired Tetralogy of Fallot (ToF). Methods Women with repaired ToF were examined, who had been enrolled in a prospective multicenter study of pregnant women with congenital heart disease. Clinical data and CMR evaluation before pregnancy were compared with uteroplacental Doppler parameters at 20 and 32 weeks gestation. In particular, pulsatility index (PI) of uterine and umbilical artery were studied. Results We studied 31 women; mean age 30 years, operated at early age. Univariable analyses showed that reduced RV ejection fraction (RVEF; P = 0.037 and P = 0.001), higher RV end-systolic volume (P = 0.004) and higher LV end-diastolic and end-systolic volume (P = 0.001 and P = 0.003, respectively) were associated with higher uterine or umbilical artery PI. With multivariable analyses (corrected for maternal age and body mass index), reduced RVEF before pregnancy remained associated with higher umbilical artery PI at 32 weeks (P = 0.002). RVEF was lower in women with high PI compared to women with normal PI during pregnancy (44% vs. 53%, p = 0.022). LV ejection fraction was not associated with uterine or umbilical artery PI. Conclusions Reduced RV function before pregnancy is associated with abnormal uteroplacental Doppler flow parameters. It could be postulated that reduced RV function on pre-pregnancy CMR (≤2 years) is a predisposing factor for impaired placental function in women with repaired ToF.
- Published
- 2020
17. Interbreed variation in serum serotonin (5-hydroxytryptamine) concentration in healthy dogs
- Author
-
Merete Fredholm, J. Lundgren Willesen, L. Mejer Sørensen, Anne-Sophie Lequarré, Valérie Chetboul, Katja Höglund, K. Mc Entee, Eija H. Seppälä, Hannes Lohi, Vassiliki Gouni, Laurent Tiret, Anne-Christine Merveille, Sofia Hanås, Ingrid Ljungvall, Jens Häggström, Maria Wiberg, Doctoral Programme in Clinical Veterinary Medicine, Maria Wiberg / Principal Investigator, Equine and Small Animal Medicine, Departments of Faculty of Veterinary Medicine, University of Helsinki, Research Programs Unit, Research Programme for Molecular Neurology, Doctoral Programme in Integrative Life Science, and Hannes Tapani Lohi / Principal Investigator
- Subjects
Male ,EXPRESSION ,0301 basic medicine ,Cardiac function curve ,Serotonin ,Time Factors ,Heart disease ,KING CHARLES SPANIELS ,040301 veterinary sciences ,Physiology ,5-HT ,Enzyme-Linked Immunosorbent Assay ,Breed difference ,HEART-DISEASE ,413 Veterinary science ,Specimen Handling ,Canine ,0403 veterinary science ,03 medical and health sciences ,Dogs ,Species Specificity ,CARDIAC-FUNCTION ,Interquartile range ,PLATELET SEROTONIN ,medicine ,Animals ,Heart valve ,BREED ,Myxomatous mitral valve ,2. Zero hunger ,PLASMA ,General Veterinary ,business.industry ,Biomarker ,04 agricultural and veterinary sciences ,medicine.disease ,MITRAL-VALVE DISEASE ,Breed ,030104 developmental biology ,medicine.anatomical_structure ,Echocardiography ,Biomarker (medicine) ,Female ,PERIPHERAL SEROTONIN ,business - Abstract
Serotonin (5-hydroxytryptamine [5-HT]) has several biological functions. In different species, excessive 5-HT has been linked to valvular lesions, similar to those seen in dogs with myxomatous mitral valve disease. Previous studies suggest higher 5-HT in healthy Cavalier King Charles Spaniels (CKCSs), a breed highly affected by myxomatous mitral valve disease, compared to other breeds.To investigate potential interbreed variation in serum 5-HT in healthy dogs.483 healthy dogs of nine breeds aged 1-7 years.Dogs were examined at five European centers. Absence of cardiovascular, organ-related, or systemic diseases was ensured by thorough clinical investigations including echocardiography. Serum was frozen and later analyzed by enzyme-linked immunosorbent assay (ELISA).Median 5-HT concentration was 252.5 (interquartile range = 145.5-390.6) ng/mL. Overall breed difference was found (p0.0001), and 42% of pairwise breed comparisons were significant. Univariate regression analysis showed association between serum 5-HT concentration and breed, center of examination, storage time, and sex, with higher 5-HT in females. In multiple regression analysis, the final model had an adjusted RInterbreed variation in serum 5-HT concentration was found in healthy dogs aged 1-7 years. These differences should be taken into account when designing clinical studies.
- Published
- 2018
18. One-year unsupervised individualized exercise training intervention enhances cardiorespiratory fitness but not muscle deoxygenation or glycemic control in adults with type 1 diabetes
- Author
-
Heikki O. Tikkanen, Juha Peltonen, Antti-Pekka E. Rissanen, Anne S. Koponen, Jyrki M. Aho, Clinicum, Department of Diagnostics and Therapeutics, and University of Helsinki
- Subjects
Blood Glucose ,Male ,Time Factors ,Sports medicine ,near-infrared spectroscopy ,Physiology ,Endocrinology, Diabetes and Metabolism ,Training intervention ,law.invention ,Hemoglobins ,0302 clinical medicine ,Randomized controlled trial ,law ,ALL-CAUSE MORTALITY ,COMPLICATIONS ,SPECTROSCOPY ,Exercise Tolerance ,Nutrition and Dietetics ,diabetes ,deoxygenation ,General Medicine ,RANDOMIZED CONTROLLED-TRIAL ,Adaptation, Physiological ,Oxygen uptake ,Treatment Outcome ,Cardiorespiratory Fitness ,SKELETAL-MUSCLE ,Adult ,medicine.medical_specialty ,030209 endocrinology & metabolism ,SPORTS-MEDICINE ,03 medical and health sciences ,Oxygen Consumption ,CARDIAC-FUNCTION ,Physiology (medical) ,Diabetes mellitus ,medicine ,Humans ,Muscle, Skeletal ,METAANALYSIS ,Glycemic ,Glycated Hemoglobin ,Type 1 diabetes ,business.industry ,Resistance Training ,Cardiorespiratory fitness ,030229 sport sciences ,medicine.disease ,Oxygen ,PHYSICAL-ACTIVITY ,Diabetes Mellitus, Type 1 ,3121 General medicine, internal medicine and other clinical medicine ,glycemic control ,Exercise Test ,Physical therapy ,OXYGEN-UPTAKE ,business ,Biomarkers - Abstract
Adaptations to long-term exercise training in type 1 diabetes are sparsely studied. We examined the effects of a 1-year individualized training intervention on cardiorespiratory fitness, exercise-induced active muscle deoxygenation, and glycemic control in adults with and without type 1 diabetes. Eight men with type 1 diabetes (T1D) and 8 healthy men (CON) matched for age, anthropometry, and peak pulmonary O2 uptake, completed a 1-year individualized training intervention in an unsupervised real-world setting. Before and after the intervention, the subjects performed a maximal incremental cycling test, during which alveolar gas exchange (volume turbine and mass spectrometry) and relative concentration changes in active leg muscle deoxygenated (Δ[HHb]) and total (Δ[tHb]) hemoglobin (near-infrared spectroscopy) were monitored. Peak O2 pulse, reflecting peak stroke volume, was calculated (peak pulmonary O2 uptake/peak heart rate). Glycemic control (glycosylated hemoglobin A1c (HbA1c)) was evaluated. Both T1D and CON averagely performed 1 resistance-training and 3–4 endurance-training sessions per week (∼1 h/session at ∼moderate intensity). Training increased peak pulmonary O2 uptake in T1D (p = 0.004) and CON (p = 0.045) (group × time p = 0.677). Peak O2 pulse also rose in T1D (p = 0.032) and CON (p = 0.018) (group × time p = 0.880). Training increased leg Δ[HHb] at peak exercise in CON (p = 0.039) but not in T1D (group × time p = 0.052), while no changes in leg Δ[tHb] at any work rate were observed in either group (p > 0.05). HbA1c retained unchanged in T1D (from 58 ± 10 to 59 ± 11 mmol/mol, p = 0.609). In conclusion, 1-year adherence to exercise training enhanced cardiorespiratory fitness similarly in T1D and CON but had no effect on active muscle deoxygenation or glycemic control in T1D.
- Published
- 2018
19. Rationale of the FIBROTARGETS study designed to identify novel biomarkers of myocardial fibrosis
- Subjects
EXTRACELLULAR-MATRIX TURNOVER ,CONGESTIVE-HEART-FAILURE ,Myocardium/metabolism ,Fibrosis/metabolism ,Heart failure ,DIASTOLIC DYSFUNCTION ,Biomarkers/analysis ,MICRORNA SIGNATURES DIFFERENTIATE ,GELATINASE-ASSOCIATED LIPOCALIN ,CARDIAC-FUNCTION ,CARDIOVASCULAR-DISEASE ,HYPERTENSIVE PATIENTS ,Research Design ,Myocardial fibrosis ,Fibrotic bioprofiles ,COLLAGEN CROSS-LINKING ,CIRCULATING BIOMARKERS ,Humans ,Animals ,Cardiomyopathies/metabolism - Abstract
Aims Myocardial fibrosis alters the cardiac architecture favouring the development of cardiac dysfunction, including arrhythmias and heart failure. Reducing myocardial fibrosis may improve outcomes through the targeted diagnosis and treatment of emerging fibrotic pathways. The European-Commission-funded 'FIBROTARGETS' is a multinational academic and industrial consortium with the main aims of (i) characterizing novel key mechanistic pathways involved in the metabolism of fibrillary collagen that may serve as biotargets, (ii) evaluating the potential anti-fibrotic properties of novel or repurposed molecules interfering with the newly identified biotargets, and (iii) characterizing bioprofiles based on distinct mechanistic phenotypes involving the aforementioned biotargets. These pathways will be explored by performing a systematic and collaborative search for mechanisms and targets of myocardial fibrosis. These mechanisms will then be translated into individualized diagnostic tools and specific therapeutic pharmacological options for heart failure. Methods and results The FIBROTARGETS consortium has merged data from 12 patient cohorts in a common database available to individual consortium partners. The database consists of >12000 patients with a large spectrum of cardiovascular clinical phenotypes. It integrates community-based population cohorts, cardiovascular risk cohorts, and heart failure cohorts. Conclusions The FIBROTARGETS biomarker programme is aimed at exploring fibrotic pathways allowing the bioprofiling of patients into specific 'fibrotic' phenotypes and identifying new therapeutic targets that will potentially enable the development of novel and tailored anti-fibrotic therapies for heart failure.
- Published
- 2018
20. Effect of eplerenone in patients with heart failure and reduced ejection fraction
- Subjects
BODY-MASS INDEX ,ADIPOSE-TISSUE ,MINERALOCORTICOID RECEPTOR ANTAGONISM ,CARDIAC-FUNCTION ,CARDIOVASCULAR-DISEASE ,CARDIOMETABOLIC RISK ,PARADOX ,ADIPOCYTE DYSFUNCTION ,Abdominal obesity ,Heart failure with reduced ejection fraction ,ALDOSTERONE BLOCKADE ,WAIST CIRCUMFERENCE ,Eplerenone - Abstract
Aims: An excessive production of aldosterone influences outcome in patients with heart failure (HF) and in obese patients. Findings from laboratory studies suggest that chronic aldosterone blockade maybe more beneficial in abdominally obese HF-prone rats. In the current study, we investigated if the clinical response to a mineralocorticoid receptor antagonist in mildly symptomatic HF patients varied by abdominal obesity. Methods and results: A total of 2587 NYHA class II, reduced ejection fraction HF (HFrEF) patients enrolled in the EMPHASIS-HF trial were randomly assigned to eplerenone and placebo. In this post hoc analysis, patients were categorized according to waist circumference (WC) (normal if WC = 88 cm in women; abdominal obesity if WC = 102 cm in men and= 88 cm women). The potential statistical interaction between the treatment and WC was assessed on the primary endpoint of death from cardiovascular causes or hospitalization for HF and other secondary endpoints. Over a median follow-up of 21 months, a significant benefit of eplerenone for the primary outcome was noted in both normal [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.61-0.98, P = 0.03] and increased (HR 0.48, 95% CI 0.37-0.63, P
- Published
- 2017
21. Human Pericardial Fluid Contains Exosomes Enriched with Cardiovascular-Expressed MicroRNAs and Promotes Therapeutic Angiogenesis
- Author
-
Fausto Sessa, Gianni D Angelini, Abas Laftah, Enrico Petretto, Gaia Spinetti, Andrew I U Shearn, Cha Rajakaruna, Cristina Beltrami, Saran Shantikumar, Costanza Emanueli, and Marie Besnier
- Subjects
Male ,Ribonuclease III ,0301 basic medicine ,Angiogenesis ,Research & Experimental Medicine ,Cardiovascular System ,CARDIOMYOCYTES ,Mice ,angiogenesis ,10 Technology ,Drug Discovery ,CARDIAC-HYPERTROPHY ,11 Medical and Health Sciences ,Genetics & Heredity ,let-7b ,Neovascularization, Pathologic ,biology ,clinical samples ,Argonaute ,microRNAs ,Cell biology ,Medicine, Research & Experimental ,Cardiovascular Diseases ,Centre for Surgical Research ,pericardial fluid ,Argonaute Proteins ,HEART ,Molecular Medicine ,Original Article ,extracellular vesicles ,Life Sciences & Biomedicine ,STEM-CELLS ,Biotechnology ,Neovascularization, Physiologic ,exosomes ,ischemia ,DIAGNOSIS ,Exosome ,human ,Animals ,Endothelial Cells ,Exosomes ,Extracellular Vesicles ,Gene Expression Profiling ,Humans ,MicroRNAs ,Pericardial Fluid ,Molecular Biology ,Genetics ,Pharmacology ,Drug Discovery3003 Pharmaceutical Science ,Pericardial Effusion ,03 medical and health sciences ,CARDIAC-FUNCTION ,microRNA ,Gene silencing ,Therapeutic angiogenesis ,Physiologic ,Neovascularization ,Pathologic ,REPAIR ,Science & Technology ,06 Biological Sciences ,DICER ,ENDOTHELIAL-CELLS ,Microvesicles ,030104 developmental biology ,Biotechnology & Applied Microbiology ,MYOCARDIAL-INFARCTION ,Immunology ,Commentary ,biology.protein ,MEDIATE ,Dicer - Abstract
The pericardial fluid (PF) is contained in the pericardial sac surrounding the heart. MicroRNA (miRNA) exchange via exosomes (endogenous nanoparticles) contributes to cell-to-cell communication. We investigated the hypotheses that the PF is enriched with miRNAs secreted by the heart and that it mediates vascular responses through exosome exchange of miRNAs. The study was developed using leftover material from aortic valve surgery. We found that in comparison with peripheral plasma, the PF contains exosomes enriched with miRNAs co-expressed in patients’ myocardium and vasculature. At a functional level, PF exosomes improved survival, proliferation, and networking of cultured endothelial cells (ECs) and restored the angiogenic capacity of ECs depleted (via Dicer silencing) of their endogenous miRNA content. Moreover, PF exosomes improved post-ischemic blood flow recovery and angiogenesis in mice. Mechanistically, (1) let-7b-5p is proangiogenic and inhibits its target gene, TGFBR1, in ECs; (2) PF exosomes transfer a functional let-7b-5p to ECs, thus reducing their TGFBR1 expression; and (3) let-7b-5p depletion in PF exosomes impairs the angiogenic response to these nanoparticles. Collectively, our data support the concept that PF exosomes orchestrate vascular repair via miRNA transfer., Graphical Abstract, The heart is surrounded by pericardial fluid contained within the pericardial sac. Beltrami et al. show that exosomes within the pericardial fluid can induce proangiogenic responses via shuttling let-7b-5p into endothelial cells. These findings identify the pericardial space as a niche of cell-to-cell communication.
