The existence of a severe toxic interaction (occasionally fatal) from the clinical use of pethidine and monoamine oxidase (MAO) inhibitors is well established. The present study evaluates the possibility of such an interaction existing for the opioid partial agonist buprenorphine. Conscious rabbits (n = 6 in each group) pretreated 18-24 h previously with physiological saline or the MAO inhibitor phenelzine 20 mg kg-1 s.c. were subsequently given physiological saline, pethidine 5 mg kg-1 i.v. or buprenorphine 0.1 or 1.0 mg kg-1 i.v. Whilst saline was without effect and phenelzine produced only a small increase in the rabbit temperature, the combination of phenelzine and pethidine produced a marked, prolonged hyperpyrexia (+4.4 +/- 0.19 degrees C; P less than 0.001), hypertension (+33.9 +/- 3.1 mm Hg; P less than 0.01) and agitation. Three rabbits died, at 35, 45 and 55 min after the pethidine-phenelzine combination. Buprenorphine was without significant effect on any parameter when given after phenelzine. In the model used buprenorphine, in contrast to pethidine, showed no interaction with the MAO inhibitor phenelzine.

The haemodynamic, metabolic and regional blood flow effects of the vasodilator, tolmesoxide (1 mg kg−1 min−1 for 20 min by intravenous infusion) were examined in two groups of greyhound dogs anaesthetized with α‐chloralose and mechanically ventilated. One group of dogs was thoracotomized and subjected to acute coronary artery occlusion. In these dogs tolmesoxide was infused 2.5 h after occlusion when there was evidence of impaired myocardial function. Tolmesoxide administration resulted in marked systemic hypotension which was associated with myocardial stimulation (increase in heart rate and LVdP/dtmax). These effects were less marked in thoracotomized dogs subjected to coronary artery occlusion. Cardiac stimulation was attenuated by pretreatment with the β‐adrenoceptor antagonist, atenolol. Peripheral resistance and left ventricular end‐diastolic pressure (LVEDP) were reduced by tolmesoxide. In spite of the systemic hypotension, the marked reduction in LVEDP resulted in an enhanced subendocardial driving pressure and an increased blood flow to ischaemic regions of the left ventricular wall as measured with Xe133 clearance. Blood flow to normal regions of the left ventricular wall was also increased by tolmesoxide. A metabolic and respiratory acidosis may have contributed to the haemodynamic effects of tolmesoxide. Plasma renin levels were significantly elevated by the drug. Tolmesoxide administration thus resulted in cardiac stimulation, reduced both pre‐load and after‐load, yet maintained coronary and pulmonary perfusion. This haemodynamic profile of tolmesoxide would explain the beneficial effects obtained with this drug in the treatment of cardiac failure.

1 The anaesthetic cyclopropane was given to intact, decerebrate and pithed unanaesthetized rabbit preparations to determine the relative importance in vivo of its central and peripheral cardiovascular effects. 2 Cyclopropane elevated both the heart rate and the mean arterial pressure in the intact rabbit. 3 In the decerebrate rabbit, cyclopropane elevated the heart rate and efferent cervical preganglionic nerve activity and diminished the magnitude of these components of the aortic baroreceptor reflex, the mean arterial pressure being unaffected. 4 Apart from slight myocardial depression, cyclopropane was largely without effect in the pithed rabbit. 5 It is concluded that cyclopropane produces its cardiovascular effects by supra-collicular activation eliciting an elevation of mean arterial pressure, a central sub-collicular activation producing an increase in heart rate, and that in vivo the peripheral effects of cyclopropane are of minimal importance in comparison to these central effects.

In the decerebrate rabbit etomidate caused dose-related decreases in mean arterial pressure and preganglionic sympathetic nerve activity. There were no significant alterations in heart rate. Etomidate was found to have no effect on the baroreceptor reflex. In pithed animals the effects of etomidate were of short duration and of a lesser magnitude than in the decerebrate animal. It was concluded that the additional effects in the decerebrate rabbit were a result of depression of central cardiovascular control. It was found that etomidate was largely without effect on the cardiovascular system at normal anaesthetic doses (0.5-1 mg-kg-1). However, larger doses (2-8 mg kg-1) produced marked depression of central cardiovascular control, the myocardium and the peripheral vasculature.

