Multiple-pulse stimulation and dantrolene in malignant hyperthermia

A potentially fatal condition, yet preventable, malignant hyperthermia (MH) lacks a satisfactory noninvasive diagnostic test. Studying the effects of intravenous dantrolene (3 mg/kg) on electrically stimulated skeletal muscle, we found that this approach does not conclusively distinguish between normal humans and those susceptible to malignant hyperthermia but nonetheless yielded important information about the action of dantrolene in man and in MH. Supramaximal single- and multiple-pulse stimulation of the common peroneal nerve produced stable torque responses of the dorsiflexor muscles (monitored in vivo), which dantrolene suppressed. With the multiple-pulse stimulation (5-6 pulses) this torque suppression was significantly less in MH-susceptible subjects than in control subjects. This distinction, also observed in MH swine, confirms this animal as a good model for human MH. That dantrolene's effect in MH can be more completely reversed with high frequency stimulation is intriguing; presumably, excitation-contraction coupling differs in MH and normal muscle.