Mechanisms of Enhanced Canine Subendocardial Perfusion

Abstract

The purpose of these experiments was to determine the effects of adenosine triphosphate (ATP) and sodium nitroprusside, two compounds used to produce controlled hypotension during surgery, on regional myocardial blood flow. Intracoronary drug infusions in open chest, anesthetized dogs were used to study the direct actions of these agents on the coronary circulation as well as to avoid systemic hemodynamic effects. The actions of the endothelium-dependent and -independent vasodilators, ATP and nitroprusside, respectively, were studied before and after administration of quinacrine (an inhibitor of phospholipase A2), which blocks formation and/or release of endothelium-derived relaxing factor (EDRF). Both vasodilators produced significant increases in transmural blood flow of the drug-perfused zone. Only ATP, the endothelium-dependent vasodilator, altered the distribution of myocardial blood flow. Perfusion to the subendocardium was preferentially increased by ATP, resulting in an increase in the subendocardial-to-subepicardial flow ratio. Quinacrine markedly inhibited the increase in endo/epi produced by ATP without changing total flow. These data suggest that ATP increases total coronary blood flow by a mechanism that is independent of EDRF, but the selective redistribution of blood flow to the subendocardium is dependent on EDRF. Nitroprusside, an endothelium-independent vasodilator, produces no redistribution of myocardial blood flow.