Pharmacological Approaches That Slow Lymphatic Flow As a Snakebite First Aid
Pharmacological Approaches That Slow Lymphatic Flow As a Snakebite First Aid
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DOI：
10.1371/journal.pntd.0002722
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发表时间：
2014-02-01
影响因子：
3.8
通讯作者：
Isbister, Geoffrey K.
中科院分区：
文献类型：
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作者：
van Helden, Dirk F.;Thomas, Paul A.;Isbister, Geoffrey K.
背景：本研究探讨了使用局部药物作为蛇咬伤急救，其中减缓毒液到达循环防止全身毒性。这是基于这样的事实，即大多数蛇毒中的毒素分子是大分子，通常首先进入并穿过淋巴系统，然后进入循环。这是之前一项研究的结果，该研究表明，局部应用一氧化氮供体减缓了人类和大鼠的淋巴流动，并且增加了皮下注射眼镜蛇毒液的呼吸停止时间。（Pseudonaja textile，Ptx;方法学/主要发现局部应用L-型钙离子的影响在麻醉的大鼠模型中检查了通道拮抗剂硝苯地平和局部麻醉剂木素生物碱抑制淋巴流动和防止毒液蛰入的作用。与对照组相比，该试剂显著增加了染料测量的淋巴通过时间，分别增加了500%和390%，并增加了呼吸停止至足注射致死剂量Ptx毒液的时间，分别增加了60%和40%。该研究还研究了Ptx毒液剂量的影响超过致命范围的0.4至1.5毫克/公斤，发现在毒液剂量和时间呼吸arrest. Conclusion/Significance之间的负线性关系-研究结果表明，一系列的代理，抑制淋巴流动可能被用作一种辅助治疗的压力包扎固定（PBI）在蛇咬伤急救。这一点很重要，因为PBI（澳大利亚国家健康和医学研究理事会推荐的蛇咬伤急救）经常被错误地应用。使用局部麻醉剂将有减少疼痛的额外优势。作者摘要蛇咬伤仍然是世界范围内的一个主要问题，每年造成成千上万的受害者死亡或严重疾病。减轻中毒负担的一种方法是提供最佳的急救程序。我们以前已经表明，局部应用的一氧化氮（NO）供体减缓淋巴液流动到类似的程度，在人类和大鼠，以及增加的时间呼吸骤停约50%的东部棕色蛇毒皮下注射到麻醉大鼠的后足。本研究探讨了其他几种局部药理学药物的使用，旨在减缓毒液毒素通过淋巴系统到达循环。该研究发现，所检查的药物与先前发现的NO供体相似。事实上，其中一种是常用的局部麻醉剂，可能是一种理想的辅助急救，因为它在减轻疼痛的同时提供急救。
Background This study examines the use of topical pharmacological agents as a snakebite first aid where slowing venom reaching the circulation prevents systemic toxicity. It is based on the fact that toxin molecules in most snake venoms are large molecules and generally first enter and traverse the lymphatic system before accessing the circulation. It follows on from a previous study where it was shown that topical application of a nitric oxide donor slowed lymph flow to a similar extent in humans and rats as well as increased the time to respiratory arrest for subcutaneous injection of an elapid venom (Pseudonaja textilis, Ptx; Eastern brown snake) into the hind feet of anaesthetized rats.Methodology/Principal Findings The effects of topical application of the L-type Ca2+ channel antagonist nifedipine and the local anesthetic lignocaine in inhibiting lymph flow and protecting against envenomation was examined in an anaesthetized rat model. The agents significantly increased dye-measured lymph transit times by 500% and 390% compared to controls and increased the time to respiratory arrest to foot injection of a lethal dose of Ptx venom by 60% and 40% respectively. The study also examined the effect of Ptx venom dose over the lethal range of 0.4 to 1.5 mg/kg finding a negative linear relationship between increase in venom dose and time to respiratory arrest.Conclusions/Significance The findings suggest that a range of agents that inhibit lymphatic flow could potentially be used as an adjunct treatment to pressure bandaging with immobilization (PBI) in snakebite first aid. This is important given that PBI (a snakebite first aid recommended by the Australian National Health and Medical research Council) is often incorrectly applied. The use of a local anesthetic would have the added advantage of reducing pain.Author Summary Snakebite remains a major problem worldwide causing death or serious illness in many tens of thousands of victims annually. An approach to reduce the burden of envenoming is to provide optimum first aid procedures. We have previously shown that topical application of a nitric oxide (NO) donor slowed lymph flow to similar extent in humans and rats as well as increased the time to respiratory arrest by approximate to 50% for subcutaneous injection of eastern brown snake venom into the hind feet of anaesthetized rats. The present study examines the use of several other topical pharmacological agents that aim to slow venom toxins reaching the circulation through the lymphatic system. The study found that the agents examined were similarly effective to that previously found for the NO donor. The fact that one of these is a commonly used topical local anesthetic may be an ideal adjunct first aid, as it provides first aid while reducing pain.