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Epidemiological studies consistently have suggested an association between low birth weight and increased rate of cardiovascular morbidity and mortality in adult life. Preterm birth, as one of the leading causes of the low birth weight, is associated with cardiovascular remodeling which consists of changes in heart chambers geometry and contraction-relaxation mode, ventricular hypertrophy, arterial wall structure and density changes. Several types of preterm birth are discussed: prematurity, associated with placental insufficiency and fetal growth restriction, preterm leaking of amniotic fluid, and twin pregnancy. DNA methylation process under the influence of epigenetic factors of the intrauterine and early postnatal development is suggested as a one of the main mechanism of cardiovascular remodeling in preterm infants. The other mechanisms of cardiovascular remodeling are discussed in terms of the modern intrauterine programming concept. The early diagnostics and prevention of cardiovascular diseases in preterm born children are discussed. The treatment during prenatal and early postnatal periods as well as prevention of the remodeling causes could diminish and even reverse the development of the negative cardiovascular events and diseases in later life according to the so called concept of “one thousand days opportunities window”. © 2020 Izdatel'stvo Meditsina. All rights reserved. Работа выполнена при финансовой поддержке ФГБОУ ВО УГМУ Минздрава России в рамках госзадания ИИФ УрО РАН (тема № АААА-А18-118020590031-8) и поддержана постановлением Правительства РФ от 16.03.2013 № 211 (соглашение 02.A03.21.0006).

Connexin 43 (Cx43) is essential for cardiac electrical coupling, but its effects on myocardial fibrosis is controversial. Here, we analyzed the role of Cx43 in myocardial fibrosis caused by angiotensin II (AngII) using Cx43fl/fl and Cx43Cre-ER(T)/fl inducible knock-out (Cx43 content: 50%) mice treated with vehicle or 4-hydroxytamoxifen (4-OHT) to induce a Cre-ER(T)-mediated global deletion of the Cx43 floxed allele. Myocardial collagen content was enhanced by AngII in all groups (n = 8–10/group, p < 0.05). However, animals with partial Cx43 deficiency (vehicle-treated Cx43Cre-ER(T)/fl) had a significantly higher AngII-induced collagen accumulation that reverted when treated with 4-OHT, which abolished Cx43 expression. The exaggerated fibrotic response to AngII in partially deficient Cx43Cre-ER(T)/fl mice was associated with enhanced p38 MAPK activation and was not evident in Cx43 heterozygous (Cx43+/-) mice. In contrast, normalization of interstitial collagen in 4-OHT-treated Cx43Cre-ER(T)/fl animals correlated with enhanced MMP-9 activity, IL-6 and NOX2 mRNA expression, and macrophage content, and with reduced a-SMA and SM22a in isolated fibroblasts. In conclusion, our data demonstrates an exaggerated, p38 MAPK-dependent, fibrotic response to AngII in partially deficient Cx43Cre-ER(T)/fl mice, and a paradoxical normalization of collagen deposition in animals with an almost complete Cx43 ablation, an effect associated with increased MMP-9 activity and inflammatory response and reduced fibroblasts differentiation. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

BACKGROUND Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death.OBJECTIVES This meta-analysis sought to gain insights into the genetic determinants of myocardial mass.METHODS We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment.RESULTS We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p CONCLUSIONS Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets. (C) 2016 by the American College of Cardiology Foundation.

Background. Adiponectin is an adipocytes-derived hormone which has been shown to possess insulin-sensitizing, antiatherogenic, and anti-inflammatory properties. In acromegaly, the data on adiponectin is contradictory. The relationship between adiponectin levels and cardiac parameters has not been studied. Objectives. The aim of this study was to find out how adiponectin levels were affected in acromegalic patients and the relationship between adiponectin levels and cardiac parameters. Material and Methods. We included 30 subjects (15 male, 15 female), diagnosed with acromegaly and 30 healthy (10 male, 20 female) subjects. Serum glucose, insulin, GH, IGF-1 and adiponectin levels were obtained and the insulin resistance of the subjects was calculated. Echocardiographic studies of the subjects were performed. Results. We determined that adiponectin levels were significantly higher in the acromegalic group than the control group. In the acromegalic group, there was no statistically significant relation between serum adiponectin and growth hormone (GH), or insulin-like growth factor-1 (IGF-1) levels (p = 0.3, p = 0.1). We demonstrated that cardiac function and structure are affected by acromegaly. IVST, PWT, LVMI, E/A ratio, DT, ET, IVRT, VPR, and LVESV values were increased and the results were statistically significant. In the acromegalic group, adiponectin levels were positively related with left ventricle mass index (LVMI) but this correlation was found to be statistically weak (p = 0.03). In our study, there was a positive correlation between VAI and LVM. We also could not find any correlation between VAI and adiponectin levels. Conclusions. Although insulin resistance and high insulin levels occur in active acromegaly patients, adiponectin levels were higher in our study as a consequence of GH lowering therapies. Our study showed that adiponectin levels may be an indicator of the cardiac involvement acromegaly. However, the usage of serum adiponectin levels in acromegalic patients as an indicator of cardiac involvement should be supported with other, wide, multi-centered studies. © Copyright by Wroclaw Medical University.

