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Background Guidelines on myocardial revascularization define recommendations for percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. Only little information exists on long-term follow-up and quality of life (QoL) after CABG preceded by PCI. The aim of our study was to evaluate the impact of prior PCI on outcome and QoL in patients with stable coronary artery disease who underwent CABG. Methods In our retrospective study, CABG patients were divided in: CABG preceded by PCI: PCI-first (PCF), and CABG-only (CO) groups. The PCF group was further divided in guideline-conform (GCO) and guideline nonconform (GNC) subgroups, according to the SYNTAX score (2014 European Society of Cardiology [ESC]/European Association for Cardio-Thoracic Surgery [EACTS] guidelines). Thirty days mortality, major adverse cardiac events, and QoL using the European Quality-of-Life–5 Dimensions were evaluated. Results A total of 997 patients were analyzed, of which 784 underwent CABG without (CO), and 213 individuals with prior PCI (PCF). The latter group consisted of 67 patients being treated in accordance (GCO), and 24 in discordance (GNC) to the 2014 ESC/EACTS guidelines. Reinfarction (PCF: 3.8% vs. CO: 1.0%; p = 0.024), re-angiography (PCF: 17.6% vs. CO: 9.0%; p = 0.004), and re-PCI (PCF: 10.4% vs. CO: 3.0%; p < 0.001) were observed more frequently in PCF patients. Also, patients reported better health status in the CO compared to PCF group (CO: 72.48 ± 19.31 vs. PCF: 68.20 ± 17.86; p = 0.01). Patients from the guideline nonconform subgroup reported poorer health status compared to the guideline-conform group (GNC: 64.23 ± 14.56 vs. GCO: 73.42 ± 17.66; p = 0.041) and were more likely to require re-PCI (GNC: 18.8% vs. GCO: 2.4%; p = 0.03). Also, GNC patients were more likely to have left main stenosis (GCO: 19.7% vs. GNC: 37.5%; p < 0.001) and showed higher preinterventional SYNTAX score (GCO: 18.63 ± 9.81 vs. GNC: 26.67 ± 5.07; p < 0.001). Conclusion PCI preceding CABG is associated with poorer outcomes such as reinfarction, re-angiography, and re-PCI, but also worse health status and higher rehospitalization. Nevertheless, results were better when PCI was guideline-conformant. This data should impact the Heart Team decision. [ABSTRACT FROM AUTHOR]

Background: A paradox of lower morbidity and mortality in overweight or obese patients undergoing cardiac surgery has been described; however, knowledge about the influence of obesity in patients with acute Type A aortic dissection (AAD) is limited. This study aimed to evaluate the effect of obesity on short- and long-term outcomes after surgical treatment for AAD. Methods: Between 01/2004 and 12/2022, 912 patients with a BMI of 18.5 or greater were operated on for AAD. Patients were grouped according to their BMI (normal weight: BMI 18.5–24.9, n = 332; overweight: BMI 25–29.9, n = 367; obesity class I: BMI 30–34.9, n = 133; obesity class II+: BMI ≥ 35, n = 67), and the obtained clinical and surgical data were compared. Results: Obese patients were younger at the time of AAD (p = 0.001) and demonstrated higher rates of typical cardiovascular comorbidities (arterial hypertension, p = 0.005; diabetes mellitus, p < 0.001). The most important preoperative parameters, as well as the surgical approach, were similar between all four groups. The occurrence of renal failure requiring dialysis was higher in patients with BMI ≥ 35 (p = 0.010), but the in-hospital (p = 0.461) and long-term survival (p = 0.894) showed no significant differences. Conclusions: There are no indications that the obesity paradox is applicable in the setting of AAD. Since obese patients are affected by AAD at a younger age, obesity might constitute a risk factor for AAD. However, obesity does not influence short- or long-term survival. Regardless of body weight, immediate surgical therapy remains the treatment of choice for AAD. [ABSTRACT FROM AUTHOR]

