Malignant hyperthermia: a runaway heat production futile cycle via the sodium channel (893.2)

Abstract

MHis a runaway heat production futile cycle mediated via the sodium channel at the myoneural receptor site. Non depolarizing muscle relaxants do not trigger MH episodes. Depolarizing muscle relaxants, i.e. succinylcholine, are potent triggers of MH. Acetycholine, a natural depolarizer, is capable of triggering MH during transport stress, fighting activity, breeding activity and other stressors. Halothane apparently destabilizes the myoneural sodium channel which results in a rapid induction of MH. The heat released by this activity drives the further release of heat accelerating MH.The MHS pig has an increased action potential amplitude at the myoneural junction that lasts longer than normal. This is thought to induce hypertrophy of muscle mass, increased metabolic rate, and other effects. The increased metabolic activity in muscle causes the post mortem release of heat in muscle, accumulation of low acidity, which denatures the muscle proteins, resulting in pale, soft, exudative, pork.Inhalation anesthetics trigger MH by degree. Sevoflurane is a very weak trigger of MH and requires several hours of exposure to initiate an episode of MH. The transition from Halothane to Sevo lead to a 11 fold decrease in the incidence of MH in the Greater Kansas City Area from 1:50,000 to 1:550,000.Organon 9426, is a nondepolarizing muscle relaxant that prevents MH when MHS pigs are challenged with halothane or succinylcholine.