Alternative cardioprotective strategy during reperfusion: postconditioning vs preconditioning

Reperfusion of ischemic myocardium is a complex biological process that involves multiple triggers, mediators and end-effectors, resulting in inflammatory and endothelial damage blood flow defects, cardiac dysfunction, necrosis and apoptosis. In the last two decades, although considerable effort has been exerted in exploring cardioprotective strategies in an attempt to limit reperfusion-induced myocardial injury, most of the clinical trails using various pharmacological agents to attenuate reperfusion injury have been rather unsatisfactory. Therefore, it is extremely valuable to explore some clinically feasible and effective therapeutic strategies that address post-ischemic myocardial injury. Reduction in infarct size and cell death with rapid sequential intermittent interruption of coronary blood flow or oxygen supply at the beginning of reperfusion or reoxygenation (i.e. ischemic or hypoxic postconditioning) has been recently reported by our laboratory. The protection with postconditioning was expressed as reduction in generation of superoxide radicals, calcium overload, endothelial dysfunction, adhesion molecule expression, necrosis and apoptosis. Mechanisms by postconditioning have been associated with preservation of endogenous autacoids such as adenosine and nitric oxide, activation of protein kinases including PI-3K-Akt and ERK1/2, opening of mitochondrial K_ ATP channels and closing of mitochondrial transition permeability pore. Reduction in infarct size by postconditioning was largely preserved after a prolonged reperfusion and this novel strategy achieved cardioprotection that was comparable to conventional ischemic preconditioning. Experimental studies and clinical observations to date have demonstrated that application of postconditioning at the onset of recovery of blood flow after ischemia opens a new therapeutic strategy in the treatment of ischemia/reperfusion injury.