Isolated, blood-perfused phrenic nerve-diaphragm preparation of the dog: description of a new method and effects of neuromuscular blocking agents on twitch tension and blood flow.

An isolated, blood-perfused phrenic nerve-diaphragm preparation of the dog was developed for pharmacological investigation. A hemi-diaphragm with the ipsi-lateral phrenic nerve intact was excised from a dog anesthetized with pentobarbital sodium and was perfused with arterial blood from a donor dog through the phrenic artery. This preparation maintained its tone and response in good condition for 10 hr without any deterioration of twitch tension. Effects of succinylcholine, d-tubocurarine, decamethonium, and gallamine on twitch tension and blood flow of this preparation were studied. Drugs were injected into the phrenic artery. All four compounds produced a dose-dependent depression of twitch tension elicited by indirect stimulation applied to the phrenic nerve without any depression in the tension elicited by direct stimulation applied to the muscle. The ratios of the potency to produce a 50% depression in twitch tension elicited by indirect stimulation among succinylcholine, decamethonium, d-tubocurarine, and gallamine were roughly 1:1/3:1/3:1/30 on a weight (mg) basis. d-Tubocurarine produced a dose-dependent increase in blood flow. Other compounds did not cause significant changes in blood flow. The increase in blood flow produced by d-tubocurarine was markedly inhibited by diphenhydramine, which suggested histamine release by d-tubocurarine.