Postischemic stunning--the case for calcium as the ultimate culprit.

Two phases of the stunning phenomenon are proposed. The first causative phase occurs almost immediately with reperfusion and is thought to be associated with cytosolic calcium overload and an apparently normal or nearly normal mechanical function. Agents enhancing calcium influx, if introduced at this stage, may worsen subsequent stunning, whereas those inhibiting calcium influx may lessen the extent of subsequent stunning. The second phase, true stunning, is associated with established hypocontractility and responds favorably to agents enhancing calcium influx, whereas calcium antagonists further impair mechanical function when given at this stage. These patterns, derived from data obtained on isolated rat-heart studies, cannot directly be extrapolated to the large animal heart, such as that of the dog, where the presence of added circulating leukocytes may confound the issue and explain the apparently contradictory benefit of the late administration of calcium antagonists. The harmful effects of free radicals are not discounted but could be explained, at least in part, by multiple membrane damage, with a consequent rise of cytosolic calcium during the reperfusion period.