Abstract：
In the absence of appropriate medical care, exposure to organophosphorus nerve agents, such as VX, can lead to respiratory failure, and potentially death by asphyxiation. Despite the critical role of respiratory disturbances in organophosphorus-induced toxicity, the nature and underlying mechanisms of respiratory failure remain poorly understood. This study aimed to characterize respiratory alterations by determining their type and duration in mice exposed to a subcutaneous sublethal dose of VX. Respiratory ventilation in Swiss mice was monitored using dual-chamber plethysmography for up to 7 days post-exposure. Cholinesterase activity was assessed via spectrophotometry, and levels of inflammatory biomarkers were quantified using Luminex technology in blood and tissues involved in respiration (diaphragm, lung, and medulla oblongata). Additionally, a histological study was conducted on these tissues to ensure their structural integrity. Ventilatory alterations appeared 20-25 minutes after the injection of 0.9 LD50 VX and increased until the end of the recording, i.e., 40 minutes after intoxication. Concurrent with the occurrence of apnea, increased inspiratory and expiratory times resulted in a significant decrease in respiratory rate in exposed mice compared to controls. Ventilatory amplitude and, consequently, minute volume were reduced, while specific airway resistance significantly increased, indicating bronchoconstriction. These ventilatory effects persisted up to 24 or even 72 hours post-intoxication, resolving on the 7th day. They were correlated with a decrease in acetylcholinesterase activity in the diaphragm, which persisted for up to 72 hours, and with the triggering of an inflammatory reaction in the same tissue. No significant histologic lesions were observed in the examined tissues. The ventilatory alterations observed up to 72 hours post-VX exposure appear to result from a functional failure of the respiratory system rather than tissue damage. This comprehensive characterization contributes to a better understanding of the respiratory effects induced by VX exposure, which is crucial for developing specific medical countermeasures.
摘要：
在没有适当医疗的情况下，接触有机磷神经毒剂，比如VX,会导致呼吸衰竭,并可能因窒息而死亡。尽管呼吸紊乱在有机磷诱导的毒性中起着关键作用，呼吸衰竭的性质和潜在机制仍然知之甚少.这项研究旨在通过确定暴露于皮下亚致死剂量VX的小鼠的呼吸改变的类型和持续时间来表征呼吸改变。使用双室体积描记术监测瑞士小鼠的呼吸通气长达7天。胆碱酯酶活性通过分光光度法进行评估，使用Luminex技术对参与呼吸的血液和组织中的炎症生物标志物水平进行定量(隔膜，肺，和延髓）。此外,对这些组织进行了组织学研究，以确保其结构完整性。在注射0.9LD50VX后20-25分钟出现通气改变，并增加到记录结束，即，中毒后40分钟。伴随着呼吸暂停的发生，与对照组相比，吸气和呼气时间的增加导致暴露小鼠的呼吸频率显着降低。通气幅度和,因此,分钟体积减少，而气道比阻力显著增加，表明支气管收缩。这些通气作用持续到中毒后24甚至72小时，在第七天解决。它们与隔膜中乙酰胆碱酯酶活性的降低有关，持续了72小时，并在同一组织中引发炎症反应。在检查的组织中未观察到明显的组织学病变。VX暴露后72小时内观察到的通气改变似乎是由于呼吸系统的功能衰竭而不是组织损伤所致。这种全面的表征有助于更好地理解VX暴露引起的呼吸效应。这对于制定具体的医疗对策至关重要。
