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 blo ckade could be differentiated from postsynaptic blockade by examining the effect of increasing rates of indirect stimulation on twitch heigh t depression (THD) on partially paralyzed in vitro rat diaphragm prepa rations. We calculated the T200/T1 ratio (force of the 200th stimuli d ivided 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 rati os were demonstrated when hexamethonium, a drug with predominantly pre synaptic effects, was compared with ct bungarotoxin, a drug with predo minantly postsynaptic effects. These results were then compared with t hose from vecuronium, rocuronium, mivacurium, and tubocurarine. Both h examethonium and rocuronium caused a marked decrease in T200/T1 ratio at higher rates of stimulation; cr bungarotoxin caused a slight increa se 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 were found when a bungarotoxin was co mpared with all other drugs at 2 Hz. Hexamethonium and rocuronium prod uced significant differences in T200/T1 ratio from those of all the ot her drugs at 1 Hz and 2 Hz. There were significant differences in the T200/T1 ratio found after hexamethonium and rocuronium compared to alp ha bungarotoxin at 0.5 Hz. No significant differences at any rate of s timulation were found between hexamethonium and rocuronium. No differe nce was observed in the effect of vecuronium, mivacurium, and tubocura rine. We conclude that, if the observed effect is the result of hexame thonium acting predominantly at presynaptic sites and ct bungarotoxin acting predominantly at postsynaptic sites, the relative contribution of small doses of notdepolarizing drugs at each site can be differenti ated by determining the T200/T1 ratio at rates of 1 Hz or 2 Hz. Our re sults are consistent with the suggestion that small doses of recuroniu m have marked presynaptic activity, but that vecuronium, mivacurium, a nd tubocurarine have both pre- and postsynaptic effects.