Background: The potent vasoconstrictor endothelin-1 (ET) may play an important pathophysiologic role in acute myocardial infarction, but its precise effects are incompletely understood, The purpose of this study was to evaluate the interrelationships between cardiac ET-1 release and infarct size, myocardial blood flow, and ventricular function. Methods: Fifteen closed chest dogs underwent 3 hours of coronary artery occlusion followed by 3 hours of reperfusion, Coronary sinus and aortic ET-1 levels during occlusion and after reperfusion were determined by radioimmunoassay, Left ventricular function and regional myocardial blood flow were measured by echocardiography and colored microspheres, respectively, Myocardial infarct size was determined by postmortem staining with blue dye and triphenyl tetrazolium chloride. Results: Coronary occlusion and reperfusion produced significant elevations of coronary sinus ET-1 Gn < 0.05) and cardiac ET-1 release (p < 0.05), and a trend toward an increase in aortic ET-1 (p = 0.08). A trend toward more ET-1 release was observed in dogs with larger infarcts (p = 0.06), and in dogs with substantial no-reflow in the reperfused territory (p = 0.05). Endothelin-1 release also was associated with increased contractility in nonischemic myocardial segments (p = 0.002), and ET-1 correlated with increased global left ventricular function (p < 0.02). Conclusions: In this canine model of coronary occlusion and reperfusion, greater increases in cardiac ET-1 release were observed in dogs with larger infarcts, and increased ET-1 release was associated,vith the no-reflow phenomenon in the reperfused territory, These data suggest that ET-1 release may have adverse consequences in acute myocardial infarction, including a reduction of myocardial blood flow in the reperfused zone after reperfusion and increased contractility in nonischemic myocardium.