The endothelin system and its role in acute myocardial infarction.

Abstract

Immediately after an acute myocardial infarction (AMI) or in models of ischemia-reperfusion injury, cardiac endothelin (ET) system is markedly activated, and plasma levels of ET are increased. In the heart, expression of the main components of the ET system (ET-1 peptide, both receptor subtypes ETA and ETB, though not endothelin converting enzyme) are increased both at the gene level and protein level, in the viable myocardium, and--even more substantially--in the necrotic area. Despite these conspicuous abnormalities, the role of ET in this setting remains unclear. In the absence of human data, most short-term studies in animals (in terms of hours to up to 8 days post-AMI) and in the reperfused ischemic heart, have found beneficial effects of ET receptor blockade on survival rate, incidence of arrhythmias, cardiac function, and morphology. In contrast, many studies in which a long-term ET inhibition was started immediately post-infarction and the late effects were examined in animals with ensuing chronic heart failure (14-100 days postinfarction), adverse effects were also observed, such as scar thinning, further ventricular dilation, or even a worse survival rate. It appears that the ET system plays a dual role during the early post-AMI period. At present, it is not clear whether the short-term beneficial effects or long-term adverse effects of ET receptor blockade would prevail. Acute use of short-acting ET receptor antagonists in patients with AMI complicated by an acute heart failure is an attractive possibility that also remains to be investigated.