Experimentelle Untersuchungen zur Wirkung von Pentaerithrityltetranitrat bei akutem Myokardinfarkt

Abstract

Pentaerithrityltetranitrate (PETN) is an organic nitrate ester with high selectivity to venous vessels and little development of tolerance. Here we report experimental results concerning the hemodynamic and antiischemic effects of intravenously administered PETN. The experiments were performed with anesthetized, open-chest minipigs (25 to 35 kg body weight [bw]). PETN (0.125, 0.25, 0.5 mg/kg bw, i.v.) dose-dependently decreased left ventricular systolic pressure without change in peripheral vascular resistance. A reflex increase in heart rate returned to normal within 20 minutes (0.125 and 0.25 mg/kg). PETN (0.5 mg/kg) also transiently (10 minutes) decreased left ventricular contractility. In additional experiments, myocardial infarction was induced by LAD occlusion (1 hour), followed by reperfusion (3 hours). PETN (0.6 mg/h, i.v.) was administered starting 20 minutes before ischemia until the end of reperfusion. While PETN did not cause hemodynamic changes, infarct size was significantly decreased compared with vehicle (56 +/- 6% vs 83 +/- 3% of area at risk, p < 0.05). Regional contractile function (ultrasound crystals) was completely abolished during ischemia and did not recover during 3 hours reperfusion in control hearts. However, PETN-treated pigs showed partial functional recovery (19 +/- 5%, p < 0.05 vs vehicle) during the first hour of reperfusion. Histologic evaluation revealed a decreased number of granulocytes accumulated in the ischemic myocardium of PETN-treated animals. Accordingly, in-vitro experiments showed a reduction by PETN of the adherence of HL-60 cells differentiated to granulocytes to vascular smooth muscle cells. Therefore, PETN reduced infarct size and improved myocardial function after LAD occlusion and reperfusion. It is concluded that the intravenous administration of PETN might be of advantage in the treatment of acute myocardial ischemia.