How does the heart (not) die? The role of autophagy in cardiomyocyte homeostasis and cell death.

Autophagy plays a critical and seemingly dual-purposed role in cardiomyocytes, being implicated as a mechanism of both cellular survival, for example, during ischemia/reperfusion injury and a mechanism of cell death at stages in which progressive myocyte alterations are beyond repair. This review aims to highlight the current literature as it relates to autophagy in cardiomyocytes. It provides background into the mechanisms of cell death, discusses the details that are known about the ubiquitin proteasome system and autophagy, delves into the pathways that are known to initiate and inhibit autophagy, and comments on the role of autophagy in cardiomyocyte homeostasis and cell death.

Persistent sexual dysfunction impairs quality of life after cardiac transplantation.

INTRODUCTION: The impact of sexual dysfunction (SD) on mental and physical health after heart transplantation (HTx) has not been established. AIM: We investigated the relationship of SD on quality of life (QoL), physical and mental health, and depressive symptoms after HTx. MAIN OUTCOME MEASURES: We evaluated SD according to the International Index of Erectile Dysfunction and the Female Sexual Function Index. QoL, physical and mental health were assessed using: 1) Short Form 12 Health Survey Questionnaire, 2) Quality of Life Enjoyment and Satisfaction Questionnaire--Short Form, and two depressive symptoms questionnaires: 1) Beck Depression Inventory-II and 2) Quick Inventory Depressive Symptomatology-Self Report. METHODS: We enrolled patients who were greater than 6 months post HTx. Patients unable to read English, had pelvic surgery or trauma, urogenital abnormalities, or sexually inactive were excluded. RESULTS: Out of 79 subjects that were screened, 33 men and 6 women participated (mean age 61.4 + 1.4). Response rates were at least 82% for all questionnaires. Overall prevalence of SD was 61%, with 78% of men being affected and 50% of women. There was no significant difference in measures between genders. HTx recipients with SD reported significantly worse QoL on measures of physical health when compared to those without SD. After HTx, patients suffering from SD had significantly worse general health (P = 0.02) and physical health (P = 0.02), including physical functioning (P = 0.01) and physical role limitation (P = 0.01). In contrast, mental health and depressive symptoms after HTx were not significantly different between those with and without SD. CONCLUSIONS: After HTx a high prevalence of SD remains among both men and women. Patients with SD had worse general and physical health but not depressive symptoms when compared to those without SD. The contributing factors may be more related to physical rather than psychological causes.

Application of zinc-bis-(DL-hydrogensaspartate) does not reduce apoptotic cell death in myocardial infarction in the rat heart.

BACKGROUND: Early studies in different stress models have shown potential beneficial effects of exogenous zinc application with reduction in the rate of apoptotic cell death. This has not been shown in models of myocardial infarction. METHODS: Rats were exposed to either brief episodes of acute ischemia followed by reperfusion (phase 1) or chronic coronary occlusion (phase 2). Animals were either treated with zinc or vehicle. Groups 1 and 3 received zinc-bis-(DL-hydrogenaspartate) 10 mg/kg body weight as a single 5-mL bolus administered intraperitoneally 24 hours prior to coronary occlusion, groups 2 and 4 received saline. The infarct sizes were determined by triphenyltetrazolium chloride staining and expressed at relative areas to areas of ischemia. Histological slices of the rat's myocardium at the border zones of the infarcts were stained with the TUNEL method to assess for apoptosis. Animals in groups 5, 7, and 9 received zinc, given once before and then repeated every 4 days after coronary occlusion, whereas groups 6, 8, and 10 received saline. Animals were observed for observation periods of 13 (groups 9 and 10), 16 (groups 7 and 8), or 19 weeks (groups 5 and 6), respectively. Two-dimensional echocardiography was performed to measure ejection fraction (EF) at baseline and at the end of the observation periods. TUNEL staining was used to detect and quantify apoptosis rate in the border zones of infarcts after the hearts were excised. RESULTS: Infarct sizes were 49% + 22% in group 1 (zinc + 30 minutes ischemia + 30 minutes reperfusion); 48% + 10% in group 2 (vehicle + 30 minutes ischemia + 30 minutes reperfusion); 42% + 11% in group 3 (zinc + 60 minutes ischemia + 30 minutes reperfusion); and 41% + 23% in group 4 (vehicle + 60 minutes ischemia + 60 minutes reperfusion). In group 1, 11% + 6% of cells were apoptotic compared to 12% + 4% in group 2, 16% + 9% in group 3, and 17% + 7% in group 4 (P > .05). In phase 2, echocardiography revealed a significant reduction in EF in all groups after coronary occlusion. There were no significant differences in EF between the 5 groups at baseline and at follow-up. TUNEL staining did not reveal any significant apoptosis after 13 to 19 weeks. CONCLUSION: Application of zinc failed to result in reduction of infarct size after temporary coronary occlusion followed by reperfusion and did not demonstrate any reduction in apoptotic cell death. In chronic coronary occlusion, zinc also did not improve EF compared to controls in the presented model in rats. The mechanisms involved in antiapoptotic effects seem to be more complex and might not be inducible by simple zinc injections.

The relationship between erectile dysfunction and cardiovascular disease. Part II: The role of PDE-5 inhibition in sexual dysfunction and cardiovascular disease.

Erectile dysfunction (ED) is a sensitive indicator of wider arterial insufficiency and an early correlate for the presence of ischemic heart disease. Among patients with coronary artery disease, prevalence reports of ED range from 42% to 75%. The US Food and Drug Administration has approved 3 phosphodiesterase-5 (PDE-5) inhibitors for treatment of male sexual dysfunction: sildenafil, tadalafil, and vardenafil. PDE-5 inhibitors also have cardiovascular effects. They inhibit PDE-5 enzymes in pulmonary vasculature, which causes vasodilation that decreases pulmonary vascular pressure. Sildenafil is approved for treatment of patients with pulmonary hypertension. PDE-5 inhibition with sildenafil improves cardiac output by balancing pulmonary and systemic vasodilation, and augments and prolongs the hemodynamic effects of inhaled nitric oxide in patients with chronic congestive heart failure and pulmonary hypertension. In vivo and in vitro studies are examining the possible beneficial effects of PDE-5 inhibitors in conditions such as myocardial infarction and endothelial dysfunction.