Objective: The presence of a significant left subclavian artery stenosis may occasionally lead to blood flow reversal through a LIMA-to-coronary artery bypass graft during left arm exertion; with "stealing" of myocardial blood supply. The aim of this study was to review our experience with carotid-subclavian bypass in patients with post-CABG coronary-subclavian steal syndrome. Methods: This is a retrospective review of all patients who underwent carotid-subclavian bypass grafting for post-CABG coronary-subclavian steal syndrome at Mainz University Hospital between 2006 and 2015. Cases were identified in our institutional database, and data were retrieved from surgical records, imaging studies, and follow-up records. Results: Nine patients (all males, mean age of 69.1 years) underwent surgical treatment for post-CABG coronary-subclavian steal syndrome. Medium interval between original CABG and carotid-subclavian bypass grafting was 86.1 months. There were no perioperative deaths, strokes or myocardial infarctions. At a mean follow-up period of 79.9 months, all patients remained asymptomatic and all carotid-subclavian bypass grafts remained patent. One patient required stenting of a common carotid artery stenosis proximal to the graft anastomosis site, and coronary artery stenting was required in four patients in regions other than those supplied by the patent LIMA graft. Conclusion: Carotid-subclavian bypass surgery is a safe treatment option even in patients with multivessel disease and severe comorbidities and should be taken into consideration in patients who are deemed fit for surgery and those who would benefit from the excellent long-term patency rates. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated an important role of oxidative stress in the pathogenesis of cardiovascular disease (CVD) in diabetic patients due to hyperglycemia. CVD remains the leading cause of premature death in the western world. Therefore, diabetes mellitus-associated oxidative stress and subsequent inflammation should be recognized at the earliest possible stage to start with the appropriate treatment before the onset of the cardiovascular sequelae such as arterial hypertension or coronary artery disease (CAD). The pathophysiology comprises increased reactive oxygen and nitrogen species (RONS) production by enzymatic and non-enzymatic sources, e.g., mitochondria, an uncoupled nitric oxide synthase, xanthine oxidase, and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). Considering that RONS originate from different cellular mechanisms in separate cellular compartments, adequate, sensitive, and compartment-specific methods for their quantification are crucial for early detection. In this review, we provide an overview of these methods with important information for early, appropriate, and effective treatment of these patients and their cardiovascular sequelae. [ABSTRACT FROM AUTHOR]

Ischemic cardiomyopathy leads to inflammation and left ventricular (LV) dysfunction. Animal studies provided evidence for cardioprotective effects of the endocannabinoid system, including cardiomyocyte adaptation, inflammation, and remodeling. Cannabinoid type-2 receptor (CB2) deficiency led to increased apoptosis and infarctions with worsened LV function in ischemic cardiomyopathy. The aim of our study was to investigate a possible cardioprotective effect of endocannabinoid anandamide (AEA) after ischemia and reperfusion (I/R). Therefore, fatty acid amide hydrolase deficient (FAAH)−/− mice were subjected to repetitive, daily, 15 min, left anterior descending artery (LAD) occlusion over 3 and 7 consecutive days. Interestingly, FAAH−/− mice showed stigmata such as enhanced inflammation, cardiomyocyte loss, stronger remodeling, and persistent scar with deteriorated LV function compared to wild-type (WT) littermates. As endocannabinoids also activate PPAR-α (peroxisome proliferator-activated receptor), PPAR-α mediated effects of AEA were eliminated with PPAR-α antagonist GW6471 i.v. in FAAH−/− mice. LV function was assessed using M-mode echocardiography. Immunohistochemical analysis revealed apoptosis, macrophage accumulation, collagen deposition, and remodeling. Hypertrophy was determined by cardiomyocyte area and heart weight/tibia length. Molecular analyses involved Taqman® RT-qPCR and immune cells were analyzed with fluorescence-activated cell sorting (FACS). Most importantly, collagen deposition was reduced to WT levels when FAAH−/− mice were treated with GW6471. Chemokine ligand-2 (CCL2) expression was significantly higher in FAAH−/− mice compared to WT, followed by higher macrophage infiltration in infarcted areas, both being reversed by GW6471 treatment. Besides restoring antioxidative properties and contractile elements, PPAR-α antagonism also reversed hypertrophy and remodeling in FAAH−/− mice. Finally, FAAH−/−-mice showed more substantial downregulation of PPAR-α compared to WT, suggesting a compensatory mechanism as endocannabinoids are also ligands for PPAR-α, and its activation causes lipotoxicity leading to cardiomyocyte apoptosis. Our study gives novel insights into the role of endocannabinoids acting via PPAR-α. We hypothesize that the increase in endocannabinoids may have partially detrimental effects on cardiomyocyte survival due to PPAR-α activation. [ABSTRACT FROM AUTHOR]

