Anti-ischemic effects of molsidomine in an experimental model of coronary artery stenosis.

Abstract

The effect of molsidomine, a novel antianginal agent, on the epicardial electrographic changes induced by reduced perfusion of the left anterior descending coronary artery (LAD) was investigated in the anesthetized dog. The LAD was cannulated and perfused at a constant volume with blood taken from a carotid artery. The perfusion volume was than reduced by approximately 75%. The sum of the ST-segment changes obtained from six unipolar epicardial leads was taken as a measure of myocardial hypoxia. Simultaneously, heart rate, blood pressure, left ventricular end-diastolic pressure, pulmonary arterial pressure, and heart contractility were also recorded. In control animals, reduction of the perfusion volume of the LAD resulted in a dramatic elevation of the ST segments lasting more than 4 hr. Molsidomine administered after the induction of the ischemia at a dose of 0.05 mg/kg i.v. resulted within 40 min in a complete normalization of the electrographic changes. This effect was evident for over 4 hr in spite of the continuous reduced perfusion of the LAD. The beneficial effect of molsidomine on the electrical changes paralleled the reduction of the left ventricular end-diastolic pressure. It is suggested that the effect of molsidomine on the ischemic electrographic changes is brought about by a reduction of the preload, resulting in a better perfusion of the ischemic zones.