The effect of rate of stimulation on force of contraction in a partially paralyzed rat phrenic nerve hemidiaphragm preparation.

This study was performed to determine whether presynaptic receptor blockade could be differentiated from postsynaptic blockade by examining the effect of increasing rates of indirect stimulation on twitch height depression (THD) on partially paralyzed in vitro rat diaphragm preparations. We calculated the T200/T1 ratio (force of the 200th stimuli divided by the force of the first stimuli) at rates of 0.2 Hz, 0.5 Hz, 1 Hz, and 2 Hz using a drug concentration which provided approximately 20% THD during stimulation at 0.1 Hz. Markedly different T200/T1 ratios were demonstrated when hexamethonium, a drug with predominantly presynaptic effects, was compared with alpha bungarotoxin, a drug with predominantly postsynaptic effects. These results were then compared with those from vecuronium, rocuronium, mivacurium, and tubocurarine. Both hexamethonium and rocuronium caused a marked decrease in T200/T1 ratio at higher rates of stimulation; alpha bungarotoxin caused a slight increase in T200/T1 ratio at higher rates of stimulation. The T200/T1 ratios produced by vecuronium, mivacurium, and tubocurarine lay intermediate between hexamethonium and alpha bungarotoxin. Significant differences in T200/T1 ratios were found when alpha bungarotoxin was compared with all other drugs at 2 Hz. Hexamethonium and rocuronium produced significant differences in T200/T1 ratio from those of all the other drugs at 1 Hz and 2 Hz. There were significant differences in the T200/T1 ratio found after hexamethonium and rocuronium compared to alpha bungarotoxin at 0.5 Hz. No significant differences at any rate of stimulation were found between hexamethonium and rocuronium. No difference was observed in the effect of vecuronium, mivacurium, and tubocurarine. We conclude that, if the observed effect is the result of hexamethonium acting predominantly at presynaptic sites and alpha bungarotoxin acting predominantly at postsynaptic sites, the relative contribution of small doses of nondepolarizing drugs at each site can be differentiated by determining the T200/T1 ratio at rates of 1 Hz or 2 Hz. Our results are consistent with the suggestion that small doses of rocuronium have marked presynaptic activity, but that vecuronium, mivacurium, and tubocurarine have both pre- and postsynaptic effects.