Background Heart surgery with extracorporeal circulation (ECC) often leads to postoperative delirium (POD). This is associated with increased morbidity resulting in longer hospital stay and associated costs. The purpose of our study was to analyze the effect of intraoperative mannitol application on POD in patients undergoing elective aortic valve replacement (AVR). Materials and Method s In our retrospective single-center study, 259 patients underwent elective AVR, using Bretschneider cardioplegic solution for cardiac arrest, between 2014 and 2017. Patients were divided in mannitol (n = 188) and nonmannitol (n = 71) groups. POD was assessed using the confusion assessment method for the intensive care unit (ICU). Statistical significance was assumed at p < 0.05. Results Baseline patient characteristics did not differ between the groups. Incidence of POD was significantly higher in the nonmannitol group (33.8 vs. 13.8%; p = 0.001). These patients required longer ventilation time (24.1 vs. 17.1 hours; p = 0.021), higher reintubation rate (11.3 vs. 2.7%; p = 0.009), ICU readmission (12.7 vs. 4.8%; p = 0.026), prolonged ICU (112 vs. 70 hours; p = 0.040), and hospital stay (17.8 vs. 12.6 days; p < 0.001), leading to higher expenses (19,349 € vs. 16,606 €, p < 0.001). A 30-day mortality was not affected, but nonmannitol group showed higher Simplified Acute Physiology Score II score (32.2 vs. 28.7; p < 0.001). Mannitol substitution was independently associated with lower incidence of POD (odds ratio: 0.40; 95% confidence interval: 0.18–0.89; p = 0.02). Conclusion Treatment with mannitol during ECC was associated with decreased incidence of POD. This was accompanied by shorter ventilation time, ICU and hospital stay, and lower treatment expenses. [ABSTRACT FROM AUTHOR]

Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent tissues, such as cardiac, hepatic, and neuronal tissues. In contrast, publications on mitochondrial dynamics from the orthopedic or trauma fields are quite rare, even if there are common cellular mechanisms in cardiovascular and bone tissue, especially regarding bone infection. The present report summarizes the spectrum of mitochondrial alterations in the cardiovascular system and compares it to the state of knowledge in the musculoskeletal system. The present paper summarizes recent knowledge regarding mitochondrial dynamics and gives a short, but not exhaustive, overview of its regulation via fission and fusion. Furthermore, the article highlights hypoxia and its accompanying increased mitochondrial fission as a possible link between cardiac ischemia and inflammatory diseases of the bone, such as osteomyelitis. This opens new innovative perspectives not only for the understanding of cellular pathomechanisms in osteomyelitis but also for potential new treatment options. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES Cardiac surgery training has become more challenging as patients and their diagnoses become more complex. Our goal was to develop a multicategorical assessment model for evaluating residents in cardiac surgery. This model is intended to ensure goal-directed progress in their training as well as to recognize and support their surgical talents. METHODS We developed a new questionnaire in a multistage, 3-round process based on the Delphi method 'estimate-talk-estimate', using 55 competencies, including 38 general and 17 domain-specific competencies. Each competency is evaluated with 1 or more questions, to which 1 (not competent) to 6 (very competent) points can be chosen as an answer. RESULTS The resulting model achieved 2 main goals: first, presenting a well-defined competency list for cardiac surgical training and second, providing an objective and realistic evaluation of trainees' abilities. Residents were assessed by all trainers to achieve a high level of objectivity. CONCLUSIONS This evaluation model is highly objective, because residents are evaluated by multiple trainers. It allows individual support and enables better transparency in residency training. Talents and skills are evaluated, recognized and adopted as a base for individual feedback and personalized training programmes. [ABSTRACT FROM AUTHOR]

Pediatric cardiac surgeries involving aortic arch reconstruction are complex and require long cardiopulmonary bypass (CPB) times with deep hypothermic circulatory arrest (DHCA). Selective perfusion techniques have been developed to prevent the deleterious consequences of DHCA associated hypoperfusion. The effectivity of low body perfusion through cannulation of the femoral artery with an arterial sheath remains to be elucidated. We compared perfusion and inflammation in patients receiving selective antegrade cerebral perfusion (ACP) only to low body perfusion (LBP) in addition to ACP during DHCA for aortic arch reconstruction surgery. There was no difference in patient characteristics, cardiac pathologies, or performed procedures between ACP and LBP groups. Lactate levels increased after cardiac arrest in both groups. However, lactate levels were lower after 1 h reperfusion, at the end of extracorporeal circulation (ECC), and after surgery in LBP group compared to ACP only. Furthermore, creatinine was increased in ACP group on postoperative day 1 compared to LBP group but no acute kidney injury was observed in any group. IL-6 concentration increased in ACP group, while remained unchanged in LBP group compared to pre surgical values and were significantly lower compared to ACP group on postoperative days 1 and 2. LBP via an arterial sheath during cardiac arrest for aortic arch reconstruction surgery in addition to ACP, improves post ECC tissue perfusion as indicated by lower lactate levels and reduces creatinine levels suggesting milder kidney injury. LBP seems to prevent postoperative inflammation through a reduction in procedural duration or enhanced perfusion and thereby improves the outcome after aortic arch reconstruction surgery. [ABSTRACT FROM AUTHOR]

