Influence of Respiratory and Metabolic Acid-Base Changes on the Effect of Nondepolarizing Muscle Relaxants in the Rat Phrenic-hemidiaphragm / 대한마취과학회지

The effects and interactions of metabolic and respiratory acid-base changes on electrically-evoked twitch response, train-of-four and tetanic stimulation with pipecuronium (Pip), vecuronium (Vec) and atracurium (Tra) were studied in the isolated rat hemi-diaphragm preparation. pip (3X10(-7) - 4X10(-6) M), Vec (3X10(-6) - 15X10(-6) M) and Tra (10(-6) - 3X10(-5) M) decreased the electrically-evoked (phrenic nerve stimulation, 0.1 Hz, 0.2 ms, 10 V) twitch response in a dose related fashion and Pip was more potent than Vec and Tra. In the alkali state (pH 7.6 or high HCO3 ), the decrements of twitch response, train-of-four and tetanus ratio induced by Pip (1.5uM) were potentiated, but the effects of Vec or Tra were markedly intensified by acid midium (pH 7.2 or low HCO3 ). And also, decreasing pH by increasing PCO2 or by decreasing HCO3 intensified the effects of Vec and Tra, whereas it reversed by Pip. Conversely, increasing pH by decreasing PCO2 or by increasing HCO3 antagonized the effects of Vec and Tra, whereas it potentiated the Pip effect. On the basis of these finding, the result of the present study suggest that neither PCO2 nor HCO3 has a specific action, but that changes in pH may be responsible for the results. In addition, the differences of the above results by each drugs may not be due to the number of quaternary ammonium of the agents. And also, indicate that the effective site of the influence of the acid-base change upon the neuromuscular blocking effects might be prejunctional nerve terminal.

Effect of Diltiazem and Verapamil on Pipecuronium-and Atracurium-induced Neuromuscular Blockade / 대한마취과학회지

The effects and interactions of pipecuronium and atracurium with diltiazem and verapalmil on the electrically-evoked twitch response, train-of-four and tetanic stimulation were studied in the isolated rat phrenic-hemidiaphragm preparation. Pipecuronium (3X10(-7) -4X10(-6)) and atracurium (10(-6) -3X10(-5) M) decreased the electrically-evoked twitch response, train-of-four and tetanus ratio in a dose-related fashion and the pipecuronium was more potent than atracurium. The inhibitory effects of pipecuronium and atracurium were potentiated by pretreatment of 5 uM diltiazem and verapamil, Ca++-channel blokers, in which the concentration of diltiazem or verapamil has no obvious effect on the twitch response itself. Futhermore, it is noteworthy that the inhibitory effects of pipecuronium and atraeurium were markedly potentiated by 150 uM hemicholinium pretreatment. On the basis of these findings, the results of present study suggests that the muscle relaxation by pipecuronium and atracurium is mediated by pre- and post-junctional receptor blockade, and that diltiazem or verapamil intensifies neuromuscular blockade produced by these musele relaxants. The potentiating effect of diltiazem or verapamil may be due to blocking influx of calcium and/or release of acetylcholine from presynaptic nerve terminals.