Preinfarction angina and myocardial preconditioning

In the current era of pharmacologic and mechanical reperfusion therapy, several studies have consistently shown that patients with myocardial infarction preceded by angina have smaller infarcts and a better in-hospital outcome after thrombolytic therapy than patients without preinfarction angina. At least three mechanisms may explain these differences between infarctions that are preceded by angina and those that are not: coronary collaterals, reperfusion rate, and ischemic preconditioning. Collaterals alone do not seem to explain the beneficial effects of preinfarction angina, although it is difficult to completely rule out their role in the clinical setting. The possibility that preinfarction angina is not protective per se, but rather is a predictor of a more rapid coronary reperfusion is attractive; however, it should be addressed by further clinical studies. Finally, it is likely that the beneficial effects of preinfarction angina are related to ischemic preconditioning. Although a direct demonstration of this hypothesis is still lacking, clinical features of preinfarction angina, which is characterized by anginal attacks preceding acute myocardial infarction, are very similar to those of ischemic preconditioning, in which brief ischemic episodes precede a prolonged ischemic period. Indeed, the demonstration of ischemic preconditioning in different clinical models of ischemia and reperfusion and the identification of some of its mediators suggest that in patients at high risk of myocardial infarction drugs known to block this endogenous form of protection should be used with caution, while drugs known to elicit preconditioning might have a relevant therapeutic role. However, the optimal timing, administration, and dosage for preconditioning-mimetic drugs in the appropriate clinical setting are still under debate and warrant further investigation.