- Published
- 2017
22. Uteroplacental Doppler flow and pregnancy outcome in women with tetralogy of Fallot
- Subjects
CONGENITAL HEART-DISEASE ,PREECLAMPSIA ,COMPLICATIONS ,pregnancy outcome ,CARDIAC-FUNCTION ,BLOOD-FLOW ,UTERINE ARTERY DOPPLER ,REPAIRED TETRALOGY ,utcroplacental Doppler flow ,congenital heart disease ,DYSFUNCTION ,SURGICAL-CORRECTION ,REFERENCE RANGES - Abstract
Objective Pregnancy in women with surgically corrected tetralogy of Fallot (ToF) is associated with cardiac, obstetric and neonatal complications. We compared uteroplacental Doppler flow (UDF) measurements and pregnancy outcome in women with ToF and in healthy women and aimed to assess whether a relationship exists between cardiac function and UDF in women with ToF.Methods We evaluated prospectively pregnant women with ToF and healthy pregnant women from the ZAHARA studies. Clinical evaluation, standardized echocardiography and UDF measurements were performed at 20 and 32weeks' gestation.Results We included 62 women with ToF and 69 healthy controls. Cardiac complications, mostly arrhythmia, occurred in 8.1% of women with ToF. There was a higher incidence of small-for-gestational age (21.0% vs 4.4%, P= 0.004) and low birth weight (16.1% vs 2.9%, P = 0.009) in the group of women with ToF than in healthy controls. In women with ToF, early diastolic notching of uterine artery waveform at 20 and 32weeks occurred more frequently (9.8% vs 1.5%, P = 0.034 and 7.0% vs 0%, P = 0.025, respectively) and the umbilical artery pulsatility index at 32weeks was higher (1.02 +/- 0.20 vs 0.94 +/- 0.17, P= 0.015) than in healthy controls. Right ventricular function parameters prepregnancy and at 20weeks' gestation were significantly associated with abnormal UDF. UDF parameters were associated with adverse neonatal outcome.Conclusion The majority of women with surgically corrected ToF tolerate pregnancy well. However, UDF indices are more frequently abnormal in these women, suggesting impaired placentation. The association of impaired right ventricular function parameters with abnormal UDF suggests that cardiac dysfunction contributes to defective placentation or placental perfusion mismatch and may explain the increased incidence of obstetric and neonatal complications.(C) 2016 ISUOG.
- Published
- 2017
23. Sports activity in adolescents in the Netherlands with a pectus excavatum; the impact of surgery
- Author
-
Gerda W. Zijp, Jan W.A. Oosterhuis, Robertine van Baren, Wietse P. Zuidema, Elly S.M. de Lange-de Klerk, Alida F. W. van der Steeg, Stefan M. van der Heide, Lodewijk W.E. van Heurn, Surgery, Amsterdam Reproduction & Development (AR&D), Epidemiology and Data Science, Pediatrics, AGEM - Re-generation and cancer of the digestive system, APH - Quality of Care, Paediatric Surgery, AGEM - Endocrinology, metabolism and nutrition, and Faculteit Medische Wetenschappen/UMCG
- Subjects
Male ,Team sport ,Chest wall deformity ,MULTICENTER ,BODY-IMAGE ,0302 clinical medicine ,QUALITY-OF-LIFE ,Surveys and Questionnaires ,IMPROVES ,Postoperative Period ,Prospective Studies ,Pectus excavatum ,Netherlands ,Pediatric ,COMPLICATIONS ,General Medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Preoperative Period ,Female ,medicine.symptom ,Thoracic wall ,Sports ,medicine.medical_specialty ,Adolescent ,Physical activity ,SURGICAL-CORRECTION ,Young Adult ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,CARDIAC-FUNCTION ,030225 pediatrics ,medicine ,Deformity ,Humans ,Sports activity ,REPAIR ,Individual sport ,business.industry ,Other Research Radboud Institute for Health Sciences [Radboudumc 0] ,PULMONARY-FUNCTION ,medicine.disease ,Surgery ,Dyspnea ,PHYSICAL-ACTIVITY ,Funnel Chest ,Pediatrics, Perinatology and Child Health ,business ,human activities - Abstract
Purpose: Pectus excavatum (PE) is the most common chest wall deformity in adolescents. The main complaint is cosmetic, but many patients also complain about exertional dyspnea. This may lead to the patient seeking surgery of the thoracic wall deformity (TWD). The assumption is that both, appearance and physical complaints will have a negative effect on being able or wanting to engage in sport activity. Methods: In December 2011 a prospective registration of sport activity in pectus excavatum patients started. Sport activity was assessed using questionnaires (CHQ SF-36 and PEEQ). Measurements were taken before corrective surgery (preoperatively) and 12 months postoperatively. Results: 127 patients have been included. The number of patients who were active in sports preoperatively and after 12 months remained steady. The type of sport activity, individual sport or team sport showed no significant change. The CHQ showed that physical activity caused fewer complaints (p
- Published
- 2019
24. A comparison of two quasi-static computational models for assessment of intra-myocardial injection as a therapeutic strategy for heart failure
- Author
-
William Whyte, Sean B. Leen, Ellen T. Roche, Yiling Fan, Peter E. McHugh, Irvin Teh, William Ronan, Claudia E. Varela, and Jürgen E. Schneider
- Subjects
Cardiac function curve ,DYNAMICS ,medicine.medical_specialty ,STRESS ,Heart Ventricles ,Finite Element Analysis ,DIFFUSION TENSOR ,Biomedical Engineering ,Biocompatible Materials ,Injections ,DELIVERY ,Imaging, Three-Dimensional ,CARDIAC-FUNCTION ,Internal medicine ,Animals ,Humans ,Medicine ,Computer Simulation ,Myocytes, Cardiac ,Myocardial infarction ,Lead (electronics) ,Molecular Biology ,Heart Failure ,Ejection fraction ,Ventricular Remodeling ,Cardiac cycle ,business.industry ,Applied Mathematics ,HYDROGEL ,Models, Cardiovascular ,Hydrogels ,medicine.disease ,VENTRICULAR-FUNCTION ,Diffusion Tensor Imaging ,medicine.anatomical_structure ,Computational Theory and Mathematics ,Ventricle ,Modeling and Simulation ,Heart failure ,MECHANICS ,Cardiology ,business ,MYOCARDIUM ,Software ,Diffusion MRI ,ACTIVE-STRAIN - Abstract
Myocardial infarction, or heart attack, is the leading cause of mortality globally. Although the treatment of myocardial infarct has improved significantly, scar tissue that persists can often lead to increased stress and adverse remodeling of surrounding tissue and ultimately to heart failure. Intra-myocardial injection of biomaterials represents a potential treatment to attenuate remodeling, mitigate degeneration, and reverse the disease process in the tissue. In vivo experiments on animal models have shown functional benefits of this therapeutic strategy. However, a poor understanding of the optimal injection pattern, volume, and material properties has acted as a barrier to its widespread clinical adoption. In this study, we developed two quasistatic finite element simulations of the left ventricle to investigate the mechanical effect of intra-myocardial injection. The first model employed an idealized left ventricular geometry with rule-based cardiomyocyte orientation. The second model employed a subject-specific left ventricular geometry with cardiomyocyte orientation from diffusion tensor magnetic resonance imaging. Both models predicted cardiac parameters including ejection fraction, systolic wall thickening, and ventricular twist that matched experimentally reported values. All injection simulations showed cardiomyocyte stress attenuation, offering an explanation for the mechanical reinforcement benefit associated with injection. The study also enabled a comparison of injection location and the corresponding effect on cardiac performance at different stages of the cardiac cycle. While the idealized model has lower fidelity, it predicts cardiac function and differentiates the effects of injection location. Both models represent versatile in silico tools to guide optimal strategy in terms of injection number, volume, site, and material properties. The authors would like to thank Ronghli Liao PhD, Sudeshna Fisch PhD, and Souen Ngoy from the Brigham and Women's Hospital (BHW) Rodent Cardiovascular Physiology core for their technical support for animal studies, Eimear Dolan PhD from NUI Galway for providing the HA‐PH‐RGD hydrogel properties, and the Irish Centre for High‐End Computing (ICHEC) for computational studies. YF acknowledges a summer scholarship from NUI Galway. peer-reviewed 2020-05-06
- Published
- 2019
25. Cholesterol-Lowering Gene Therapy Prevents Heart Failure with Preserved Ejection Fraction in Obese Type 2 Diabetic Mice
- Author
-
Mudit Mishra, Joseph Pierre Aboumsallem, Ilayaraja Muthuramu, and Bart De Geest
- Subjects
0301 basic medicine ,Apolipoprotein E ,STATIN THERAPY ,Diabetic Cardiomyopathies ,Chemistry, Multidisciplinary ,030204 cardiovascular system & hematology ,lcsh:Chemistry ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Dietary Sucrose ,Diabetic cardiomyopathy ,oxidative stress ,lcsh:QH301-705.5 ,Spectroscopy ,hypercholesterolemia ,General Medicine ,Dependovirus ,gene therapy ,Computer Science Applications ,Chemistry ,Cholesterol ,CARDIOVASCULAR-DISEASE ,Physical Sciences ,Female ,lipids (amino acids, peptides, and proteins) ,type 2 diabetes ,Life Sciences & Biomedicine ,Cardiac function curve ,heart failure with preserved ejection fraction ,medicine.medical_specialty ,Biochemistry & Molecular Biology ,Diet, High-Fat ,COENZYME Q(10) ,Article ,Catalysis ,APOLIPOPROTEIN-E ,Inorganic Chemistry ,03 medical and health sciences ,CARDIAC-FUNCTION ,Internal medicine ,medicine ,Animals ,Physical and Theoretical Chemistry ,ROSUVASTATIN ,Molecular Biology ,Heart Failure ,Science & Technology ,CARDIOMYOPATHY ,Tumor Necrosis Factor-alpha ,business.industry ,Organic Chemistry ,nutritional and metabolic diseases ,Stroke Volume ,Genetic Therapy ,medicine.disease ,DYSFUNCTION ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,Diabetes Mellitus, Type 2 ,Receptors, LDL ,chemistry ,lcsh:Biology (General) ,lcsh:QD1-999 ,MYOCARDIAL-INFARCTION ,Heart failure ,LDL receptor ,Heart failure with preserved ejection fraction ,business ,Lipoprotein - Abstract
Hypercholesterolemia may be causally related to heart failure with preserved ejection fraction (HFpEF). We aimed to establish a HFpEF model associated with hypercholesterolemia and type 2 diabetes mellitus by feeding a high-sucrose/high-fat (HSHF) diet to C57BL/6J low-density lipoprotein receptor (LDLr)&minus, /&minus, mice. Secondly, we evaluated whether cholesterol-lowering adeno-associated viral serotype 8 (AAV8)-mediated LDLr gene transfer prevents HFpEF. AAV8-LDLr gene transfer strongly (p <, 0.001) decreased plasma cholesterol in standard chow (SC) mice (66.8 ±, 2.5 mg/dl versus 213 ±, 12 mg/dl) and in HSHF mice (84.6 ±, 4.4 mg/dl versus 464 ±, 25 mg/dl). The HSHF diet induced cardiac hypertrophy and pathological remodeling, which were potently counteracted by AAV8-LDLr gene transfer. Wet lung weight was 19.0% (p <, 0.001) higher in AAV8-null HSHF mice than in AAV8-null SC mice, whereas lung weight was normal in AAV8-LDLr HSHF mice. Pressure&ndash, volume loop analysis was consistent with HFpEF in AAV8-null HSHF mice and showed a completely normal cardiac function in AAV8-LDLr HSHF mice. Treadmill exercise testing demonstrated reduced exercise capacity in AAV8-null HSHF mice but a normal capacity in AAV8-LDLr HSHF mice. Reduced oxidative stress and decreased levels of tumor necrosis factor-&alpha, may mediate the beneficial effects of cholesterol lowering. In conclusion, AAV8-LDLr gene therapy prevents HFpEF.
