HEMODYNAMIC-EFFECTS OF NEWER PHOSPHODIEST ERASE INHIBITORS IN PATIENTS WITH CORONARY HEART-DISEASE - A COMPARISON OF ENOXIMONE AND R80122

At present, phosphodiesterase III inhibitors are commonly used for the treatment of low cardiac output states. Despite their positive inotro pic and lusitropic effects, these drugs are still under discussion bec ause of certain adverse effects like thrombopaenia, elevation of trans aminases, abdominal disregulation, and excessive periphereal vasodilat ation. As a consequence, more cardioselective phosphodiesterase inhibi tors were developed with the aim of reducing these adverse effects. On e of them, enoximone (Marion Merrell Dow, Fig. 1), an imidazole deriva tive, has nearly no influence on platelets and abdominal organ functio n. In addition, in many studies vasodilatation was found to be absent. Recently a new substance, R80122 (Janssen, Belgium, Fig.1), was devel oped. First experimental studies showed high cardioselectivity of this substance. The aim of this study was to compare the haemodynamic effe cts of enoximone and R80122 in patients with ischaemic heart disease. Methods. This study was thoroughly discussed and approved by the local Ethics Committee; all patients gave written informed consent. Twenty male patients (Table 1) with normal left ventricular function who were about to undergo elective coronary artery bypass surgery were randoml y allocated to receive a bolus of either 1.0 mg/kg enoximone or 0.3 mg /kg R80122 after induction of anaesthesia. Premedication consisted of 2 mg flunitrazepam orally the evening before and in the morning Ih bef ore operation. Anaesthesia was induced with 0.007 mg/kg fentanyl, 0.2m g/kg etomidate, and 0.1mg/kg pancuronium bromide and maintained by a c ontinuous infusion of 0.02 mg/min fentanyl and 0.3 mg/min midazolam. A fter induction of anaesthesia haemodynamic measurements were performed and blood gas samples were taken preoperatively under steady-state co nditions before and 5, 30, and 60 min after drug administration. Resul ts. The results of both groups are shown in Table 2 as mean values wit h standard deviations. Individual changes of cardiac index (CI), mean arterial pressure (MAP), and systemic Vascular resistance (SVR) are de picted in Fig. 2. Peak percentage changes of the haemodynamic paramete rs are shown in Fig. 3. Both substances improved cardiac function; 5 m in after drug administration CI increased by 31% and 26%, respectively . This was accompanied by increases in stroke volume (13% and 14%, res pectively) and heart rate (15% and 10%, respectively). At the same tim e, there were declines in SVR (38% and 36%, respectively) and MAP (19% and 21%, respectively). Although mean values of pulmonary arterial an d wedge pressure decreased after drug administration, these changes we re inconsistent and not of clinical relevance. There were no statistic ally significant differences between the haemodynamic effects of both substances at any time in this study. Conclusions. Both enoximone and R80122 showed the expected inotropic effects. Nevertheless, both subst ances have a distinct vasodilative effect, which leads to a decline in MAP. R80122 does not have higher cardioselectivity than enoximone.