A quantitative in vitro study has been made of the actions of glyceryl trinitrate and sodium nitrite on vascular smooth muscle (dog femoral artery and saphenous vein; rat portal vein); these have been compared with the actions of papaverine, isoprenaline, salbutamol, pentaerythritol tetranitrate and trimetazidine. Glyceryl trinitrate was more active on the saphenous vein than on the femoral artery in inhibiting noradrenaline and potassium‐induced tone. Unlike glyceryl trinitrate, sodium nitrite and isoprenaline, papaverine and diazoxide inhibited noradrenaline‐induced contractions of venous and arterial smooth muscle to the same extent. The selective dilator effects of glyceryl trinitrate on venous smooth muscle may explain its action in alleviating the pain of angina pectoris. It is suggested that the use of these three vascular smooth muscle preparations (arterial, and veins with and without spontaneous myogenic activity) is a useful initial screening procedure for prospective antianginal drugs acting by venodilatation.

A pithed rabbit preparation is described that allows selective stimulation of the vertebral outflows. The responses to stimulation of sympathetic vasopressor fibres were blocked by hexamethonium and phentolamine but potentiated by cocaine, whereas the responses to stimulation of cardio‐accelerator fibres were blocked by propranolol. Ketamine, althesin and pentobarbitone enhanced the effects of noradrenaline and attenuated the effects of sympathetic nerve stimulation. Thiopentone enhanced the effects of both noradrenaline and sympathetic nerve stimulation. In pithed rabbits a transient, dose‐related cardiovascular depression was produced by each agent irrespective of whether vasomotor tone was present whereas in decerebrate rabbits the corresponding cardiovascular depression was longer lasting. It is concluded that the cardiovascular depression produced by intravenous anaesthetics in intact rabbits is due to a combination of central and peripheral effects.

Rabbits have a high rate of ventilation which makes it difficult to obtain a sample of end-tidal gas by the usual procedures. An occlusion technique was developed which provided a gas sample equivalent to an end-tidal gas sample. MAC values were determined using this sampling method. The values obtained +/- SEM were: cyclopropane 15.6 +/- 1.7%, halothane 0.63 +/- 0.06% and ether 2.7 +/- 0.2%.

The effect of i.v. ketamine on arterial pressure and heart rate were examined in pithed rats, rabbits and cats. In all three species ketamine caused a brief decrease in arterial pressure and heart rate. In the rat, but not in the other two species, this initial decrease in arterial pressure was followed by a pressor response which was resistant to alpha-adrenoceptor blockade, depletion of tissue noradrenaline stores and adrenalectomy. It is concluded that the peripherally mediated pressor response found in the pithed rat is specific to this species, is not a result of liberation of peripheral catecholamines and does not explain the pressor effect of ketamine found in man and several animal species.

In decerebrate rabbits which were mechanically ventilated, both Althesin and thiopentone depressed preganglionic sympathetic activity and arterial pressure. Conduction through central baroreceptor pathways, tested by depressor nerve stimulation, showed a selective inhibition of the heart rate response by both agents. Effects were similar with Althesin injection in animals which were lightly anaesthetized with pentobarbitone. Depression of the arterial pressure and sympathetic components of the baroreceptor reflex was apparent only with high doses.

The katharometer detector is better suited to the analysis of gaseous halothane (0.2-4%) than is the flame ionization detector, since the peak heights are directly proportional to concentration, and are more reproducible.

In rabbits which were initially conscious or lightly anaesthetized with pentobarbitone, ketamine respectively increased or did not change arterial pressure, whereas in mechanically ventilated animals there was prolonged depression of both pressure and pregangkioinic sympathetic activity. Although respiratory rate slowed during spontaneous ventilation, blood-gas changes were not responsible for these differences. Following bilateral division of the carotid sinus and aortic nerves, a depressor response to ketamine occurred during spontaneous respiration. When respiratory rate was slowed coincidentally with ketamine injection during mechanical ventilation, the circulatory responses were similar to those during spontaneous respiration; this did not occur after carotid and aortic denervation. These variations in the circulatory effects of ketamine, according to respiratory pattern and background anaesthesia, are discussed.

In rabbits which were ventilated mechanically, with a background anaesthetic of pentobarbitone or after decerebration, ketamine depressed preganglionic sympathetic activity and arterial pressure. Conduction through central baroreceptor pathways, tested by depressor nerve stimulation, showed a selective inhibition of the heart rate response.