- Published
- 2019
26. Effective Treatment of Diabetic Cardiomyopathy and Heart Failure with Reconstituted HDL (Milano) in Mice
- Author
-
Bart De Geest, Joseph Pierre Aboumsallem, Ilayaraja Muthuramu, Mudit Mishra, and Herman Kempen
- Subjects
A-IMILANO APOPROTEIN ,0301 basic medicine ,obesity ,CHOLESTEROL EFFLUX ,Diabetic Cardiomyopathies ,type 2 diabetes mellitus ,Chemistry, Multidisciplinary ,030204 cardiovascular system & hematology ,lcsh:Chemistry ,Mice ,0302 clinical medicine ,Diabetic cardiomyopathy ,Hyperinsulinemia ,diabetic cardiomyopathy ,ESC GUIDELINES ,lcsh:QH301-705.5 ,Spectroscopy ,METABOLIC SYNDROME ,INSULIN-RESISTANCE ,General Medicine ,Computer Science Applications ,Drug Combinations ,Chemistry ,ADIPOSE-TISSUE ,Physical Sciences ,Phosphatidylcholines ,Female ,Lipoproteins, HDL ,Life Sciences & Biomedicine ,Biochemistry & Molecular Biology ,medicine.medical_specialty ,Systole ,Diastole ,Cardiomegaly ,Decreased cardiac output ,Diet, High-Fat ,GENE-TRANSFER ,Article ,Catalysis ,Diabetes Mellitus, Experimental ,Inorganic Chemistry ,03 medical and health sciences ,CARDIAC-FUNCTION ,Internal medicine ,medicine ,Animals ,Physical and Theoretical Chemistry ,Molecular Biology ,Pathological ,Heart Failure ,Science & Technology ,Apolipoprotein A-I ,business.industry ,Organic Chemistry ,Type 2 Diabetes Mellitus ,medicine.disease ,Fibrosis ,Obesity ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,Diabetes Mellitus, Type 2 ,MYOCARDIAL-INFARCTION ,lcsh:Biology (General) ,lcsh:QD1-999 ,Heart failure ,HIGH-DENSITY-LIPOPROTEINS ,business - Abstract
The risk of heart failure (HF) is prominently increased in patients with type 2 diabetes mellitus. The objectives of this study were to establish a murine model of diabetic cardiomyopathy induced by feeding a high-sugar/high-fat (HSHF) diet and to evaluate the effect of reconstituted HDLMilano administration on established HF in this model. The HSHF diet was initiated at the age of 12 weeks and continued for 16 weeks. To investigate the effect of reconstituted HDLMilano on HF, eight intraperitoneal administrations of MDCO-216 (100 mg/kg protein concentration) or of an identical volume of control buffer were executed with a 48-h interval starting at the age of 28 weeks. The HSHF diet-induced obesity, hyperinsulinemia, and type 2 diabetes mellitus. Diabetic cardiomyopathy was present in HSHF diet mice as evidenced by cardiac hypertrophy, increased interstitial and perivascular fibrosis, and decreased myocardial capillary density. Pressure-volume loop analysis indicated the presence of both systolic and diastolic dysfunction and of decreased cardiac output in HSHF diet mice. Treatment with MDCO-216 reversed pathological remodelling and cardiac dysfunction and normalized wet lung weight, indicating effective treatment of HF. No effect of control buffer injection was observed. In conclusion, reconstituted HDLMilano reverses HF in type 2 diabetic mice. ispartof: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES vol:20 issue:6 ispartof: location:Switzerland status: published
- Published
- 2019
27. miR-210 enhances the therapeutic potential of bone-marrow-derived circulating proangiogenic cells in the setting of limb ischemia
- Author
-
Stefano Gasparino, Michele Schiavulli, Paolo Madeddu, Biagina Maimone, Germana Zaccagnini, Valentina Bollati, Fabio Martelli, Elena Sangalli, Marie Besnier, Paola Fuschi, Rosa Vono, Daniel Da Silva, Gaia Spinetti, Costanza Emanueli, Massimo Caputo, Sezin Aday, Laura Cantone, and Amanda Facoetti
- Subjects
0301 basic medicine ,Male ,Angiogenesis ,bone-marrow-derived circulating cells ,Research & Experimental Medicine ,Cell therapy ,Neovascularization ,Mice ,angiogenesis ,Bone Marrow ,Ischemia ,10 Technology ,Drug Discovery ,IN-VIVO ,Tube formation ,Genetics & Heredity ,Neovascularization, Pathologic ,Transfection ,CARDIOMYOCYTE APOPTOSIS ,11 Medical And Health Sciences ,Hindlimb ,medicine.anatomical_structure ,Medicine, Research & Experimental ,Molecular Medicine ,Original Article ,Female ,limb ischemia ,medicine.symptom ,Life Sciences & Biomedicine ,Biotechnology ,Adult ,Endothelium ,microRNA-210 ,Neovascularization, Physiologic ,Bone Marrow Cells ,HEART-DISEASE ,Cell Line ,MESENCHYMAL STEM-CELLS ,03 medical and health sciences ,CARDIAC-FUNCTION ,Genetics ,medicine ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,Molecular Biology ,ENDOTHELIAL PROGENITOR CELLS ,Pharmacology ,Science & Technology ,business.industry ,EXTRACELLULAR VESICLES ,Endothelial Cells ,Hypoxia (medical) ,06 Biological Sciences ,EFNA3 ,Chemokine CXCL12 ,DIABETIC-PATIENTS ,Mice, Inbred C57BL ,MicroRNAs ,030104 developmental biology ,Biotechnology & Applied Microbiology ,MYOCARDIAL-INFARCTION ,TUBE FORMATION ,Cancer research ,Bone marrow ,cell therapy ,business - Abstract
Therapies based on circulating proangiogenic cells (PACs) have shown promise in ischemic disease models but require further optimization to reach the bedside. Ischemia-associated hypoxia robustly increases microRNA-210 (miR-210) expression in several cell types, including endothelial cells (ECs). In ECs, miR-210 represses EphrinA3 (EFNA3), inducing proangiogenic responses. This study provides new mechanistic evidences for a role of miR-210 in PACs. PACs were obtained from either adult peripheral blood or cord blood. miR-210 expression was modulated with either an inhibitory complementary oligonucleotide (anti-miR-210) or a miRNA mimic (pre-miR-210). Scramble and absence of transfection served as controls. As expected, hypoxia increased miR-210 in PACs. In vivo, migration toward and adhesion to the ischemic endothelium facilitate the proangiogenic actions of transplanted PACs. In vitro, PAC migration toward SDF-1α/CXCL12 was impaired by anti-miR-210 and enhanced by pre-miR-210. Moreover, pre-miR-210 increased PAC adhesion to ECs and supported angiogenic responses in co-cultured ECs. These responses were not associated with changes in extracellular miR-210 and were abrogated by lentivirus-mediated EFNA3 overexpression. Finally, ex-vivo pre-miR-210 transfection predisposed PACs to induce post-ischemic therapeutic neovascularization and blood flow recovery in an immunodeficient mouse limb ischemia model. In conclusion, miR-210 modulates PAC functions and improves their therapeutic potential in limb ischemia.
- Published
- 2018
28. Maternal right ventricular function, uteroplacental circulation in first trimester and pregnancy outcome in women with congenital heart disease
- Author
-
Henk Groen, Steven V. Koenen, M. A. M. Kampman, Yoran M. Hummel, D.J. Van Veldhuisen, M. W. M. De Laat, Martijn A. Oudijk, Petronella G. Pieper, Anne S. Siegmund, A.P.J. van Dijk, Gertjan T. Sieswerda, Barbara J.M. Mulder, Krystyna M. Sollie-Szarynska, Caterina M. Bilardo, Amsterdam Reproduction & Development (AR&D), Obstetrics and Gynaecology, Cardiology, APH - Personalized Medicine, APH - Aging & Later Life, ACS - Heart failure & arrhythmias, Reproductive Origins of Adult Health and Disease (ROAHD), Value, Affordability and Sustainability (VALUE), and Cardiovascular Centre (CVC)
- Subjects
Heart disease ,uteroplacental circulation ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,GUIDELINES ,RECOMMENDATIONS ,0302 clinical medicine ,Pregnancy ,FAILURE ,030212 general & internal medicine ,Prospective Studies ,Uterine artery ,Subclinical infection ,030219 obstetrics & reproductive medicine ,Radiological and Ultrasound Technology ,Obstetrics ,Pregnancy Outcome ,Obstetrics and Gynecology ,General Medicine ,ASSOCIATION ,congenital heart disease ,PREECLAMPSIA ,Uterine Artery ,Pulsatile Flow ,Uteroplacental Circulation ,Gestation ,Female ,Adult ,Heart Defects, Congenital ,medicine.medical_specialty ,Pregnancy Complications, Cardiovascular ,PARAMETERS ,Preeclampsia ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,CARDIAC-FUNCTION ,medicine.artery ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Placental Circulation ,Fetus ,BLOOD-FLOW ,business.industry ,medicine.disease ,DOPPLER FLOW ,right ventricular function ,Pregnancy Trimester, First ,Reproductive Medicine ,Ventricular Function, Right ,Vascular Resistance ,Pregnant Women ,business ,TASK-FORCE - Abstract
Objective Pregnant women with congenital heart disease (CHD) have an increased risk of abnormal uteroplacental flow, measured from the second trimester onwards, which is associated with pregnancy complications affecting the mother and the fetus. Maternal right ventricular (RV) dysfunction has been suggested as a predisposing factor for impaired uteroplacental flow in these women. The aim of this study was to investigate the association of first-trimester uteroplacental flow measurements with prepregnancy maternal cardiac function and pregnancy complications in women with CHD, with particular focus on the potential role of RV (dys)function.Methods This study included 138 pregnant women with CHD from the prospective ZAHARA III study (Zwangerschap bij Aangeboren HARtAfwijkingen; Pregnancy and CHD). Prepregnancy clinical and echocardiographic data were collected. Clinical evaluation, echocardiography (focused on RV function, as assessed by tricuspid annular plane systolic excursion (TAPSE)) and uterine artery (UtA) pulsatility index (PI) measurements were performed at 12,20 and 32 weeks of gestation. Univariable and multivariable regression analyses were performed to assess the association between prepregnancy variables and UtA-PI during pregnancy. The association between UtA-PI at 12 weeks and cardiovascular, obstetric and neonatal complications was also assessed.Results On multivariable regression analysis, prepregnancy TAPSE was associated negatively with UtA-PI at 12 weeks of gestation (beta = -0.026; P= 0.036). Women with lower prepregnancy TAPSE ( 20mm) had higher UtA-PI at 12 weeks (LS +/- 0.5 vs 1.2 +/- 0.6; P=0.047). Increased UtA-PI at 12 weeks was associated with obstetric complications (P = 0.003), particularly hypertensive disorders (pregnancy-induced hypertension and pre-eclampsia, P = 0.019 and P= 0.026, respectively).Conclusions In women with CHD, RV dysfunction before pregnancy seems to impact placentation, resulting in increased resistance in UtA flow, which is detectable as early as in the first trimester. This, in turn, is associated with pregnancy complications. Early monitoring of uteroplacental flow might be of value in women with CHD with pre-existing subclinical RV dysfunction to identify pregnancies that would benefit from close obstetric surveillance. Copyright (C) 2018 ISUOG. Published by John Wiley & Sons Ltd.
- Published
- 2018
29. A genotype-directed comparative effectiveness trial of Bucindolol and metoprolol succinate for prevention of symptomatic atrial fibrillation/atrial flutter in patients with heart failure: Rationale and design of the GENETIC-AF trial
- Author
-
William H. Sauer, Hussein R. Al-Khalidi, Dirk J. van Veldhuisen, Gordon Davis, Richard Clark, William T. Abraham, Patricia Dignacco, Stephen B. Wilton, Christopher Dufton, Ryan G. Aleong, Benjamin A. Steinberg, Debra Marshall, Michael R. Bristow, Laura L. Emery, Stuart J. Connolly, Michel White, Jonathan P. Piccini, Inder S. Anand, Jeff S. Healey, and Cardiovascular Centre (CVC)
- Subjects
Male ,030204 cardiovascular system & hematology ,law.invention ,Propanolamines ,chemistry.chemical_compound ,DOUBLE-BLIND ,0302 clinical medicine ,Randomized controlled trial ,law ,Atrial Fibrillation ,Clinical endpoint ,THERAPEUTIC RESPONSE ,Prospective Studies ,030212 general & internal medicine ,education.field_of_study ,Ejection fraction ,Atrial fibrillation ,Middle Aged ,Treatment Outcome ,Atrial Flutter ,IDIOPATHIC DILATED CARDIOMYOPATHY ,Cardiology ,SURVIVAL ,Female ,Cardiology and Cardiovascular Medicine ,Anti-Arrhythmia Agents ,Metoprolol ,medicine.medical_specialty ,Genotype ,Population ,03 medical and health sciences ,BETA-BLOCKER TREATMENT ,Double-Blind Method ,CARDIAC-FUNCTION ,Internal medicine ,medicine ,Humans ,Genetic Testing ,education ,Aged ,Heart Failure ,Dose-Response Relationship, Drug ,business.industry ,MORTALITY ,Bucindolol ,Stroke Volume ,DNA ,BETA(1)-ADRENERGIC RECEPTOR ,medicine.disease ,POLYMORPHISM ,chemistry ,Heart failure ,RHYTHM MANAGEMENT AFFIRM ,Adrenergic alpha-1 Receptor Antagonists ,Receptors, Adrenergic, beta-1 ,business ,Atrial flutter ,Follow-Up Studies - Abstract
Background Few therapies are available for the safe and effective treatment of atrial fibrillation (AF) in patients with heart failure. Bucindolol is a non-selective beta-blocker with mild vasodilator activity previously found to have accentuated antiarrhythmic effects and increased efficacy for preventing heart failure events in patients homozygous for the major allele of the ADRB1 Arg389Gly polymorphism (ADRB1 Arg389Arg genotype). The safety and efficacy of bucindolol for the prevention of AF or atrial flutter (AFL) in these patients has not been proven in randomized trials. Methods/design The Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Metoprolol Succinate for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients with Heart Failure (GENETIC-AF) trial is a multicenter, randomized, double-blinded “seamless” phase 2B/3 trial of bucindolol hydrochloride versus metoprolol succinate, for the prevention of symptomatic AF/AFL in patients with reduced ejection fraction heart failure (HFrEF). Patients with pre-existing HFrEF and recent history of symptomatic AF are eligible for enrollment and genotype screening, and if they are ADRB1 Arg389Arg, eligible for randomization. A total of approximately 200 patients will comprise the phase 2B component and if pre-trial assumptions are met, 620 patients will be randomized at approximately 135 sites to form the Phase 3 population. The primary endpoint is the time to recurrence of symptomatic AF/AFL or mortality over a 24-week follow-up period, and the trial will continue until 330 primary endpoints have occurred. Conclusions GENETIC-AF is the first randomized trial of pharmacogenetic guided rhythm control, and will test the safety and efficacy of bucindolol compared with metoprolol succinate for the prevention of recurrent symptomatic AF/AFL in patients with HFrEF and an ADRB1 Arg389Arg genotype. ( ClinicalTrials.gov NCT01970501 ).
