Effect of dipyridamole on myocardial adenosine metabolism and coronary flow in hypoxia and reactive hyperemia in the isolated perfused guinea pig heart

Abstract

The effect of dipyridamole on adenosine metabolism and coronary flow in the hypoxic intact myocardium was studied in normal and hypertrophied isolated perfused guinea pig hearts. The presence of dipyridamole in the normal guinea pig heart resulted in a significant increase in the level of tissue adenosine (67%) with a concomitant increase in coronary flow (85%) and a decrease in the rate of adenosine release (18%) from the myocardium during perfusion with normoxic and hypoxic solutions. Directional changes in hypertrophied hearts were the same as for normal hearts. Tissue levels of adenosine in normal dipyridamole-treated hearts during normoxic perfusion were significantly increased above those of untreated hearts at the peak of reactive hyperemia (× 1.5), after 30 s of aortic occlusion (× 2.3) and during steady state flow (× 2.0). Furthermore, the presence of dipyridamole in normal hearts during reactive hyperemia, produced by 30 s of aortic occlusion, increased the volume and duration of coronary flow by 44% and 75%, respectively. These findings are in accord with the hypothesis that adenosine is a mediator of coronary flow and that dipyridamole potentiates the vasodilator effect of endogenous as well as exogenous adenosine.