There is overwhelming evidence that regular exercise training is protective against cardiovascular disease (CVD), the main cause of death worldwide. Despite the benefits of exercise, the intricacies of their underlying molecular mechanisms remain largely unknown. Non-coding RNAs (ncRNAs) have been recognized as a major regulatory network governing gene expression in several physiological processes and appeared as pivotal modulators in a myriad of cardiovascular processes under physiological and pathological conditions. However, little is known about ncRNA expression and role in response to exercise. Revealing the molecular components and mechanisms of the link between exercise and health outcomes will catalyse discoveries of new biomarkers and therapeutic targets. Here we review the current understanding of the ncRNA role in exercise-induced adaptations focused on the cardiovascular system and address their potential role in clinical applications for CVD. Finally, considerations and perspectives for future studies will be proposed. © 2018 The Author(s).

Background/Aims: Pressure-overload (PO) causes cardiac hypertrophy (CH), and eventually leads to heart failure (HF). HF ventricular myocytes present transverse-tubules (TT) loss or disarrangement and decreased sarcoplasmic reticulum (SR) density, and both contribute to altered Ca2+ signaling and heart dysfunction. It has been shown that TT remodeling precedes HF, however, it is unknown whether SR structural and functional remodeling also starts early in CH. Methods: Using confocal microscopy, we assessed TT (with Di-8-ANNEPS) and SR (with SR-trapped Mag-Fluo-4) densities, as well as SR fluorophore diffusion (fluorescence recovery after photobleach; FRAP), cytosolic Ca2+ signaling and ex vivo cardiac performance in a PO rat hypertrophy model induced by abdominal aortic constriction (at 6 weeks). Results: Rats developed CH, while cardiac performance, basal and upon β-adrenergic stimulation, remained unaltered. TT density decreased by ∼14%, without spatial disarrangement, while SR density decreased by ∼7%. More important, FRAP was ∼30% slower, but with similar maximum recovery, suggesting decreased SR interconnectivity. Systolic and diastolic Ca2+ signaling and SR Ca2+ content were unaltered. Conclusion: SR remodeling is an early CH event, similar to TT remodeling, appearing during compensated hypertrophy. Nevertheless, myocytes can withstand those moderate structural changes in SR and TT, preserving normal Ca2+ signaling and contractility. © 2015 S. Karger AG, Basel.

Lysyl oxidase (LOX) controls matrix remodeling, a key process that underlies cardiovascular diseases and heart failure; however, a lack of suitable animal models has limited our knowledge with regard to the contribution of LOX to cardiac dysfunction. Here, we assessed the impact of LOX overexpression on ventricular function and cardiac hypertrophy in a transgenic LOX (TgLOX) mouse model with a strong cardiac expression of human LOX. TgLOX mice exhibited high expression of the transgene in cardiomyocytes and cardiofibroblasts, which are associated with enhanced LOX activity and H2O2 production and with cardiofibroblast reprogramming. LOX overexpression promoted an age-associated concentric remodeling of the left ventricle and impaired diastolic function. Furthermore, LOX transgenesis aggravated angiotensin II (Ang II)–induced cardiac hypertrophy and dysfunction, which triggered a greater fibrotic response that was characterized by stronger collagen deposition and cross-linking and high expression of fibrotic markers. In addition, LOX transgenesis increased the Ang II–induced myocardial inflammatory infiltrate, exacerbated expression of proinflammatory markers, and decreased that of cardioprotective factors. Mechanistically, LOX overexpression enhanced oxidative stress and potentiated the Ang II–mediated cardiac activation of p38 MAPK while reducing AMPK activation. Our findings suggest that LOX induces an age-dependent disturbance of diastolic function and aggravates Ang II–induced hypertrophy, which provides novel insights into the role of LOX in cardiac performance. © FASEB.

