Hämodynamische Effekte verschiedener Dosierungen des Phosphodiesterase-III-Hemmers R80122

Abstract

Selective inhibitors of the phosphodiesterase isoenzyme III (PDE-III) are well known for the treatment of catecholamine-resistent acute cardiac failure because of their inotropic, lusitropic, and vasodilative properties. The aim of this clincial study was to investigate the hemodynamic effects of increasing doses of the PDE-III-inhibitor R80122 in order to determine the optimal dosage of R80122 for the treatment of acute cardiogenic failure.¶ Thirty male patients with coronary artery disease were investigated prior to coronary artery bypass grafting. They were randomly assigned to one of the five following groups: a control group not receiving R80122 and 4 groups receiving an incremental bolus dose of R80122 from 0.1mg/kg to 0.4mg/kg bodyweight. Hemodynamic measurements were performed before and 5, 10, 15, 30, 45, and 60 minutes after i.v. injection of R80122.¶ A dosage of 0.2mg/kg to 0.4mg/kg R80122 induced a significant increase in cardiac index immediately after administration which then continued during the entire measurement period. This increase in cardiac index was accompanied by an increase in heart rate at dosages of 0.3mg/kg and 0.4mg/kg R80122. Only after 0.3mg/kg R80122 an increase in stroke volume index was found 10 minutes after drug administration. A concomitant decrease in mean arterial pressure was observed in the first 15 minutes after drug application at dosages of 0.2mg/kg to 0.4mg/kg R80122. This was mainly caused by a dose-dependent decrease in systemic vascular resistance index. A maximal decrease in systemic vascular resistance index was found during the first 15 minutes after administration of the PDE-III-inhibitor.¶ The results of our study demonstrate that R80122 significantly increases cardiac index in patients with coronary artery disease. Increasing doses of R80122, however, elicit the risk of undesireable hemodynamic effects. Therefore, an initial dosage of 0.2mg/kg R80122 seems to be adequate for the treatment of acute cardiac failure because of a minimal increase in heart rate und decrease of mean arterial pressure.