A delayed treatment model for the evaluation of scopolamine for VX nerve agent intoxication.

Autor: Cornelissen AS; TNO Defence, Safety and Security, CBRN Protection, Rijswijk, the Netherlands. Electronic address: Alex.cornelissen@tno.nl., Garcia EE; Biomedical Advanced Research and Development Authority (BARDA), Assistant Secretary for Preparedness and Response (ASPR), Department of Health and Human Services (HHS), United States., Raulli RE; Biomedical Advanced Research and Development Authority (BARDA), Assistant Secretary for Preparedness and Response (ASPR), Department of Health and Human Services (HHS), United States., Laney J; Biomedical Advanced Research and Development Authority (BARDA), Assistant Secretary for Preparedness and Response (ASPR), Department of Health and Human Services (HHS), United States., Joosen MJA; TNO Defence, Safety and Security, CBRN Protection, Rijswijk, the Netherlands.
Jazyk: angličtina
Zdroj: Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2021 Sep 15; Vol. 427, pp. 115650. Date of Electronic Publication: 2021 Jul 15.
DOI: 10.1016/j.taap.2021.115650
Abstrakt: Most research on medical countermeasures for nerve agent exposure assumes a military scenario, in which (autoinjector) treatment is envisaged to be available immediately. In a civilian setting however, treatment is delayed until arrival of first-aid responders. This may significantly affect treatment efficacy and the requirements for secondary intensive care. The aim of the current study was to develop a guinea pig model to evaluate the efficacy of delayed treatment following nerve agent exposure. We identified a trigger-to-treat based on a progressive stage of the toxidrome following VX exposure, which was associated with the subsiding of clonic movements. This paradigm resulted in treatment consistently being administered between 15 and 25 min post-exposure. Using the model, we investigated the potential for the anticholinergic scopolamine to act as a delayed treatment either as a standalone treatment, or as an adjunct to delayed treatment with Standard of Care (SOC), containing atropine, 2-PAM, and midazolam. The study provides a framework for a small animal model for evaluating the efficacy of treatment administered at a specific stage of the toxidrome, when immediate treatment is absent. As an adjunct, scopolamine treatment did not result in improved survival, but did show a beneficial effect on recovery, in terms of general posture. As a standalone treatment, scopolamine showed a significant, dose-responsive, beneficial effect on survival and recovery. These promising results warrant additional studies to investigate which observed physiological improvements are relevant for the recovery process and residual injury.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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