Malignant hyperthermia: Fatigue characteristics of skeletal muscle

Abstract

Although the defects in cellular Ca2+ homeostasis associated with malignant hyperthermia (MH) have been extensively studied, the functional consequences of the MH mutation are not clear. We used continuous and intermittent high‐frequency stimulation to determine whether this mutation might alter the fatigue resistance of muscle from MH susceptible (MHS) pigs. Force decline with 10 s continuous stimulation (150 Hz) was significantly less in MHS muscle (58.4 ± 1.0%) than in normal muscle (50.5 ± 3.0%). With intermittent stimulation, there was no significant difference in tension decline between muscle types. Post‐stimulation twitch and tetanus responses were similar in MHS and normal muscles except: 1) twitch potentiation was significantly greater in normal muscle after continuous stimulation, and 2) recovery of tetanic tension was slowed in MHS muscle. Although the MH defect does not cause major functional abnormalities, subtle differences in MHS muscle response to fatiguing stimulation are apparent. Therefore, it is unlikely the work capacity of MH patients would be limited by any MH associated defect within the muscle. © 2000 John Wiley & Sons, Inc. Muscle Nerve 23: 223–230, 2000.

Survey of Long-Term Sequelae in Survivors of a Malignant Hyperthermia Reaction

“…Durham et al proposed a feed-forward mechanism by which a lower temperature threshold activates the ryanodine receptor type 1 (RyR1) gene in MHS muscle, causing heat stroke, myopathy, and mitochondrial damage [2]. Research by Balog et al suggests that recovery of MH-susceptible muscle of pigs from tetanic stimulation was significantly slowed as compared to normal muscle tissue [3]. Giulivi et al demonstrated that increased production of reactive oxygen species, and a decrease in mitochondrial proteins in the presence of RyR1 mutations promote dysregulation of signaling pathways in mice [4].…”