Verapamil is not a therapeutic adjunct to dantrolene in porcine malignant hyperthermia.
We have investigated the hypothesis that the calcium antagonist verapamil might be useful for prevention or treatment of malignant hyperthermia (MH) in MH-susceptible (MHS) swine. MH episodes were triggered in four groups of four swine with halothane alone or combined with succinylcholine (SCh) and, with and without verapamil. MH episodes were reversed by therapy with dantrolene and NaHCO3 in all groups. Verapamil did not alter MH episodes triggered by halothane alone or combined with SCh. The dantrolene-NaHCO3 requirements for reversal of MH were greater for the groups receiving halothane-SCh, but did not differ in groups pretreated with and without verapamil. In vitro verapamil (25 microM) did not reduce responses of intact muscle fibers to halothane and, in fact, exaggerated some halothane-induced responses. High concentrations of verapamil (0.5 mM) caused contractures in MHS but not in normal muscles. Neither our in vivo nor in vitro results support the use of verapamil in the treatment of MH. Further, doses of dantrolene used to reverse these MH episodes, although admittedly small (1-2 mg/kg), did not produce myocardial depression when used in combination with verapamil.
D000769:Anesthesia, Inhalation; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D003620:Dantrolene / Q000627:therapeutic use*; D004357:Drug Synergism; D006221:Halothane / Q000009:adverse effects; D006339:Heart Rate / Q000187:drug effects; D007263:Infusions, Parenteral; D008305:Malignant Hyperthermia / Q000139:chemically induced; D009119:Muscle Contraction / Q000187:drug effects; D013390:Succinylcholine / Q000009:adverse effects; D013552:Swine; D014700:Verapamil / Q000627:therapeutic use*
D014700:Verapamil; D003620:Dantrolene; D013390:Succinylcholine; D006221:Halothane