Purpose To find out how resistin and leptin levels were affected in patients with acromegaly and whether there is a relation between resistin levels and cardiac parameters. We also aimed to investigate whether resistin and leptin may be a link between insulin resistance and cardiac functions as well as these affected cardiac functions in the patients with acromegaly. Methods We included 30 subjects (15 men and 15 women) who had a diagnosis of acromegaly and 30 healthy (10 men and 20 women) subjects. Serum glucose, insulin, growth hormone, insulinlike growth factor 1 (IGF-1), resistin, and leptin levels were obtained, and insulin resistance of subjects were calculated. Echocardiographic studies of the subjects were performed. Results Resistin levels of the patients with acromegaly were found lower than controls. This difference was statistically significant ( P = 0.001). Leptin levels were lower in the patients with acromegaly than in the controls, but this difference was not statistically significant. Resistin and leptin levels were not correlated with growth hormone, IGF-1, and with insulin-like growth factor binding protein 3 levels. Homeostasis model assessment of insulin resistance was positively correlated with resistin levels. ( P = 0.03; r = 0.531) but not correlated with leptin levels. There was a positive correlation between body mass index and leptin levels in the patients with acromegaly ( P = 0.007; r = 0.482). Interventricular septum thickness, posterior wall thickness, left ventricle mass index, peak early mitral inflow velocity–peak late mitral inflow velocity ratio, deceleration time, ejection time, isovolumetric relaxation time, velocity propagation, and left ventricular end-systolic volume values were significantly greater in the patients with acromegaly. Leptin levels in the acromegalic patients were not correlated with any of them. Conclusions We found biventricular hypertrophy and impairment of diastolic and systolic function in the patients with acromegaly. We conclude that changes in resistin and leptin levels are unlikely to account for the insulin resistance of acromegaly. They do not also seem to be contributing factors of cardiovascular changes in patients with acromegaly.

A calcified left ventricular aneurysm (CLVA) is a rare, serious complication of acute myocardial infarction. It can lead to angina pectoris, thromboembolism of ventricular origin, ventricular arrhythmia, ventricular pseudoaneurysm or rupture, progressively enlarging aneurysms, congestive heart failure, and death. Treatment is surgical for symptomatic or asymptomatic LVAs larger than 5 cm, particularly when there is comorbid coronay artery disease. Its standard treatment is a ventriculoplasty and aneurysmectomy using the Dor technique. The aim of surgical treatment of an LVA is to reduce oxygen consumption in the LV by reducing end-diastolic volume (EDV), creating the ideal ventricle geometry, and preventing thrombus formation. The surgical results are often good. This article presents a patient with CLVA in whom we performed surgery. Copyright © 2016 by Türkiye Klinikleri.

FUNDAMENTO: A relevância do padrão de remodelamento no modelo de ratos infartados não é conhecida. OBJETIVO: Analisar a presença de diferentes padrões de remodelamento nesse modelo e suas implicações funcionais. MÉTODOS: Ratos infartados (n=46) foram divididos de acordo com o padrão de geometria, analisado pelo ecocardiograma: normal (índice de massa normal e espessura relativa normal), remodelamento concêntrico (índice de massa normal e espessura relativa aumentada), hipertrofia concêntrica (índice de massa aumentado e espessura relativa aumentada) e hipertrofia excêntrica (índice de massa aumentado e espessura relativa normal). Os dados estão em mediana e intervalo interquartil. RESULTADOS: Ratos infartados apresentaram apenas dois dos quatro padrões de geometria: padrão normal (15%) e hipertrofia excêntrica - HE (85%). Os grupos de padrão normal e HE não apresentaram diferenças nos valores de fração de variação de área (Normal = 32,1 - 28,8 a 50,7; HE = 31,3 - 26,5 a 36,7; p=0,343). Dos animais infartados, 34 (74%) apresentaram disfunção sistólica, detectada pela fração de variação de área. Considerando os dois padrões de geometria, 77% dos animais com hipertrofia excêntrica e 57% com geometria normal apresentaram disfunção sistólica (p=0,355). A espessura relativa da parede, os padrões de geometria e o índice de massa não foram fator de predição de disfunção ventricular (p>0,05). Por outro lado, o tamanho do infarto foi fator de predição de disfunção ventricular na análise univariada (p 0.05). On the other hand, infarct size was a predictive factor for ventricular dysfunction in univariate analysis (p

