COMPARATIVE INVESTIGATIONS ON THE CARDIOVASCULAR EFFECTS OF ORG NC45 AND PANCURONIUM IN DOGS

Cardiovascular effects of Org NC 45 and pancuronium were examined in seven anaesthetized dogs. Systemic circulatory effects were measured after increasing doses administered as a single i.v. bolus. Cardiac effects were measured after intracoronary (i.e.) injection of the equivalent dose of the respective neuromuscular blocking agent, which produced 90 % neuromuscular blockade. Org NC 45 i.v. did not cause any significant cardiovascular changes, whereas pancuronium i.v. produced significant and dose-related increases in heart rate, left ventricular (LV) dP/dtmax and cardiac output (CO). After i.e. injection of equipment doses, neither drug induced any significant change in haemodynamic measurements. This implies that neither drug exerted a direct influence on cardiac contractility, the increases in LV dP/dr max and CO following pancuronium being dependent on heart rate. Cardiovascular effects of non-depolarizing neuromuscular blocking drugs are important, espe-cially in the anaesthetic management of patients with cardiac disease. It has been shown that Org NC45 (3a, 17 0-diacetoxy-2 0,16 0-dipiperidino-5a androstane 16 fi-N monometho-bromide) has mini-mal effects on the cardiovascular system in the experimental animal (Booij et al., 1980) and in clinical practice (Lienhart et al., 1981; Morris etal., 1981; Barnes et al., 1982). A clinical dose of Org NC45 produced neither vagolytic activity (Lee Son and Waud, 1980) nor an inhibition of the neuronal and extraneuronal uptake of noradrenaline (Salt, Barnes and Conway, 1980). However, the direct effects of Org NC45 on myocardial contractility have not been studied extensively. The present study was undertaken to examine the direct effects of Org NC 45 on the inotropic state of the myocar-dium, using an animal model which enabled us to differentiate between systemic and "pure " cardiac effects. The results obtained following administra-tion of Org NC 45 were compared with those follow-ing pancuronium, a neuromuscular blocker with a similar chemical structure but which is known to increase cardiac activity (Kelman and Kennedy, 1971; Coleman et al., 1972). MATERIALS AND METHOD