Acute Cardiovascular Effects of Naja Oxiana Venom in Anesthetized Rats

Abstract

Cobra bite is a prevalent phenomenon in the northwest province of Iran, which is situated in the Middle East. The envenomation of Naja naja oxiana manifests through neurological symptoms, including ptosis and drooling, among others. The objective of this preliminary study was to examine the hemodynamic abnormalities induced by intravascular injection of this venom in rats. Furthermore, the neutralizing effects of various premedications were examined. A total of twenty male Wistar rats, with a body weight ranging from 200 to 250 grams, were methodically assigned to four distinct groups, with a sample size of five rats per group. Group one was selected as the control group, while the other groups were intravenously inoculated with crude venom (300 µg/kg, 600 µg/kg, and 1,500 µg/kg) dissolved in normal saline (200 µL) over a period of two minutes. Atropine, dexamethasone, heparin, and aminoguanidine were injected intraperitoneally ten minutes before envenomations to counteract its deleterious effects. The animals were euthanized using cervical dislocation, and their abdominal areas were examined for signs of bleeding. Different organs (lung, heart, and kidney) were extracted and prepared for hematoxylin and eosin (H&E) staining to reveal the pathological events. N. oxiana venom (1500 µg/kg) induced significant ionotropic changes following intravenous infusion, and all animals expired eight minutes later due to hypotension. Despite the absence of any arrhythmias, a statistically significant decrease in heart rate was observed in this group (p < 0.001). Pretreatment with aminoguanidine (29±2.1%) and heparin (21±1.2%) was found to be effective in preventing hypotension at 8 minutes; however, all animals ultimately succumbed to the disease at 20 minutes. A disruption of the alveolar walls of the lung was observed, accompanied by the presence of red blood cells and inflammatory components. However, no pathological abnormalities were detected using a light microscope in other organs. It is important to acknowledge that, as indicated by the findings from our ionotropic and chronotropic assessments, the final group was chosen to proceed with further examination.In this preliminary study, it was observed that the administration of elevated doses of the substance in question could produce significant negative ionotropic effects in rats. The results of the study indicate that systemic vasodilation plays a significant role. Pretreatment with heparin and aminoguanidine significantly diminished this effect. Additionally, no pathological abnormalities were observed in other organs except the lungs. It appears that increasing the dosage of heparin and aminoguanidine has the potential to extend the survival of envenomed rats over a brief period. This observation is supported by the fact that all animals succumbed to their injuries within 20 minutes. Copyright © 2023 by Razi Vaccine & Serum Research Institute.