The effect of a cyclodextrin vehicle on the cardiovascular profile of propofol in rats.
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.
Bielen
S J
SJ
Department of Biological Research, Ohmeda Pharmaceutical Products Division, Inc., Murray Hill, New Jersey, USA.
Lysko
G S
GS
Gough
W B
WB
D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001146:Arrhythmia, Sinus / Q000139:chemically induced; D001285:Atropine / Q000494:pharmacology; D001919:Bradycardia / Q000139:chemically induced; D018678:Cholinergic Agents / Q000494:pharmacology; D003505:Cyclodextrins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D005217:Fat Emulsions, Intravenous; D006321:Heart / Q000187:drug effects*; D006323:Heart Arrest / Q000139:chemically induced; D006327:Heart Block / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D014677:Pharmaceutical Vehicles; D015742:Propofol / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects; D047392:beta-Cyclodextrins
D018686:Anesthetics, Intravenous; D018678:Cholinergic Agents; D003505:Cyclodextrins; D005217:Fat Emulsions, Intravenous; D014677:Pharmaceutical Vehicles; D047392:beta-Cyclodextrins; C083507:propofol hydroxypropyl-beta-cyclodextrin; D001285:Atropine; D015742:Propofol