Myoplasmic free [Ca2+] during a malignant hyperthermia episode in swine.
Malignant hyperthermia (MH) is a genetic syndrome usually initiated by exposure to volatile anesthetic agents or depolarizing neuromuscular blocking agents. We have used Ca2+-selective microelectrodes to measure in vivo the intracellular ionized calcium ([Ca2+]i) in skeletal muscle fibers of MH-susceptible swines before and during hyperthermic episodes and also after dantrolene administration. The animals were anesthetized with thiopental and fentanyl and maintained with a mixture of nitrous oxide (66%) and oxygen (34%). The malignant hyperthermic episode was triggered by exposure to halothane. Determinations of [Ca2+]i during the episode show an increase from 0.44 +/- 0.01 microM +/- SEM, n = 20) to 8.44 +/- 0.68 microM (mean +/- SEM, n = 10). Administration of dantrolene (2 mg/kg) during the hyperthermic episode reduces [Ca2+]i to 0.17 + 0.01 microM (mean +/- SEM, n = 10) and reverses the clinical symptoms. These results show that the MH episode is associated with an increase in the myoplasmic free Ca2+ concentration and that the therapeutic effect of dantrolene is related to a decrease in [Ca2+]i.
López
J R
JR
Centro de Biofisica y Bioquimica, Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela.
Allen
P D
PD
Alamo
L
L
Jones
D
D
Sreter
F A
FA
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003620:Dantrolene / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D008305:Malignant Hyperthermia / Q000378:metabolism* / Q000503:physiopathology; D008564:Membrane Potentials / Q000187:drug effects; D009132:Muscles / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D009994:Osmolar Concentration; D013552:Swine
D003620:Dantrolene; D002118:Calcium; D006221:Halothane