The reduction of skeletal muscle lesions after experimental stress in stress-susceptible pigs protected with dantrolene

Malignant hyperthermia (MH) is a naturally occurring disease of stress-susceptible (SS) pigs subjected to triggering agents or stress. MH is characterized by accelerated muscle metabolism and hyperthermia due to abnormally increased myoplasmic Ca2+ levels. Dantrolene is used for the treatment of MH and acts by reducing the myoplasmic Ca2+ levels. Muscle lesions can be induced by experimental restraint stress in SS pigs and are suspected to be caused by increased myoplasmic Ca2+ levels. This experiment was performed in order to study if stress induced muscle lesions could be reduced by dantrolene. Nine SS pigs were exposed to experimental restraint stress provoked by a 12 min intravenous (i.v.) infusion of the depolarizing myorelaxant succinylcholine. Five pigs were orally dosed with dantrolene (5 mg/kg), twice, about 24 and 5 h before the stress (group A). The other four pigs were treated with a single i.v. infusion of dantrolene (5 mg/kg), 30 min before stress (group B). The animals were necropsied approximately 48 h after the stress and 24 skeletal muscles were examined macro- and microscopically. No clinical signs of MH occurred during the experiment. The required dose of succinylcholine was higher in group B (0.08 mg/kg/min) than in group A (0.03 mg/kg/min) indicating decreased sensitivity to succinylcholine in SS pigs after i.v. treatment with dantrolene. The pigs in group A, but not in group B showed slightly increased serum levels of creatine kinase (CK) and aspartate aminotransferase (ASAT) at time of necropsy. A significant reduction in acute muscle lesions was observed in both groups, especially in group B, when compared with SS pigs subjected to restraint stress, but not treated with dantrolene. The muscle lesions induced by the stress model are considered to be induced by increased myoplasmic Ca2+ levels since they can be reduced by dantrolene treatment.