• Janeyuth Chaisakul, Geoffrey K Isbister, Nicki Konstantakopoulos, Marianne Tare, Helena C Parkington, and Wayne C Hodgson.
• Monash Venom Group, Department of Pharmacology, Monash University, Victoria, Australia.
• Toxicol. Lett. 2012 Sep 3;213(2):243-8.

Abstract'Sudden collapse' following envenoming by some Australasian elapids is a poorly understood cause of mortality. We have previously shown that Oxyuranus scutellatus venom causes cardiovascular collapse in anaesthetized rats. Prior administration of a sub lethal dose of venom attenuated the response to subsequent administration of higher (lethal) venom doses. In this study, we investigated the possible mechanisms mediating this 'protective effect'. Papuan taipan venom (5μg/kg, i.v.) produced a small transient hypotension in anaesthetized rats, while 10μg/kg resulted in a 73±12% decrease in arterial pressure. Venom (20μg/kg or 50μg/kg) produced cardiovascular collapse in all animals tested (n=12). Cardiovascular collapse by 50μg/kg venom was prevented by prior administration of 'priming' doses of venom (5, 10 and 20μg/kg). Also, prior administration of indomethacin (30mg/kg, i.v.) or heparin (300units/kg, i.v.) prevented sudden collapse induced by venom (20μg/kg). Venom was without effect in isolated hearts indicating that a direct cardiac effect was unlikely to be responsible for 'sudden collapse'. Venom induced endothelium-dependent and -independent relaxation in pre-contracted rat mesenteric artery rings which was inhibited by indomethacin, IbTx and Rp-8-CPT-cAMPs. This relaxation was markedly reduced upon second exposure. Our results indicate that cardiovascular collapse induced by O. scutellatus venom may be due to a combination of release of dilator autacoids and to direct relaxation of vascular smooth muscle involving the cAMP/protein kinase A cascade. Further work will involve identification of the venom component(s) responsible for this action and may provide insight into the management of envenomed patients.Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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