Myocardial protection: The adenosine story

It has been recognized for many years that the purine nucleoside adenosine exerts numerous effects in mammalian myocardium. During the last decade, an in particular over the last 5 years, substantial evidence has accumulated that adenosine also exerts beneficial effects in the ischemic/reperfused myocardium. The cardioprotective effects of adenosine are manifest by attenuation of reversible postischemic ventricular dysfunction (i.e., stunning) and reduction of myocardial infarct size. These effects can be produced by augmenting endogenous adenosine levels with adenosine deaminase inhibitors and nucleoside transport inhibitors and by infusing adenosine (intracoronary or intravenous). Similar to adenosine's effects in nonischemic hearts, the cardioprotective effects of adenosine are mediated by activation of extracellular adenosine receptors. The results of studies with adenosine receptor agonists and antagonists indicate that adenosine's beneficial effect in reversibly and irreversibly injured myocardium is mediated primarily via adenosine A1 receptor activation. The protective effects of adenosine appear to occur during ischemia since adenosine infusion during reperfusion neither attenuates stunning nor reduces infarct size. Adenosine is cardioprotective in rats, rabbits, dogs, and pigs, and initial clinical reports indicate that adenosine may enhance myocardial protection during open heart surgery in humans. This review will summarize the current state of knowledge on the cardioprotective effects of adenosine in experimental and clinical studies. Drug Dev. Res. 39:314–318, 1996 © 1997 Wiley-Liss, Inc.