Reperfusion Injury: Basic Concepts and Protection Strategies

Prolonged ischemia such as that following myocardial infarction or occurring during long-term coronary bypass procedures causes serious damage to the myocardium. Early reperfusion is an absolute prerequisite for the survival of ischemic tissue. However, reperfusion has been referred to as the "double edged sword" because reperfusing ischemic myocardium carries with it a component of injury known as reperfusion injury. Reperfusion injury includes a number of events, such as reperfusion arrhythmias, myocardial infarction, stunning, vascular damage, and endothelial dysfunction. The underlying mechanism of reperfusion injury is not entirely known, but the existing evidence suggests that oxygen free radicals generated during the first few minutes of reflow lead to damage of cellular membranes, intracellular calcium overload, and uncoupling of excitation-contraction coupling. Although controversial, free radical scavengers, in general, are highly effective in the attenuation of reperfusion injury in animal models. Newer endogenous protection strategies, which include ischemic and heat shock preconditioning, are known to reduce reperfusion injury following ischemia.