Adenosine and cardioprotection during reperfusion - an overview

Ischemic heart disease includes a number of entities that have been grouped in accordance with physiopathology and evolutive criteria. In recent years 'new' ischemic syndromes have been described. Within the 'new' ischemic syndromes, ventricular post-ischemic dysfunction - also known as 'stunned myocardium' - is worth mentioning. In this route, several studies have suggested that reperfusion per se could cause cellular injury ( reperfusion injury). In previous years, a protective effect on the injury caused by ischemia and reperfusion in the heart has been attributed to adenosine. These effects have been documented in different experimental in vivo and in vitro models. Thus, the administration of exogenous adenosine, or agonists of adenosine receptors prior to ischemia reduces the size of the infarction, improves the recovery of the ventricular function during reperfusion ( attenuating stunning) and prolongs the time period to the ischemic contracture. However, focusing on a potential therapeutic application, it is of the utmost importance to find this protection and learn the mechanisms involved when procedures are applied during early reperfusion. We showed that adenosine, administered from the beginning of reperfusion, attenuated systolic and diastolic ( myocardial stiffness) alterations of the stunned myocardium. This protective effect was mediated by the activation of A(1) adenosine receptors, and without modification on infarct size. According to some authors, adenosine can decrease the release of endothelin, during early reperfusion, and reduce an overload of Ca2+ that could cause a cellular lesion. Finally, ischemic preconditioning involves a series of intracellular events that are initiated with the activation of the A(1) receptor, and end at the sensitive K+ ATP channels of the mitochondria. The phosphorylation and opening of these channels would cause the protective effect. Activation of this specific mechanism during reperfusion has not been studied extensively.