Comparison of myocardial ischemia induced by endothelin vs. mechanical stenosis 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, coronary flow was reduced 15, 30, and 50% from baseline values with a mechanical stenosis (n = 7) or increasing doses of intracoronary ET-1 (n = 8). The inner-to-outer flow ratio decreased with decreasing total flow during mechanical stenosis, and S-T segment elevation occurred predominantly in the subendocardium. In contrast, the inner-to-outer flow ratio exceeded 1.0 and actually increased during ET-1 infusion. ET-1 limited the electrocardiographic evidence of subendocardial ischemia and attenuated contractile dysfunction compared with mechanical stenosis at the same coronary flows, even though lactate flux was similar. Reactive hyperemia was retained with ET-1, even when coronary flow was reduced enough to cause lactate production. These results demonstrate a more uniform transmural distribution of flow caused by microvascular constriction than by a large-vessel stenosis.