Effect of Pyridostigmine on the Physiologic and Morphologic Changes Induced by Soman at the Human Neuromuscular Junction

Pre-treatment of American troops with pyridostigmine bromide (PB) has been advocated as an effective way to counteract the potential lethal effect of nerve-agent exposure during military operations. This policy is based on experimental evidence indicating that PB provides partial protection to animals exposed to soman. The protecting mechanism of PB involves a temporary inhibition of the end-plate acetylcholinesterase (AChE) which prevents an ensuing irreversible inhibition induced by a nerve agent. Human studies have been limited to the use of the erythrocyte AChE inhibition as a surrogate marker of PB efficacy. However, it remains unproven that the level of erythrocyte AChE activity is a reliable indicator of the protection provided by PB against nerve agents in humans. This application proposes to use intracellular microelectrode studies, electron microscopy, and chemical assessment of the AChE to study the effects of soman on the neuromuscular junction (NMJ) of human intercostal muscles pre-exposed to PB. The muscle specimens will be donated by consenting patients undergoing thoracic surgery at the University of California, Davis Medical Center. This study may provide very important and relevant data that may direct future policies regarding the PB pre-treatment of military personnel under the threat of nerve-agent exposure.