Beneficial role of adenosine in myocardial ischemic and reperfusion injury

Adenosine has been recognized as an important regulator of myocardial function and coronary vascular tone in the ischemic myocardium. 5′-Nucleotides, which converts 5′-adenosine monophosphate to adenosine, is responsible for adenosine production in the ischemic myocardium. We have found that α₁-adrenergic receptors activated in ischemic hearts increase both 5′-nucleotidase activity and adenosine production. The primary role of endogenous adenosine is to increase coronary blood flow through adenosine A₂ receptors. This adenosine-induced coronary vasodilation is amplified by α₂-adenosine stimulation. Stimulation of adenosine A₂ receptors also attenuates both free radical generation by activated leukocytes and the aggregation of platelets. In turn, adenosine A₁ receptor activation attenuates β-adrenoceptor-mediated increases in myocardial contractility, Ca²⁺ influx into myocytes and norepinephrine release form the presynaptic nerves. Any or all of these effects may attenuate ischemic and reperfusion injury. Indeed, endogenous and exogenous adenosine appears to ameliorate contractile dysfunction and infarct size following ischemia and reperfusion. Therefore, we believe that adenosine plays an important role as a modulator of ischemic and reperfusion injury. © 1993 Wiley-Liss, Inc.