Novel Interventions for Heat/Exercise Induced Sudden Death and Fatigue.

摘要

This study was designed to identify human mutation that caused Exertional and/or environmental heat stroke (EHS) and exertional rhabdomyolysis (ER) and to develop new interventions to prevent EHS and ER. We identified RyR1 mutations as a major cause of exertional rhabdomyolysis. 82% of the individuals that were enrolled in the study that had a family history of MH were positive for disease-associated mutations in the RYR1 gene, while 10.5% of index cases enrolled for a history of unexplained or recurrent ER were positive for disease-associated mutations in the RYR1 gene. All of these cases were CHCT positive. Although AICAR was not effective in preventing isoflurane or heat induced episodes in hyper-metabolic response in pigs homozygous for an RyR1 mutation, AICAR was effective in preventing heat-induced hyper-metabolic responses in the heterozygous mouse model of malignant hyperthermia.