Defence Research & Development Canada-Suffield, Box 4000, Medicine Hat, Alberta, Canada T1A 8K6.
Toxicology. 2012 Apr 11;294(2-3):85-93. doi: 10.1016/j.tox.2012.02.003. Epub 2012 Feb 16.
The protective effects of selected anesthetic regimens on sarin (GB) were investigated in domestic swine. At 30% oxygen, the toxicity of this agent in isoflurane anesthetized animals (LD(50)=10.1μg/kg) was similar to literature sited values in awake swine (LD(50)=11.8μg/kg) and slightly higher than that of both ketamine (LD(50)=15.6μg/kg) and propofol (LD(50)=15.3μg/kg) anesthetized swine. Use of 100% oxygen in ketamine anesthetized animals resulted in three-fold protective effects compared to 30% oxygen. Use of 100% oxygen in both isoflurane and propofol anesthetized animals, compared to 30% resulted in profound protection against GB poisoning (>33×). There were no differences in the severity of the poisoning or recovery time in animals treated over dose ranges of 10-350μg/kg (isoflurane) or 15-500μg/kg GB (propofol). Survivors of high GB challenges that were revived from propofol anesthetic exhibited no signs of cognitive impairment seven days later. Protective treatments did not attenuate cholinesterase (ChE) inhibition; survivors of otherwise supralethal GB concentrations exhibited very low blood ChE activities. This work indicates that propofol has protective effects against GB, and that oxygen tension may have an important role in treating nerve agent casualties. More importantly, it demonstrates that non-cholinergic protective mechanisms exist that may be exploited in the future development of medical countermeasures against organophosphorous nerve agents.
选择的麻醉方案对沙林（GB）的保护作用在国内猪进行了研究。在 30%的氧气，这种药物在异氟醚麻醉动物（LD（50）= 10.1μg/kg）的毒性类似于文献中的值在清醒猪（LD（50）= 11.8μg/kg）和略高于氯胺酮（LD（50）= 15.6μg/kg）和丙泊酚（LD（50）= 15.3μg/kg）麻醉猪。在氯胺酮麻醉动物中使用 100%氧气与 30%氧气相比具有三倍的保护作用。与 30%氧气相比，在异氟醚和丙泊酚麻醉动物中使用 100%氧气对 GB 中毒有显著的保护作用（> 33×）。在 10-350μg/kg（异氟醚）或 15-500μg/kg GB（丙泊酚）的剂量范围内，动物中毒的严重程度或恢复时间无差异。从丙泊酚麻醉中复活的高 GB 挑战的幸存者七天后没有表现出认知障碍的迹象。保护治疗并没有减弱胆碱酯酶（ChE）的抑制作用；否则，高致死性 GB 浓度的幸存者表现出非常低的血液 ChE 活性。这项工作表明丙泊酚对 GB 有保护作用，氧张力可能在治疗神经毒剂伤亡方面发挥重要作用。更重要的是，它表明存在非胆碱能保护机制，可能在未来开发针对有机磷神经毒剂的医疗对策中得到利用。
