Differentiation of Peripheral and Central Actions of Soman-Produced Respiratory Arrest

摘要

The observations from this study support the conclusion that soman-produced, acute respiratory arrest in unprotected animals is mediated within the CNS. Furthermore, lethal levels of soman exposure leave the neuromuscular junction functional. The major additional evidence provided by this study is that medullary respiratory-related units appear to be an affected in a progressive manner. Initially, there appears to be an uncoupling of the regulation of unit activity, as exemplified by unit phase shift. This disruption of normal activity progresses in severity until the system is incapable of sustained, organized respiratory effort. It was not until the cats were in severe respiratory distress that significant alterations were seen in the cardiovascular system. The specific sites and mechanisms of soman's actions remain to be elucidated. The work by Stewart and Anderson, referred to earlier, certainly demonstrates that there are highly localized, nerve agent sensitive site within the brain stem. As indicated in the introduction, the cholinosensitivity of medullary respiratory-related units is relatively vague due to the discrepancy between lack of responsiveness to iontophoresed ACh and apparent binding of QNB. The apparent sensitivity of respiratory-related units to direct application of cholinesterase inhibitors and the lack of correlation between this response and cellular cholinosensitivity suggests an alternative explanation of soman's action. That is, nerve agents may have direct actions on neural membranes and these actions may occur irrespective of specific neurotransmitter recognition sites.