Mediators of burn-induced neuromuscular changes in mice

1. Muscle paresis and aberrant pharmacological responses are two important pathophysiological changes that have been observed at the neuromuscular junction following thermal injury. By use of the mouse model of 20%, 30% and 50% total body surface area (BSA) burn, we examined the significance of intracellular mediators, adenosine 3':5'-cyclic monophosphate (cyclic AMP) and prostaglandin E2 (PGE2) in perturbing the physiological function of tension development and the pharmacological response to (+)-tubocurarine (+)-Tc at day 21 post-burn. 2. Cyclic AMP levels increased with the size of burn. The relationship between mean cyclic AMP levels and burn size was significant (R2 = 0.96, r = 0.98). Significant (P less than 0.05) reductions in tension development (g) were observed for the 30% and 50% BSA burn group compared to controls (30.3 +/- 8.3 and 34.1 +/- 5.9 vs 59.1 +/- 1.0, respectively). Tension alterations were associated with increased cyclic AMP levels; the relationship between increased cyclic AMP levels and tension decrease was significant (R2 = 0.82, r = 0.91). The dose of (+)-Tc required to inhibit twitch tension increased in proportion to burn size and was statistically significant in the 50% BSA burn group compared to controls (0.3320 +/- 0.09 vs 0.1093 +/- 0.11 mg kg-1, P less than 0.05). The alterations in the effective dose of (+)-Tc were significantly correlated to increases in cyclic AMP levels (R2 = 0.70, r = 0.83). Although PGE2 levels were elevated in the 30% and 50% burn groups, no relation was seen to either tension or (+)-Tc doses. 3. These studies, therefore, support the hypothesis that cyclic AMP plays a significant role in physiological and pharmacological responses in skeletal muscle following thermal injury.