Apoptosis: pathophysiology and therapeutic implications for the cardiac surgeon

Abstract

Cardiomyocyte apoptosis has been associated with the pathogenesis of heart failure as well as ischemic and inflammatory myocardial conditions. The aim of this study is to give a critical synopsis of cardiomyocyte apoptosis and identify methods to prevent or attenuate apoptosis in patients undergoing cardiac surgery. Clinical conditions and agents associated with decreased apoptotic index are early repair or replacement of valvular pathology before deterioration of ventricular function, afterload reduction with medication or intraaortic balloon pulsation in patients with acute increase in afterload or in hemodynamically compromised patients, decreasing catecholamine-induced cardiotoxicity by using beta-blockers, phosphodiesterase inhibitors, or early insertion of intraaortic balloon pulsation or ventricular assist device. Prompt coronary revascularization, which reduces myocardial ischemia time, is the most effective antiapoptotic therapy. Reduction of myocardial apoptosis associated with cardiopulmonary bypass and aortic cross-clamping are other therapeutic targets. Some investigational therapies include ischemic preconditioning and use of antiapoptotic medication such as the caspase inhibitors, antioxidants, calcium-channel blockers, the insulin-like growth factor-1, and the poly-adenosine diphosphate-ribose-synthetase inhibitors. Most of the therapeutic implications in reducing cardiomyocyte apoptosis are still in the experimental phase. Some options are already incorporated in the clinical practice of the cardiovascular surgeon. New therapeutic considerations include avoiding sustained and long-term use of catecholamines and reducing or avoiding cardiopulmonary bypass-when clinically feasible. Noncatecholamine inotropes should be preferred for patients undergoing heart failure surgery and for patients with low output syndrome after open-heart surgery. The lessons learned from apoptosis research reinforce more liberal and early insertion of intraaortic balloon pulsation or ventricular assist device in clinical low output states.