Monash Venom Group, Department of Pharmacology, Monash University, Victoria, Australia.
Toxicol Lett. 2013 Aug 29;221(3):205-11. doi: 10.1016/j.toxlet.2013.06.235. Epub 2013 Jul 2.
The Pseudonaja genus (Brown snakes) is widely distributed across Australia and bites account for significant mortality. Venom-induced consumption coagulopathy (VICC) and, less often, early cardiovascular collapse occur following envenoming by these snakes. We have previously examined possible mechanism(s) behind the early cardiovascular collapse following Papuan taipan (Oxyuranus scutellatus) envenoming. In the present study, we investigate early cardiovascular collapse in anaesthetized rats following administration of eastern brown snake (Pseudonaja textilis) venom, and prevention of this effect with prior administration of 'priming' doses (i.e. doses of venom which caused a transient hypotensive response) of venom. P. textilis venom (5-10 μg/kg, i.v.) induced cardiovascular collapse in anaesthetized rats, characterized by a rapid decrease in systolic blood pressure until non recordable. Prior administration of 'priming' doses of P. textilis venom (2 and 3 μg/kg) or, at least, 4-5 doses of O. scutellatus (2 μg/kg, i.v.) or Daboia russelii limitis (20 μg/kg, i.v.) venoms prevented cardiovascular collapse induced by P. textilis venom. Moreover, early collapse was also inhibited by prior administration of 2 discrete doses of Acanthophis rugosus venom. Prior administration of commercial polyvalent snake antivenom (500-3000 units/kg, i.v.) or heparin (300 units/kg, i.v.) also inhibited P. textilis venom-induced cardiovascular collapse. Our results indicate that P. textilis venom-induced cardiovascular collapse can be prevented by prior administration of sub-lethal doses of venom from P. textilis, O. scutellatus, A. rugosus and D. russelii limitis. This suggests that sudden cardiovascular collapse following envenoming is likely to involve a common mechanism/pathway activated by different snake venoms.
棕蛇属（Brown snakes）广泛分布于澳大利亚，其咬伤是导致高死亡率的主要原因。被这些蛇咬伤后，会出现毒液诱导的消耗性凝血病（VICC），且早期心血管衰竭的情况也时有发生。我们之前已经研究了棕伊澳蛇（Oxyuranus scutellatus）咬伤后早期心血管衰竭的可能机制。在本研究中，我们在麻醉大鼠中研究了东部棕蛇（Pseudonaja textilis）毒液给药后早期心血管衰竭的情况，并研究了用毒液的“预激”剂量（即引起短暂低血压反应的剂量）预先给药预防这种作用的情况。P. textilis 毒液（5-10 μg/kg，静脉注射）可引起麻醉大鼠心血管衰竭，其特征为收缩压迅速下降，直至无法记录。预先给予 P. textilis 毒液的“预激”剂量（2 和 3 μg/kg），或者至少给予 4-5 剂棕伊澳蛇（2 μg/kg，静脉注射）或内陆太攀蛇（Daboia russelii limitis）（20 μg/kg，静脉注射）毒液，可预防 P. textilis 毒液引起的心血管衰竭。此外，早期衰竭也可被预先给予 2 剂不同的棘鳞蝰（Acanthophis rugosus）毒液所抑制。预先给予商业多价蛇抗毒血清（500-3000 单位/公斤，静脉注射）或肝素（300 单位/公斤，静脉注射）也可抑制 P. textilis 毒液引起的心血管衰竭。我们的结果表明，P. textilis 毒液引起的心血管衰竭可以通过预先给予来自 P. textilis、棕伊澳蛇、棘鳞蝰和内陆太攀蛇的亚致死剂量的毒液来预防。这表明，蛇咬伤后突然发生心血管衰竭可能涉及不同蛇毒激活的共同机制/途径。
