Increases in
acetylcholine receptors (AChRs) at the muscle membrane, induced by
burn injury, have been associated with a hyperkalemic response to
succinylcholine and resistance to
d-tubocurarine-like drugs. 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-tubocurarine in subparalytic doses exaggerates the upregulation of AChRs induced by
burn trauma. Subparalytic doses were used to avoid the confounding effects of immobilization.
METHODS: Three days after an approximate 50% body surface area
burn or
sham injury, the animals received an infusion of 3.03 +/- 0.05 micrograms/h of
d-tubocurarine or equal volume of saline directly to the left gastrocnemius muscle via
catheter connected to a subcutaneously implanted osmotic pump. After 7 days of
d-tubocurarine or saline infusion, the AChRs were quantitated using 125I-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 intergroup comparisons 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.
Weight loss in the
burn-injury animals receiving
d-tubocurarine or saline was similar, confirming that the infusion of
d-tubocurarine did not impair the mobility of the animals to move and feed. The plasma
d-tubocurarine 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 consistently greater than in the contralateral right gastrocnemius muscles within the same group, indicating that manipulation of the area alone can result in upregulation of AChRs. The AChRs in the right gastrocnemius of
burn-injured animals were greater than those in the same muscle of
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 were significantly greater than those in
burn- or
sham-injury animals receiving 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 upregulation of AChRs is accentuated by infusion of subparalytic doses of
d-tubocurarine. Concomitant administration of
d-tubocurarine to
burn-injured patients may result in further exaggeration of the aberrant responses to neuromuscular relaxants.