Aggravation of Left Ventricular Remodeling by a Novel Specific Endothelin ETA Antagonist EMD94246 in Rats with Experimental Myocardial Infarction

Publisher Website
Google Scholar
Abstract
An endothelin (ETA) antagonist reduced mortality and an ETA + ETB antagonist prevented left ventricular dilatation in rats with large myocardial infarction. This study tested the hypothesis that long-term blockade of the ETA receptor would have beneficial effects on left ventricular function and remodeling. Three hours after coronary artery ligation or sham operation in rats, EMD94246 (100 mg/kg/day, n = 62) or placebo (n = 62) was given by gavage. Eight weeks later, left ventricular hemodynamic measurements were performed and left ventricular volume determined with a double-lumen catheter after KCl-induced cardiac arrest. EMD94246 treatment had no effects on mortality or hemodynamic parameters. In rats with large infarcts, EMD94246 significantly increased left ventricular volume (2.5 ± 0.1 vs. 2.2 ± 0.1 ml/kg; p < 0.05). The nonpeptide ETA-selective antagonist EMD94246 promoted chronic left ventricular dilatation in rats with large myocardial infarction.