PROTECTIVE EFFECTS OF ADENOSINE IN MYOCARDIAL-ISCHEMIA

Endogenous adenosine, released from the heart in response to a decrease in the oxygen supply/demand ratio, and pharmacological concentrations of exogenous adenosine have protective effects in the ischemic myocardium. Adenosine is effective in limiting regional and global reperfusion injury and infarct size and appears to play a role in the phenomenon of preconditioning. The cardioprotective actions of adenosine are derived from several mechanisms: 1) coronary and collateral vessel vasodilation (increase in O2 supply), 2) negative inotropism, chronotropism, and dromotropism (decrease in O2 demand), 3) enhanced glycolytic flux and purine salvage, 4) reduction in microvascular injury during postischemic reperfusion by direct effect on the endothelium and by inhibition of neutrophil release of superoxide anions and platelet aggregation, and 5) possibly by stimulation of angiogenesis in states of chronic hypoxia or ischemia. The use of adenosine agonists may provide new methods for 1) preconditioning, 2) myocardial protection after thrombolytic or angioplastic recanalization of occluded or stenotic coronary arteries, 3) cardioplegic arrest, and, 4) organ preservation for cardiac transplantation.