Intraperitoneal endotoxin but not protein malnutrition shifts d-tubocurarine dose-response curves in mouse gastrocnemius muscle

Abstract

Burn injury-induced changes at the neuromuscular junction include muscle weakness and altered response to neuromuscular blocking drugs. Protein malnutrition and sepsis can concomitantly occur with burn trauma. The role of pure malnutrition or sepsis, in the absence of burn injury, in inducing neuromuscular changes was studied in the mouse gastrocnemius muscle. Additionally, cAMP levels in muscle were evaluated to reflect metabolic activity. Sepsis was studied using doses of endotoxin at one-fourth or one-third the dose evoking 50% lethality. Diets of 5% protein and 5% protein + 35% fiber achieved protein and protein/calorie malnutrition, respectively. In each model neuromuscular function was evaluated by maximal tension developed. Pharmacologic responses were measured through effective dose to paralyze active tension by either 50 or 95%. Protein and protein/calorie malnutrition leading to an approximate 8% body weight loss caused a depression of maximal tension developed; this depression in tension was associated with a 10-fold increase in cAMP levels. Effective doses of d-tubocurarine for twitch inhibition during malnutrition were not significantly different from controls. Sepsis at 2 weeks caused an approximate 8% body weight loss, a significant decrease in maximal tension and at least a 3- to 5-fold shift to the right in dose-response curves to d-tubocurarine. In contrast to malnutrition, cAMP levels were significantly decreased (P less than .001) in sepsis to 1/400 of controls. The altered neuromuscular function and pharmacology observed in sepsis are similar to changes observed in burn injury. Protein malnutrition common to these two states may be important in functional but not pharmacological changes at the neuromuscular junction.