Understanding Neuromuscular Weakness of Acute Organophosphate Poisoning the Significance of Metabolic Energy Muscle Protein Degradation and Amino Acids

Abstract

Prolonged severe muscle weakness of Type II paralysis is a serious consequence of acute OPP that results in increased morbidity, mortality and high cost of treating patients. Type II paralysis may last for 1 3 weeks and is postulated to result from persistent inhibition of AChE at the neuromuscular junction. Paralysis from AChE inhibition is a result of a depolarized muscle membrane. Muscle loss is a feature of acute severe organophosphate poisoned patients that may account for the slow reversibility of Type II paralysis. Immobility is well known to lead to muscle loss and weakness. In addition to weakness arising from the inhibition of AChE, the extended periods of immobility that accompany Type II paralysis may also contribute to muscle loss and weakness of acute OPP. Muscle loss is initially a slow process. However once degradation sets in, the process may be difficult to reverse. Muscle loss mainly occurs by the degradation of muscle proteins particularly through the ubiquitin - proteasome pathway. Muscle weakness of acute OPP could therefore be a result of acetylcholine-induced depolarization of the muscle and immobility stress induced muscle wasting. Studies of muscle pathophysiology of acute OPP have mostly examined the effect of AChE inhibition. Only a few studies have addressed the cellular and metabolic basis of muscle weakness following acute organophosphate poisoning. The overall conclusions of these studies are: (a) prolonged muscle weakness following acute OPP may be prevented if AChE at the neuromuscular junction is protected from severe persistent inhibition. (b) Inhibition of AChE and immobility stress may contribute to muscle wasting and weakness of acute OPP. (c) Addressing metabolic insufficiency of glycemic substrates and protein degradation in the muscle may prevent muscle weakness. The role of such interventions in reducing the duration and adverse outcome of Type II paralysis in acute OPP need to be explored.