EFFECT OF A CALCIUM-SENSITIZING POSITIVE INOTROPIC AGENT MCI-154 AND ITS COMBINED USE WITH ENALAPRIL ON POSTISCHEMIC CONTRACTILE DYSFUNCTION OF DOG HEARTS

We wished to elucidate the effects of the calcium-sensitizing positive inotropic agent MCI-154 and its combined use with an angiotensin-conv erting enzyme (ACE) inhibitor enalapril on postischemic contractile dy sfunction. Anesthetized dogs underwent a 30-min occlusion of the left anterior descending coronary artery (LAD) followed by 2 h of reperfusi on. Regional myocardial segment shortening in the ischemic LAD area wa s assessed by sonomicrometry. Myocardial segment shortening decreased in response to the LAD occlusion and remained decreased during 2-h rep erfusion. The intravenous infusion of MCI-154 (0.1 or 0.3 mu g/kg/min) initiated 10 min after occlusion and throughout reperfusion significa ntly improved the recovery of segment shortening. The alleviation of t he postischemic contractile dysfunction by MCI-154 was augmented when the animals were treated with a bous injection of enalapril (0.3 mg/kg ) 15 min before ischemia followed by an infusion of the drug (0.003 mg /kg/min). The pretreatment with enalapril alone (0.3 mg/kg plus 0.003 mg/kg/min or 1 mg/kg plus 0.01 mg/kg/min) did not alleviate the postis chemic dysfunction, however, although it decreased systemic blood pres sure (BP). Ischemic bed size, myocardial necrosis (by triphenyltetrazo lium chloride staining), and collateral blood flow (by colored microsp heres) were similar in all experimental groups. These results indicate that MCI-154 improves the postischemic contractile function of dog he art, whereas enalapril fails to improve it. ACE inhibitors may also au gment the efficacy of cardiotonics on postischemic dysfunction.