Efficacy of atropine and scopolamine on airway contractions following exposure to the nerve agent VX

Nerve agents are highly toxic organophosphorus compounds that inhibit acetylcholinesterase resulting in rapid accumulation of the neurotransmitter acetylcholine (ACh) causing a cholinergic syndrome including respiratory failure. In the present study, respiratory responses and antimuscarinic treatment efficacy was evaluated ex vivo using rat precision-cut lung slices (PCLS) exposed to the nerve agent VX. The respiratory effects were evaluated either by adding exogenous ACh directly to the culture medium or by applying electric-field stimulation (EFS) to the PCLS to achieve a release of endogenous ACh from neurons in the lung tissue. The airway contraction induced by both methods was enhanced by VX and resulted in lingering airway recovery, in particular when airways were exposed to a high VX-dose. Both contractions induced by EFS and exogenously added ACh were significantly reduced by administration of the antimuscarinic drugs atropine or scopolamine. Two additions of atropine or scopolamine after maximal ACh-induced airway response was demonstrated effective to reverse the contraction. By adding consecutive doubled doses of antimuscarinics, high efficiency to reduce the cholinergic airway response was observed. However, the airways were not completely recovered by atropine or scopolamine, indicating that non-muscarinic mechanisms were involved in the smooth muscle contractions. In conclusion, it was demonstrated that antimuscarinic treatment reversed airway contraction induced by VX but supplemental pharmacological interventions are needed to fully recover the airways. Further studies should therefore clarify the mechanisms of physiological responses in lung tissue following nerve agent exposures to improve the medical management of poisoned individuals.