Experimental evaluation of the hemodynamic changes induced with intravascular injection of the Echis carinatus venom in rats

Introduction: Echis carinatus (E.carinatus) is recognized, as one of the most dangerous snakes globally that inhabits in Iran. In this study, the hemodynamic responses of this venom were evaluated in rats. The neutralizing effects of the Iranian polyvalent antivenom and different drugs were assessed. In addition, the induced pathological malformations in different organs were investigated. Methods: Animals were anesthetized and placed supine on the surgical table. Administration of the venom and drugs (heparin, epinephrine, atropine, ketorolac, dexamethasone, polyvalent antivenom) were performed via a cannula that was placed in to the left femoral vein. The arterial cannula was connected to a pressure transducer (MLT844, AD instruments, Australia) for continuous recording of the hemodynamic changes by means of a powerlab acquisition system. At the end of the study, the animals were killed with cervical dislocation and their internal organs (heart, kidney, liver, and the lungs) preserved for pathological analysis in formalin solution (10%).Results: Injection of the E.carinatus venom (40 μg per rat) intravenously caused a prominent hypotension subsequent to transient hypertension leading to the death in few minutes accompanied with the marked decrease in the heart rate. This venom had no arrhythmogenic activity while there was decrease of the pulmonary rate within the experiment. Pretreatment with the Iranian polyvalent antivenom (pepsin derived product), 10 minutes before venom injection, neutralized the hemodynamic responses while this remedy had no effect when instilled two minutes after venom injection. Heparin (300IU/kg) and epinephrine (0.5μg per rat) prevented hemodynamic responses when used 10 minutes before venom instillation while atropine (1 mg/kg), dexamethasone (1 mg/kg) and ketorolac (10mg/ml) had no effects. Histologically the lung was the most vulnerable organ with mononuclear infiltration, microcystic formation and significant capillary congestion. There was prominent renal pathological deteriorations including mesangial cell infiltration and diffuse bleeding leading to the acute tubular necrosis.Conclusion: This experimental study demonstrate that injection of the E.carinatus venom intravenously in one minute, causes hypotension leading to death, bradycardia and decrease in pulmonary rate without histologically significant changes in the heart. In future studies, the cardiotropic potencies of this venom on the rat isolated heart muscle should be investigated.