EFFECTS OF VERATRIDINE ON MECHANICAL RESPONSES OF HUMAN-MALIGNANT HYPERTHERMIC MUSCLE-FIBERS

Background: To determine if alteration in the function of the sodium c hannel may in turn modify halothane-induced changes in mechanical resp onses of muscle bundles from patients susceptible to malignant hyperth ermia (MH). Methods: Mechanical responses of muscle bundles from 12 MH -susceptible and 20 MH non-susceptible patients were measured prior to and during administration of halothane alone and in the presence of 1 0 mu M veratridine, an inhibitor of sodium channel inactivation. Peak tension (PT), time to peak tension (TPT), positive peak of isometric t ension derivative (+dP/dtmax) were used to characterize the inotropic state. Analysis of relaxation process was performed using half relaxat ion time (RT1/2) and the negative peak of isometric tension derivative (-dP/dtmax). The ratio (R)=(+dP/dtmax)/(-dP/dtmax) was used to measur e the coupling between contraction and relaxation under isometric cond ition. Results: Veratridine significantly enhanced the 0.5, 1, 2 and 3 vol% halothane-induced contracture and induced a negative inotropic e ffect in Mil-susceptible muscle bundles. R increased by nearly 90% ind icating that the combined effects were more pronounced in the relaxati on phase. In MH non-susceptible muscle, veratridine did not significan tly enhance the effects of halothane. Conclusions: These results on cu t MH-susceptible human muscle bundles support the hypothesis that halo thane-induced contracture in MH can be modified by the binding of an i nhibitor of sodium channel inactivation.