Introduction: Cardiac hypertrophy has substantial clinical significance because many hypertrophic cells have markedly prolonged repolarization behavior, which may lead to increased risk for cardiac arrhythmias. Spontaneously hypertensive rat (SHR) is one model of hypertension that is studied extensively and is considered to be the best laboratory model of human hypertension. We extended our previously published model of the rat ventricular myocyte to simulate the effects of hypertrophy in SHR. Methods and Results: In SHR it has been shown that the membrane capacitance is increased, the density of transient outward K+ current is decreased, the sarcoplasmic reticulum Ca2+ ATPase activity is reduced, and the cell volumes are increased compared to those of the normal rat. We introduced these changes into our previous model of the rat ventricular myocyte and simulated the ventricular action potential of SHR. Our results demonstrated increased action potential duration (APD) and increased peak systolic value of the intracellular calcium transient in SHR. Simulations with reduced extracellular K+ concentration ([K+]o) have shown that there is increased APD shortening in SHR compared to that of the normal rat. Conclusions: Our computational model qualitatively simulated the electrophysiologic changes observed in SHR and provided the plausible mechanistic linkage between the prolonged APD and increased inotropy. Our model results also demonstrated the electrophysiologic changes observed with reduced [K+]o in SHR, a finding that is clinically significant in hypertensive patients with left ventricular hypertrophy undergoing diuretic treatment. (J Cardiovasc Electrophysiol, Vol. 14, pp. 990-995, September 2003)

AIM It is unknown how the heart distinguishes various overloads, such as exercise or hypertension, causing either physiological or pathological hypertrophy. We hypothesize that alpha-calcitonin-gene-related peptide (αCGRP), known to be released from contracting skeletal muscles, is key at this remodelling. METHODS The hypertrophic effect of αCGRP was measured in vitro (cultured cardiac myocytes) and in vivo (magnetic resonance imaging) in mice. Exercise performance was assessed by determination of maximum oxygen consumption and time to exhaustion. Cardiac phenotype was defined by transcriptional analysis, cardiac histology and morphometry. Finally, we measured spontaneous activity, body fat content, blood volume, haemoglobin mass and skeletal muscle capillarization and fibre composition. RESULTS While αCGRP exposure yielded larger cultured cardiac myocytes, exercise-induced heart hypertrophy was completely abrogated by treatment with the peptide antagonist CGRP(8-37). Exercise performance was attenuated in αCGRP(-/-) mice or CGRP(8-37) treated wild-type mice but improved in animals with higher density of cardiac CGRP receptors (CLR-tg). Spontaneous activity, body fat content, blood volume, haemoglobin mass, muscle capillarization and fibre composition were unaffected, whereas heart index and ventricular myocyte volume were reduced in αCGRP(-/-) mice and elevated in CLR-tg. Transcriptional changes seen in αCGRP(-/-) (but not CLR-tg) hearts resembled maladaptive cardiac phenotype. CONCLUSIONS Alpha-calcitonin-gene-related peptide released by skeletal muscles during exercise is a hitherto unrecognized effector directing the strained heart into physiological instead of pathological adaptation. Thus, αCGRP agonists might be beneficial in heart failure patients.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:26:54Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:31:44Z : No. of bitstreams: 1 2-s2.0-84864510746.pdf: 274160 bytes, checksum: dcd3b5e90752c938a89d8fa48f8c7362 (MD5) Made available in DSpace on 2014-05-27T11:26:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-08-08 Background: The pathogenesis of pulmonary hypertension (PH) in hemodialysis is still unclear. The aim of thisstudy was to identify the risk factors associated with the presence of PH in chronic hemodialysis patients and toverify whether these factors might explain the highest mortality among them.Methods: We conducted a retrospective study of hemodialysis patients who started treatment from August 2001to October 2007 and were followed up until April 2011 in a Brazilian referral medical school. According to theresults of echocardiography examination, patients were allocated in two groups: those with PH and those withoutPH. Clinical parameters, site and type of vascular access, bioimpedance, and laboratorial findings were comparedbetween the groups and a logistic regression model was elaborated. Actuarial survival curves were constructed andhazard risk to death was evaluated by Cox regression analysis.Results: PH > 35 mmHg was found in 23 (30.6%) of the 75 patients studied. The groups differed in extracellularwater, ventricular thickness, left atrium diameter, and ventricular filling. In a univariate analysis, extracellular waterwas associated with PH (relative risk = 1.194; 95% CI of 1.006 1.416; p = 0.042); nevertheless, in a multiple model,only left atrium enlargement was independently associated with PH (relative risk =1.172; 95% CI of 1.010 1.359;p = 0.036). PH (hazard risk = 3.008; 95% CI of 1.285 7.043; p = 0.011) and age (hazard risk of 1.034 per year of age;95% CI of 1.000 7.068; p = 0.047) were significantly associated with mortality in a multiple Cox regression analysis.However, when albumin was taken in account the only statistically significant association was between albuminlevel and mortality (hazard risk = 0.342 per g/dL; 95% CI of 0.119 0.984; p = 0.047) while the presence of PH lost itsstatistical significance (p = 0.184). Mortality was higher in patients with PH (47.8% vs 25%) who also had astatistically worse survival after the sixth year of follow up.Conclusions: PH in hemodialysis patients is associated with parameters of volume overload that sheds light on itspathophysiology. Mortality is higher in hemodialysis patients with PH and the low albumin level can explain thisassociation.© 2012 Greenfield et al.; licensee BioMed Central Ltd. Division of Pulmonology Botucatu School of Medicine State University of São Paulo UNESP, Botucatu, SP Division of Nephrology Botucatu School of Medicine State University of São Paulo UNESP, Botucatu, SP Division of Cardiology Botucatu School of Medicine State University of São Paulo UNESP, Botucatu, SP Division of Pulmonology Botucatu School of Medicine State University of São Paulo UNESP, Botucatu, SP Division of Nephrology Botucatu School of Medicine State University of São Paulo UNESP, Botucatu, SP Division of Cardiology Botucatu School of Medicine State University of São Paulo UNESP, Botucatu, SP