- Published
- 2018
30. Tgf-β1/cd105 signaling controls vascular network formation within growth factor sequestering hyaluronic acid hydrogels
- Author
-
Sivan G. Marcus, Kevin E. Healy, Amit K. Jha, Yerem Yeghiazarians, Shane Browne, and Kurosh Ameri
- Subjects
0301 basic medicine ,Cell signaling ,Physiology ,Angiogenesis ,Cellular differentiation ,medicine.medical_treatment ,Cell ,Cell- and Tissue-Based Therapy ,mesenchymal stem-cells ,lcsh:Medicine ,02 engineering and technology ,Signal transduction ,Cardiovascular Physiology ,Biochemistry ,Epithelium ,Neovascularization ,Endocrinology ,Engineering ,Tissue engineering ,Animal Cells ,therapeutic angiogenesis ,Medicine and Health Sciences ,tgf-beta receptor ,Myocytes, Cardiac ,Hyaluronic Acid ,lcsh:Science ,Cells, Cultured ,cardiosphere-derived cells ,Multidisciplinary ,Tissue Scaffolds ,Chemistry ,Endoglin ,Signaling cascades ,Neurochemistry ,Cell Differentiation ,Hydrogels ,progenitor cells ,021001 nanoscience & nanotechnology ,myocardial-infarction ,3. Good health ,Cell biology ,medicine.anatomical_structure ,Physical Sciences ,Neurochemicals ,Cellular Types ,Anatomy ,medicine.symptom ,0210 nano-technology ,Network Analysis ,Research Article ,Computer and Information Sciences ,Materials by Structure ,Cell Survival ,Amorphous Solids ,Drug Compounding ,Materials Science ,Neovascularization, Physiologic ,Nitric Oxide ,Transforming Growth Factor beta1 ,03 medical and health sciences ,Growth Factors ,Spheroids, Cellular ,medicine ,Humans ,Healy [BRII applicant] ,Cell Proliferation ,Biology and life sciences ,Endocrine Physiology ,heart-failure ,Myocardium ,Growth factor ,cardiac-function ,lcsh:R ,Endothelial Cells ,Epithelial Cells ,Signaling Networks ,Biological Tissue ,030104 developmental biology ,TGF-beta signaling cascade ,Mixtures ,molecular-weight ,lcsh:Q ,endothelial-cell ,Gels ,Neuroscience ,Developmental Biology ,Transforming growth factor - Abstract
Cell-based strategies for the treatment of ischemic diseases are at the forefront of tissue engineering and regenerative medicine. Cell therapies purportedly can play a key role in the neovascularization of ischemic tissue; however, low survival and poor cell engraftment with the host vasculature following implantation limits their potential to treat ischemic diseases. To overcome these limitations, we previously developed a growth factor sequestering hyaluronic acid (HyA)-based hydrogel that enhanced transplanted mouse cardiosphere-derived cell survival and formation of vasculature that anastomosed with host vessels. In this work, we examined the mechanism by which HyA hydrogels presenting transforming growth factor beta-1 (TGF-beta 1) promoted proliferation of more clinically relevant human cardiospherederived cells (hCDC), and their formation of vascular-like networks in vitro. We observed hCDC proliferation and enhanced formation of vascular-like networks occurred in the presence of TGF-beta 1. Furthermore, production of nitric oxide (NO), VEGF, and a host of angiogenic factors were increased in the presence of TGF-beta 1. This response was dependent on the co-activity of CD105 (Endoglin) with the TGF-beta R2 receptor, demonstrating its role in the process of angiogenic differentiation and vascular organization of hCDC. These results demonstrated that hCDC form vascular-like networks in vitro, and that the induction of vascular networks by hCDC within growth factor sequestering HyA hydrogels was mediated by TGF-beta 1/CD105 signaling.
- Published
- 2018
31. The Preterm Heart in Childhood : Left Ventricular Structure, Geometry, and Function Assessed by Echocardiography in 6-Year-Old Survivors of Periviable Births
- Author
-
Mohlkert, Lilly‐Ann, Hallberg, Jenny, Broberg, Olof, Rydberg, Annika, Halvorsen, Cecilia Pegelow, Liuba, Petru, Fellman, Vineta, Domellöf, Magnus, Sjöberg, Gunnar, Norman, Mikael, Clinicum, Lastentautien yksikkö, Children's Hospital, and HUS Children and Adolescents
- Subjects
Male ,Time Factors ,Systole ,Heart Ventricles ,tissue Doppler imaging ,Gestational Age ,BLOOD-PRESSURE ,PEDIATRIC ECHOCARDIOGRAM ,Ventricular Function, Left ,Ventricular Dysfunction, Left ,CARDIAC-FUNCTION ,Diastole ,Predictive Value of Tests ,Pediatric Cardiology ,Developmental biology ,Humans ,Cardiac and Cardiovascular Systems ,Prospective Studies ,MYOCARDIAL-FUNCTION ,Child ,speckle tracking echocardiography ,GESTATIONAL-AGE ,Original Research ,AMERICAN-SOCIETY ,Z-SCORE VALUES ,Kardiologi ,ultrasound ,Age Factors ,ACTIVE PERINATAL-CARE ,preterm birth ,Prognosis ,Echocardiography, Doppler ,BORN EXTREMELY PRETERM ,Phenotype ,Case-Control Studies ,Infant, Extremely Premature ,3121 General medicine, internal medicine and other clinical medicine ,Premature Birth ,Female ,cardiovascular development ,PLANE SYSTOLIC EXCURSION - Abstract
Background-Preterm birth has been associated with increased risk of cardiovascular morbidity in adult life. We evaluated whether preterm birth is associated with deviating cardiac structure and function before school start. Methods and Results-In total, 176 children aged 6 years and born extremely preterm (EXPT; gestational age of 22-26weeks) and 134 children born at term (control [CTRL]) were studied. We used echocardiography to assess left heart dimensions, geometry, and functions. Recording and off-line analyses of echocardiographic images were performed by operators blinded to group belonging. Body size, blood pressure, and heart rate were also measured. Rates of family history of cardiovascular disease and sex distribution were similar in the EXPT and CTRL groups. Heart rate and systolic blood pressure did not differ, whereas diastolic blood pressure was slightly higher in EXPT than CTRL participants. After adjusting for body surface area, left ventricular length, width, and aortic valve annulus diameter were 3% to 5% smaller in EXPT than CTRL participants. Left ventricular longitudinal shortening and systolic tissue velocity were 7% to 11% lower, and transversal shortening fraction was 6% higher in EXPT than CTRL participants. The EXPT group also exhibited lower atrial emptying velocities than the CTRL group. Sex, fetal growth restriction, or a patent ductus arteriosus in the neonatal period did not contribute to cardiac dimensions or performance. Conclusions-Six-year-old children born extremely preterm exhibit a unique cardiac phenotype characterized by smaller left ventricles with altered systolic and diastolic functions than same-aged children born at term.
- Published
- 2018
32. Sauna bathing, health, and quality of life among octogenarian men: the Helsinki Businessmen Study
- Author
-
Athanase Benetos, Arto Y. Strandberg, Kaisu H. Pitkälä, Timo E. Strandberg, Timo Strandberg / Principal Investigator, Department of Medicine, Clinicum, University of Helsinki, Department of General Practice and Primary Health Care, HUS Internal Medicine and Rehabilitation, and Teachers' Academy
- Subjects
Gerontology ,Male ,Aging ,STRESS ,Bathing ,Cross-sectional study ,IMPROVEMENT ,030204 cardiovascular system & hematology ,PROFILE ,Vitality ,Steam Bath ,03 medical and health sciences ,Sauna bathing ,0302 clinical medicine ,CARDIAC-FUNCTION ,Quality of life ,Waon therapy ,Surveys and Questionnaires ,BENEFITS ,Medicine ,Humans ,030212 general & internal medicine ,Aged ,Aged, 80 and over ,business.industry ,MORTALITY ,architecture.style ,Lifestyle ,CHRONIC HEART-FAILURE ,Cross-Sectional Studies ,Health ,architecture ,3121 General medicine, internal medicine and other clinical medicine ,Finnish Sauna ,FINNISH SAUNA ,Cohort ,Quality of Life ,Geriatrics and Gerontology ,Sauna ,business ,Demography - Abstract
Sauna-type bathing has increased worldwide, and it has been related to both harmful and beneficial effects. There are few studies of bathing in sauna in very old age. The series consists of 524 mostly home-living survivors of the Helsinki Businessmen Study (HBS, mean age 86 years, range 80-95), who in 2015 responded to a questionnaire survey about lifestyle (including sauna bathing), prevalent diseases, and health-related quality of life (HRQoL, RAND-36). Of the men 57.6% (n = 302) reported all-year round and 17.6% (n = 92) part-year sauna bathing. Sauna was currently used mostly once a week, but 10% bathed more than twice a week. Median time in the hot room was 15 min at 80 A degrees C. Among 45.7% of the men, the habit had decreased with ageing, and 130 (24.8%) did not attend sauna. However, 92.2% of the latter had discontinued an earlier habit, respective proportions 20.7% and 75.0% among all-year and part-year users. Overall, reasons for decreased sauna bathing were nonspecific or related to mobility problems or diverse health reasons (n = 63). The most frequent motivations for sauna were relaxation and hygienic reasons. Of the RAND-36 domains physical function, vitality, social functioning, and general health were significantly better among sauna users than non-users. These differences partly remained after adjusting for prevalent diseases and mobility-disability. Regular sauna bathing was common among octogenarian men and was associated with better HRQoL. However, reverse causality must be taken into account in this cross-sectional study. The bathing habit seemed to be prudent and had decreased in almost half of the cohort.
