Effects of propofol on the systolic and diastolic performance of the postischaemic, reperfused myocardium in rabbits.

BACKGROUND AND OBJECTIVE: The effect of propofol on myocardial dysfunction during ischaemia and reperfusion is controversial yet important because of its frequent use in cardiac anaesthesia. Although animal studies suggest a free radical-scavenging potential, the cardioprotective properties of propofol have not been demonstrated consistently in vivo. Previous studies focused on systolic function while diastolic function may be a more sensitive marker of ischaemic injury. The main aim was to document the effect of propofol on diastolic function in isolated, blood perfused rabbit hearts subjected to moderate global ischaemia and reperfusion. METHODS: Propofol 168 micromol L(-1), or the equivalent of its vehicle, Intralipid, was administered to 34 paced parabiotic Langendorff blood-perfused isolated rabbit hearts before and after 30 min of global normothermic ischaemia. Recovery of systolic function was quantified with the maximum rate of rise of left ventricular pressure. Diastolic performance was assessed using the time constant of the decline in left ventricular pressure (tau) and chamber stiffness (VdP/dV at 12 mmHg). RESULTS: Recovery of systolic function during reperfusion was comparable in the two groups. There was no difference in left ventricular pressure between the two groups at any time during the experiments. Chamber stiffness increased significantly during ischaemia and reperfusion in the control group (from 34 +/- 9 to 54 +/- 8 mmHg during ischaemia, and 43 +/- 5 mmHg after 30 min reperfusion; mean +/-95% confidence interval) but not in the propofol-treated group (29 +/- 5, 36 +/- 8 and 30 +/- 8 at baseline, ischaemia and 30 min reperfusion, respectively). CONCLUSIONS: Propofol has no protective effect on active relaxation or on systolic function in the present model, but it reduces ischaemic and postischaemic chamber stiffness.

Effect of clevidipine, an ultra-short acting 1,4-dihydropyridine calcium channel blocking drug, on the potency of isoflurane in rats and dogs.

Clevidipine is a new lipophilic, ultra-short acting 1, 4-dihydropyridine calcium channel antagonist for intraoperative use. Because sarcolemnal calcium currents are involved in the mechanism of action of anaesthetics we questioned whether clevidipine alters the potency of volatile anaesthetics. We studied the effects of clevidipine on minimal alveolar concentration and the time to awaken from isoflurane anaesthesia. Sprague-Dawley rats were anaesthetized with isoflurane, and were allocated to one of four treatments prior to minimal alveolar concentration determination: (a) saline control; (b) clevidipine 20 nmol kg-1 min-1; (c) clevidipine 40 nmol kg-1 min-1; (d) clonidine 1 microg kg-1 - positive control. Ten mongrel dogs were anaesthetized with isoflurane and received a continuous infusion of clevidipine 6 nmol kg-1 min-1 or the solvent (Intralipid 20% - control). After 2 h of steady-state anaesthesia, minimal alveolar concentration awake and the time to awakening were recorded. Clevidipine reduced minimal alveolar concentration to a small but statistically significant extent (from 1.40 +/- 0.16 control to 1.23 +/- 0.13 vol % with 20 nmol kg-1 min-1 and to 1.27 +/- 0.12 vol % with 40 nmol kg-1 min-1; mean +/- SD; P < 0.05) in rats. Clonidine reduced minimal alveolar concentration to 0.90 +/- 0.17 vol % (mean +/- SD; P < 0.05). Minimal alveolar concentration awake and the duration of sleep were not affected by clevidipine in dogs. Clevidipine mildly reduces minimal alveolar concentration of isoflurane but does not prolong the duration of sleep and does not affect minimal alveolar concentration awake after a 2-h steady-state isoflurane anaesthesia.

Effects of tramadol on minimum alveolar concentration (MAC) of isoflurane in rats.

It has been suggested previously that tramadol increases central nervous system activity and 'lightens' anaesthesia with volatile agents. We assessed the effects of tramadol on the minimum alveolar concentration (MAC) of isoflurane in 56 Wistar rats, instrumented chronically with an arterial and central venous catheter. The MAC of isoflurane was determined using the tail clamp method under three conditions: (1) after injection of saline (control); (2) after administration of tramadol 10 mg kg-1 i.v.; and (3) after administration of morphine 1 mg kg-1 i.v. The studies were repeated after treatment with the antagonists naloxone or yohimbine. Tramadol and morphine both reduced the MAC of isoflurane from mean 1.38 (SEM 0.05)% to 1.22 (0.06)% and 1.17 (0.06)%, respectively (P < 0.05). Concomitant administration of yohimbine did not abolish this reduction in MAC. In contrast, after pretreatment with naloxone, tramadol (1.47 (0.04)%) or morphine (1.38 (0.07)%) did not cause a reduction in the MAC of isoflurane compared with controls (1.39 (0.06)%). We conclude that tramadol and morphine reduced the MAC of isoflurane to a small but significant extent. For both drugs, this effect was related to their action at opioid receptors.