Cardioprotective roles of adenosine against ischemic and reperfusion injury

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This study was undertaken to elucidate whether alpha_1-adrenoceptor activity is beneficial for contractile dysfunction during ischemia and reperfusion in open-chest dogs. Myocardial ischemia increased release of adenosine with reductions of coronary blood flow and fractional shortening. Prazosin (4 ug/kg/min, ic) further deteriorated contractile dysfunction with attenuated adenosine release and coronary blood flow. In turn, methoxamine (1ug/kg/min, ic), which does not affect basal coronary vascular tones, increased both adenosine release and coronary blood flow during ischemia and improved contractile function. This augmentation of adenosine release and coronary blood flow due to methoxamine increased fractional shortening, which was inhibited by 8-phenyltheophylline. These results indicate that alpha_1- adrenoceptor activity increases adenosine release during myocardial ischemia and attenuates contractile dysfunction.Furthermore, we examined the effects of alpha_1-adrenoceptor activity on myocardial stunning assessed at 3 hours after the onset of reperfusion followed by 15 min of complete occlusion of the left anterior descending coronary artery. Prazosin attenuated fractional shortening (12.7* 0.6 vs. 6.9 * 0.4 % with prazosin treatment, p<0.001). On the other hand, methoxamine attenuated contractile dysfunction. Both adenosine release and hyperemic coronary flow response during early reperfusion period were attenuated in the prazosin-treated group, and both were enhanced in the methoxamine-treated group. Thus we conclude that (1) alpha_1-adrenoceptor activity improves myocardial function during ischemia and reperfusion and (2) its cellular mechanism is due to enhanced adenosine release by alpha_1-adrenoceptor activity.