THE REDUCTION OF SKELETAL-MUSCLE LESIONS AFTER EXPERIMENTAL STRESS INSTRESS-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 t o abnormally increased myoplasmic Ca2+ levels. Dantrolene is used for the treatment of MH and acts by reducing the myoplasmic Ca2+ levels. M uscle lesions can be induced by experimental restraint stress in SS pi gs and are suspected to be caused by increased myoplasmic Ca2+ levels. This experiment was performed in order to study if stress induced mus cle 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 s ingle i.v. infusion of dantrolene (5 mg/kg), 30 min before stress (gro up 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 gro up A (0.03 mg/kg/min) indicating decreased sensitivity to succinylchol ine 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 creat ine kinase (CK) and aspartate aminotransferase (ASAT) at time of necro psy. A significant reduction in acute muscle lesions was observed in b oth groups, especially in group B, when compared with SS pigs subjecte d to restraint stress, but not treated with dantrolene. The muscle les ions induced by the stress model are considered to be induced by incre ased myoplasmic Ca2+ levels since they can be reduced by dantrolene tr eatment.