Continuous administration of pyridostigmine improves immobilization-induced neuromuscular weakness.
OBJECTIVE
To investigate the effects of continuous pyridostigmine infusion on immobilization-induced muscle weakness. Critical illness often results in immobilization of limb and respiratory muscles, leading to muscle atrophy and up-regulation of nicotinic acetylcholine receptors. Pyridostigmine reversibly blocks acetylcholinesterase and has the potential to improve neuromuscular transmission and decrease acetylcholine receptor number.


METHODS
Prospective, randomized, controlled experimental study.


METHODS
Animal laboratory, university hospital.


METHODS
Male Sprague-Dawley rats.


METHODS
A total of 40 rats were immobilized in one hind limb by pinning knee and ankle joints. Rats received either continuous pyridostigmine (15 mg.kg.day) or saline subcutaneously via implanted osmotic pumps.


RESULTS
After 7 days and 14 days of immobilization, neuromuscular function, atracurium pharmacodynamics, and expression of acetylcholine receptors were evaluated. At 7 days and 14 days after immobilization, muscle force decreased in all untreated groups, whereas effective doses for paralysis with atracurium and acetylcholine receptor number in the tibialis were significantly increased. Pyridostigmine-treated rats showed a significantly improved muscle force and muscle mass in the immobilized limb. This was associated with an attenuation of acetylcholine receptor up-regulation in the respective leg. At this time, the dose-response curve for atracurium on the immobilized side was shifted to the left in the pyridostigmine group. After 14 days, muscle tension was still less depressed with pyridostigmine infusion, and resistance to the effects of atracurium was still attenuated. However, there were no differences in acetylcholine receptor expression between the immobilized sides of both groups.


CONCLUSIONS
Continuous pyridostigmine infusion improves muscle weakness after 7 days and 14 days of immobilization. The up-regulation of acetylcholine receptors and the concomitant resistance to atracurium is attenuated in animals treated with pyridostigmine after 7 days of immobilization.
Frick
Christiane G
CG
Klinik für Anaesthesiologie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Helming
Marc
M
Martyn
J A Jeevendra
JA
Blobner
Manfred
M
Fink
Heidrun
H
D000818:Animals; D001279:Atracurium / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D006614:Hindlimb / Q000294:innervation; D007103:Immobilization; D007260:Infusion Pumps; D055104:Infusions, Subcutaneous; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D053580:Muscle Strength / Q000187:drug effects / Q000502:physiology; D018908:Muscle Weakness / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000503:physiopathology*; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000187:drug effects* / Q000502:physiology*
D002800:Cholinesterase Inhibitors; D003473:Neuromuscular Nondepolarizing Agents; D011950:Receptors, Cholinergic; D001279:Atracurium; D011729:Pyridostigmine Bromide