The protection of ischemic myocardium: applications in human medicine and experimental prospects

Acute myocardial infarction (AMI) is a serious condition, associated with a high mortality rate in western countries. The emergence of revascularisation techniques for occluded arteries has improved the prognosis considerably, but the time to revascularisation remains critical. New cardioprotective strategies were therefore needed to further improve myocardial salvage. These strategies were for a long time based on meeting the myocardium’s demand in oxygen. In recent years however, new substances were developed to oppose directly the cell disorders associated with ischemia-reperfusion, or to induce an endogenous adaptation of the myocardium through preconditioning. Another approach includes reducing the body temperature during the ischemic process to delay infarct extension.L'infarctus du myocarde est une affection grave, à l'origine d'une mortalité élevée dans les pays occidentaux. L'émergence des techniques de revascularisation des artères occluses a permis d'améliorer considérablement le pronostic de cette affection mais les délais de revascularisation restent incompressibles. Le développement de stratégies cardioprotectrices additionnelles était donc nécessaire. Ces stratégies ont pendant longtemps reposé sur la nécessité de satisfaire les besoins en oxygène du myocarde. Plus récemment, des substances ont été développées dans le but de s'opposer directement aux désordres cellulaires liés à l'ischémie-reperfusion ou d'induire une adaptation endogène du myocarde par préconditionnement. Une autre approche consiste à réduire la température de l'organisme au cours du processus ischémique en vue de retarder l'extension de l'infarctus

Repeated coronary artery occlusions during routine balloon angioplasty do not induce myocardial preconditioning in humans

AbstractObjectives.The purpose of the present study was to assess whether brief, repeated coronary artery occlusions during balloon angioplasty induce a myocardial ischemic protective effect.Background.In animals, brief coronary artery occlusions preceding a more prolonged occlusion result in reduced infarct size. Whether myocardial protection against ischemia could also occur in humans during angioplasty remains controversial.Methods.Thirteen patients with a proximal left anterior descending coronary artery stenosis with no angiographic collateral circulation underwent percutaneous transluminal coronary artery balloon angioplasty. Three 120-s balloon inflations separated by a 5-min equilibrium period were performed. For each inflation, intracoronary ST segment modifications, septal wall thickening (M-mode echocardiography), left ventricular pressures and time derivatives were measured at baseline and at 30, 60 a d 90 s after balloon inflation and 120 s after balloon deflation.Results.Intracoronary electrocardiographic analysis showed that the time course of the maximal ST segment elevation was identical at each inflation, as were wall motion changes assessed by the decrease in septal wall thickening. For the first and last inflations, peak positive dP/dt decreased significantly by 13 ± 9% (mean ± SD) and 14 ± 13%, whereas peak negative dP/dt increased by 23 ± 15% and 22 ± 10%, respectively (all p < 0.01 from baseline values). The relaxation time constant, tau, was altered similarity during the different inflations, from 44 ± 6 to 74 ± 13 ms and from 57 ± 13 to 77 ± 13 ms (all p < 0.001) for the first and last inflations, respectively. Left ventricular endiastolic pressure increased to the same level after each inflation. In contrast to other hemodynamic variables, tau and left ventricular end-diastolic pressure did not return to baseline values in between the inflations, which may be due to myocardial stunning.Conclusions.In patients with proximal left anterior descending coronary artery stenosis and no evidence of collateral circulation, brief periods of ischemia, such as those used during routine coronary balloon angioplasty, do not provide any protection against myocardial ischemia

Development of a human model for the study of effects of hypoxia, exercise, and sildenafil on cardiac and vascular function in chronic heart failure

