title: Thermal injury induces greater resistance to d-tubocurarine in local rather than in distant muscles in the rat.
abstract: We tested the hypothesis that resistance to d-tubocurarine (dTC) is more intense in muscles closer to, than distant from, burn, and is related to the expression of immature and total acetylcholine receptors (AChRs). Anesthetized rats received approximately 4% surface area burn over the tibialis muscle of one leg with the contralateral leg serving as control, or approximately 45% of the flank burn, with sham-burned pair fed controls. At 1, 4, 7, or 14 days later, the 50% effective dose of dTC, membrane AChRs, and messenger ribonucleic acid (mRNA) that encode the AChR gamma-subunit (AChRgamma-mRNA) were quantified in the tibialis. After the local leg burn, AChRs increased at Days 4, 7, and 14, and AChRgamma-mRNA at Days 4 and 7 after burn. The increased AChRgamma-mRNA correlated with total AChRs (r = 0.82), suggesting that the up-regulated AChRs may contain the immature isoform. The 50% effective dose of dTC after the local leg burn increased 1.2- to 1.5-fold at all periods and correlated significantly with AChRs (r = 0.54) and AChRgamma-mRNA (r = 0.57). After the flank burn, resistance was seen at Day 14 in association with muscle atrophy; AChRs and AChRgamma-mRNA were unaltered. The resistance to dTC after a local burn occurs sooner, is more marked, and is probably related to both increases and isoform changes in AChRs. The resistance at distant muscles appears unrelated to AChR changes.
  
  
  CONCLUSIONS
  The resistance to d-tubocurarine after a burn differs between muscles near and distant from the burn and seems to depend on quantitative and qualitative changes in acetylcholine receptors and muscle atrophy associated with the insult.
authors.affiliation: Department of Anesthesiology and Critical Care, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors.forename: C
authors.initials: C
authors.lastname: Ibebunjo
authors.forename: J A
authors.initials: JA
authors.lastname: Martyn
mesh_terms: D000818:Animals; D002056:Burns / Q000378:metabolism / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005508:Food Deprivation; D006614:Hindlimb / Q000293:injuries; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D019148:Neuromuscular Blockade; D003473:Neuromuscular Nondepolarizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000378:metabolism; D014403:Tubocurarine / Q000493:pharmacokinetics / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D003473:Neuromuscular Nondepolarizing Agents; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D014403:Tubocurarine