- Published
- 2017
33. Effect of eplerenone in patients with heart failure and reduced ejection fraction: potential effect modification by abdominal obesity: insight from the EMPHASIS-HF trial
- Author
-
Olivier, Arnaud, Pitt, Bertram, Girerd, Nicolas, Lamiral, Zohra, Machu, Jean-Loup, McMurray, John J.V., Swedberg, Karl, van Veldhuisen, Dirk J., Collier, Timothy J., Pocock, Stuart J., Rossignol, Patrick, Zannad, Faiez, Pizard, Anne, and Cardiovascular Centre (CVC)
- Subjects
BODY-MASS INDEX ,ADIPOSE-TISSUE ,MINERALOCORTICOID RECEPTOR ANTAGONISM ,CARDIAC-FUNCTION ,CARDIOVASCULAR-DISEASE ,CARDIOMETABOLIC RISK ,PARADOX ,ADIPOCYTE DYSFUNCTION ,heart failure with reduced ejection fraction ,Abdominal obesity ,ALDOSTERONE BLOCKADE ,WAIST CIRCUMFERENCE ,Eplerenone - Abstract
Aims:\ud An excessive production of aldosterone influences outcome in patients with heart failure (HF) and in obese patients. Findings from laboratory studies suggest that chronic aldosterone blockade maybe more beneficial in abdominally obese HF-prone rats. In the current study, we investigated if the clinical response to a mineralocorticoid receptor antagonist in mildly symptomatic HF patients varied by abdominal obesity.\ud \ud Methods and results:\ud A total of 2587 NYHA class II, reduced ejection fraction HF (HFrEF) patients enrolled in the EMPHASIS-HF trial were randomly assigned to eplerenone and placebo. In this post hoc analysis, patients were categorized according to waist circumference (WC) (normal if WC < 102 cm in men and
- Published
- 2017
34. Radiotherapy-induced global and regional differences in early-stage left-sided versus right-sided breast cancer patients : speckle tracking echocardiography study
- Author
-
Suvi Sirkku Tuohinen, Pekka Raatikainen, Tuija Poutanen, Pirkko-Liisa Kellokumpu-Lehtinen, Vesa Virtanen, Tanja Skyttä, Heini Huhtala, Kardiologian yksikkö, Department of Medicine, Clinicum, and HUS Heart and Lung Center
- Subjects
Time Factors ,medicine.medical_treatment ,Speckle tracking echocardiography ,030204 cardiovascular system & hematology ,Ventricular Function, Left ,Basal (phylogenetics) ,Electrocardiography ,0302 clinical medicine ,Breast cancer ,Risk Factors ,FIBROSIS ,Prospective Studies ,Prospective cohort study ,COMPLICATIONS ,Laterality ,Middle Aged ,3. Good health ,Treatment Outcome ,Echocardiography ,030220 oncology & carcinogenesis ,Cardiology ,End-diastolic volume ,Female ,Radiology ,Cardiology and Cardiovascular Medicine ,Cardiac function curve ,medicine.medical_specialty ,STRAIN ,Heart Diseases ,medicine.drug_class ,Breast Neoplasms ,HEART-DISEASE ,MECHANISMS ,03 medical and health sciences ,CARDIAC-FUNCTION ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Radiation Injuries ,Aged ,Speckle tracking ,Aromatase inhibitor ,Chi-Square Distribution ,Radiotherapy ,business.industry ,MORTALITY ,Reproducibility of Results ,Stroke Volume ,medicine.disease ,Myocardial Contraction ,DYSFUNCTION ,IRRADIATION ,Radiation therapy ,Logistic Models ,3121 General medicine, internal medicine and other clinical medicine ,Multivariate Analysis ,Linear Models ,RADIATION ,Radiotherapy, Adjuvant ,Radiotherapy, Conformal ,business - Abstract
Radiotherapy (RT) to the thoracic region increases late cardiovascular morbidity and mortality. The impact of breast cancer laterality on cardiac function is largely unknown. The aim of this prospective study was to compare RT-induced changes in left-sided and right-sided breast cancer patients using speckle tracking echocardiography (STE). Sixty eligible patients with left-sided breast cancer and 20 with right-sided breast cancer without chemotherapy were evaluated prospectively before and early after RT. A comprehensive echocardiographic examination included three dimensional measurements and STE of the left ventricle (LV). The global longitudinal strain (GLS) was reduced from -18.3 +/- 3.1 to -17.2 +/- 3.3% (p = 0.003) after RT in patients with left-sided breast cancer. Similarly, regional analysis showed a reduction in the apical strain from -18.7 +/- 5.3 to -16.7 +/- 4.9% (p = 0.002) and an increase in basal values from -21.6 +/- 5.0 to -23.3 +/- 4.9% (p = 0.024). Patients with right-sided breast cancer showed deterioration in basal anterior strain segments from -26.3 +/- 7.6 to -18.8 +/- 8.9% (p
- Published
- 2017
35. Uteroplacental Doppler flow and pregnancy outcome in women with tetralogy of Fallot
- Author
-
Kampman, MAM, Siegmund, AS, Bilardo, CM, Veldhuisen, DJ, Balci, A, Oudijk, MA, Groen, H, Mulder, BJM, Roos - Hesselink, Jolien, Sieswerda, G, de Laat, MWM, Sollie-Szarynska, KM, Pieper, PG, Reproductive Origins of Adult Health and Disease (ROAHD), Cardiovascular Centre (CVC), Methods in Medicines evaluation & Outcomes research (M2O), Value, Affordability and Sustainability (VALUE), Amsterdam Reproduction & Development (AR&D), Obstetrics and Gynaecology, Cardiology, APH - Personalized Medicine, APH - Aging & Later Life, and ACS - Heart failure & arrhythmias
- Subjects
CONGENITAL HEART-DISEASE ,PREECLAMPSIA ,COMPLICATIONS ,pregnancy outcome ,CARDIAC-FUNCTION ,BLOOD-FLOW ,UTERINE ARTERY DOPPLER ,REPAIRED TETRALOGY ,utcroplacental Doppler flow ,congenital heart disease ,DYSFUNCTION ,SURGICAL-CORRECTION ,REFERENCE RANGES - Abstract
Pregnancy in women with surgically corrected tetralogy of Fallot (ToF) is associated with cardiac, obstetric and neonatal complications. We compared uteroplacental Doppler flow (UDF) measurements and pregnancy outcome in women with ToF and in healthy women and aimed to assess whether a relationship exists between cardiac function and UDF in women with ToF. We evaluated prospectively pregnant women with ToF and healthy pregnant women from the ZAHARA studies. Clinical evaluation, standardized echocardiography and UDF measurements were performed at 20 and 32 weeks' gestation. We included 62 women with ToF and 69 healthy controls. Cardiac complications, mostly arrhythmia, occurred in 8.1% of women with ToF. There was a higher incidence of small-for-gestational age (21.0% vs 4.4%, P = 0.004) and low birth weight (16.1% vs 2.9%, P = 0.009) in the group of women with ToF than in healthy controls. In women with ToF, early diastolic notching of uterine artery waveform at 20 and 32 weeks occurred more frequently (9.8% vs 1.5%, P = 0.034 and 7.0% vs 0%, P = 0.025, respectively) and the umbilical artery pulsatility index at 32 weeks was higher (1.02 ± 0.20 vs 0.94 ± 0.17, P = 0.015) than in healthy controls. Right ventricular function parameters prepregnancy and at 20 weeks' gestation were significantly associated with abnormal UDF. UDF parameters were associated with adverse neonatal outcome. The majority of women with surgically corrected ToF tolerate pregnancy well. However, UDF indices are more frequently abnormal in these women, suggesting impaired placentation. The association of impaired right ventricular function parameters with abnormal UDF suggests that cardiac dysfunction contributes to defective placentation or placental perfusion mismatch and may explain the increased incidence of obstetric and neonatal complications. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd
- Published
- 2017
36. Pregnancy in women with corrected aortic coarctation: Uteroplacental Doppler flow and pregnancy outcome
- Author
-
Tjark Ebels, M. A. M. Kampman, Dirk J. van Veldhuisen, Gertjan T. Sieswerda, Arie P.J. van Dijk, Anne S. Siegmund, Martijn A. Oudijk, Ali Balci, Jolien W. Roos-Hesselink, Krystyna M. Sollie-Szarynska, Barbara J.M. Mulder, Petronella G. Pieper, Steven V. Koenen, Zahara investigators, Caterina M. Bilardo, Reproductive Origins of Adult Health and Disease (ROAHD), Cardiovascular Centre (CVC), Cardiology, ARD - Amsterdam Reproduction and Development, Obstetrics and Gynaecology, APH - Personalized Medicine, APH - Aging & Later Life, ACS - Amsterdam Cardiovascular Sciences, ACS - Heart failure & arrhythmias, Obstetrics and gynaecology, and ACS - Atherosclerosis & ischemic syndromes
- Subjects
Adult ,Cardiac function curve ,medicine.medical_specialty ,Heart disease ,Birth weight ,Pregnancy Complications, Cardiovascular ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Coarctation of the aorta ,030204 cardiovascular system & hematology ,PARAMETERS ,Cohort Studies ,Aortic coarctation ,03 medical and health sciences ,0302 clinical medicine ,CARDIAC-FUNCTION ,MEDICATION ,Pregnancy ,Internal medicine ,medicine.artery ,Laser-Doppler Flowmetry ,medicine ,Humans ,Placental Circulation ,Prospective Studies ,030212 general & internal medicine ,Uterine artery ,ULTRASOUND ,Retrospective Studies ,REPAIR ,COMPLICATIONS ,BLOOD-FLOW ,HYPERTENSION ,Obstetrics ,business.industry ,Infant, Newborn ,Pregnancy Outcome ,Umbilical artery ,ADULTS ,medicine.disease ,CONGENITAL HEART-DISEASE ,Cardiology ,Gestation ,Female ,Uteroplacental circulation ,Cardiology and Cardiovascular Medicine ,business - Abstract
Objective: Women with repaired coarctation of the aorta (rCoA) are at risk of hypertensive disorders and other complications during pregnancy. Hypertensive disorders in pregnant women are associated with inadequate uteroplacental flow, which is related to adverse offspring outcome. The aim of this study was to investigate the relationship of maternal cardiac function, placental function and pregnancy complications in women with rCoA.Methods: We included 49 pregnant women with rCoA and 69 controls from the prospective ZAHARA-studies (Zwangerschap bij Aangeboren HARtAfwijkingen, pregnancy in congenital heart disease). Clinical evaluation, echocardiography and uteroplacental Doppler flow (UDF) measurements were performed at 20 and 32 weeks gestation. Univariable regression analysis was performed.Results: Comparison of rCoA and healthy women. In women with rCoA, tricuspid annular plane systolic excursion (TAPSE) decreased during pregnancy (25.7 mm to 22.8 mm, P = 0.006). UDF indices and pregnancy complication rates were similar in both groups. Offspring of rCoA women had lower birth weight (3233 g versus 3578 g, P = 0.001), which was associated with beta-blocker use during pregnancy (beta = -418.0, P = 0.01).Association of cardiac function and UDF. Right ventricular (RV) function before pregnancy (TAPSE) and at 20 weeks gestation (TAPSE and RV fractional area change) were associated with impaired UDF indices (umbilical artery pulsatility index at 20 weeks beta = -0.02, P = 0.01, resistance index at 20 and 32 weeks beta = -0.01, P = 0.02 and beta = -0.02, P = 0.01 and uterine artery pulsatility and resistance index at 20 weeks gestation beta = -0.02, P = 0.05 and beta = -0.01, P = 0.02).Conclusions: Women with rCoA tolerate pregnancy well. However, RV function is altered and is associated with impaired placentation.
- Published
- 2017
37. Applicability and technical aspects of two-dimensional ultrasonography for assessment of fetal heart function
- Author
-
Alex Sandro Rolland Souza, Luciano Marcondes Machado Nardozza, Nathalie Jeanne Bravo-Valenzuela, Alberto Borges Peixoto, Edward Araujo Júnior, Junior, Edward Araujo https://orcid.org/0000-0002-6145-2532, Peixoto, Alberto https://orcid.org/0000-0002-1655-3609, Bravo-Valenzuela, Nathalie Jeanne https://orcid.org/0000-0003-1491-4877, Junior, Edward Araujo/E-1228-2012, Peixoto, Alberto/L-6074-2016, and Bravo-Valenzuela, Nathalie Jeanne/M-9387-2015
- Subjects
Heart Defects, Congenital ,Cardiac function curve ,medicine.medical_specialty ,Aortic Isthmus ,Acoustics and Ultrasonics ,Heart disease ,Pulmonary Venous Flow ,Cardiac-Function ,Volume overload ,Fetal Heart Function ,Spatiotemporal Image Correlation ,030204 cardiovascular system & hematology ,Ultrasonography, Prenatal ,03 medical and health sciences ,Fetal Heart ,0302 clinical medicine ,Pregnancy ,Septum-Primum ,Reference Values ,Internal medicine ,Blood-Flow ,medicine ,M-Mode ,Humans ,Radiology, Nuclear Medicine and imaging ,Myocardial Performance Index ,Subclinical infection ,Intrauterine Growth Restriction ,Fetus ,030219 obstetrics & reproductive medicine ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Radiology, Nuclear Medicine & Medical Imaging ,Reproducibility of Results ,Acoustics ,medicine.disease ,embryonic structures ,Hyperdynamic circulation ,Cardiology ,Female ,Color Doppler ,Tissue Doppler ,business ,2d Ultrasonography ,Fetal echocardiography - Abstract
Made available in DSpace on 2019-09-12T16:56:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2017 In the recent years, fetal echocardiography has been used for the screening and diagnosis of anatomical heart defects and for the detailed study of fetal cardiac function. This method is characterized by its easy implementation and good reproducibility, allowing the diagnosis of myocardial dysfunction even in its subclinical phase. The functional assessment of the fetal heart should be routinely performed in fetuses with congenital heart disease and those without anatomical malformation. Several extra-cardiac conditions may alter fetal cardiac function, by increased placental resistance, volume overload or hyperdynamic circulation, compression, or maternal systemic disease with involvement of the fetal myocardium. This review addresses the main ultrasound techniques and various Doppler echocardiographic parameters available for the analysis of fetal heart function, and correlates them with clinical applicability. Various parameters available for the assessment of fetal myocardium, including those that evaluate atrial dynamics, can be used in this analysis and should be selected considering specific conditions. [Magioli Bravo-Valenzuela, Nathalie Jeanne] Universidade de Taubaté (Unitau) , Fetal Echocardiog Unit [Magioli Bravo-Valenzuela, Nathalie Jeanne; Peixoto, Alberto Borges; Machado Nardozza, Luciano Marcondes; Araujo Junior, Edward] Fed Univ Sao Paulo EPM UNIFESP, Paulista Sch Med, Dept Obstet, Sao Paulo, SP, Brazil [Peixoto, Alberto Borges] Univ Uberaba UNIUBE, Mario Palmerio Univ Hosp, Uberaba, MG, Brazil [Rolland Souza, Alex Sandro] Fed Univ Pernambuco UFPE, Dept Maternal & Child Hlth, Recife, PE, Brazil
- Published
- 2017
38. Intracoronary administration of allogeneic adipose tissue-derived mesenchymal stem cells improves myocardial perfusion but not left ventricle function, in a translational model of acute myocardial infarction
- Author
-