Background: Pulmonary hypertension is associated with poor outcome in patients with chronic heart failure (CHF) and may be a therapeutic target. Our aims were to develop a noninvasive model for studying pulmonary vasoreactivity in CHF and characterize sildenafil's acute cardiovascular effects. Methods and Results: In a crossover study, 18 patients with CHF participated 4 times [sildenafil (2 × 20 mg)/or placebo (double-blind) while breathing air or 15% oxygen] at rest and during exercise. Oxygen saturation (SaO2) and systemic vascular resistance were recorded. Left and right ventricular (RV) function and transtricuspid systolic pressure gradient (RVTG) were measured echocardiographically. At rest, hypoxia caused SaO2 (P = 0.001) to fall and RVTG to rise (5 ± 4 mm Hg; P = 0.001). Sildenafil reduced SaO2 (−1 ± 2%; P = 0.043), systemic vascular resistance (−87 ± 156 dyn·s−1·cm−2; P = 0.034), and RVTG (−2 ± 5 mm Hg; P = 0.05). Exercise caused cardiac output (2.1 ± 1.8 L/min; P &lt; 0.001) and RVTG (19 ± 11 mm Hg; P &lt; 0.0001) to rise. The reduction in RVTG with sildenafil was not attenuated by hypoxia. The rise in RVTG with exercise was not substantially reduced by sildenafil. Conclusions: Sildenafil reduces SaO2 at rest while breathing air, this was not exacerbated by hypoxia, suggesting increased ventilation–perfusion mismatching due to pulmonary vasodilation in poorly ventilated lung regions. Sildenafil reduces RVTG at rest and prevents increases caused by hypoxia but not by exercise. This study shows the usefulness of this model to evaluate new therapeutics in pulmonary hypertension

Coronary and contractile effects of intracoronary bradykinin and their modulation by ACE inhibitor in normal conscious dogs

为满足各种各样的应用程序的需求,EJB容器的服务框架必须能支持各种服务的集成.该文给出了一个EJB容器的可扩展服务框架的设计和实现.该EHB容器允许服务以Interceptor的方式加入容器.当EJB容器发生函数调用等事件时,容器自动触发这些相应的服务,从而能实现透明地在EJB容器中添加额外的服务

073 Right Ventricle Contractile Reserve as a Pre-operative Tool for Assessing RV failure after Continuous Flow LVAD Implantation

IntroductionLatest generation continuous flow left ventricular assist devices (LVADs) have been proposed as an alternative to heart transplantation for end-stage heart failure. However, postoperative right ventricle (RV) dysfunction remains common and has a negative impact on prognosis. Purpose of our study was to identify echocardiographic or hemodynamic parameters that could predict early RV failure after LVAD implantation in patients with biventricular dysfunction.MethodsFourteen patients with biventricular dysfunction who have been evaluated for LVAD implantation were included. Right and left ventricular dysfunction were respectively defined as: tricuspid annular plane excursion < 16 mm (TAPSE) and LV ejection fraction < 35%. In all patients, preoperative measurements were obtained at rest. In 7 patients, right heart catheterization was performed simultaneously with increasing doses of dobutamine (15γ/Kg/min). Primary endpoint was death caused by right ventricle systolic dysfunction or need for right ventricle mechanical support within 30 days after surgery (RVSD+).ResultsMean recipient age was 58±7 years. Primary end-point (RVSD+) was noted in five patients. Preoperative demographic, echocardiographic and hemodynamic data were similar between RVSD+ and RVSD- patients (Table). Percent increase of TAPSE and systolic PAP between basal and high dobutamine dose was significantly lower in RVSD+ than in RVSD- patients.ConclusionPercent increase of TAPSE and systolic PAP induced by high dose dobutamine infusion might be two interesting criteria to assess RV contractile reserve and predict RV outcome after LVAD implantation in patient with biventricular dysfunction.Baseline Measurement (n=14)Change after Dobutamine infusion,% (n=7)RVSD-RVSD+pRVSD-RVSD+pN95TAPSE, mm14±214±20.955±526±20.03Systolic PAP, mmHg51±753±60.842±84±70.05Cardiac Output, l/min3.3±0.53.5±0.50.987±1093±470.7Pulm Vasc Res, Wood3.9±14.3±10.62±41-36±70.

Interplay between right ventricular function and cardiac resynchronization therapy : an analysis of the CARE-HF trial (cardiac resynchronization–heart failure)