The CX3CL1/CX3CR1 axis mediates recruitment and extravasation of CX3CR1-expressing subsets of leukocytes and plays a pivotal role in the inflammation-driven pathology of cardiovascular disease. The cardiac immune response differs depending on the underlying causes. This suggests that for the development of successful immunomodulatory therapy in heart failure due to chronic pressure overload induced left ventricular (LV) hypertrophy, the underlying immune patterns must be examined. Here, the authors demonstrate that Fraktalkine-receptor CX3CR1 is a prerequisite for the development of cardiac hypertrophy and left ventricular dysfunction in a mouse model of transverse aortic constriction (TAC). The comparison of C57BL/6 mice with CX3CR1 deficient mice displayed reduced LV hypertrophy and preserved cardiac function in response to pressure overload in mice lacking CX3CR1. Moreover, the normal immune response following TAC induced pressure overload which is dominated by Ly6Clow macrophages changed to an early pro-inflammatory immune response driven by neutrophils, Ly6Chigh macrophages and altered cytokine expression pattern in CX3CR1 deficient mice. In this early inflammatory phase of LV hypertrophy Ly6Chigh monocytes infiltrated the heart in response to a C-C chemokine ligand 2 burst. CX3CR1 expression impacts the immune response in the development of LV hypertrophy and its absence has clear cardioprotective effects. Hence, suppression of CX3CR1 may be an important immunomodulatory therapeutic target to ameliorate pressure-overload induced heart failure. [ABSTRACT FROM AUTHOR]

CpG postconditioning after reperfused myocardial infarction is associated with modulated inflammation, less apoptosis, and better left ventricular function. Am J Physiol Heart Circ Physiol 319: H995-H1007, 2020. First published August 28, 2020; doi:10.1152/ajpheart.00269.2020.--Postconditioning attenuates inflammation and fibrosis in myocardial infarction (MI). The aim of this study was to investigate whether postconditioning with the cytosine-phosphate-guanine (CpG)-containing Toll-like receptor-9 (TLR9) ligand 1668-thioate (CpG) can modulate inflammation and remodeling in reperfused murine MI. Thirty minutes of left descending coronary artery (LAD) occlusion was conducted in 12-wk-old C57BL/6 mice. Mice were treated with CpG intraperitoneally 5 min before reperfusion. The control group received PBS; the sham group did not undergo ischemia. M-mode echocardiography (3, 7, and 28 days) and Millar left ventricular (LV) catheterization were performed (7 and 28 days) before the hearts were excised and harvested for immunohistochemical (6 h, 24 h, 3 days, 7 days, and 28 days), gene expression (6 h, 24 h, and 3 days; Taqman RT-qPCR), protein, and FACS analysis (24 h and 3 days). Mice treated with CpG showed significantly better LV function after 7 and 28 days of reperfusion. Protein and mRNA expressions of proinflammatory and anti-inflammatory cytokines were significantly induced after CpG treatment. Histology revealed fewer macrophages in CpG mice after 24 h, confirmed by FACS analysis with a decrease in both classically M1- and alternative M2a-monocytes. CpG treatment reduced apoptosis and cardiomyocyte loss and was associated with induction of adaptive mechanisms, e.g., of heme-oxigenase-1 and =-/--myosin heavy chain (MHC) ratio. Profibrotic markers collagen type I- (Col-±-) and Col-III induction was abrogated in CpG mice, accompanied by fewer myofibroblasts. This led to the formation of a smaller scar. Differential matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) expression contributed to attenuated remodeling in CpG, resulting in preserved cardiac function in a Toll-like receptor 1- and TLR9-dependent manner. Our study suggests a cardioprotective mechanism of CpG postconditioning, involving Toll-like receptordriven modulation of inflammation. This is followed by attenuated remodeling and preserved LV function. NEW & NOTEWORTHY Cytosine-phosphate-guanine (CpG) postconditioning seems to mediate inflammation via Toll-like receptor-1 and Toll-like receptor-9 signaling. Enhanced cytokine and chemokine expressions are partly attenuated by IL-10 and matrix metalloproteinase- 8 (MMP8) induction, being associated with lower macrophage infiltration and M1-monocyte differentiation. Furthermore, switch from -- to =-MHC and balanced MMP/TIMP expression led to lesser cardiomyocyte apoptosis, smaller scar size, and preserved cardiac function. Data of pharmacological postconditioning have been widely disappointing to date. Our study suggests a new pathway promoting myocardial postconditioning via Toll-like receptor activation. [ABSTRACT FROM AUTHOR]

