Abstract

The primary aim of this study was to develop a method for the rapid, reproducible estimation of the relative effects of neuromuscular blocking agents on neuromuscular transmission of intrafusal fibers in muscle spindles as compared to their effects on extrafusal muscle fibers. To this end, the stretch reflex in decerebrate cats was studied; a decerebrate preparation was chosen because of the presence of tonic innervation of the intrafusal fibers of muscle spindles.

Eighty cats were decerebrated by midcollicular cauterization via stereotaxically placed electrodes. Thirty-five animals survived for periods longer than 24 hours. Twenty-four to 48 hours after decerebration the reflex contractions of gastrocnemius and soleus muscles to stretch were obtained. Concomitantly, the contractions of the contralateral muscles induced by tetanic sciatic nerve stimulation were recorded.

The total tension developed upon stretching was characterized by initial peak contraction (phasic) with a decrement to a lower sustained tension (tonic). The degree of passive tension developed to stretch, exclusive of reflex activity, was taken as that amount of muscle tension which was obtained after section of the sciatic nerve or after succinylcholine-induced neuromuscular blockade.

The muscles were subjected to 10-second, step-function stretches every 30 seconds; the magnitude of the extension ranged from 3.5 to 13.5 mm; the velocity ranged from 3.3 to 135 mm/second; the initial base-line tensions ranged from 30 to 100 g. The magnitude of the phasic and tonic reflexes increased linearly with increases in magnitude of stretch or initial tension. The phasic reflex response increased with velocity up to approximately 20 mm/second. The tonic tension was not appreciably altered by changes in velocity.

Cumulative dose-effect relationships for depression of the above responses were established for tubocurarine, decamethonium and four polymethylene bis-isoquinolinium derivatives. Tubocurarine produced depression of the sustained tetanic nerve-muscle response followed, in order of inhibition, by the initial tetanic response, the tonic reflex, the twitch, and finally, the phasic reflex. The sustained tetanic response was eight to nine times more sensitive than the phasic reflex or twitch response.

The patterns of effects of the four bis-isoquinolinium derivatives were similar to those of tubocurarine. In contrast, given doses of decamethonium produced almost equal inhibition of all the responses assessed.

It is concluded that the results obtained are consistent with the postulate that these agents act primarily at the neuromuscular junctions of extrafusal muscle fibers and that any depression of the fusimotor nerve-muscle transmission takes place with doses equal to or larger than those required to block extrafusal junctions.