Objectives: The aim of this study was to investigate the impact of cardiac resynchronization therapy (CRT) on right ventricular (RV) function and the influence of RV dysfunction on the echocardiographic and clinical response to CRT among patients enrolled in the CARE-HF (Cardiac Resynchronization-Heart Failure) trial. Background: Cardiac resynchronization therapy prolongs survival in appropriately selected patients with heart failure but the benefit might be diminished in patients with RV dysfunction. Methods: Of 813 patients enrolled in the CARE-HF study, 688 had tricuspid plane systolic excursion (TAPSE) measured at baseline, and 345 of these were assigned to CRT. Their median (interquartile range) age was 66 (58 to 71) years, left ventricular (LV) ejection fraction was 24% (21% to 28%), and TAPSE was 19 (16 to 22) mm. Baseline LV function and size and QRS duration were similar among TAPSE tertiles, but those in the worst tertile (TAPSE < 17.4 mm) were more likely to have ischemic heart disease. Results: Overall, CRT improved LV but not RV structure and function with little evidence of an interaction with TAPSE. During a median (interquartile range) follow-up of 748 (582 to 950) days, 213 deaths occurred. Patients with lower TAPSE had a higher mortality, regardless of assigned treatment (p < 0.001). Greater inter-ventricular mechanical delay, New York Heart Association functional class, mitral regurgitation, and N-terminal pro-B-type natriuretic peptide, lower TAPSE, and assignment to the control group were independently associated with higher mortality. Reduction in mortality with CRT was similar in each tertile of TAPSE. Conclusions: Right ventricular dysfunction is a powerful determinant of prognosis among candidates for CRT, regardless of treatment assigned, but did not diminish the prognostic benefits of CRT among patients enrolled in the CARE-HF trial. (Care-HF CArdiac Resynchronization in Heart Failure; NCT00170300) © 2013 American College of Cardiology Foundation

Glutathione Deficiency in Cardiac Patients Is Related to the Functional Status and Structural Cardiac Abnormalities

International audienceBACKGROUND: The tripeptide glutathione (L-gamma-glutamyl-cysteinyl-glycine) is essential to cell survival, and deficiency in cardiac and systemic glutathione relates to heart failure progression and cardiac remodelling in animal models. Accordingly, we investigated cardiac and blood glutathione levels in patients of different functional classes and with different structural heart diseases. METHODS: Glutathione was measured using standard enzymatic recycling method in venous blood samples obtained from 91 individuals, including 15 healthy volunteers and 76 patients of New York Heart Association (NYHA) functional class I to IV, undergoing cardiac surgery for coronary artery disease, aortic stenosis or terminal cardiomyopathy. Glutathione was also quantified in right atrial appendages obtained at the time of surgery. RESULTS: In atrial tissue, glutathione was severely depleted (-58%) in NYHA class IV patients compared to NYHA class I patients (P = 0.002). In patients with coronary artery disease, this depletion was related to the severity of left ventricular dysfunction (P = 0.006). Compared to healthy controls, blood glutathione was decreased by 21% in NYHA class I patients with structural cardiac disease (P<0.01), and by 40% in symptomatic patients of NYHA class II to IV (P<0.0001). According to the functional NYHA class, significant depletion in blood glutathione occurred before detectable elevation in blood sTNFR1, a marker of symptomatic heart failure severity, as shown by the exponential relationship between these two parameters in the whole cohort of patients (r = 0.88). CONCLUSIONS: This study provides evidence that cardiac and systemic glutathione deficiency is related to the functional status and structural cardiac abnormalities of patients with cardiac diseases. These data also suggest that blood glutathione test may be an interesting new biomarker to detect asymptomatic patients with structural cardiac abnormalities

Impact des bêtabloquants sur l'apnée du sommeil chez l'insuffisant cardiaque chronique

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

ETUDE DE LA BRADYKININE DANS L'HYPERTROPHIE VENTRICULAIRE GAUCHE CHEZ LA SOURIS AU TRAVERS D'UNE TRIPLE APPROCHE ECHOGRAPHIQUE PHARMACOLOGIQUE ET GENETIQUE (DES PATHOLOGIE CARDIOVASCULAIRE)

PARIS5-BU Méd.Cochin (751142101) / SudocPARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

L' échocardiographie de la souris (applications dans des modèles de pathologie cardiaque)

Les pathologies cardio-vasculaires représentent un problème de santé publique majeur. Les souris génétiquement modifiées permettent d'explorer les mécanismes impliqués dans ces pathologies. L'étude du phénotype cardiaque chez ces animaux dans des conditions physiologiques est extrêmement difficile. L'échocardiographie est un outil idéal à cette fin. Les dimensions et la fonction ventriculaire gauche (VG) peuvent être évaluées par échocardiographie transthoracique. Nous avons validé une méthode d'échocardiographie de contraste afin d'étudier la perfusion myocardique et une technique d'échocardiographie transoesophagienne afin d'évaluer les dimensions et la fonction ventriculaire droite. Nous avons appliqué ces techniques à des souris déficientes en synthase endothéliale du monoxyde d'azote (NOS3) et avons mis en évidence un rôle bénéfique de NOS3 qui limite le remodelage VG après infarctus du myocarde et surcharge de pression et le remodelage ventriculaire droit en hypoxie chronique.PARIS12-CRETEIL BU Multidisc. (940282102) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF