THE EFFECT OF A CYCLODEXTRIN VEHICLE ON THE CARDIOVASCULAR PROFILE OFPROPOFOL IN RATS

We studied an aqueous solution of propofol dissolved in hydroxypropyl- beta-cyclodextrin (HP beta CD) 20% to determine whether the cardiovasc ular profile differed from that measured for propofol prepared in Intr alipid(R) 10% (Diprivan(R)). Conscious male rats were given an intrave nous bolus of propofol, 5.0 mg/kg, the minimum dose that induces a los s of righting. Immediately severe bradycardia occurred which was the r esult of a combination of sinus arrest and atrioventricular block; a s ignificant decrease of blood pressure resulted. A bolus of HP beta CD produced no significant changes in heart rate or rhythm. The severe br adycardia produced by propofol in HP beta CD was blocked by both atrop ine and bilateral cervical vagotomy. Therefore, the effects of propofo l in HP beta CD are cholinergic and neurally mediated. These results a re consistent with the hypothesis that propofol reduces sympathetic to ne prior to reducing vagal tone, and thereby produces a period of time during which vagal tone is dominant.