Coronary vasodilation during global myocardial hypoxia: effects of adenosine deaminase

Isolated, perfused guinea pig hearts were infused with intracoronary adenosine deaminase to investigate the contribution of endogenous adenosine to the coronary vasodilation of global myocardial hypoxia. Coronary perfusate pressure was held constant at 70 cmH2O throughout the experiment. We measured retrograde aortic inflow (assumed to equal total antegrade coronary flow) for 3-5 min of hypoxia before and 4 min after initiation of intracoronary adenosine deaminase infusion (4 U.g-1.min-1). In the absence of adenosine deaminase mild global hypoxia increased coronary perfusate flow 60%. In the presence of adenosine deaminase the response was limited to a 5% increment. Myocardial O2 consumption was significantly reduced during hypoxia in the presence of adenosine deaminase. In a second group of hearts, moderate global hypoxia increased coronary perfusate flow 125%. This was limited to a 53% increment in the presence of adenosine deaminase. Adenosine deaminase vehicle had no measurable effect on coronary perfusate flow responses to repeat mild hypoxia in a third group of hearts. We conclude that endogenous adenosine is singularly important in the coronary vasodilation of mild global myocardial hypoxia, but that other regulatory mechanisms might also contribute during moderate hypoxia.