Increased quantal release of acetylcholine at the neuromuscular junction following scald injury in the rat

Following severe burns, patients frequently develop a profound resistance to nondepolarizing neuromuscular blockers. Several mechanisms have been proposed to account for this, including upregulation of nicotinic acetylcholine receptors. We investigated the effects of a 30% body surface area (BSA) scald on neuromuscular transmission in slow‐twitch soleus (SOL) and fast‐twitch extensor digitorum longus (EDL) of rats. Rats were sacrificed 72 h after the injury, a time at which sepsis is unlikely and body weight gain and core temperature have returned to normal. Further groups of rats were sham operated and either pair fed to the scalded rats or freely fed to assess the influence of food restriction. When compared with muscle from pair‐fed control rats, scald resulted in an almost 50% increase in miniature endplate potential (mEPP) frequency in both SOL and EDL. However, scald did not increase mean mEPP amplitude in SOL, although it did cause a 10% increase in EDL. Scald injury did produce a significant increase in the size of the evoked endplate potential in SOL (33%) and EDL (37%). These data indicate that a significant increase in the quantal content of evoked transmitter released in SOL (38%) and EDL (30%) occurred by 72 h after scald. Such an increase may contribute to the resistance to nondepolarizing neuromuscular blockers documented in patients following thermal injury. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 1660–1666, 1999

[1]  M. Hirose,et al.  d-Tubocurarine Accentuates the Burn-induced Upregulation of Nicotinic Acetylcholine Receptors at the Muscle Membrane , 1995, Anesthesiology.

[2]  C. Slater,et al.  Action potential generation in rat slow‐ and fast‐twitch muscles. , 1995, The Journal of physiology.

[3]  R. Morton,et al.  Low quantal content of the endplate potential reduces safety factor for neuromuscular transmission in the diaphragm of the newborn rat. , 1994, British journal of anaesthesia.

[4]  C. Badetti,et al.  Curares et brûlure , 1994 .

[5]  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.

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

[7]  N. Rothwell,et al.  Clenbuterol, a beta 2-adrenergic agonist, reverses muscle wasting due to scald injury in the rat. , 1993, Burns : journal of the International Society for Burn Injuries.

[8]  R. Morton,et al.  Age-dependent variation in response to tubocurarine in the isolated rat diaphragm. , 1992, British journal of anaesthesia.

[9]  J. Harris,et al.  Neuromuscular transmission at newly formed neuromuscular junctions in the regenerating soleus muscle of the rat. , 1991, The Journal of physiology.

[10]  G. Sieck,et al.  Effect of acute nutritional deprivation on diaphragm structure and function. , 1990, Journal of applied physiology.

[11]  G. Bashein,et al.  Routine Use of Transesophageal Echocardiography is Expensive and Time Consuming , 1989 .

[12]  N. Rothwell,et al.  Muscle wasting associated with endotoxemia in the rat: Modification by theβ2-adrenoceptor agonist clenbuterol , 1989, Bioscience reports.

[13]  S.J. Hong,et al.  Use of geographutoxin II (u‐conotoxin) for the study of neuromuscular transmission in mouse , 1989, British journal of pharmacology.

[14]  J. Martyn,et al.  Intraperitoneal endotoxin but not protein malnutrition shifts d-tubocurarine dose-response curves in mouse gastrocnemius muscle. , 1989, The Journal of pharmacology and experimental therapeutics.

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

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

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

[18]  Chungsook Kim,et al.  Burn Injury to Rat Increases Nicotinic Acetylcholine Receptors in the Diaphragm , 1988, Anesthesiology.

[19]  R. Ruff,et al.  Inhibitors of prostaglandin synthesis or cathepsin B prevent muscle wasting due to sepsis in the rat. , 1984, The Journal of clinical investigation.

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

[21]  A. R. Martin,et al.  Non‐linear summation of end‐plate potentials in the frog and mouse. , 1981, The Journal of physiology.

[22]  K. Frayn,et al.  The post-scald metabolic response in the growing rat: Evidence for a transient phase of muscle protein breakdown , 1980 .

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

[24]  S. S. Kelly.  The effect of nutritional state on neuromuscular transmission in the rat. , 1979, The Journal of physiology.

[25]  A. Mason,et al.  Development and analysis of a small animal model simulating the human postburn hypermetabolic response. , 1978, The Journal of surgical research.

[26]  A. Pestronk,et al.  Effect of muscle disuse on acetylcholine receptors , 1976, Nature.

[27]  B. Katz,et al.  On the factors which determine the amplitude of the ‘miniature end‐plate potential’ , 1957, The Journal of physiology.

[28]  A. R. Martin,et al.  A further study of the statistical composition of the end‐plate potential , 1955, The Journal of physiology.

[29]  A. Moritz,et al.  Studies of Thermal Injury: III. The Pathology and Pathogenesis of Cutaneous Burns. An Experimental Study. , 1947, The American journal of pathology.