Role of adenosine in postocclusion coronary vasodilation

Coronary vasodilation after brief (less than 15 s) occlusions was studied in closed-chest, anesthetized dogs, using constant-flow perfusion of a large coronary artery. We assumed occlusion duration to be a measure of the concentration of endogeneous adenosine and determined adenosine dose-response curves by varying occlusion duration and measuring the resulting drop in vascular resistance. The curves were compared to dose-response curves measured by continuously infusing adenosine. Both dose-response relations were found to follow the Hill equation for ligand receptor interaction; the slopes of the two curves were not significantly different, and the estimated adenosine accumulation rate in the myocardium was found to be in close agreement with data in the literature, measured by direct tissue assay. The time course of recovery of vascular tone after short occlusions was not very sensitive to flow, at least not for normal flow levels or higher. The results confirm that adenosine accumulation plays an important role in causing postocclusion vasodilation. However, autoregulation of coronary flow based on an adenosine washout mechanism additionally requires tissue clearance to be highly flow dependent for flow levels below normal, but approaches a constant value when flow increases above normal.