title: Cardiovascular actions of the venom from the Irukandji (Carukia barnesi) jellyfish: effects in human, rat and guinea-pig tissues in vitro and in pigs in vitro.
abstract: 1. We have investigated the cardiovascular pharmacology of the crude venom extract (CVE) from the potentially lethal, very small carybdeid jellyfish Carukia barnesi, in rat, guinea-pig and human isolated tissues and anaesthetized piglets. 2. In rat and guinea-pig isolated right atria, CVE (0.1-10 microg/mL) caused tachycardia in the presence of atropine (1 micromol/L), a response almost completely abolished by pretreatment with tetrodotoxin (TTX; 0.1 micromol/L). In paced left atria from guinea-pig or rat, CVE (0.1-3 microg/mL) caused a positive inotropic response in the presence of atropine (1 micromol/L). 3. In rat mesenteric small arteries, CVE (0.1-30 microg/mL) caused concentration-dependent contractions that were unaffected by 0.1 micromol/L TTX, 0.3 micromol/L prazosin or 0.1 micromol/L omega-conotoxin GVIA. 4. Neither the rat right atria tachycardic response nor the contraction of rat mesenteric arteries to CVE were affected by the presence of box jellyfish (Chironex fleckeri) antivenom (92.6 units/mL). 5. In human isolated driven right atrial trabeculae muscle strips, CVE (10 microg/mL) tended to cause an initial fall, followed by a more sustained increase, in contractile force. In the presence of atropine (1 micromol/L), CVE only caused a positive inotropic response. In separate experiments in the presence of propranolol (0.2 micromol/L), the negative inotropic effect of CVE was enhanced, whereas the positive inotropic response was markedly decreased. 6. In anaesthetized piglets, CVE (67 microg/kg, i.v.) caused sustained tachycardia and systemic and pulmonary hypertension. Venous blood samples demonstrated a marked elevation in circulating levels of noradrenaline and adrenaline. 7. We conclude that C. barnesi venom may contain a neural sodium channel activator (blocked by TTX) that, in isolated atrial tissue (and in vivo), causes the release of transmitter (and circulating) catecholamines. The venom may also contain a 'direct' vasoconstrictor component. These observations explain, at least in part, the clinical features of the potentially deadly Irukandji syndrome.
authors.affiliation: Department of Pharmacology, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Winkel
authors.forename: James
authors.initials: J
authors.lastname: Tibballs
authors.forename: Peter
authors.initials: P
authors.lastname: Molenaar
authors.forename: Gavin
authors.initials: G
authors.lastname: Lambert
authors.forename: Peter
authors.initials: P
authors.lastname: Coles
authors.forename: Mark
authors.initials: M
authors.lastname: Ross-Smith
authors.forename: Carolyn
authors.initials: C
authors.lastname: Wiltshire
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Fenner
authors.forename: Lisa-Ann
authors.initials: LA
authors.lastname: Gershwin
authors.forename: Gabrielle M
authors.initials: GM
authors.lastname: Hawdon
authors.forename: Christine E
authors.initials: CE
authors.lastname: Wright
authors.forename: James A
authors.initials: JA
authors.lastname: Angus
mesh_terms: D000818:Animals; D000997:Antivenins / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002319:Cardiovascular System / Q000187:drug effects*; D003064:Cnidarian Venoms / Q000633:toxicity*; D037462:Cubozoa / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D013552:Swine
chemical_list: D000997:Antivenins; D003064:Cnidarian Venoms; D010276:Parasympatholytics; D001285:Atropine; D011433:Propranolol