Background: The mechanisms involved in cardiac remodeling in left (LV) and right ventricles (RV) after myocardial infarction (MI) are still unclear. We assayed factors involved in collagen turnover in both ventricles following MI in rats either presenting signs of heart failure (pulmonary congestion and increased LVEDP) or not (INF-HF or INF, respectively). Methods: MI was induced in male rats by ligation of the left coronary artery. Four weeks after MI gene expression of collagen I, connective tissue growth factor (CTGF), transforming growth factor beta (TGF-beta) and lysyl oxidase (LOX), metalloproteinase-2 (MMP2) and tissue inhibitor metalloproteinase-2 (TIMP2) as well as cardiac hemodynamic in both ventricles were evaluated. Results: Ventricular dilatation, hypertrophy and an increase in interstitial fibrosis and myocyte size were observed in the RV and LV from INF-HF animals, whereas only LV dilatation and fibrosis in RV was present in INF. The LV fibrosis in INF-HF was associated with higher mRNA of collagen I, CTGF, TGF-beta and LOX expressions than in INF and SHAM animals, while MMP2/TIMP2 mRNA ratio did not change. RV fibrosis in INF and INF-HF groups was associated with an increase in LOX mRNA and a reduction in MMP2/TIMP2 ratio. CTGF mRNA was increased only in the INF-HF group. Conclusions: INF and INF-HF animals presented different patterns of remodeling in both ventricles. In the INF-HF group, fibrosis seems to be consequence of collagen production in LV, and by reductions in collagen degradation in RV of both INF and INF-HF animals.

Uma das estratégias mais utilizadas para o estudo das alterações fisiopatológicas decorrentes da oclusão coronariana é o uso do modelo do infarto experimental no rato. Entre outros fatores, esse fato é decorrência da similaridade com as alterações fisiopatológicas que ocorrem após o infarto, em humanos. Devemos considerar, entretanto, que esse modelo possui características que podem dificultar tanto o uso como a interpretação de eventuais resultados. Assim, essa revisão tem como objetivo discutir as principais características do modelo do infarto experimental no rato, abordando a técnica da oclusão coronariana, as consequências e os métodos de avaliação morfológica e funcional do infarto e suas implicações clínicas. One of the most often used strategies to study the physiopathological alterations caused by coronary occlusion is the use of the experimental infarction model in rats. Among other factors, this is due to the similarities in the physiopathological alterations that occur after the infarction in humans. One must consider, however, that this model has characteristics that can hinder the use as well as the interpretation of eventual outcomes. Thus, this review aims at analyzing the main characteristics of the experimental infarction model in rats, discussing the coronary occlusion technique, the consequences and the methods of morphological and functional assessment of the infarction and its clinical implications. Una de las estrategias que se utiliza más en el estudio de las alteraciones fisiopatológicas resultantes de la oclusión coronaria es el uso del modelo del infarto experimental en el ratón. Entre otros factores, este hecho resulta de la similitud con las alteraciones fisiopatológicas que ocurren tras el infarto, en humanos. Sin embargo, debemos tener en cuenta que este modelo tiene características que pueden dificultar tanto el empleo como la interpretación de eventuales resultados. Así, esta revisión tiene por objeto discutir las principales características del modelo del infarto experimental en el ratón, y que se aborde la técnica de la oclusión coronaria, las consecuencias y los métodos de evaluación morfológicos y funcionales del infarto y sus implicaciones clínicas.

