Pronounced antiarrhythmic effects of ischemic preconditioning

Brief periods of ischemia, induced either by complete coronary artery occlusion or by rapid ventricular pacing, greatly reduce the severity of those live-threatening ventricular arrhythmias that occur during a subsequent more prolonged occlusion of a major branch of the left coronary artery. The increased tolerance achieved by brief ischemia, either regional or global, has been termed ischemic preconditioning. This was originally defined as the reduction in ultrastructural changes and infarct size resulting from coronary artery occlusion and reperfusion by prior, brief, usually multiple ischemic periods. The reduction in the severity of arrhythmias by preconditioning, which has been described in several different species using both in vivo and in vitro models, depends on the duration and number of the short preconditioning occlusions and also on the time between the preconditioning period and the subsequent prolonged coronary artery occlusion. Under optimal conditions the antiarrhythmic effect of ischemic preconditioning is as pronounced as that with standard antiarrhythmic drugs. Unfortunately, the protection if also short-lived (usually less than 1 hour). If, however, we understood the precise mechanisms involved, we might be able to exploit them to ultimate therapeutic advantage. At least in the dog, the evidence suggests that the protection involves the release (from coronary vascular endothelial cells?) of endogenous myocardial protective substances such as bradykinin, nitric oxide and prostacyclin.