Dalton Christopher, Hall Charlotte, Lydon Helen, Jenner John, Chipman J Kevin, Graham John S, Chilcott Robert P
a CBR Division , Dstl Porton Down , Salisbury , UK.
b School of Biosciences , University of Birmingham , Birmingham , UK.
Cutan Ocul Toxicol. 2018 Jun;37(2):172-179. doi: 10.1080/15569527.2017.1365883. Epub 2017 Aug 30.
The aim of this study was to evaluate a candidate haemostat (WoundStat™), down-selected from previous in vitro studies, for efficacy as a potential skin decontaminant against the chemical warfare agent pinacoyl methylfluorophosphonate (Soman, GD) using an in vivo pig model.
An area of approximately 3 cm was dermatomed from the dorsal ear skin to a nominal depth of 100 µm. A discrete droplet of C-GD (300 µg kg) was applied directly onto the surface of the damaged skin at the centre of the dosing site. Animals assigned to the treatment group were given a 2 g application of WoundStat™ 30 s after GD challenge. The decontamination efficacy of WoundStat™ against GD was measured by the direct quantification of the distribution of C-GD, as well as routine determination of whole blood cholinesterase and physiological measurements.
WoundStat™ sequestered approximately 70% of the applied C-GD. Internal radiolabel recovery from treated animals was approximately 1% of the initially applied dose. Whole blood cholinesterase levels decreased to less than 10% of the original value by 15 min post WoundStat™ treatment and gradually decreased until the onset of apnoea or until euthanasia. All treated animals showed signs of GD intoxication that could be grouped into early (mastication, fasciculations and tremor), intermediate (miosis, salivation and nasal secretions) and late onset (lacrimation, body spasm and apnoea) effects. Two of the six WoundStat™ treated animals survived the study duration.
The current study has shown that the use of WoundStat™ as a decontaminant on damaged pig ear skin was unable to fully protect against GD toxicity. Importantly, the findings indicate that the use of WoundStat™ in GD contaminated wounds would not exacerbate GD toxicity. These data suggest that absorbent haemostatic products may offer some limited functionality as wound decontaminants.
本研究旨在评估一种从先前体外研究中筛选出的候选止血剂（WoundStat™），使用体内猪模型，作为针对化学战剂甲基氟膦酸频哪酯（梭曼，GD）的潜在皮肤去污剂的功效。
从猪耳背部皮肤切取一块面积约3平方厘米的皮片，使其名义厚度达到100微米。将一滴离散的C-GD（300微克/千克）直接滴加在给药部位中心受损皮肤的表面。在GD攻击后30秒，给分配到治疗组的动物涂抹2克WoundStat™。通过直接定量C-GD的分布、常规测定全血胆碱酯酶以及进行生理测量，来测定WoundStat™对GD的去污效果。
WoundStat™螯合了约70%的涂抹C-GD。经治疗动物体内的放射性标记物回收率约为最初给药剂量的1%。在WoundStat™治疗后15分钟，全血胆碱酯酶水平降至初始值的不到10%，并持续逐渐下降，直至出现呼吸暂停或直至安乐死。所有接受治疗的动物均表现出GD中毒迹象，可分为早期（咀嚼、肌束震颤和震颤）、中期（瞳孔缩小、流涎和鼻分泌物）和晚期（流泪、身体痉挛和呼吸暂停）效应。在接受WoundStat™治疗的六只动物中，有两只存活至研究结束。
当前研究表明，在受损猪耳皮肤上使用WoundStat™作为去污剂无法完全预防GD毒性。重要的是，研究结果表明在GD污染伤口中使用WoundStat™不会加剧GD毒性。这些数据表明，吸收性止血产品作为伤口去污剂可能具有一些有限的功能。
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