'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.