Myocardial ischaemia: metabolic disorders leading to cell death.

Experimental studies have demonstrated that reperfusion is associated with a host of distinctive pathophysiological derangements, among which the most important are reperfusion arrhythmias, transient mechanical dysfunction or "myocardial stunning", and cell death. Reperfusion arrhythmias and myocardial stunning occur in experimental animals after transient ischemia followed by reperfusion, and there is considerable evidence that they also develop in patients, although the existence of malignant reperfusion arrhythmias in humans remains uncertain. Both reperfusion arrhythmias and myocardial stunning can ben considered a manifestation of sublethal, reversible cellular injury. Although the pathogenesis of reperfusion arrhythmias and stunning has not been conclusively established, there is considerable evidence that generation of oxygen radicals and perturbations of calcium homeostasis play an important role. Accordingly, antioxidants or calcium antagonists have been shown to be beneficial in mitigating these manifestations of reperfusion injury. In contrast, the existence of a lethal reperfusion-induced injury remains highly controversial. Although many studies have reported reduction of infarct size with antioxidants, numerous other investigation have failed to reproduce these results. As a consequence, intense controversy persists regarding whether oxygen radicals contribute to extending cell death upon reperfusion and whether reperfusion in itself causes cell death. It is unlikely that such controversy will be resolved any time soon and that clinical therapies aimed at reducing reperfusion-induced cell death will become available in the near future.