Joaquim Bobi, Santiago Roura, Javier Sánchez-González, Ana Paula Dantas, José Ramírez, Borja Ibanez, Ana García-Álvarez, Carlos Galán-Arriola, Rodrigo Fernández-Jiménez, Antoni Bayes-Genis, Carolina Gálvez-Montón, Elisabet Rigol‐Monzó, Leticia Fernández-Friera, Jaume Aguero, Núria Solanes, Manel Sabaté, Montserrat Rigol, Mercè Roqué, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Instituto de Salud Carlos III, Ministerio de Educación y Ciencia (España), Fundación Jesús Serra, Fundación Interhospitalaria de Investigación Cardiovascular, Medis Medical Imaging, Ministerio de Economía, Industria y Competitividad (España), Fundación ProCNIC, Fundación La Caixa, Government of Catalonia (España), Fundación La Marató TV3, and Universitat de Barcelona
- Subjects
0301 basic medicine ,Male ,Time Factors ,RANDOMIZED PHASE-1 TRIAL ,Translational Studies ,Computed Tomography Angiography ,Sus scrofa ,Myocardial Infarction ,PROMOTE ANGIOGENESIS ,Infarction ,Perfusion scanning ,030204 cardiovascular system & hematology ,Coronary Angiography ,adipose tissue-derived mesenchymal stem cells ,allogeneic origin ,THERAPY ,Ventricular Function, Left ,DISEASE ,Ventricular Dysfunction, Left ,0302 clinical medicine ,Coronary Heart Disease ,Myocardial infarction ,Angiogenic Proteins ,Cells, Cultured ,Original Research ,adipose tissue‐derived mesenchymal stem cells ,Ejection fraction ,Stem Cells ,Animal models in research ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Adipose Tissue ,PORCINE MODEL ,Cardiology ,Cytokines ,HEART-FAILURE ,Cardiology and Cardiovascular Medicine ,myocardial perfusion ,medicine.medical_specialty ,Perfusion Imaging ,Green Fluorescent Proteins ,Neovascularization, Physiologic ,Mesenchymal Stem Cell Transplantation ,Transfection ,03 medical and health sciences ,Coronary circulation ,CARDIAC-FUNCTION ,Internal medicine ,Coronary Circulation ,Multidetector Computed Tomography ,medicine ,Animals ,Regeneration ,Transplantation, Homologous ,Ischemic cardiomyopathy ,business.industry ,Myocardium ,Cell Therapy ,ISCHEMIC CARDIOMYOPATHY ,Mesenchymal Stem Cells ,Adipose tissues ,Recovery of Function ,medicine.disease ,Disease Models, Animal ,Teixit adipós ,Infart de miocardi ,030104 developmental biology ,PROGENITOR CELLS ,Coronary occlusion ,Heart failure ,vascular density ,ISCHEMIA/REPERFUSION ,Models animals en la investigació ,business - Abstract
Background Autologous adipose tissue–derived mesenchymal stem cells ( ATMSC s) therapy is a promising strategy to improve post–myocardial infarction outcomes. In a porcine model of acute myocardial infarction, we studied the long‐term effects and the mechanisms involved in allogeneic ATMSC s administration on myocardial performance. Methods and Results Thirty‐eight pigs underwent 50 minutes of coronary occlusion; the study was completed in 33 pigs. After reperfusion, allogeneic ATMSC s or culture medium (vehicle) were intracoronarily administered. Follow‐ups were performed at short (2 days after acute myocardial infarction vehicle‐treated, n=10; ATMSC s‐treated, n=9) or long term (60 days after acute myocardial infarction vehicle‐treated, n=7; ATMSC s‐treated, n=7). At short term, infarcted myocardium analysis showed reduced apoptosis in the ATMSC s‐treated animals (48.6±6% versus 55.9±5.7% in vehicle; P =0.017); enhancement of the reparative process with up‐regulated vascular endothelial growth factor, granulocyte macrophage colony‐stimulating factor, and stromal‐derived factor‐1α gene expression; and increased M2 macrophages (67.2±10% versus 54.7±10.2% in vehicle; P =0.016). In long‐term groups, increase in myocardial perfusion at the anterior infarct border was observed both on day‐7 and day‐60 cardiac magnetic resonance studies in ATMSC s‐treated animals, compared to vehicle (87.9±28.7 versus 57.4±17.7 mL/min per gram at 7 days; P =0.034 and 99±22.6 versus 43.3±14.7 22.6 mL/min per gram at 60 days; P =0.0001, respectively). At day 60, higher vascular density was detected at the border zone in the ATMSC s‐treated animals (118±18 versus 92.4±24.3 vessels/mm 2 in vehicle; P =0.045). Cardiac magnetic resonance–measured left ventricular ejection fraction of left ventricular volumes was not different between groups at any time point. Conclusions In this porcine acute myocardial infarction model, allogeneic ATMSC s‐based therapy was associated with increased cardioprotective and reparative mechanisms and with better cardiac magnetic resonance–measured perfusion. No effect on left ventricular volumes or ejection fraction was observed.
- Published
- 2017
39. Extracellular matrix components of adipose derived stromal cells promote alignment, organization, and maturation of cardiomyocytes in vitro
- Author
-
Martin C. Harmsen, Marja J. A. van Luyn, Ewa Przybyt, Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), and Vascular Ageing Programme (VAP)
- Subjects
EXPRESSION ,Stromal cell ,Materials science ,Angiogenesis ,extracellular matrix ,Biomedical Engineering ,cardiomyocytes ,Periostin ,MURINE MYOCARDIAL-INFARCTION ,Biomaterials ,Extracellular matrix ,Mice ,adipose derived stromal cells ,Paracrine signalling ,CARDIAC-FUNCTION ,Animals ,Myocytes, Cardiac ,SCAR FORMATION ,Cell Proliferation ,REPAIR ,MODULATOR ,biology ,Matricellular protein ,Metals and Alloys ,Cell Differentiation ,HUMANS ,Hypertrophy ,Juxtacrine signalling ,Rats ,Cell biology ,MODEL ,Fibronectin ,myocardial infarction ,Adipose Tissue ,Animals, Newborn ,TISSUE ,Immunology ,Ceramics and Composites ,biology.protein ,Stromal Cells ,STEM-CELLS - Abstract
Adipose derived stromal cells (ADSC) are relevant therapeutic agents to treat myocardial infarction (MI) in clinical trials. Soluble factors secreted by ADSC, such as growth factors and cytokines, suppress inflammation and apoptosis while promoting angiogenesis and the proliferation of cardiomyocytes (CM). Moreover, ADSC synthesize extracellular matrix (ECM) components into the intercellular space which might contribute to their therapeutic capacity. Thus, ADSC might directly modulate the post-MI microenvironment through a combination of paracrine and juxtacrine signaling. In this study, the juxtacrine role of ADSC and ADSC-derived ECM on the organization and maturation of CM was investiagated. Human ADSC synthesized and deposited a heterogenous and complex mixture of ECM components such as collagen I, III, IV, fibronectin, elastin as well as the matricellular protein periostin. Cocultures of rodent CM with human ADSC or with human ADSC-derived ECM components enhanced the cardiomyocyte alignment, their intercellular connections and the maturation of their sarcomeres, while the proliferation rate of the CM was increased and their level of hypertrophy reduced. The use of human ADSC-derived ECM could serve both to augment in vitro tissue-engineered myocardial constructs and to improve myocardial remodeling after infarction. (c) 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1840-1848, 2015.
- Published
- 2014
40. The Effect of Metformin on Diastolic Function in Patients Presenting with ST-Elevation Myocardial Infarction
- Author
-
Erik Lipsic, Dirk J. van Veldhuisen, Yoran M. Hummel, Iwan C. C. van der Horst, Chris P. H. Lexis, Joost P. van Melle, Pim van der Harst, Minke H. T. Hartman, Lawien Al Ali, Adriaan A. Voors, Cardiovascular Centre (CVC), and Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE)
- Subjects
Male ,endocrine system diseases ,Cardiovascular Procedures ,Deceleration ,medicine.medical_treatment ,Myocardial Infarction ,Placebo-controlled study ,lcsh:Medicine ,030204 cardiovascular system & hematology ,Ventricular Function, Left ,Diagnostic Radiology ,Ventricular Dysfunction, Left ,Endocrinology ,Postoperative Complications ,0302 clinical medicine ,Diastole ,Ultrasound Imaging ,Medicine and Health Sciences ,Medicine ,LEFT ATRIAL VOLUME ,030212 general & internal medicine ,Myocardial infarction ,lcsh:Science ,Multidisciplinary ,Ejection fraction ,Radiology and Imaging ,Physics ,Classical Mechanics ,Middle Aged ,FILLING PATTERN ,Magnetic Resonance Imaging ,Metformin ,CHRONIC HEART-FAILURE ,EUROPEAN-SOCIETY ,Echocardiography ,Physical Sciences ,Cardiology ,Female ,Stents ,Research Article ,medicine.drug ,medicine.medical_specialty ,Endocrine Disorders ,Imaging Techniques ,Surgical and Invasive Medical Procedures ,Research and Analysis Methods ,Placebo ,EJECTION FRACTION ,03 medical and health sciences ,Percutaneous Coronary Intervention ,CARDIAC-FUNCTION ,Diagnostic Medicine ,LEFT-VENTRICULAR FUNCTION ,Diabetes mellitus ,Internal medicine ,Diabetes Mellitus ,Humans ,Aged ,business.industry ,Angioplasty ,lcsh:R ,Percutaneous coronary intervention ,PERCUTANEOUS INTERVENTION ,medicine.disease ,TISSUE DOPPLER ,DIABETIC-PATIENTS ,Metabolic Disorders ,ST Elevation Myocardial Infarction ,lcsh:Q ,business ,Coronary Angioplasty - Abstract
IntroductionDiastolic dysfunction is an important predictor of poor outcome after myocardial infarction. Metformin treatment improved diastolic function in animal models and patients with diabetes. Whether metformin improves diastolic function in patients presenting with ST-segment elevation myocardial infarction (STEMI) is unknown.MethodsThe GIPS-III trial randomized STEMI patients, without known diabetes, to metformin or placebo initiated directly after PCI. The previously reported primary endpoint was left ventricular ejection fraction at 4 months, which was unaffected by metformin treatment. This is a predefined substudy to determine an effect of metformin on diastolic function. For this substudy trans-thoracic echocardiography was performed during hospitalization and after 4 months. Diastolic dysfunction was defined as having the combination of a functional alteration (i.e. decreased tissue velocity: mean of septal e' and lateral e') and a structural alteration (i.e. increased left atrial volume index (LAVI)). In addition, left ventricular mass index and transmitral flow velocity (E) to mean e' ratio (E/e') were measured to determine an effect of metformin on individual echocardiographic markers of diastolic function.ResultsIn 237 (63%) patients included in the GIPS-III trial diastolic function was measured during hospitalization as well as at 4 months. Diastolic dysfunction was present in 11 (9%) of patients on metformin and 11 (9%) patients on placebo treatment (P = 0.98) during hospitalization. After 4 months 22 (19%) of patients with metformin and 18 (15%) patients with placebo (P = 0.47) had diastolic dysfunction. In addition, metformin did not improve any of the individual echocardiographic markers of diastolic function.ConclusionsIn contrast to experimental and observational data, our randomized placebo controlled trial did not suggest a beneficial effect of short-term metformin treatment on diastolic function in STEMI patients.
- Published
- 2016
41. Nitric oxide donor molsidomine favors features of atherosclerotic plaque stability and reduces myocardial infarction in mice
- Author
-
Peter Paul De Deyn, Lynn Roth, Besa Emini Veseli, Guido R.Y. De Meyer, Debby Van Dam, Carole Van der Donckt, Wim Martinet, Arnold G. Herman, and Molecular Neuroscience and Ageing Research (MOLAR)
- Subjects
0301 basic medicine ,Mice, Knockout, ApoE ,Physiology ,Fibrillin-1 ,NO-DONOR ,Myocardial Infarction ,PROGRESSION ,BRAIN-INJURY ,030204 cardiovascular system & hematology ,Ventricular Function, Left ,DISEASE ,chemistry.chemical_compound ,0302 clinical medicine ,SYNTHASE ,Myocardial infarction ,Ventricular Remodeling ,Pharmacology. Therapy ,Fibrous cap ,Cerebral hypoxia ,MOUSE MODEL ,Plaque, Atherosclerotic ,APOPTOSIS ,ISCHEMIA ,3. Good health ,medicine.anatomical_structure ,Cardiology ,Molecular Medicine ,Female ,Hypertrophy, Left Ventricular ,Cardiac function curve ,medicine.medical_specialty ,Molsidomine ,Diastole ,Ischemia ,Motor Activity ,Sudden death ,Necrosis ,03 medical and health sciences ,CARDIAC-FUNCTION ,VASCULAR CALCIFICATION ,Internal medicine ,medicine ,Animals ,Nitric Oxide Donors ,Biology ,Pharmacology ,Rupture, Spontaneous ,business.industry ,Myocardium ,Atherosclerosis ,medicine.disease ,Fibrosis ,Myocardial Contraction ,Disease Models, Animal ,030104 developmental biology ,chemistry ,Mutation ,Human medicine ,business - Abstract
Nitric oxide (NO) donors are commonly used for the prevention and treatment of ischemic heart disease. Besides their effects on the heart, NO donors may also prevent hypoxic brain damage and exert beneficial effects on atherosclerosis by favoring features of plaque stability. We recently described that apolipoprotein E (ApoE) deficient mice with a mutation in the fibrillin-1 (Fbn1) gene (ApoE(-/-)Fbn1(C1039G+/-) develop accelerated atherosclerosis, plaque rupture, myocardial infarction, cerebral hypoxia and sudden death. In the present study, we evaluated the effects of chronic treatment with the NO donor molsidomine on atherosclerotic plaque stability, cardiac function, neurological symptoms and survival in the ApoE(-/-)Fbn1(C1039G+/-) mouse model. Female ApoE(-/-)Fbn1(C1039G+/-) mice were fed a Western diet (WD). After 8 weeks of WD, the mice were divided into two groups receiving either molsidomine via the drinking water (1 mg/kg/day; n = 34) or tap water (control; n = 36) until 25 weeks of WD. Survival tended to increase after molsidomine treatment (68% vs. 58% in controls). Importantly, atherosclerotic plaques of molsidomine-treated mice had a thicker fibrous cap (11.1 +/- 1.2 vs. 8.1 +/- 0.7 mu m) and showed an increased occurrence of plaque macrocalcifications (30% vs. 0%), indicative of a more stable phenotype. Molsidomine also improved cardiac function, as fractional shortening was increased (40 +/- 2% vs. 27 +/- 2%) combined with a decreased end diastolic (3.1 +/- 0.2 vs. 3.9 +/- 0.2 mm) and end systolic diameter (1.9 +/- 0.1 vs. 2.9 +/- 0.2 mm). Furthermore, perivascular fibrosis (23 +/- 2 vs. 30 +/- 2%) and the occurrence of myocardial infarctions (12% vs. 36%) was significantly reduced. Track width, a measure of the animal's hind limb base of support and representative of hypoxic brain damage, was also normalized as a result of molsidomine treatment (2.54 +/- 0.04 vs. 2.91 +/- 0.09 cm in controls). These findings demonstrate that the NO donor molsidomine improves cardiac function, reduces neurological symptoms and enhances atherosclerotic plaque stability.