Background: Patients with acute myocardial infarction (AMI) are at high risk when undergoing emergency coronary artery bypass graft (CABG)-surgery. Their outcome remains poor despite increased use of extracorporeal membrane oxygenation (ECMO). We investigated the impact of timing for perioperative ECMO-support in these patients.Methods: In this retrospective double-center study, we evaluated 201 patients with AMI undergoing CABG, dividing them into the following groups: No-ECMO (n = 101), preoperative ECMO (pre-ECMO, n = 6), intraoperative ECMO (ECC-ECMO, n = 67), and postoperative ECMO (post-ECMO, n = 27). We evaluated the impact of ECMO timing on postoperative mortality, organ function, and length of stay, comparing these to predicted outcome using different risk-scores.Results: Post-ECMO patients showed lowest 30-day-survival (40.7%), while earlier ECMO-start was associated with better outcome (50.7% in extracorporeal circulation [ECC]-ECMO and 66.7% in pre-ECMO patients). On admission, only pre-ECMO and ECC-ECMO patients showed higher surgery- and intensive-care-unit (ICU)-related risk-scores. In pre- and ECC-ECMO patients, the first significant increase in lactate-levels (>4 mmol/L) was observed preoperatively, while this occurred 1 hour postoperatively in post-ECMO patients. Bilirubin was increased in all patients, decreasing after 3 and 12 days in pre- and ECC-ECMO patients, respectively, but only after 18 days in post-ECMO patients. Multiple ICU risk-scores did not discriminate survival-probability correctly. Only the ECMO-related survival after veno-arterial-ECMO-score correctly predicted the significantly lower survival in post-ECMO patients.Conclusion: Our study shows that timely ECMO-support is associated with earlier bilirubin-downtrend and higher survival in patients with AMI after CABG. Lactate-increase greater than 4 mmol/L seems to be a helpful threshold to trigger the timely onset of ECMO-therapy, providing better survival. [ABSTRACT FROM AUTHOR]

Background Crystalloid priming is a cost-effective, free from immunological reactions, and independent from human plasma delivery. However, there is some debate on the negative impact of low plasma colloid pressure and higher incidence of systemic inflammatory response syndrome (SIRS). The aim of the study was to rule out any adverse effects of crystalloid priming on the postoperative outcome. Methods We investigated 520 consecutive patients, including emergencies, who had isolated on-pump coronary artery bypass grafting in 2009 by retrospective analysis in our clinic. Crystalloid priming (n = 294) was introduced as an alternative to albumin (n = 226). Reviewing patient charts and IT-based data generated a dataset of perioperative parameters. Results There were no differences with respect to demographical data and preexisting comorbidities between both groups. Despite equal perfusion times, more volume had to be substituted during extracorporeal circulation following crystalloid priming. However, this did not influence the inhospital outcomes. According to the definition of the "Sepsis-3 Guidelines," the incidence of SIRS was similar. There was no difference in the need for a vasopressor treatment, and only transient higher serum lactate levels were found in the crystalloid group. The incidence of neurologic and organ-related adverse events, as well as 30-day mortality was comparable. Conclusion The use of crystalloid priming is safe in coronary artery bypass grafting surgery in adults. However, there might be a greater need for crystalloid fluids during surgery. [ABSTRACT FROM AUTHOR]

Background: Pressure-volume loops (PVL) provide vital information regarding ventricular performance and pathophysiology in cardiac disease. Unfortunately, acquisition of PVL by conductance technology is not feasible in neonates and small children due to the available human catheter size and resulting invasiveness. The aim of the study was to validate the accuracy of PVL in small hearts using volume data obtained by real-time three-dimensional echocardiography (3DE) and simultaneously acquired pressure data. Methods: In 17 piglets (weight range: 3.6–8.0 kg) left ventricular PVL were generated by 3DE and simultaneous recordings of ventricular pressure using a mini pressure wire (PVL3D). PVL3D were compared to conductance catheter measurements (PVLCond) under various hemodynamic conditions (baseline, alpha-adrenergic stimulation with phenylephrine, beta-adrenoreceptor-blockage using esmolol). In order to validate the accuracy of 3D volumetric data, cardiac magnetic resonance imaging (CMR) was performed in another 8 piglets. Results: Correlation between CMR- and 3DE-derived volumes was good (enddiastolic volume: mean bias -0.03ml ±1.34ml). Computation of PVL3D in small hearts was feasible and comparable to results obtained by conductance technology. Bland-Altman analysis showed a low bias between PVL3D and PVLCond. Systolic and diastolic parameters were closely associated (Intraclass-Correlation Coefficient for: systolic myocardial elastance 0.95, arterial elastance 0.93, diastolic relaxation constant tau 0.90, indexed end-diastolic volume 0.98). Hemodynamic changes under different conditions were well detected by both methods (ICC 0.82 to 0.98). Inter- and intra-observer coefficients of variation were below 5% for all parameters. Conclusions: PVL3D generated from 3DE combined with mini pressure wire represent a novel, feasible and reliable method to assess different hemodynamic conditions of cardiac function in hearts comparable to neonate and infant size. This methodology may be integrated into clinical practice and cardiac catheterization programs and has the capability to contribute to clinical decision making even in small hearts. [ABSTRACT FROM AUTHOR]

