Ischemic preconditioning in humans - Models, mediators, and clinical relevance

Ischemic preconditioning, a powerful form of endogenous protection against myocardial infarction, has been demonstrated in several animal species and, recently, in isolated human cardiomyocytes. For both logistic and ethical reasons, no clinical study can meet the strict conditions of experimental s tudies on preconditioning with infarct size as the end-point. Nevertheless, the demonstration of adaptation to ischemia observed during in vitro studi es on human atrial trabeculae, in patients in the setting of coronary bypas s surgery, and in the setting of coronary angioplasty in the absence of col lateral vessel recruitment strongly suggests that ischemic preconditioning occurs in humans. This notion is further supported by the observation that in these human models, the adaptation to ischemia is influenced by drugs ac ting on K-ATP channels and on purinergic and alpha-adrenergic receptors, si milar to what is observed in accepted experimental models of ischemic preco nditioning. This important form of myocardial endogenous protection may als o play a role in the warm-up phenomenon and in mediating the beneficial eff ects of preinfarction angina. The demonstration of ischemic preconditioning in humans and the identification of some of its mediators suggests that in patients at high risk for myocardial infarction, drugs known to block this endogenous form of protection should be used with caution, whereas drugs k nown to elicit preconditioning might have a relevant therapeutic role.