title: Porcine malignant hyperthermia--failure of dantrolene dose response to diagnose susceptibility (halothane effect).
abstract: Dantrolene, a skeletal muscle relaxant, has been proven prophylactic and therapeutic for malignant hyperthermia (MH) in swine. This study examined the feasibility of using a dantrolene dose response as measured by indirectly evoked foretoe twitch depression as a means to safely discriminate MH susceptibility in swine. The effect of halothane on the dantrolene response was quantified. Subjects were five Poland China malignant hyperthermia susceptible (MHS) and five Hampshire malignant hyperthermia resistant (MHR) swine. Dantrolene dose response was determined twice in each anaesthetized subject, once with thiopentone and subsequently with thiopentone and halothane. Dantrolene in incremental doses, 0.15 mg.kg-1, was given to a cumulative dose of 2--3 mg.kg-1. Under thiopentone anaesthesia, the dantrolene dose responses were similar in MHS and MHR animals. The presence of halothane augmented dantrolene twitch depression in MHS but not MHR animals when compared to their response under thiopentone. Under halothane, the MHS animals had significantly augmented dantrolene response compared to MHR pigs, but three MHS animals had developed the MH syndrome prior to receiving dantrolene. We conclude that dantrolene muscle relaxant dose response cannot be used as a diagnostic test for MHS in swine. Halothane augments dantrolene twitch depression in MHS swine.
mesh_terms: D000818:Animals; D003620:Dantrolene / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006221:Halothane / Q000008:administration & dosage; D008297:Male; D008305:Malignant Hyperthermia / Q000175:diagnosis*; D013552:Swine; D013874:Thiopental / Q000008:administration & dosage
chemical_list: D003620:Dantrolene; D013874:Thiopental; D006221:Halothane