Studies using pharmacological and genetic approaches have shown that increased activity/expression of the Na+/H+ exchanger isoform 1 (NHE1) play a critical role in the pathogenesis of cardiac hypertrophy. Despite the importance of NHE1 in cardiac hypertrophy, severe cerebrovascular side effects were associated with the use of NHE1 inhibitors when administered to patients with myocardial infarctions. p90 ribosomal S6 Kinase (RSK), a downstream regulator of the mitogen-activated protein kinase pathway, has also been implicated in cardiac hypertrophy. We hypothesized that RSK plays a role in the NHE1 induced cardiomyocyte hypertrophic response. Infection of H9c2 cardiomyoblasts with the active form of the NHE1 adenovirus induced hypertrophy and was associated with an increase in the phosphorylation of RSK (P

Objectives We sought to quantify the left ventricle systolic dysfunction by a geometric index from two-dimensional (2D) echocardiography by implementing an automated fuzzy logic edge detection algorithm for the segmentation. Background The coronary injuries have repercussions on the left ventricle producing changes on wall contractility, the shape of the cavity, and as a whole changes on the ventricular function. Methods 2D echocardiogram and M-mode recordings were performed over the control group and those with the dysfunctions. From 2D recordings, individual frames were extracted for at least five cardiac cycles and then segmentation of left ventricle was done by automated fuzzy systems. In each frame, the volumes are measured and a geometric index, eccentricity ratio (ER), was derived. The endocardial fractional shortening (FS), midwall fractional shortening (mFS), and the relative wall thickness (RWT) were also measured in each case. Results Depressed value of endocardial FS (20.39 +/- 5.43 vs 34.28 +/- 9.36, P = 0.0046), mFS (33 +/- 8.3 vs 52.5 +/- 11.7, P = 0.0047), and the RWT (0.337 +/- 0.096 vs 0.525 +/- 0.119, P = 0.0002) was observed with dysfunction. ER measured at end-diastole (2.86 +/- 0.703 vs 4.14 +/- 0.38) and end-systole (3.14 +/- 0.79 vs 5.48 +/- 0.74) was found to be decreased in the dysfunction group and more significant at the end-systole (P = 0.00017 vs 6.6E-06). Conclusion This work concludes that the regional and global left ventricle systolic dysfunction can be assessed by the ER measured at end-diastole and end-systole from 2D echocardiogram and may contribute to the high rate of cardiovascular disorders.

We present a case of a 36-year-old woman suffering from mobile right atrial thrombus and pulmonary embolism associated with cardiogenic shock. Two-dimensional echocardiography demonstrated a mass in the right atrium prolapsing through the tricuspid valve into the right ventricle during diastole, and leading to partial inflow obstruction. Computed tomography revealed a large mass into the left and right main pulmonary artery leading to obstruction. The laboratory findings of the patients revealed protein C deficiency. An emergency operation was performed and the thrombus in the right atrium and both pulmonary arteries were successfully extracted with using cardiopulmonary bypass. Previously unsuspected a large patent foramen ovale was closed primarily. This exemplary case highlights the benefit of surgical intervention rather than more conservative approaches such as anticoagulation and/or thrombolysis.

Objective: Angiotensin converting enzyme (ACE) is a key enzyme in angiotensin II production which causes myocardial hypertrophy and hyperplasia. In this study we aimed to investigate the relation between ACE I/D gene polymorphism and left ventricular mass (LVM), dimensions and systolic functions calculated by mitral annular motion (MAM) in young healthy male subjects. Methods: Complete echocardiographic examination was performed in 49 male healthy subjects (mean age 22.9±2.1 years) consisting of 18 ACE DD, 18 ACE DI and 13 ACE II genotypes. We calculated LVM and mass index (LVMI) by M-Mode echocardiography. The systolic MAM was recorded at 4 sites (septal, lateral, anterior, and posterior) by M-mode echocardiography and the MAM-ejection fraction (EF) was calculated from above four sites. Ejection fraction was also calculated by Simpson's method. Results: There was no significant difference among the three genotypes according to age, body mass index, systolic and diastolic blood pressure and heart rate. Interventricular septum (IVS) and left ventricular posterior wall (LVPW) diastolic thickness, LVM and LVMI were found significantly different among 3 ACE genotypes. Those measurements were higher in DD genotype in comparison to the DI and II genotypes. There was no significant difference among the three genotypes according to EF-MAM and EF by Simpson's method. Conclusion: In young healthy male subjects having ACE DD genotype, even though LVM and LVMI were within normal limits, their measurements were found to be higher than in subjects with ACE DI and II genotypes respectively. There was no difference among the three genotypes according to left ventricular systolic functions.