Background: Unresolved inflammation resulting in capillary leakage with endothelial barrier dysfunction is a major contributor to postoperative morbidity and mortality after coronary artery bypass graft (CABG). Angiopoietins (ANGs) are vascular growth factors, also mediating inflammation and disruption of the endothelium, thus inducing capillary leakage. We hypothesized that changes in the relative serum levels of ANG1 and ANG2 influence endothelial barrier function and perioperative morbidity after CABG.Methods: After approval and informed consent, serum samples (n = 28) were collected pre CABG surgery, 1, 6, and 24 h after aortic de-clamping. ANG1, ANG2, soluble ANG receptor TIE2 (sTIE2), and IL-6 serum concentrations were analyzed by ELISA. Human pulmonary microvascular endothelial cells (HPMECs) were incubated with patient serum and FITC-dextran permeability was assessed. Furthermore, ANG2 secretion of HPMECs was analyzed after incubation with IL-6-containing patient serum.Results: CABG induced an early and sustained increase of ANG2/ANG1 ratio (5-fold after 24 h compared to pre-surgery). These changes correlated with elevated serum lactate levels, fluid balance, as well as the duration of mechanical ventilation. Permeability of HPMECs significantly increased after incubation with post-surgery serum showing a marked shift of ANG2/ANG1 balance (18-fold) compared to serum with a less pronounced increase (6-fold). Furthermore, CABG resulted in increased IL-6 serum content. Pre-incubation with serum containing high levels of IL-6 amplified the ANG2 secretion by HPMECs; however, this was not influenced by blocking IL-6.Conclusions: CABG affects the balance between ANG1 and ANG2 towards a dominance of the barrier-disruptive ANG2. Our data suggest that this ANG2/ANG1 imbalance contributes to an increased postoperative endothelial permeability, likewise being reflected by the clinical course. The results strongly suggest a biological effect of altered angiopoietin balance during cardiac surgery on endothelial permeability. [ABSTRACT FROM AUTHOR]

Aims: Post-infarction remodelling (PIR) determines left-ventricular (LV) function and prognosis after myocardial infarction. The aim of this study was to evaluate transthoracic ultrasound-mediated microbubble stimulation (UMS) as a novel gene- and cell-free therapeutic option after acute myocardial infarction and reperfusion (AMI/R) in mice. Methods and Results: For myocardial delivery of UMS, a novel therapeutic ultrasound-system (TIPS, Philips Medical) and commercially available microbubbles (BR1, Bracco Suisse SA) were utilized in a closed-chest mouse model. UMS was performed as myocardial post-conditioning (PC) on day four after 30 minutes of coronary occlusion and reperfusion. LV-morphology, as well as global and regional function were measured repeatedly with reconstructive 3-dimensional echocardiography applying an additional low-dose dobutamine protocol after two weeks. Scar size was quantified by means of histomorphometry. A total of 41 mice were investigated; 17 received PC with UMS. Mean ejection fraction (EF) prior UMS was similar in both groups 53%±10 (w/o UMS) and 53%±14 (UMS, p = 0.5), reflecting comparable myocardial mass at risk 17%±8 (w/o UMS), 16%±13 (UMS, p = 0.5). Two weeks after AMI/R, mice undergoing UMS demonstrated significantly better global LV-function (EF = 53%±7) as compared to the group without PC (EF = 39%±11, p<0.01). The fraction of akinetic myocardial mass was significantly lower among mice undergoing UMS after AMI/R [27%±10 (w/o UMS), 13%±8 (UMS), p<0.001)]. Our experiments showed a fast onset of transient, UMS-induced upregulation of vascular-endothelial and insulin-like growth factor (VEGF-a, IGF-1), as well as caveolin-3 (Cav-3). The mice undergoing PC with UMS after AMI/R showed a significantly lower scar size. In addition, the microvascular density was significantly higher in the borderzone of UMS-treated animals. Conclusion: UMS following AMI/R ameliorates PIR in mice via up-regulation of VEGF-a, IGF-1 and Cav-3, and consecutive improvement of myocardial borderzone vascularization. [ABSTRACT FROM AUTHOR]

