Role of Sympathetic Activity in Porcine Malignant Hyperthermia

Abstract

Malignant hyperthermia (MH) is characterized in part by sympathetic hyperactivity associated with increased levels of circulating catecholamines. Total spinal anesthesia with resulting sympathetic denervation was used in genetically susceptible Poland China swine to investigate whether the sympathetic nervous system is in some way abnormal and primarily contributing to MH, or whether the sympathetic response is secondary to the stress of MH originating from skeletal muscle. Isobaric tetracaine, 1.2-2.2 mg/kg was injected via the sacral hiatus into the CSF to produce total spinal anesthesia (paralysis of all 4 limbs). Total spinal anesthesia failed to prevent the occurrence or attenuate the course of MH in swine given halothane, 1% (5 pigs) or halothane and succinylcholine, 3 mg/kg (1 pig). Total spinal anesthesia did prevent the expected increases in norepinephrine and epinephrine during MH in all 6 swine. Since dantrolene is specifically therapeutic in MH, its effect on the sympathetic response to stress was measured in 2 other susceptible swine. Treatment with dantrolene, 10 mg/kg, i.v., did not prevent increases in catecholamines due to stress caused by either respiratory and metabolic acidosis (PaCO2, 110 torr. base excess-20) combined or hemorrhagic hypotension (mean pressure 40 torr). The sympathetic nervous system was involved in porcine MH only as a secondary response to stress; the conduction anesthesia did not protect pigs from MH and the efficacy of dantrolene in porcine MH was due to its effects on skeletal muscle rather than to depression of the sympathetic nervous system.