Nonselective endothelin receptor antagonist initiated soon after the onsetof myocardial infarction may deteriorate 24-hour survival

To investigate the effects of endothelin blockade initiated immediately aft er the onset of myocardial infarction on survival and left ventricular remo deling, treatment with the nonselective receptor antagonist TAK-044 (n = 22 ) or saline (n = 19) for 3 weeks was initiated immediately after coronary l igation in rats. The 24-h survival rate was significantly lower in the TAK- 044 group than in the saline group. The systolic blood pressure 24 h after the onset of myocardial infarction was similar in the saline and TAK-044 gr oups, although it was significantly lower in the TAK-044 group during the 3 -week protocol. Heart weight/tibial length was significantly increased in t he TAK-044 group compared with the saline group. As all deaths in the TAK-0 44 group occurred within 24 h after myocardial infarction, we performed add itional experiments using a separate group of rats 12-16 h after myocardial infarction, Plasma and myocardial endothelin-l levels were significantly i ncreased, and a bolus injection of TAK-044 significantly reduced left ventr icular dP/dt(max) in these rats that had had a myocardial infarction compar ed with sham-operated rats. Endothelin receptor blockade initiated immediat ely after the onset of myocardial infarction may deteriorate acute-phase su rvival and left ventricular remodeling. Inhibition of the positive inotropi c action of endothlin-1 may partially explain the increased 24-h mortality.