Pulmonary inflammation, increased vascular permeability, and pulmonary edema, occur in response to primary pulmonary infections like pneumonia but are also evident in endotoxemia or sepsis. Mechanical ventilation augments pre-existing lung injury and inflammation resulting from exposure to microbial products. The objective of this study was to test the hypothesis that low-tidal-volume prevent ventilation induced lung injury in sepsis. 10–12-week-old male C57BL/6N-mice received an intraperitoneal (i.p.) injection with equipotent dosages of LPS, 1668-thioate, 1612-thioate, or PBS. 120 min after injection, mice were randomized to low- (LV, 7 ± 1 ml/kg) or high-tidal-volume (HV, 25 ± 1 ml/kg) ventilation. Hemodynamic and ventilatory parameters were recorded and inflammatory markers were analyzed form BAL that was generated after 90 minute ventilation. Arterial blood pressures declined during mechanical ventilation in all groups. pO 2 decreased in LPS injected and CO 2 increased in sham, LPS, and 1612-thioate administered mice at 45 min and in 1668-thioate injected mice after 90 minute LV ventilation compared to respective HV groups. BAL protein concentrations increased in HV ventilated and 1668- or 1612-thioat pre-treated mice. BAL TNF-α protein concentrations increased in both LPS- and 1668-thioate-injected and IL-1β protein concentrations only in LPS-injected and HV ventilated mice. Most notably, no increased protein concentrations were observed in any of the LV ventilated groups. We conclude that low-tidal-volume ventilation may be a potential strategy for the prevention of ventilator induced lung injury in a murine model of systemic TLR agonist induced lung injury. [ABSTRACT FROM AUTHOR]

Non-communicable diseases (NCDs) are fatal for more than 38 million people each year and are thus the main contributors to the global burden of disease accounting for 70% of mortality. The majority of these deaths are caused by cardiovascular disease (CVD). The risk of NCDs is strongly associated with exposure to environmental stressors such as pollutants in the air, noise exposure, artificial light at night, and climate change, including heat extremes, desert storms, and wildfires. In addition to the traditional risk factors for CVD such as diabetes, arterial hypertension, smoking, hypercholesterolaemia, and genetic predisposition, there is a growing body of evidence showing that physicochemical factors in the environment contribute significantly to the high NCD numbers. Furthermore, urbanization is associated with accumulation and intensification of these stressors. This comprehensive expert review will summarize the epidemiology and pathophysiology of environmental stressors with a focus on cardiovascular NCDs. We will also discuss solutions and mitigation measures to lower the impact of environmental risk factors with focus on CVD., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Revascularization strategy in coronary artery bypass grafting (CABG) surgery usually depends on coronary dimension and stenosis severity. Little is known about the relation of preoperative evaluation of scarcely or invisibly chronic occluded coronary arteries (chronic total occlusion [CTO]) and revascularization rate or anastomosis quality. We aimed to evaluate the success rates of CTO revascularization in CABG surgery and determine the influence of coronary lumen visibility and collateralization in preoperative angiograms on revascularization rates, bypass blood flow, and target vessel diameter., Method: Preoperative coronary angiograms were evaluated for 938 consecutive patients who underwent isolated CABG surgery between 2014 and 2016 and screened for occluded coronary arteries. The occluded vessels were scored for visibility using the Rentrop grading of collateral filling. Intraoperatively, dimensions of the occluded arteries were measured using conventional vessel probes, and anastomosis quality was assessed by transit time flow measurement., Results: A total of 404 (43.1%) patients were identified with at least one CTO. Revascularization rates differed from 96.2% in the left anterior descending artery, to 85.0% in left circumflex artery-dependent vessels, and 78.8% in right coronary artery territory. Coronary visibility and grade of collateralization in the preoperative angiogram had no influence on intraoperatively measured coronary diameter. Bypass blood flow in grafts revascularizing CTOs lacking collateralization were not significantly lower than those grafts leading to CTOs with higher Rentrop scores., Conclusion: Preoperative coronary assessment often differs from intraoperative findings. Our study confirms that even patients with scarcely collateralized CTOs and impaired visibility in the coronary angiogram have a high chance of complete revascularization during CABG surgery., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Providing anesthesia for pediatric patients undergoing congenital cardiac surgery is complex and requires profound knowledge and clinical experience. Prospective studies on best anesthetic management are missing, partially due to different standards. The aim of the present study was to survey the current standard practice in anesthetic management in pediatric cardiac surgical centers in Germany., Methods: All 78 cardiac surgical centers in Germany were reviewed for a congenital cardiac surgery program. Centers with an active program for congenital cardiac surgery were interviewed to participate in the present online questionnaire to assess their current anesthetic practice., Results: Twenty-seven German centers running an active program for congenital heart surgery were identified, covering more than 3,000 pediatric cardiac surgeries annually. Of these centers, 96.3% (26/27) participated in our survey. Standard induction agents were etomidate in 26.9% (7/26), propofol in 19.2% (5/26), a combination of benzodiazepines and ketamine in 19.2% (5/26), and barbiturates in 11.5% (3/26). General anesthesia was preferentially maintained using volatile agents, 61.5% (16/26), with sevoflurane being the most common volatile agent within this group, 81.2% (13/16). Intraoperative first-choice/first-line inotropic drug was epinephrine, 53.8% (14/26), followed by milrinone, 23.1% (6/26), and dobutamine 15.4% (4/26). Fast-track programs performing on-table extubation depending on the type of surgical procedure were established at 61.5% (16/26) of the centers., Conclusion: This study highlights the diversity of clinical standards in pediatric cardiac anesthesia for congenital cardiac surgery in Germany.

