Female gender, myocardial remodeling and cardiac failure: Are women protected from increased myocardiocyte apoptosis?

Heart failure appears to be less common and less severe in females, and elderly women have a better overall survival after myocardial infarction than males and also a decreased risk of arrhythmic death. Human and animal studies also show that females display more favorable cardiac remodeling in several experimental and clinical conditions. However, the underlying pathophysiologic mechanisms have not been established, even though estrogens, beta-adrenergic stimulation, the renin-angiotensin system, and a greater resistance to myocardiocyte apoptosis in females have been proposed as hypothetical contributing factors. Indeed, epidemiologic, experimental and clinical evidence of gender differences in myocardial remodeling and heart failure favoring women could prompt the use of female myocardial progenitor or stem cells for cellular replacement therapy in cardiac failure, on the premises of a greater protection from myocardial apoptosis and unfavorable remodeling in women. © 2004 CEPI Srl

Clinical relevance of apoptosis in early and late post-infarction left ventricular remodeling

Apoptosis may represent an important pathophysiological mechanism causing progressive myocardiocyte loss and left ventricular dilation, even late after acute myocardial infarction (AMI). This review discusses the role of myocardial apoptosis on the basis of findings from experimental studies in animals and from observational studies in humans with the purpose of assessing the clinical relevance, determinants and mechanisms of myocardial apoptosis and the potential therapeutic implications. A more profound understanding of the impact of myocardiocyte loss on prognosis and of the mechanisms involved may lead to an improved understanding of cardiac remodeling and possibly to an improved patient care. In fact, among the potential modulators of myocardial apoptosis, angiotensin-converting enzyme inhibitors and beta-adrenergic receptor blockers have already been shown to improve the prognosis and symptoms in patients with post-infarction heart failure, and a reduction in myocardial apoptosis could partly contribute to such a beneficial effect. Several other putative factors could also modulate myocardial apoptosis after AMI, and many are currently under intense investigation. In particular, the infarct-related artery patency late after AMI may be a major clinical determinant of myocardial apoptosis and clinical benefits deriving from an open artery (the "open-artery hypothesis"), such as a slowing down of the remodeling process and 4 reduced arrhythmic risk, could be due, at least in part, to a reduced apoptotic myocardiocyte loss

Ritmo circadiano della frequenza cardiaca in fibrillanti trattati con digossina e gitoformato.

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High-Risk clinical increased post-infarction myocardial apoptosis and the benefits as a result of an open infarct-related artery

Background Infarct-related artery (IRA) patency after acute myocardial infarction (AMI) is associated with a more favourable clinical course, in particular in patients with high-risk features. As it has been recently reported that IRA patency is associated with a reduced postinfarction apoptotic rate (AR), the aim of our study was to assess whether IRA status late after AMI had a different impact on AR in high- vs. low-risk patients. Methods and results Co-localization of TUNEL and caspase-3 was used to calculate the AR at the site of infarction at the time of death in 30 subjects.The Norris coronary prognostic index (NI) was calculated (computing age, presence of pulmonary congestion, heart size and history of previous additional AMI) in order to define the patients\u2019 individual risk at the time of hospitalization. According to the NI ( 64 7 vs. > 7), subjects were divided into low and high risk, as NI > 7 carries an approximate threefold higher risk of death. The NI was significantly correlated with the AR at the time of death both in infarct and remote areas. Twenty subjects had IRA occlusion at the time of death, and in these patients AR was significantly higher both in infarct and remote areas (P < 0\ub7001 and P = 0\ub7009 vs. the others, respectively). However the impact of IRA occlusion on AR was significantly different comparing high- vs. low-risk subjects. In particular, AR at the infarct site was 10-fold higher in the high-risk subjects with IRA occlusion (26\ub71% [20\ub74 \u201328\ub77%]) vs. those with open IRA (2\ub73% [0\ub76\u20133\ub75%]; P = 0\ub7002) and was nonsignificantly different in the low-risk subjects vs. those without IRA occlusion (8\ub72% [2\ub75\u201317\ub75%] vs. 5\ub74% [1\ub75\u20137\ub79%]; P = 0\ub748). Similarly, in the high-risk subjects, AR in remote areas was significantly greater in cases with occluded vs. open IRA (0\ub77% [0\ub74\u20130\ub79%] vs. 0\ub73% [0\ub73\u20130\ub732%]; P = 0\ub7009). Conclusion A significantly higher AR is associated with IRA occlusion late post AMI in subjects with high-risk clinical features, and not in low-risk patients. The diverse impact of IRA occlusion on AR in subjects with different risk profiles may explain the greater benefit associated with coronary reperfusion in high-risk subjects. The overall lower AR in low- risk subjects, independently from the IRA status, may be correlated with the better long- term prognosis after AMI in this case