Awake Triggering: Exercise and Heat Stroke

Porcine environmental stress such as exercise, heat stress, anoxia, apprehension, and excitement triggers MH (see "History").^{[46] [72]} These responses are related to muscle movement or to increased temperature. Susceptible swine in vitro or in vivo react to carbachol or heat (41°C to 42°C) with abnormally increased oxygen consumption and lactate production, but not to α-sympathetic or β-sympathetic agonists, or both. ^[72] Abnormal responses can be blocked or delayed by nondepolarizing relaxants.^{[15] [46] [56] [97]} However, mechanisms in porcine awake MH may not relate to human awake MH.

Epidemiologic studies reveal that exercise-induced symptoms occur more frequently in MHS patients,^[106] including exercise-induced rhabdomyolysis.^{[107] [108]} A novel mutation with an Arg401Cys substitution in the amino terminus occurred in three cases of exercise-induced rhabdomyolysis.^[108] There was a stress-induced hyperthermic death of a 12-year-old boy. He had an MH episode during sevoflurane anesthesia and was treated successfully with dantrolene. ^[109] Eight months later, after a football game in the setting of an ambient temperature of 80°F (26.7°C), he complained of weakness, tingling in his extremities, and muscle stiffness. He was hot, diaphoretic, and hyperventilating. Seizures and respiratory arrest occurred; jaw rigidity prevented endotracheal intubation. Ventricular fibrillation occurred, and cardiopulmonary resuscitation was begun. In the hospital, his rectal temperature was 108°F (42.2°C), pH was 6.76, and potassium level was 8.8 mEq/L. Despite dantrolene, resuscitation was unsuccessful. Autopsy revealed normal cardiac anatomy and no explanatory pathology. Analysis of DNA in the boy (postmortem) and his father revealed an altered RYR1 gene sequence of C487T, with a substitution of arginine for cysteine 163. Other reports relate heat stroke, sudden and unexpected death, unusual stress and fatigue, or myalgias to possible awake MH episodes.^{[110] [111] [112] [113]} Stresses include exercise and environmental exposure to volatile vapors. Despite these rare exceptions, susceptible

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