Research on cardiac hypertrophy and heart failure is frequently based on pressure overload mouse models induced by TAC. The standard procedure is to perform a partial thoracotomy to visualize the transverse aortic arch. However, the surgical trauma caused by the thoracotomy in open-chest models changes the respiratory physiology as the ribs are dissected and left unattached after chest closure. To prevent this, we established a minimally invasive, closed chest approach via lateral thoracotomy. Herein we approach the aortic arch via the 2 nd intercostal space without entering the chest cavities, leaving the mouse with a less traumatic injury to recover from. We perform this operation using standard laboratory settings for open chest TAC procedures with equal survival rates. Apart from maintaining physiological breathing patterns due to the closed chest approach, the mice seem to benefit by showing rapid recovery, as the less invasive technique appears to facilitate a fast healing process and to reduce immune response after trauma.

Aims: Post-infarction remodelling (PIR) determines left-ventricular (LV) function and prognosis after myocardial infarction. The aim of this study was to evaluate transthoracic ultrasound-mediated microbubble stimulation (UMS) as a novel gene- and cell-free therapeutic option after acute myocardial infarction and reperfusion (AMI/R) in mice., Methods and Results: For myocardial delivery of UMS, a novel therapeutic ultrasound-system (TIPS, Philips Medical) and commercially available microbubbles (BR1, Bracco Suisse SA) were utilized in a closed-chest mouse model. UMS was performed as myocardial post-conditioning (PC) on day four after 30 minutes of coronary occlusion and reperfusion. LV-morphology, as well as global and regional function were measured repeatedly with reconstructive 3-dimensional echocardiography applying an additional low-dose dobutamine protocol after two weeks. Scar size was quantified by means of histomorphometry. A total of 41 mice were investigated; 17 received PC with UMS. Mean ejection fraction (EF) prior UMS was similar in both groups 53%±10 (w/o UMS) and 53%±14 (UMS, p = 0.5), reflecting comparable myocardial mass at risk 17%±8 (w/o UMS), 16%±13 (UMS, p = 0.5). Two weeks after AMI/R, mice undergoing UMS demonstrated significantly better global LV-function (EF = 53%±7) as compared to the group without PC (EF = 39%±11, p<0.01). The fraction of akinetic myocardial mass was significantly lower among mice undergoing UMS after AMI/R [27%±10 (w/o UMS), 13%±8 (UMS), p<0.001)]. Our experiments showed a fast onset of transient, UMS-induced upregulation of vascular-endothelial and insulin-like growth factor (VEGF-a, IGF-1), as well as caveolin-3 (Cav-3). The mice undergoing PC with UMS after AMI/R showed a significantly lower scar size. In addition, the microvascular density was significantly higher in the borderzone of UMS-treated animals., Conclusion: UMS following AMI/R ameliorates PIR in mice via up-regulation of VEGF-a, IGF-1 and Cav-3, and consecutive improvement of myocardial borderzone vascularization.