Role of nitric oxide in regulation of coronary blood flow during myocardial ischemi in dogs

Objectives. This study was undertaken to examine whether nitric oxide released in ischemic myocardium decreases the coronary vascular resistance and attenuates the severity of contractile and metabolic dysfunction. Background. Endothelium-derived relaxing factor, recently identified as nitric oxide, is potent relaxant of coronary smooth muscle. Methods. The left anrterior descending coronary artery was perfused through an extracorporeal bypass tube placed in the carotid artery in 56 open chest dogs. After hemodynamic stabilization, we occluded this bypass tube to decrease coronary blood flow to one third of the control flow. Thereafter, we maintained constant coronary perfusion pressure(40.9 ± 3.1mm Hg). Results. Under ischemic conditions, the coronary arteriovenous differences in nitrate and nitrite (end products of nitric oxide) increased (from 3.5 ± 0.4 [mean ± SEM] to 12.9 ± 2.1 μmol/liter, p < 0.01). image0-Monomethyl image-arginine (3 μg/kg body weight per min, intracoronary) decreased the coronary arteriovenous differences in nitrate and nitrite (5.0 ± 0.9 μmol/liter, p < 0.05) and coronary blood flow (from 29.8 ± 0.5 to 18.1 ± 1.1 ml/100 g per min, p < 0.001). Fractional shortening (from 3.7 ± 1.0 to −1.3 ± 0.7%, p < 0.001) and lactate extraction ration (from −44.0 ± 4.1 to −59.2 ± 4.9%, p < 0.005) of the perfused are also decreased. These values were restored by the concomitant administration of image-arginine. Blood flow to the endomyocardium was decreased relative to the epimyocardium. reduction in coronary blood flow and worsening of myocardial contractile and metabolic functions due to the administration of imageG-monomethyl image-arginine during ischemi were observed in denervated hearts. reduction in coronary blood flow in ischemic myocardium was observed with the administration of imageW-nitro-image-arginene methyl ester as well, although neither imageW-nitro-image-arginine methyl ester nor imageG-monomethyl image-arginine changed coronary blood flow and myocardial contractile and metabolic functions in the nonischemic myocardium. The cyclic guanosine monophosphate content of epicardial coronary artery increased due to myocardial ischemia; this increased was attenuated with imageG-monomethyl image-arginine treatment. Conclusions. We conclude that endogenous nitric oxide predominantly decreases the coronary vascular resistance of ischemic endomyocardium, thereby improving myocardial contractility and metabolic function.