title: Mediators of burn-induced neuromuscular changes in mice.
abstract: 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.
authors.affiliation: Department of Anaesthesiology, Harvard Medical School, Boston, Massachusetts.
authors.forename: J F
authors.initials: JF
authors.lastname: Tomera
authors.forename: J
authors.initials: J
authors.lastname: Martyn
mesh_terms: D000818:Animals; D002056:Burns / Q000503:physiopathology*; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology; D015232:Dinoprostone / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D009119:Muscle Contraction; D009132:Muscles / Q000378:metabolism / Q000503:physiopathology*; D009469:Neuromuscular Junction / Q000502:physiology*
chemical_list: D000242:Cyclic AMP; D015232:Dinoprostone