An in-vitro model of malignant hyperthermia: differential effects of inhalation anesthetics on caffeine-induced muscle contractures.
Clinical concentrations of anesthetics augment caffeine-induced contracture of frog sartorius muscle; however, anesthetics differ in this characteristic. The potentiation was quantitated using six paired sartorius muscles for each specified concentration of anesthetic and controls. At a concentration of 1 MAC, the greatest potentiation occurred with 2 mM caffeine for all anesthetics studied. Under these conditions the order of magnitude of augmentations was: chloroform (15 times); halothane (11 times); methoxyflurane (10 times); cyclopropane (5 times); enflurane (4 times); isoflurane (3 times); diethyl ether (2 times); Baxter 3224 (2 times); fluroxene (1.4 times); nitrous oxide (1.3 times). Halothane at .5 MAC augments the 2 mM caffeine-induced contracture almost seven times, and at 2 MAC almost 13 times, whereas 2 MAC isoflurane potentiates the caffeine-induced contracture only four times and 4 MAC diethyl ether only two and a half times. It is postulated that those anesthetics that most potentiate caffeine-induced contracture may be the most potent triggering agents of malignant hyperthermia.
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001001:Anura; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004357:Drug Synergism; D066298:In Vitro Techniques; D008305:Malignant Hyperthermia / Q000209:etiology; D008931:Mitochondria, Muscle / Q000378:metabolism; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects*; D011894:Rana pipiens; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D000777:Anesthetics; D002110:Caffeine; D002118:Calcium