The cardiovascular, coagulation and haematological effects of Tiger Snake (Notechis scutatus) prothrombin activator and investigation of release of vasoactive substances

Abstract

The cardiovascular, coagulation and haematological effects of prothrombin activator from Tiger Snake (Notechis scutatus) venom were investigated in anaesthetized mechanically ventilated dogs. Infusion caused dose-related systemic hypotension, marked decreases in cardiac output and stroke volume, marked increases in pulmonary artery pressure, pulmonary artery occlusion pressure and pulmonary vascular resistance. Effects occurred within several minutes but abated over 30 to 40 minutes. Evidence of procoagulation included prolongation and prothrombin and partial thromboplastin times and depletion of serum fibrinogen. Thrombocytopenia and leucopenia occurred. All effects were prevented by prior administration of heparin but none by inhaled nitric oxide. Oesophageal echocardiography during infusion identified thrombi within the heart, right ventricular dilatation and dyskinesia. Electrocardiography suggested myocardial ischaemia. Pulmonary thromboemboli were identified histologically post mortem. Cardiovascular effects of the activator were not due to a variety of endogenous substances as indicated by use of antagonists to platelet activating factor and thromboxane A2, indomethacin, dexamethasone, serotonin, ketanserin, histamine, promethazine and ondansetron. Tiger Snake prothrombin activator caused bilateral ventricular failure by thrombotic obstruction of the pulmonary vasculature and possible by coronary ischaemia.