THE EFFECT OF DRUGS UPON NEUROMUSCULAR TRANSMISSION IN THE ISOLATED GUINEA PIG DIAPHRAGM

¹ Department of Pharmacology, University of California School of Medicine, 405 Hilgard, Los Angeles 24, California

The properties of the guinea pig phrenic nerve diaphragm preparation are described and its reactions to various neuromuscular blocking agents are reported in detail. These reactions are essentially the same as those shown by the rabbit lumbrical nerve muscle preparation in vitro. Tubocurarine produces a progressive neuromuscular block which reaches a steady state in 20-40 minutes without any action on the response to direct stimulation. Decamethonium produces two phases of action of which the first resembles the depolarization block observed in vivo and the second resembles in many respects the block produced by tubocurarine.

The main difference noted between this preparation and the rabbit lumbrical preparation was the presence of a contracture in response to C10 and related drugs. This contracture may be related to the age of the guinea pigs used.

Decamethonium, succinylcholine, acetylcholine, carbachol and tetramethyl-ammonium all produce the typical biphasic action and their relative activities are in this order.

The effect of a second dose of decamethonium superimposed upon a previous dose depends upon the interval between the two doses. The phase I effect is always less than if the two doses were given together. The ultimate phase II block which is achieved is independent of the number of doses and intervals between them and depends upon the total dose given.

The necessary recovery time after washing out the drug is highly dependent upon the duration of exposure to the first dose, and on the temperature. At 40°C., after 30 minutes exposure to C10, three hours recovery is necessary before a similar response will occur.

Precise reproduction of the original effect has not been obtained with any recovery period. Successive doses separated by adequate recovery periods produce increasing phase I effects, a smaller and earlier maximum recovery between phase I and phase II, and a more rapid phase II block.

Diaphragms taken from animals weighing over 250 grams often show a neuromuscular block which appears to be due to anoxia. The necessity of using diaphragms thin enough to allow sufficient oxygen to diffuse into them is emphasized.