Characterization of the Train-of-Four Response in Fast and Slow Muscles

Abstract
The in vivo cat soleus and gastrocnemius muscles were used to compare isometric contraction strength and the train-of-four (T4) response (2 Hz for 2 s) of 2 muscle types (fast and slow) during onset of competitive neuromuscular blockade to determine the extent of the correlation between twitch depression and T4 fade. Prior to drug administration the muscles that were studied differed significantly in that the T4 ratio was 1.0 in the gastrocnemius and only 0.87 in the soleus. Three competitive neuromuscular-blocking agents were compared: d-tubocurarine, pancuronium and vecuronium. d-Tubocurarine produced a close correlation between the degrees of twitch strength depression and T4 for both muscles. These muscles demonstrated significantly different ED50 values (105 .mu.g/kg for gastrocnemius, 150 .mu.g/kg for soleus). Pancuronium also produced a similar relationship between twitch strength depression and T4 decrement for each muscle. There was little difference in their ED50 values for twitch depression (11.5 .mu.g/kg for gastrocnemius, 13 .mu.g/kg for soleus). The effects of vecuronium were quite different from the other 2 muscle relaxants. Although vecuronium produced a comparable correlation between twitch tension and T4 fade in fast muscle, no such relationships existed in slow muscle. Even when the twitch strength was blocked to 18% of control, the soleus T4 response was depressed to only 75% of control. These results highlight major differences among competitive neuromuscular-blocking agents and suggest multiple sites of action.