Thermal injury induces greater resistance to d-tubocurarine in local rather than in distant muscles in the rat.

UNLABELLED 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. IMPLICATIONS 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.

[1]  D. Fung,et al.  Deep sedation and mechanical ventilation without paralysis for 3 weeks in normal beagles: exaggerated resistance to metocurine in gastrocnemius muscle. , 1999, Anesthesiology.

[2]  C. Ibebunjo,et al.  Mechanisms for the paradoxical resistance to d-tubocurarine during immobilization-induced muscle atrophy. , 1997, The Journal of pharmacology and experimental therapeutics.

[3]  J. Martyn,et al.  Na+ channel and acetylcholine receptor changes in muscle at sites distant from burns do not simulate denervation. , 1997, Journal of applied physiology.

[4]  Yost Cs,et al.  Potency of Agonists and Competitive Antagonists on Adult- and Fetal-Type Nicotinic Acetylcholine Receptors , 1997 .

[5]  T. Sculley,et al.  DNaseI treatment is a prerequisite for the amplification of cDNA from episomal-based genes. , 1996, BioTechniques.

[6]  N. Cohen,et al.  Changes in acetylcholine receptor number in muscle from critically ill patients receiving muscle relaxants: an investigation of the molecular mechanism of prolonged paralysis. , 1995, Critical care medicine.

[7]  Q. Chen,et al.  Antagonist and partial agonist actions of d-tubocurarine at mammalian muscle acetylcholine receptors , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[8]  J. Slattery,et al.  Large Burns Magnify and Prolong Increases in Acetylcholine Receptors and Resistance to Nondepolarizing Muscle Relaxants in Muscle under Burned Skin in Rats , 1994 .

[9]  K. Rosen,et al.  Acetylcholine receptor subunit mRNA changes in burns are different from those seen after denervation: the 1993 Lindberg Award. , 1993, The Journal of burn care & rehabilitation.

[10]  J. Martyn,et al.  Burn injury—induced nicotinic acetylcholine receptor changes on muscle membrane , 1993, Muscle & nerve.

[11]  R. S. Jaffe,et al.  Up‐and-down Regulation of Skeletal Muscle Acetylcholine Receptors Effects on Neuromuscular Blockers , 1992, Anesthesiology.

[12]  C. Hogue,et al.  Tolerance and upregulation of acetylcholine receptors follow chronic infusion of d-tubocurarine. , 1992, Journal of applied physiology.

[13]  B. Sakmann,et al.  Neural factors regulate AChR subunit mRNAs at rat neuromuscular synapses , 1991, The Journal of cell biology.

[14]  C. Hogue,et al.  Resistance to d-tubocurarine in lower motor neuron injury is related to increased acetylcholine receptors at the neuromuscular junction. , 1990, Anesthesiology.

[15]  J. Martyn,et al.  Neuromuscular Blockade with Vecuronium in Paediatric Patients with Burn Injury , 1989, British journal of clinical pharmacology.

[16]  D. Heimbach,et al.  Effect of thermal injury on the pharmacokinetics and pharmacodynamics of atracurium in humans. , 1989, Anesthesiology.

[17]  R. Haschke,et al.  Acetylcholine receptor density and acetylcholinesterase activity in skeletal muscle of rats following thermal injury. , 1989, Anesthesiology.

[18]  P. Marathe,et al.  Resistance to Atracurium in Thermally Injured Rats The Roles of Time, Activity, and Pharmacodynamics , 1988, Anesthesiology.

[19]  J. Martyn,et al.  Burn injury to trunk of rat causes denervation-like responses in the gastrocnemius muscle. , 1988, Journal of applied physiology.

[20]  J. Martyn,et al.  Evaluation of atracurium neuromuscular blockade in paediatric patients with burn injury. , 1988, British journal of anaesthesia.

[21]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[22]  D. Heimbach,et al.  Patients with burns are resistant to atracurium. , 1986, Anesthesiology.

[23]  Y. Amaki,et al.  Disuse and d–Tubocurarine Sensitivity in Isolated Muscles , 1985, Anesthesia and analgesia.

[24]  J. Martyn,et al.  The neuromuscular effects of pancuronium in burned children. , 1983, Anesthesiology.

[25]  R. Kaplan,et al.  Metocurine requirements and plasma concentrations in burned paediatric patients. , 1983, British journal of anaesthesia.

[26]  H. H. Ali,et al.  Increased d-tubocurarine requirement following major thermal injury. , 1980, Anesthesiology.

[27]  J. Brockes,et al.  Acetylcholine receptors in normal and denervated rat diaphragm muscle. II. Comparison of junctional and extrajunctional receptors. , 1975, Biochemistry.

[28]  A. Mason,et al.  A standard animal burn. , 1968, The Journal of trauma.