- Published
- 2019
42. Uterine and fetal placental Doppler indices are associated with maternal cardiovascular function
- Author
-
J. Tay, Christoph Lees, Carmel M. McEniery, Giulia Masini, Caroline J. Shaw, Dino A. Giussani, Phillip R. Bennett, Ian B. Wilkinson, McEniery, Carmel [0000-0003-3636-0705], Giussani, Dino [0000-0002-1308-1204], Wilkinson, Ian [0000-0001-6598-9399], and Apollo - University of Cambridge Repository
- Subjects
VELOCITY WAVE-FORMS ,Cardiac output ,FLOW ,Maternal Health ,fetal growth restriction ,Cohort Studies ,Fetal Development ,0302 clinical medicine ,Pre-Eclampsia ,Pregnancy ,Reference Values ,GROWTH RESTRICTION ,1114 Paediatrics And Reproductive Medicine ,Medicine ,Prospective Studies ,030212 general & internal medicine ,Cardiac Output ,Uterine artery ,Fetal Growth Retardation ,030219 obstetrics & reproductive medicine ,HUMAN UMBILICAL ARTERY ,Obstetrics & Gynecology ,Obstetrics and Gynecology ,Uterine Artery ,medicine.anatomical_structure ,Cardiovascular Diseases ,Pulsatile Flow ,Heart Function Tests ,Infant, Small for Gestational Age ,Cardiology ,circulation ,Gestation ,Female ,Life Sciences & Biomedicine ,Adult ,Cardiac function curve ,medicine.medical_specialty ,placenta ,PRECONCEPTION ,Gestational Age ,Risk Assessment ,Ultrasonography, Prenatal ,Preeclampsia ,preeclampsia ,03 medical and health sciences ,CARDIAC-FUNCTION ,medicine.artery ,Internal medicine ,VELOCIMETRY ,PREGNANCIES ,Humans ,pulsatility index ,Placental Circulation ,Obstetrics & Reproductive Medicine ,Fetus ,Science & Technology ,HYPERTENSION ,hypoxia ,business.industry ,Ultrasonography, Doppler ,medicine.disease ,peripheral vascular resistance ,Vascular resistance ,business - Abstract
Background The mechanism underlying fetal-placental Doppler index changes in preeclampsia and/or fetal growth restriction are unknown, although both are associated with maternal cardiovascular dysfunction. Objective We sought to investigate whether there was a relationship between maternal cardiac output and vascular resistance and fetoplacental Doppler findings in healthy and complicated pregnancy. Study Design Women with healthy pregnancies (n=62), preeclamptic pregnancies (n=13), preeclamptic pregnancies with fetal growth restriction (n=15), or fetal growth restricted pregnancies (n=17) from 24–40 weeks gestation were included. All of them underwent measurement of cardiac output with the use of an inert gas rebreathing technique and derivation of peripheral vascular resistance. Uterine and fetal Doppler indices were recorded; the latter were z scored to account for gestation. Associations were determined by polynomial regression analyses. Results Mean uterine artery pulsatility index was higher in fetal growth restriction (1.37; P=.026) and preeclampsia+fetal growth restriction (1.63; P=.001) but not preeclampsia (0.92; P=1) compared with control subjects (0.8). There was a negative relationship between uterine pulsatility index and cardiac output (r2=0.101; P=.025) and umbilical pulsatility index z score and cardiac output (r2=0.078; P=.0015), and there were positive associations between uterine pulsatility index and peripheral vascular resistance (r2=0.150; P=.003) and umbilical pulsatility index z score and peripheral vascular resistance (r2= 0.145; P=.001). There was no significant relationship between cardiac output and peripheral vascular resistance with cerebral Doppler indices. Conclusion Uterine artery Doppler change is abnormally elevated in fetal growth restriction with and without preeclampsia, but not in preeclampsia, which may explain the limited sensitivity of uterine artery Doppler changes for all these complications when considered in aggregate. Furthermore, impedance within fetoplacental arterial vessels is at least, in part, associated with maternal cardiovascular function. This relationship may have important implications for fetal surveillance and would inform therapeutic options in those pathologic pregnancy conditions currently, and perhaps erroneously, attributed purely to placental maldevelopment. Uterine and fetal placental Doppler indices are associated significantly with maternal cardiovascular function. The classic description of uterine and fetal Doppler changes being initiated by placental maldevelopment is a less plausible explanation for the pathogenesis of the conditions than that relating to maternal cardiovascular changes.
- Published
- 2019
43. Cardiomyogenic differentiation potential of human lipoaspirate-derivedstem cells on hyaluronic acid/gelatin plasma gels
- Author
-
Esra Gov, Zehra Seda Halbutoğullari, Erdal Karaoz, Halime Kenar, Kazim Yalçin Arğa, Gov, Esra, Kenar, Halime, Halbutogullari, Zehra Seda, Arga, Kazim Yalcin, and Karaoz, Erdal
- Subjects
0301 basic medicine ,EXPRESSION ,food.ingredient ,Physiology ,HYDROGELS ,Matrix (biology) ,Biology ,Microbiology ,Gelatin ,SCAFFOLDS ,CARDIOMYOCYTES ,HUMAN ADIPOSE-TISSUE ,03 medical and health sciences ,chemistry.chemical_compound ,food ,Tissue engineering ,HA/G plasma gel ,CARDIAC-FUNCTION ,stem cells ,Hyaluronic acid ,Gene expression ,Genetics ,EXTRACELLULAR-MATRIX ,Cardiomyogenic differentiation,stem cells,human adipose-derived stem cells,HA/G plasma gel,biomaterials,tissue engineering ,Molecular Biology ,Growth medium ,Mesenchymal stem cell ,Cell Biology ,Cardiomyogenic differentiation ,CANCER ,Cell biology ,030104 developmental biology ,chemistry ,human adipose-derived stem cells ,tissue engineering ,Stem cell ,General Agricultural and Biological Sciences ,biomaterials - Abstract
Cardiomyogenic differentiation from mesenchymal stem cells has emerged as a novel approach for repair of damaged myocardium. Cell transplantation through direct cell injection is not an optimal method due to the lack of cell-extracellular matrix interactions. In the present study, differentiation potential of human adipose-derived stem cells (ASCs) to cardiomyocytes has been investigated by growing them on hyaluronic acid/gelatin (HA/G) plasma gels and coverslips and supplementing the growth medium with chemical modifiers (activin-a, BMP-4, insulin, valproic acid, and 5-azacytidine) in various combinations. The HA/G plasma gels were produced from human blood plasma-derived fibrinogen, gelatin, and human umbilical cord-derived hyaluronic acid. A network-based approach was employed to select marker genes for cardiomyogenic differentiation, and the expression levels of three markers (GATA4, TBX5, and cTnI) were followed by RT-qPCR to investigate the cardiomyogenic differentiation potential of ASCs. Results indicated that each combination of chemical modifiers led to different expression levels in the aforementioned cardiac markers, and this was material-dependent, too. The cardiac gene expression on HA/G plasma gels in the presence of activin-a + BMP-4 or insulin + valproic acid was more pronounced than in the presence of 5-azacytidine only, and scaffold and chemical modifier combinations were crucial for cardiomyogenic differentiation.
- Published
- 2016
44. Notch-independent RBPJ controls angiogenesis in the adult heart
- Author
-
Pilar Ruiz-Lozano, Ramón Díaz-Trelles, Danh Tran, Mark Mercola, Kirk L. Peterson, Anna Monosov, Edward Monosov, Paul J. Bushway, Pedro Cabrales, Stacey Rentschler, and Maria Cecilia Scimia
- Subjects
0301 basic medicine ,Male ,HIPPEL-LINDAU PROTEIN ,MYOCARDIAL-ISCHEMIA ,Angiogenesis ,General Physics and Astronomy ,Cardiovascular ,Regenerative Medicine ,Neovascularization ,PATHWAY ,Mice ,Myocytes, Cardiac ,Myocardial infarction ,TRANSCRIPTION FACTOR ,Hypoxia ,Regulation of gene expression ,Multidisciplinary ,GENE-TARGETED MICE ,Coronary Vessels ,Multidisciplinary Sciences ,Heart Disease ,Immunoglobulin J Recombination Signal Sequence-Binding Protein ,Science & Technology - Other Topics ,Female ,Hypoxia-Inducible Factor 1 ,medicine.symptom ,Cardiac ,Science ,Neovascularization, Physiologic ,Biology ,alpha Subunit ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,CARDIAC-FUNCTION ,Paracrine Communication ,Genetics ,medicine ,Animals ,Humans ,RECEPTOR KINASE 1 ,Physiologic ,Transcription factor ,Heart Disease - Coronary Heart Disease ,Myocytes ,Science & Technology ,RBPJ ,HEK 293 cells ,General Chemistry ,Hypoxia (medical) ,medicine.disease ,Hypoxia-Inducible Factor 1, alpha Subunit ,CONDUCTANCE CATHETER ,030104 developmental biology ,HEK293 Cells ,Gene Expression Regulation ,ENDOTHELIAL GROWTH-FACTOR ,Microvessels ,Cancer research ,THERAPEUTIC ANGIOGENESIS - Abstract
Increasing angiogenesis has long been considered a therapeutic target for improving heart function after injury such as acute myocardial infarction. However, gene, protein and cell therapies to increase microvascularization have not been successful, most likely because the studies failed to achieve regulated and concerted expression of pro-angiogenic and angiostatic factors needed to produce functional microvasculature. Here, we report that the transcription factor RBPJ is a homoeostatic repressor of multiple pro-angiogenic and angiostatic factor genes in cardiomyocytes. RBPJ controls angiogenic factor gene expression independently of Notch by antagonizing the activity of hypoxia-inducible factors (HIFs). In contrast to previous strategies, the cardiomyocyte-specific deletion of Rbpj increased microvascularization of the heart without adversely affecting cardiac structure or function even into old age. Furthermore, the loss of RBPJ in cardiomyocytes increased hypoxia tolerance, improved heart function and decreased pathological remodelling after myocardial infarction, suggesting that inhibiting RBPJ might be therapeutic for ischaemic injury., Heart function after injury improves upon formation of new blood vessels. Here, the authors show that ablating a transcription factor RBPJ in the murine heart increases vascularization and maintains cardiac function after injury by increasing responsiveness to hypoxia, suggesting a new approach to treat heart injury.
- Published
- 2016
45. Renal failure induces telomere shortening in the rat heart
- Subjects
CHRONIC KIDNEY-DISEASE ,DAMAGE ,telomere ,myocardial infarction ,MYOCARDIAL-INFARCTION ,CARDIAC-FUNCTION ,HYPERTENSION ,TISSUE ,LENGTH ,OXIDATIVE STRESS ,UREMIC RATS ,kidney failure ,LIFE-SPAN - Abstract
Background. Renal failure aggravates pathological cardiac remodelling induced by myocardial infarction (MI). Cardiac remodelling is associated with telomere shortening, a marker for biological ageing. We investigated whether mild and severe renal failure shorten cardiac telomeres and excessively shorten telomeres after MI.Methods. Rats were subjected to sham, unilateral (UNX) or 5/6th nephrectomy (5/6NX) to induce none, mild or severe renal failure. MI was induced by left coronary artery ligation. Renal function parameters and blood pressure were measured. DNA was isolated from non-infarcted cardiac tissue. Telomere length was assessed by quantitative polymerase chain reaction (PCR).Results. Proteinuria was unchanged in UNX and MI compared with control, but strongly increased in 5/6NX, UNX+MI and 5/6NX+MI. Serum creatinine levels were increased fourfold in 5/6NX and tenfold in 5/6NX+MI. 5/6NX and groups with both renal failure and MI showed an approximate 20% reduction of telomere length, similar to the MI group. No excess telomere shortening was observed in hearts from rats with renal ablation after MI.Conclusion. Severe renal failure, but not mild renal failure, leads to shortening of cardiac telomeres; to a similar extent as found after MI. Renal failure did not induce excessive telomere shortening after MI. (Neth Heart J 2009;17:190-4.)
