TNO Defence, Security and Safety, BU CBRN Protection, Rijswijk, The Netherlands.
Chem Biol Interact. 2010 Oct 6;188(1):255-63. doi: 10.1016/j.cbi.2010.06.010. Epub 2010 Jun 23.
The nerve agent VX is most likely to enter the body via liquid contamination of the skin. After percutaneous exposure, the slow uptake into the blood, and its slow elimination result in toxic levels in plasma for a period of several hours. Consequently, this has implications for the development of toxic signs and for treatment onset. In the present study, clinical signs, toxicokinetics and effects on respiration, electroencephalogram and heart rate were investigated in hairless guinea pigs after percutaneous exposure to 500 microg/kg VX. We found that full inhibition of AChE and partial inhibition of BuChE in blood were accompanied by the onset of clinical signs, reflected by a decline in respiratory minute volume, bronchoconstriction and a decrease in heart rate. Furthermore, we investigated the therapeutic efficacy of a single dose of atropine, obidoxime and diazepam, administered at appearance of first clinical signs, versus that of repetitive dosing of these drugs on the reappearance of signs. A single shot treatment extended the period to detrimental physiological decline and death for several hours, whereas repetitive administration remained effective as long as treatment was continued. In conclusion, percutaneous VX poisoning showed to be effectively treatable when diagnosed on time and when continued over the entire period of time during which VX, in case of ineffective decontamination, penetrates the skin.
神经毒剂 VX 很可能通过皮肤的液体污染进入人体。经皮暴露后，由于缓慢吸收到血液中以及缓慢消除，导致血浆中毒水平持续数小时。因此，这对毒性体征的发展和治疗开始时间有影响。在本研究中，我们在无毛豚鼠身上研究了经皮暴露于 500μg/kg VX 后，临床症状、毒代动力学以及对呼吸、脑电图和心率的影响。我们发现，血液中 AChE 完全抑制和 BuChE 部分抑制伴随着临床症状的出现，表现为呼吸分钟量下降、支气管收缩和心率下降。此外，我们研究了在出现首个临床症状时单次给予阿托品、解磷定和地西泮，与在症状重现时重复给予这些药物的治疗效果。单次注射治疗可将有害的生理下降和死亡时间延长数小时，而只要继续治疗，重复给药仍有效。总之，经皮 VX 中毒在及时诊断并在 VX 未能有效清除穿透皮肤的整个时间段内持续治疗时，可有效治疗。
