Propofol potentiates both pre- and postsynaptic effects of vecuronium in the rat hemidiaphragm.
We have measured twitch tension in response to train-of-four stimulation in rat isolated phrenic nerve-hemidiaphragm preparations. Propofol inhibited nerve evoked twitch tension, with 50% inhibition occurring at 420 (SD 29) mumol litre-1. Although propofol 100 mumol litre-1 by itself had no effect on nerve evoked twitch tension, it potentiated the neuromuscular blocking effects of vecuronium. The decrease in train-of-four ratio with vecuronium was directly proportional to the degree of twitch inhibition, regardless of whether twitch was depressed by vecuronium alone or in combination with propofol. The finding that the train-of-four ratio was a function of the degree of block, rather than simply a function of vecuronium concentration, indicates that propofol also contributed to train-of-four fade and potentiated both pre- and postsynaptic effects of the neuromuscular blocker. The concentrations of propofol used in this study are much greater than human therapeutic blood concentrations, which are typically 25-35 mumol litre-1 (4-6 micrograms ml-1) immediately after a bolus dose of 2 mg kg-1, suggesting that neither muscle weakness nor potentiation of vecuronium-induced neuromuscular block should be of concern at propofol concentrations occurring clinically.
Lebeda
M D
MD
V.A. Medical Center, Iowa City, IA 52246.
Wegrzynowicz
E S
ES
Wachtel
R E
RE
D000818:Animals; D003964:Diaphragm / Q000294:innervation; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009469:Neuromuscular Junction / Q000502:physiology*; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D014673:Vecuronium Bromide / Q000494:pharmacology
D014673:Vecuronium Bromide; D015742:Propofol