A pharmacological investigation of the venom extract of the Australian box jellyfish, Chironex fleckeri, in cardiac and vascular tissues

The pharmacology of Australian box jellyfish, Chironex fleckeri, unpurified (crude) nematocyst venom extract (CVE) was investigated in rat isolated cardiac and vascular tissues and in anaesthetised rats.In small mesenteric arteries CVE (0.01–30 μg/ml) caused contractions (EC50 1.15 ± 0.19 μg/ml) that were unaffected by prazosin (0.1 μM), bosentan (10 μM), CGRP8–37 (1 μM) or tetrodotoxin (1 μM). Box jellyfish antivenom (5–92.6 units/ml) caused rightward shifts of the CVE concentration–response curve with no change in the maximum. In the presence of l-NAME (100 μM) the sensitivity and maximum response to CVE were increased, whilst MgSO4 (6 mM) decreased both parameters. CVE (1–10 μg/ml) caused inhibition of the contractile response to electrical sympathetic nerve stimulation.Left atrial responses to CVE (0.001–30 μg/ml) were bi-phasic, composed of an initial positive inotropy followed by a marked negative inotropy and atrial standstill. CVE (0.3 μg/ml) elicited a marked decrease in right atrial rate followed by atrial standstill at 3 μg/ml. These responses were unaffected by 1 μM of propranolol, atropine or CGRP8–37. Antivenom (54 and 73 units/ml) caused rightward shifts of the CVE concentration–response curve and prevented atrial standstill in left and right atria.The effects of CVE do not appear to involve autonomic nerves, post-synaptic α1- or β1-adrenoceptors, or muscarinic, endothelin or CGRP receptors, but may occur through direct effects on the cardiac and vascular muscle. Box jellyfish antivenom was effective in attenuating CVE-induced responses in isolated cardiac and vascular tissues.

► This study examined the pharmacology of Australian box jellyfish venom extract CVE.
► CVE caused vascular contraction unaffected by prazosin, bosentan or tetrodotoxin.
► Box jellyfish antivenom and MgSO4 inhibited CVE-induced vascular contraction.
► In cardiac tissues, CVE caused marked negative inotropy and bradycardia.
► CVE effects do not involve autonomic nerves, adrenoceptors or muscarinic receptors.