D-TUBOCURARINE ACCENTUATES THE BURN-INDUCED UP-REGULATION OF NICOTINIC ACETYLCHOLINE-RECEPTORS AT THE MUSCLE MEMBRANE

Background: Increases in acetylcholine receptors (AChRs) the muscle me mbrane, induced by burn injury, have been associated with a hyperkalem ic response to succinylcholine and resistance to d-tubocurarine-like d rugs, Muscle relaxants often are administered to burn-injured patients in the intensive care unit to facilitate mechanical ventilation. This study in rats tested whether continuous administration of d-tubocurar ine in subparalytic doses exaggerates the upregulation of AChRs induce d by burn trauma. Subparalytic doses were used to avoid the confoundin g effects of immobilization. Methods: Three days after an approximate 50% body surface area burn or sham injury, the animals received an inf usion of 3.03 +/- 0.05 mu g/h of d-tubocurarine or equal volume of sal ine directly to the left gastrocnemius muscle via a catheter connected to a subcutaneously implanted osmotic pump. After 7 days of d-tubocur arine or saline infusion, the AChRs were quantitated using I-125-alpha -bungarotoxin. The AChRs on the d-tubocurarine or saline-infused left gastrocnemius were compared to the contralateral gastrocnemius in the same group. The right or left gastrocnemius AChRs were compared to the ipsilateral muscles between groups. These intra- and inter-group comp arisons allowed the delineation of the effects of catheter irritation, burns, or d-tubocurarine on AChRs. Results: Daily examination of the withdrawal response to toe-pinch revealed no evidence of paralysis. We ight loss in the burn-injury animals receiving d-tubocurarine or salin e was similar, confirming that the infusion of d-tubocurarine did not impair the mobility of the animals to move and feed. The plasma d-tubo curarine concentration after 7 days of infusion was 26.0 +/- 12 ng/ml (mean +/- SE). Regardless of burn or sham injury or of d-tubocurarine or saline infusion, the concentration of AChRs on the left was consist ently greater than in the contralateral right gastrocnemius muscles wi thin the same group, indicating that manipulation of the area alone ca n result in upregulation of AChRs. The AChRs in the right gastrocnemiu s of burn-injured animals were greater than those in the same muscle o f sham-injured animals, regardless of saline (7.24 +/- 0.9 vs. 5.7 +/- 0.5 fmoles/mg protein, P = 0.06) or d-tubocurarine (7.3 +/- 0.4 vs. 5 .7 +/- 0.5, P < 0.05) infusion to the burn-injury groups. AChRs in the left gastrocnemius of burn-injury animals receiving d-tubocurarine we re significantly greater than those in burn- or sham-injury animals re ceiving saline (13.9 +/- 1.1 vs. 9.8 +/- 1.2 and 7.1 +/- 0.5 fmoles/mg protein, respectively, P < 0.05). Conclusions: Burn-induced upregulat ion of AChRs is accentuated by infusion of subparaltic doses of d-tubo curarine, Concomitant administration of d-tubocurarine to burn-injured patients may result in further exaggeration of the aberrant responses to neuromuscular relaxants.