Impaired vasodilatation of epicardial coronary arteries and resistance vessels following myocardial ischemia and reperfusion in anesthetized dogs

Abstract

To study whether the reactivity of the large coronary artery in vivo is affected by coronary artery occlusion and reperfusion, left circumflex coronary artery diameter, coronary blood flow, systemic arterial blood pressure, and heart rate were measured in anesthetized, open-chest dogs. Intracoronary injections of acetylcholine and glyceryl trinitrate (an endothelium-independent vasodilator) produced increases in both coronary artery diameter (0.06 ± 0.02 mm and 0.15 ± 0.02 mm, respectively) and coronary blood flow (58±15 mL/min and 50 ± 11 mL/min, respectively) under control conditions. Neither arterial blood pressure nor heart rate was affected by the vasodilators. After 60 minutes of coronary artery occlusion and 30 minutes of reperfusion, baseline coronary artery diameter and coronary blood flow were reduced (P & 0.05), and the increases produced by acetylcholine and glyceryl trinitrate in coronary artery diameter (0.01 ± 0.02 mm and 0.09 ± 0.01 mm, respectively) and coronary blood flow (2014 mL/min and 19 ± 5 mL/min, respectively) were significantly attenuated (P&0.05). Electron microscopy revealed endothelial cell injury and focal regions of detachment from underlying subendothelium and adherence of leukocytes to the endothelium of the ischemic large coronary artery. Leukocyte plugging of capillaries in the ischemic myocardium was also occurred. In isolated arterial ring preparations, acetylcholine-induced relaxation (maximum = 59% 19%) was attenuated by ischemia and reperfusion (maximum = 15%14%; P<0.05), whereas glyceryl trinitrate-induced relaxation was not affected. Thus, coronary artery occlusion and reperfusion attenuate endothelium-dependent and -independent dilatation of large coronary arteries and coronary resistance vessels in vivo, whereas only endothelium-dependent relaxation is inhibited in isolated arterial ring experiments. Thus, endothelial dysfunction is not the only factor contributing to reduced vasodilator responses after ischemia and reperfusion. The ischemia-induced constriction of the coronary circulation may restrict the responsiveness to exogenous vasodilators. Also, reduced vasodilator reserve caused by capillary plugging may contribute to the attenuation of the normal increases in coronary blood flow produced by both endothelium-dependent and -independent vasodilators.