[Hemodynamic effects of new phosphodiesterase inhibitors in patients with coronary heart disease. A comparison between enoximone and R80122].
At present, phosphodiesterase III inhibitors are commonly used for the treatment of low cardiac output states. Despite their positive inotropic and lusitropic effects, these drugs are still under discussion because of certain adverse effects like thrombopaenia, elevation of transaminases, abdominal disregulation, and excessive peripheral vasodilatation. As a consequence, more cardioselective phosphodiesterase inhibitors were developed with the aim of reducing these adverse effects. One of them, enoximone (Marion Merrell Dow, Fig. 1), an imidazole derivative, has nearly no influence on platelets and abdominal organ function. In addition, in many studies vasodilatation was found to be absent. Recently a new substance, R80122 (Janssen, Belgium, Fig. 1), was developed. First experimental studies showed high cardioselectivity of this substance. The aim of this study was to compare the haemodynamic effects 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 randomly 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 1 h before operation. Anaesthesia was induced with 0.007 mg/kg fentanyl, 0.2 mg/kg etomidate, and 0.1 mg/kg pancuronium bromide and maintained by a continuous infusion of 0.02 mg/min fentanyl and 0.3 mg/min midazolam. After induction of anaesthesia haemodynamic measurements were performed and blood gas samples were taken preoperatively under steady-state conditions before and 5, 30, and 60 min after drug administration. RESULTS. The results of both groups are shown in Table 2 as mean values with standard deviations. Individual changes of cardiac index (CI), mean arterial pressure (MAP), and systemic vascular resistance (SVR) are depicted in Fig. 2. Peak percentage changes of the haemodynamic parameters are shown in Fig. 3. Both substances improved cardiac function; 5 min after drug administration CI increased by 31% and 26%, respectively. This was accompanied by increases in stroke volume (13% and 14%, respectively) and heart rate (15% and 10%, respectively). At the same time, there were declines in SVR (38% and 36%, respectively) and MAP (19% and 21%, respectively). Although mean values of pulmonary arterial and wedge pressure decreased after drug administration, these changes were inconsistent and not of clinical relevance. There were no statistically 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 substances have a distinct vasodilative effect, which leads to a decline in MAP. R80122 does not have higher cardioselectivity than enoximone.
Kazmaier
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Zentrum Anaesthesiologie, Rettungs- und Intensivmedizin der George-August-Universität Göttingen.
Stephan
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Sonntag
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D000328:Adult; D000368:Aged; D000758:Anesthesia; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology*; D017335:Enoximone / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011799:Quinazolines; C076518:R 80122; D017335:Enoximone
Hämodynamische Effekte neuerer Phosphodiesterase-III-Hemmer bei Patienten mit koronarer Herzkrankheit. Ein Vergleich zwischen Enoximon und R80122.