Portopulmonary hypertension has been reported in 2% to 9% of candidates for liver transplantation (OLT). If it is moderate to severe, it represents a contraindication to the procedure until pulmonary vasodilatative therapy has been optimized. We report the case of a 43-year-old man, scheduled for OLT due to alcoholic cirrhosis with hemosiderosis. His Model for End-Stage Liver Disease was 25 at that time. The preoperative evaluation showed a severe alteration of diffusion (pO2 68 mm Hg), without hepatopulmonary syndrome or portopulmonary hypertension (PPH) upon basal and dobutamine stress echocardiography. At the beginning of the OLT the hemodynamic profile showed mean pulmonary artery pressure (mPAP) 38 mm Hg, wedge pressure (WP) 19 mm Hg, cardiac output (CO) 9.1 L/min, pulmonary vascular resistance (PVR) 166 dyne s/cm5, transpulmonary gradient (TPG) 19 mm Hg, which lead us to promptly initiate inhaled nitric oxide (iNO) and intravenous epoprostenol 2 to 5 ng/kg/min. Upon graft reperfusion the hemodynamic profile was: mPAP 47 mm Hg, WP 23 mm Hg, CO 14.2 L/min, PVR 135 dyne s/cm5, TPG 24 mm Hg, and at the end of surgery, mPAP 39 mm Hg, WP 20 mm Hg, CO 10.6 L/min, PVR 123 dyne s/cm5, TPG 19 mm Hg. On postoperative day (POD) 3, we observed severe worsening of PPH: mPAP 60 mm Hg, WP 10 mm Hg, CO 9.8 L/min, PVR 395 dyne s/cm5, TPG 50 mm Hg even with maximal pulmonary vasodilatatory therapy (ambrisentan 5 mg, intravenous sildenafil 20 mg × 3 and epoprostenol 22 ng/kg/min, iNO). Severe acute respiratory distress syndrome (ARDS) was presents. Therefore we decided to begin veno-venous extracorporeal membrane oxygenation (v-v ECMO) to correct the hypoxic vasoconstriction. Subsequent weaning from inotropic support with iNO and epoprostenol was possible on POD 7 due to mPAP 42 mm Hg, WP 15 mm Hg, CO 7.9 L/min, PVR 273 dyne s/cm5, and TPG 27 mm Hg. On POD 11 he was weaned from ECMO due to: mPAP 40 mm Hg, WP 16 mm Hg, CO 6.5 L/min, PVR 295 dyne s/cm5 and TPG 24 mm Hg. The patient was extubated on POD 17. The cardiac catheterization 1 month after OLT showed: mPAP 28 mm Hg, WP 13 mm Hg, CO 5.4 L/min, PVR 220 dyne s/cm5 and TPG 15 mm Hg. ECMO rescue therapy in this "extreme" case allowed us to correct hypoxemia responsible for worsening of pulmonary hypertension allowing time to reach the goal of vasodilatatory therapy. © 2013 by Elsevier Inc. All rights reserved.

Young male rats were exposed to a biphasic training program in which a 7-week preconditioning period of moderate treadmill exercise was followed by 8 weeks of strenuous endurance running. In comparison with sedentary control animals, the trained rats at 20 weeks of age had developed myocardial hypertrophy of the right ventricle (20%) and interventricular septum (23%), but there was no difference in the weight of the left ventricular free wall. Myocyte hypertrophy (26%) in the right ventricle was achieved through an increase in mean cell length (24%) and the addition of new sarcomere units in series. Exercise induced no acceleration of capillary growth in either ventricle, leading to significant decreases in the capillary luminal volume density (-21%) and surface density (-16%) in the right ventricle. Such alterations in the structural properties of the microvasculature implicated in oxygen availability and diffusion suggest that vigorous exercise, even after a preconditioning period, may still be detrimental to the myocardium. The techniques of myocardial morphometry were examined with respect to potential errors associated with oblique tissue sections and the use of light versus electron microscopy for cell counting. It was shown that the practical effects of obliquity are negligible and that electron microscopic resolution is essential.