- Published
- 2009
46. Myocardial infarction does not further impair renal damage in 5/6 nephrectomized rats
- Author
-
Ying Xu, Robert H. Henning, Willemijn A.K.M. Windt, Richard P. E. van Dokkum, Dick de Zeeuw, Alex C. A. Kluppel, Groningen University Institute for Drug Exploration (GUIDE), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), and Groningen Institute for Organ Transplantation (GIOT)
- Subjects
Male ,medicine.medical_specialty ,CORONARY-ARTERY ,medicine.medical_treatment ,Urology ,ACE-INHIBITORS ,Renal function ,Angiotensin-Converting Enzyme Inhibitors ,Nephrectomy ,Renin-Angiotensin System ,CARDIAC-FUNCTION ,INSUFFICIENCY ,Lisinopril ,Internal medicine ,CARDIOVASCULAR RISK-FACTORS ,medicine ,Animals ,Renal Insufficiency ,Myocardial infarction ,Rats, Wistar ,UREMIC RATS ,GENERAL-POPULATION ,Transplantation ,Kidney ,ACEi therapy ,5/6 nephrectomy ,business.industry ,Hemodynamics ,CONSCIOUS RATS ,Glomerulosclerosis ,URINARY ALBUMIN EXCRETION ,medicine.disease ,Rats ,myocardial infarction ,medicine.anatomical_structure ,Endocrinology ,Nephrology ,Creatinine ,Renal blood flow ,HEART-FAILURE ,cardiorenal interaction ,Hemodialysis ,business ,Kidney disease - Abstract
Background. Recent observational studies show that reduced renal function is an independent risk factor for the development of cardiovascular disease. Previously, we reported that myocardial infarction (MI) indeed enhanced mild renal function decline in rats after unilateral nephrectomy (NX) and that RAAS intervention inhibited this decline. The effects of an MI on pre-existing sever renal function loss and the effects of RAAS intervention interrupting this hypothesized cardiorenal interaction are however unknown and clinically even more relevant.Methods. Male Wistar rats underwent MI, sham MI, 5/6NX, or 5/6NX and MI. Six weeks later, the NX rats were treated with an angiotensin-converting enzyme inhibitor (ACEi) or vehicle for 6 weeks.Results. An MI did not significantly induce more proteinuria (303 +/- 46 versus 265 +/- 24 mg/24 h) and glomerulosclerosis (40 +/- 11 versus 28 +/- 4 arbitrary units) in 5/6NX+MI compared to 5/6NX, and ACEi therapy was equally effective in reducing renal damage in these groups. In the 5/6NX+MI group, decreased renal blood flow and creatinine clearance were observed compared to 5/6NX (2.2 +/- 0.6 versus 3.6 +/- 0.4 ml/min/kg and 2.1 +/- 0.3 versus 2.9 +/- 0.3 ml/min/kg), which both increased after ACEi to levels comparable found in the group that underwent 5/6NX alone.Conclusions. MI does not further deteriorate structural renal damage induced by 5/6NX compared with 5/6NX alone. Furthermore, renal haemodynamic impairment occurs after MI, which can be improved applying ACEi therapy. Therefore, we conclude that treatment with ACEi should be optimized in patients with chronic kidney disease after MI to improve renal function.
- Published
- 2008
47. Sex differences and heritability of two indices of heart rate dynamics
- Author
-
Harold Snieder, Julian F. Thayer, Lorenz J.P. van Doornen, Dorret I. Boomsma, and Biological Psychology
- Subjects
Adult ,Male ,Netherlands Twin Register (NTR) ,ANGIOTENSIN-CONVERTING ENZYME ,medicine.medical_specialty ,ACUTE MYOCARDIAL-INFARCTION ,RESPIRATORY SINUS ARRHYTHMIA ,FREQUENCY ,Correlation ,SDG 3 - Good Health and Well-being ,CARDIAC-FUNCTION ,Heart Rate ,SPECTRAL-ANALYSIS ,Internal medicine ,Heart rate ,Genetic model ,Twins, Dizygotic ,Humans ,Medicine ,Heart rate variability ,Arrhythmia, Sinus ,Vagal tone ,Genetics (clinical) ,Analysis of Variance ,Sex Characteristics ,Communication ,PERIOD VARIABILITY ,Models, Genetic ,business.industry ,MORTALITY ,Confounding ,Models, Cardiovascular ,Obstetrics and Gynecology ,Twins, Monozygotic ,RATE-VARIABILITY ,ASSOCIATION ,Middle Aged ,Heritability ,Twin study ,Pediatrics, Perinatology and Child Health ,Cardiology ,Regression Analysis ,Female ,business - Abstract
We investigated whether women show larger heart rate variability (HRV) than men after controlling for a large number of health-related covariates, using two indices of HRV, namely respiratory sinus arrhythmia (RSA) and approximate entropy (ApEn). In a twin design, the heritability of both indices was examined. The covariation between RSA and ApEn, a measure of heart rate dynamics derived from nonlinear dynamical systems theory, was decomposed into genetic and environmental components. Subjects were 196 male and 210 female middle-aged twins. Females showed larger HRV than men before (ApEn: p < .001; RSA: p = .052) and after adjustment for covariates (ApEn: p < .001; RSA: p = .015). This sex difference was confirmed by significant intrapair differences in the opposite-sex twin pairs for both ApEn (p < .001) and RSA (p = .03). In addition to sex, only heart period and age (both p < .001) were found to be independent predictors of ApEn, whereas RSA was also influenced by respiration rate and smoking (both p < .001). Age explained 16% and 6% of the variance in RSA and ApEn, respectively. Oral contraceptive use and menopausal status had no effect on HRV. Genetic model fitting yielded moderate heritability estimates for RSA (30%) and ApEn (40%) for both males and females. The correlation between RSA and ApEn (r = .60) could be attributed to genetic factors (48%), environmental factors (36%) and age (16%). The present study found support for a gender difference in HRV with women having greater HRV than men even after controlling for a large number of potential confounders. Indices of heart rate dynamics derived from nonlinear dynamical systems theory are moderately heritable and may be more sensitive than traditional indices of HRV to reveal subtle sex differences with important implications for health and disease.
- Published
- 2007
48. Bone marrow-derived mesenchymal stem cells have innate procoagulant activity and cause microvascular obstruction following intracoronary delivery: amelioration by antithrombin therapy
- Author
-
Frank Barry, Sujith Kumar, M. Gopala-Krishnan Pillai, Birgitta M. Gleeson, Alessia Stocca, Derek Whelan, Kenneth Martin, Mohammed T. Ali, John F. O'Sullivan, Noel M. Caplice, Arun H.S. Kumar, Timothy O'Brien, and Wisam Khider
- Subjects
Swine ,coronary flow reserve ,030204 cardiovascular system & hematology ,Pharmacology ,Biology ,heparin ,Mesenchymal Stem Cell Transplantation ,Thromboplastin ,03 medical and health sciences ,Tissue factor ,randomized-trial ,0302 clinical medicine ,Fibrinolytic Agents ,Bone Marrow ,medicine ,Animals ,Humans ,acute myocardial-infarction ,Platelet ,cardiovascular diseases ,Blood Coagulation ,Cells, Cultured ,030304 developmental biology ,stromal cells ,0303 health sciences ,mesenchymal stem cells ,model ,ischemic cardiomyopathy ,cardiac-function ,Antithrombin ,Mesenchymal stem cell ,percutaneous coronary intervention ,Cell Biology ,Heparin ,tissue factor ,Coronary Vessels ,medicine.anatomical_structure ,myocardial infarction ,transendocardial injection ,mediated induction ,Microvessels ,Immunology ,Molecular Medicine ,Female ,Bone marrow ,Fibrinolytic agent ,Developmental Biology ,medicine.drug - Abstract
Mesenchymal stem cells (MSCs) are currently under investigation as tools to preserve cardiac structure and function following acute myocardial infarction (AMI). However, concerns have emerged regarding safety of acute intracoronary (IC) MSC delivery. This study aimed to characterize innate prothrombotic activity of MSC and identify means of its mitigation toward safe and efficacious therapeutic IC MSC delivery post-AMI. Expression of the initiator of the coagulation cascade tissue factor (TF) on MSC was detected and quantified by immunofluorescence, FACS, and immunoblotting. MSC-derived TF antigen was catalytically active and capable of supporting thrombin generation in vitro. Addition of MSCs to whole citrated blood enhanced platelet thrombus deposition on collagen at arterial shear, an effect abolished by heparin coadministration. In a porcine AMI model, IC infusion of 25 × 106 MSC during reperfusion was associated with a decrease in coronary flow reserve but not when coadministered with an antithrombin agent (heparin). Heparin reduced MSC-associated thrombosis incorporating platelets and VWF within the microvasculature. Heparin-assisted therapeutic MSC delivery also reduced apoptosis in the infarct border zone at 24 hours, significantly improved infarct size, left ventricular (LV) ejection fraction, LV volumes, wall motion, and attenuated histologic evidence of scar formation at 6 weeks post-AMI. Heparin alone or heparin-assisted fibroblast control cell delivery had no such effect. Procoagulant TF activity of therapeutic MSCs is associated with reductions in myocardial perfusion when delivered IC may be successfully managed by heparin coadministration. This study highlights an important mechanistic insight into safety concerns associated with therapeutic IC MSC delivery for AMI. Stem Cells 2015;33:2726–2737
- Published
- 2015
49. Dynamics of pulmonary venous flow in fetuses with intrauterine growth restriction
- Author
-
Bravo-Valenzuela, Nathalie Jeanne Magioli, Zielinsky, Paulo, Huhta, James Clifford, Acácio, Gregório Lorenzo, Nicoloso, Luiz Henrique Soares, Piccoli, Antonio, Busato, Stefano, Klein, Caroline, Zielinsky, Paulo https://orcid.org/0000-0002-9268-1450, Bravo-Valenzuela, Nathalie Jeanne https://orcid.org/0000-0003-1491-4877, Zielinsky, Paulo/L-6946-2015, and Bravo-Valenzuela, Nathalie Jeanne/M-9387-2015
- Subjects
Genetics & Heredity ,Fetal-Growth ,Velocities ,Cardiac-Function ,Doppler ,Obstetrics & Gynecology ,Weight - Abstract
Made available in DSpace on 2019-09-12T16:53:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2015 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) Fundo de Apoio do IC/FUC à Ciência e Cultura (FAPICC) ObjectiveTo test the hypothesis that the pulmonary vein pulsatility index (PVPI) is higher in fetuses with growth restriction (IUGR) than in normal fetuses. MethodsTwenty-two fetuses with IUGR and twenty-one (21) fetuses with appropriate growth for gestational age from healthy mothers were studied. PVPI was calculated by Doppler echocardiography [maximal velocity (systolic or diastolic peak)-pre-systolic peak/mean velocity]. Obstetric ultrasound was used to assess fetal biometry and Doppler to assess the uterine, umbilical and middle cerebral arteries PI. Statistical analysis used t test and Pearson's correlation. ResultsMean gestational age was 31.5+/-2.1weeks in the control group and 31.4+/-3.1weeks in IUGR (P=0.91). The PI of uterine and umbilical arteries were higher in IUGR than in controls (P
- Published
- 2015
50. Cardiomyocyte-Specific Overexpression of Nitric Oxide Synthase 3 Improves Left Ventricular Performance and Reduces Compensatory Hypertrophy After Myocardial Infarction
- Author
-
Stefan Janssens, Pieter Vermeersch, Zsolt Szelid, Peter Jans, Marielle Scherrer-Crosbie, Desire Collen, Luc Schoonjans, Frans Van de Werf, Kenneth D. Bloch, Peter Pokreisz, Michael H. Picard, Marijke Pellens, Marc Tjwa, and Hilde Gillijns
- Subjects
Physiology ,Myocardial Infarction ,Nitric Oxide Synthase Type II ,Ventricular Function, Left ,angiogenesis ,Mice ,chemistry.chemical_compound ,contractile function ,Myocyte ,rat ,Myocytes, Cardiac ,Transgenes ,Myocardial infarction ,Promoter Regions, Genetic ,myocyte hypertrophy ,Ultrasonography ,left ventricular remodeling ,Ventricular Remodeling ,biology ,nitric oxide synthase ,Adrenergic beta-Agonists ,Nitric oxide synthase ,modulation ,myocardial infarction ,Organ Specificity ,Enzyme Induction ,Circulatory system ,cardiovascular system ,Cardiology ,Hypertrophy, Left Ventricular ,Cardiology and Cardiovascular Medicine ,Cardiac function curve ,medicine.medical_specialty ,mice ,Nitric Oxide Synthase Type III ,nitric-oxide synthase ,Recombinant Fusion Proteins ,Ischemia ,Mice, Transgenic ,ischemia ,Nitric oxide ,Ventricular Myosins ,Internal medicine ,medicine ,Animals ,Humans ,cardiovascular diseases ,heart-failure ,business.industry ,cardiac-function ,Isoproterenol ,Hypertrophy ,medicine.disease ,mortality ,Fibrosis ,Myocardial Contraction ,Mice, Inbred C57BL ,Endocrinology ,chemistry ,Heart failure ,biology.protein ,Nitric Oxide Synthase ,business - Abstract
Nitric oxide (NO) is an important modulator of cardiac performance and left ventricular (LV) remodeling after myocardial infarction (MI). We tested the effect of cardiomyocyte-restricted overexpression of one NO synthase isoform, NOS3, on LV remodeling after MI in mice. LV structure and function before and after permanent LAD coronary artery ligation were compared in transgenic mice with cardiomyocyte-restricted NOS3 overexpression (NOS3-TG) and their wild-type littermates (WT). Before MI, systemic hemodynamic measurements, echocardiographic assessment of LV fractional shortening (FS), heart weight, and myocyte width (as assessed histologically) did not differ in NOS3-TG and WT mice. The inotropic response to graded doses of isoproterenol was significantly reduced in NOS3-TG mice. One week after LAD ligation, the infarcted fraction of the LV did not differ in WT and NOS3-TG mice (34±4% versus 36±12%, respectively). Four weeks after MI, however, end-systolic LVID was greater, and fractional shortening and maximum and minimum rates of LV pressure development were less in WT than in NOS3-TG mice. LV weight/body weight ratio was greater in WT than in NOS3-TG mice (5.3±0.2 versus 4.6±0.5 mg/g; P P
- Published
- 2004
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.