ABSTRACT
We studied the aqueous solution of propofol dissolved in hydroxypropyl-beta-cyclodextrin (HP beta CD) 20% to determine whether the cardiovascular profile differed from that measured for propofol prepared in Intralipid 10% (Diprivan). Conscious male rats were given an intravenous bolus of propofol, 5.0 mg/kg, the minimum dose that induces a loss of righting. Immediately severe bradycardia occurred which was the result of a combination of sinus arrest and atrioventricular block; a significant decrease of blood pressure resulted. A bolus of HP beta CD produced no significant changes in heart rate rhythm. The severe bradycardia produced by propofol in HP beta CD was blocked by both atropine and bilateral cervical vagotomy. Therefore, the effects of propofol in HP beta CD are cholinergic and neurally mediated. These results are consistent with the hypothesis that propofol reduces sympathetic tone prior to reduction in vagal tone, and thereby produces a period of time during which vagal tone is dominant.
Subject(s)
Anesthetics, Intravenous/pharmacology , Cyclodextrins/pharmacology , Heart/drug effects , Propofol/pharmacology , beta-Cyclodextrins , Anesthetics, Intravenous/administration & dosage , Anesthetics, Intravenous/antagonists & inhibitors , Animals , Arrhythmia, Sinus/chemically induced , Atropine/pharmacology , Bradycardia/chemically induced , Cholinergic Agents/pharmacology , Cyclodextrins/administration & dosage , Cyclodextrins/antagonists & inhibitors , Drug Interactions , Fat Emulsions, Intravenous , Heart Arrest/chemically induced , Heart Block/chemically induced , Heart Rate/drug effects , Injections, Intravenous , Male , Pharmaceutical Vehicles , Propofol/administration & dosage , Propofol/antagonists & inhibitors , Rats , Rats, Sprague-Dawley , Vagotomy , Vagus Nerve/drug effectsABSTRACT
The anesthetic potency of racemic isoflurane and the optically pure stereoisomers was examined in rats. The (+) isomer was 53% more potent than the (-) isomer (minimum alveolar concentration (MAC) = 1.06 +/- 0.07% vs. 1.62 +/- 0.02%, P < 0.05). MAC for racemic isoflurane was 1.32 +/- 0.03%. Both stereoisomers and the racemic isoflurane produced similar depression of arterial pressure. However, the (+) isomer blunted the cardiovascular response to a painful stimulus to a greater extent than did an equi-MAC dose of the (-) isomer. These are the first data to describe pharmacological differences between stereoisomers of a volatile anesthetic administered in vivo by the conventional route (inhaled) and measuring the clinically relevant index of anesthesia, MAC. These data are consistent with a receptor-mediated anesthetic mechanism by volatile anesthetics.
