CARDIAC ENDOTHELIN RELEASE AND INFARCT SIZE, MYOCARDIAL BLOOD-FLOW, AND VENTRICULAR-FUNCTION IN CANINE INFARCTION AND REPERFUSION

Background: The potent vasoconstrictor endothelin-1 (ET) may play an i mportant pathophysiologic role in acute myocardial infarction, but its precise effects are incompletely understood, The purpose of this stud y was to evaluate the interrelationships between cardiac ET-1 release and infarct size, myocardial blood flow, and ventricular function. Met hods: Fifteen closed chest dogs underwent 3 hours of coronary artery o cclusion 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 b lood flow were measured by echocardiography and colored microspheres, respectively, Myocardial infarct size was determined by postmortem sta ining with blue dye and triphenyl tetrazolium chloride. Results: Coron ary occlusion and reperfusion produced significant elevations of coron ary sinus ET-1 Gn < 0.05) and cardiac ET-1 release (p < 0.05), and a t rend 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), an d in dogs with substantial no-reflow in the reperfused territory (p = 0.05). Endothelin-1 release also was associated with increased contrac tility in nonischemic myocardial segments (p = 0.002), and ET-1 correl ated with increased global left ventricular function (p < 0.02). Concl usions: In this canine model of coronary occlusion and reperfusion, gr eater increases in cardiac ET-1 release were observed in dogs with lar ger infarcts, and increased ET-1 release was associated,vith the no-re flow phenomenon in the reperfused territory, These data suggest that E T-1 release may have adverse consequences in acute myocardial infarcti on, including a reduction of myocardial blood flow in the reperfused z one after reperfusion and increased contractility in nonischemic myoca rdium.