Antagonism of Polymyxin B-induced Neuromuscular and Cardiovascular Depression by 4-Aminopyridine in the Anesthetized Cat

Abstract

In an attempt to find a better antidote to polymyxin B-induced neuromuscular blockade, 4-aminopyridine, 0.4-1 mg/kg was tested in 10 anesthetized cats. The sciatic-tibialis anterior nerve-muscle preparation was used. The neuromuscular blockade was successfully reversed in all cats. Rapidity of reversal depended on the dose of 4-aminopyridine administered. At 0.6-1mg/kg reversal of the twitch response from 20% of control to 80% of control required 2.4 (SE [standard error] 0.5) min; to 100%, 14.4 (SE, 3.7) min. An overshoot of the recovery of neuromuscular blockade of 6-10 h duration followed the reversal. The mechanical twitch response reached a peak of approximately 140% of control at 2 h. At a lower dosage, 0.4 mg/kg, 2 of 3 cats took more than an hour for complete recovery of the twitch response, and the overshoot was approximately 10% of control. The hypotensive effect of polymyxin B was partially reversed, but the bradycardia was not. 4-aminopyridine is an effective antidote to polymyxin B-induced neuromuscular blockade in the cat.