Effects of veratridine on mechanical responses of human malignant hyperthermic muscle fibers.
BACKGROUND
To determine if alteration in the function of the sodium channel may in turn modify halothane-induced changes in mechanical responses of muscle bundles from patients susceptible to malignant hyperthermia (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 10 microM veratridine, an inhibitor of sodium channel inactivation. Peak tension (PT), time to peak tension (TPT), positive peak of isometric tension derivative (+dP/dtmax) were used to characterize the inotropic state. Analysis of relaxation process was performed using half relaxation time (RT 1/2) and the negative peak of isometric tension derivative (-dP/dtmax). The ratio (R) = (+dP/dtmax)/(-dP/dtmax) was used to measure the coupling between contraction and relaxation under isometric condition.


RESULTS
Veratridine significantly enhanced the 0.5, 1, 2 and 3 vol% halothane-induced contracture and induced a negative inotropic effect in MH-susceptible muscle bundles. R increased by nearly 90% indicating that the combined effects were more pronounced in the relaxation phase. In MH non-susceptible muscle, veratridine did not significantly enhance the effects of halothane.


CONCLUSIONS
These results on cut MH-susceptible human muscle bundles support the hypothesis that halothane-induced contracture in MH can be modified by the binding of an inhibitor of sodium channel inactivation.
Adnet
P J
PJ
Service d'Accueil et d'Urgences, Centre Hospitalier et Universitaire de Lille, France.
Etchrivi
T S
TS
Halle
I
I
Haudecoeur
G
G
Reyford
H G
HG
Krivosic-Horber
R M
RM
D002118:Calcium / Q000378:metabolism; D006221:Halothane / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008305:Malignant Hyperthermia / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects*; D015222:Sodium Channels / Q000187:drug effects*; D014701:Veratridine / Q000494:pharmacology*
D015222:Sodium Channels; D014701:Veratridine; D002118:Calcium; D006221:Halothane