To determine the compensatory reserve capacity of the ventricular myocardium following infarction, the left coronary artery in rats was ligated, and the animals were killed 40 days later. Infarcts affecting an average 23% of the left ventricle were characterized by a 27% hypertrophic growth of the remaining myocardium that produced a complete replacement of the necrotic tissue. In contrast, infarcts with an average 50% loss of mass resulted in 83% expansion of the spared myocardium that was inadequate for a complete restoration of ventricular tissue. Myocyte hypertrophy was 26% and 78% in small and large infarcts, respectively. Cellular hypertrophy in both cases involved significant increases in myocyte transverse area and myocyte length. After large infarcts, there was an 18% reduction in capillary surface and a 16% increase in the diffusion distance. Corresponding values for small infarcts were -10% and 9%. These alterations combined with the deficient reconstitution of myocardial mass following large infarcts resulted in 25%, 29%, and 30% deficits in the absolute amounts of capillary lumen, surface, and length per ventricle respectively. Even with small infarcts, a deficit was seen in capillary luminal surface (-16%), and length (-19%). In conclusion, we have demonstrated that cardiac hypertrophy following myocardial infarction is consistent with cellular shape changes characteristic of a combination of concentric and eccentric hypertrophic growth. However, cardiac muscle cells appear to be unable to compensate for the loss of mass induced by a 50% infarct. The inadequate adaptation of the capillary vasculature in the infarcted hearts suggests that the injured ventricle is more vulnerable to additional ischemic episodes.

For determination of the effects of myocardial infarction on the recovery potential of muscle mass in the surviving tissue, ligation of the left coronary artery was performed in 3-month-old rats, and the infarcted ventricles were analyzed morphometrically a month after surgery. Comparisons were made with 4-month-old control rats that underwent sham operations and with 3-month-old control rats that were not operated upon for evaluation of the magnitude of infarct size and discrimination of the relative contribution of tissue growth that occurred in the surviving myocardium solely as a result of the change in age, from 3 to 4 months (postoperative tissue growth, or POTG), from the additional growth induced by infarction (hypertrophic growth, or HG). Coronary occlusion induced a 276-cu mm loss of ventricular tissue volume that corresponded to 43% of the total left ventricular mass, 648 cu mm. Over a 30-day period the remaining 372 cu mm of viable tissue expanded by 90% with an overall volume gain of 334 cu mm. This tissue augmentation consisted of 20% POTG, 67 cu mm, and 80% HG, 267 cu mm. Total myocyte volume increased 89%, from 302 cu mm to 571 cu mm, and average myocyte cell volume per nucleus increased 92%, from 16,500 cu mu to 31,600 cu mu. The expansion of the myocyte mass was the result of a 21% POTG and a 79% HG. Corresponding values for the myocyte population were 19% and 81%.

The response of the left ventricle (LV) during the development of spontaneous hypertension (SH) in rats was studied morphometrically at 21, 28, 35, and 45 days after birth and compared with that of normotensive (WK) controls. LV hypertrophy, varying from 24 to 27%, was characterized by the preservation of the volume fraction of capillary lumen and capillary luminal surface in the myocardium, as a result of capillary proliferation. From 21 to 45 days the number of capillaries per unit area of myocardium increased 68% in SH rats by the insertion in parallel of new capillary elements among the myocytes. This estimation was obtained by correcting the value of capillary density at 45 days for the amount of spreading produced by myocyte growth during this interval. On a similar basis capillary proliferation was only 24% in WK rats. Myocyte growth in experimental animals (151%) was achieved by a 77% enlargement in myocyte cross-sectional area (MCSA) and by a 42% lengthening of the cells. In controls myocyte expansion (124%) was the result of comparable increments in MCSA (47%) and myocyte length (53%).

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:24:46Z No. of bitstreams: 0 Made available in DSpace on 2014-05-27T11:24:46Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-08-13 Background: The aim of this study was to analyze stable hypertrophied myocardial function and its response to inotropic maneuvers in rats submitted to renovascular hypertension for a 10-week period (RHT group, n=10). Material/Methods: Myocardial performance was studied in isolated left ventricle papillary muscles in isometric contraction under the following conditions: at postrest contraction of 30 seconds (PRC), at extracellular calcium (ECa 2+) chloride concentration of 1.25 and 5.20 mM, and after beta-adrenergic stimulation with 10 -6 M isoproterenol (ISOP). Results: The results were compared with normotensive Wistar controls rats (C group, n=10). In basal condition, resting tension, and contraction time (TPT) were greater, while relaxation time (RT 50) tended to be longer in RHT than C group. PRC and ISOP promoted a similar change in muscle function response intensity (Δ) in both groups. ECa 2+ shift did not change TPT in the C group and decreased TPT in the RHT animals; Δ was different between these groups. RT 50 increased in C and decreased in RHT, both without statistical significance; however, Δ was different. Conclusions: These results suggest that hypertrophied myocardial dysfunction may be attibuted to changes in intracellular calcium cycling. © Med Sci Monit, 2010. Botucatu Medical School UNESP - São Paulo State University, Botucatu Botucatu Medical School UNESP - São Paulo State University, Botucatu