COMPARISON OF MYOCARDIAL-ISCHEMIA INDUCED BY ENDOTHELIN VS MECHANICALSTENOSIS IN PIGS

We have determined the transmural distribution of myocardial flow and ischemia during endothelin (ET-1) infusion and compared these results with the effects of mechanical stenosis. In anesthetized pigs, coronar y flow was reduced 15, 30, and 50% from baseline values with a mechani cal stenosis (n = 7) or increasing doses of intracoronary ET-1 (n = 8) . The inner-to-outer flow ratio decreased with decreasing total flow d uring mechanical stenosis, and S-T segment elevation occurred predomin antly in the subendocardium. In contrast, the inner-to-outer flow rati o exceeded 1.0 and actually increased during ET-1 infusion. ET-1 limit ed the electrocardiographic evidence of subendocardial ischemia and at tenuated contractile dysfunction compared with mechanical stenosis at the same coronary flows, even though lactate flux was similar. Reactiv e hyperemia was retained with ET-1, even when coronary flow was reduce d enough to cause lactate production. These results demonstrate a more uniform transmural distribution of flow caused by microvascular const riction than by a large-vessel stenosis.