THE MYONEURAL EFFECTS OF PROPOFOL EMULSION (DIPRIVAN) ON THE NERVE-MUSCLE PREPARATIONS OF RATS

The potential effects of propofol emulsion (Diprivan) on the neuromuscular transmission and muscular contraction were studied using in vitro and in vivo nerve-muscle preparations of rats. The contractions of the isolated rat diaphragm elicited by either indirect or direct electrical stimulation were inhibited by propofol emulsion at threshold concentrations of 42 and 112 μmol l −1 , respectively. Similarly, the gastrocnemius muscle contractions induced by either indirect or direct electrical stimulation in vivo were inhibited by propofol emulsion administration as a bolus injection of 2.5 mg kg −1 intravenously, followed by intravenous infusion of 150 μg kg −1 min −1 for 1 h into rats. The inhibitory effects of propofol in both preparations were greater with indirect rather than direct stimulation. Propofol emulsion was found to be capable of enhancing the paralysis of the indirectly stimulated rat diaphragm in vitro and gastrocnemius muscle in vivo induced by either pipecuronium or succinylcholine. The combination of propofol and pipecuronium led to a synergistic inhibition of the neuromuscular transmission, while the combination of propofol and succinylcholine led to additive inhibition. Pretreatment with propofol emulsion at these threshold concentrations markedly inhibited the stimulant effects of aminophylline and digoxin on the indirectly and directly induced diaphragmatic contractions. Also, the enhancement effects of aminophylline on the indirectly and directly and of digoxin on indirectly induced rat gastrocnemius muscle contractions were markedly inhibited by propofol emulsion administration to rats. Pretreatment with propofol emulsion at the threshold concentrations enhanced the inhibitory effects of verapamil on diaphragmatic contractions elicited either indirectly or directly and enhanced the inhibitory effect of adenosine on the contractions elicited indirectly. Similarly, the inhibitory effects of verapamil on the indirectly and directly and of adenosine on indirectly induced rat gastrocnemius muscle contractions were markedly potentiated by propofol emulsion administration to rats. In addition, doubling the concentration of calcium in the bathing fluid produced no change in the inhibitory effects of propofol emulsion on either indirectly or directly elicited diaphragmatic contractions, while doubling the concentration of external magnesium potentiated the propofol effects. Pretreatment with 4-aminopyridine suppressed the inhibitory effects of propofol emulsion on diaphragmatic contractions elicited either indirectly or directly. These results suggest that propofol acts presynaptically to inhibit the neuromuscular transmission and acts at the muscle membrane to inhibit the muscular contraction.