Effects of sea snake venom (Lapemis hardwickii) on renal functions in dogs

Abstract

The present study was undertaken to clarify the mechanism responsible for the sea snake venom (SSV) action on cardiovascular and renal functions in experimental dogs after intramuscular injection of the venom. Three series of experiments were carried out in anesthetized dogs. The first series was performed on two groups of five animals each, which the animals were given either a single low dose of SSV (0.16 mg/kg. of lyophilized venom in distilled water, Gr.I) or a single high dose of SSV 0.34 mg/kg. (Gr.II). The second series was condusted on two groups of five animals each. A similar protocol was applied as in the first series except the animals were pretreated with sustaining infusion of 4.2 gm% NaHCO3 solution to develop the alkalinized urine 30 minutes before envenomation in either low dose (Gr.III) or a high dose (Gr.IV). The third series was conducted on two groups of five animals each. A similar protocol was applied as in the first series except the animals received sustaining infusion of 4.2 gm% NaHCO3 solution to develop the alkalinized urine which was given 1 hr. after injection of SSV in either low dose (Gr.V) or a high dose (Gr.IV). Measurements of general circulation, renal hemodynamics and renal functions were carried over 3 hr. after envenomation. In group I dogs, there were no significant changes in cardiac output (CO), heart rate (HR), total peripheral resistance (TPR) and packed cell volume (PCV) whereas mean arterial blood pressure (MAP) significantly increased at 120 and 180 minutes after a low dose of SSV injection alone. In group II animals, there were no significant changes in MAP, PP, and PCV whereas HR significantly decreased at 180 minutes (P<0.05). Stroke volume (SV) significantly increased at 180 minutes (P<0.05) after SSV injection alone. No significant changes in the urine flow rate (V), glomerular filtration rate (GFR) and renal vascular resistance (RVR) were apparent in group I. Effective renal plasma flow (ERPF) and effective renal blood flow (ERBF) significantly decreased while a significant increase in filtration fraction (FF) was noted. In group II, V and GFR significantly decreased at 180 minutes (P<0.05). There were significant decrease in ERPF and ERBF in group II animals at 180 minute after envenomation. In both groups I and II, urinary myoglobin (UMb) significantly increased at 180 minutes (P<0.05), plasma lactate dehydrogenase (PLDH) significantly increased at 60 minutes (P<0.05) and 180 minutes (P<0.01) and plasma creatine phosphokinase (PCPK) significantly increased at 60 minutes (P<0.05) and 180 minutes (P<0.05). In groups III and IV of the animals pretreated with NaHCO3, there were no significant changes of the general irculation after given either a low dose or a high dose of SSV throughout the period of study except the HR increased significantly at 60 minutes (P<0.05) in animals given a low dose of SSV. There were no changes in GFR, ERPF, ERBF and RVR in group III dogs, whereas V and FF significantly increased at 120 and 180 minutes (P<0.05). In group IV dogs given a high dose of SSV, there were no significant changes in GFR, ERPF, ERBF and FF whereas V significantly increased at 120 minutes (P<0.05). Animals in groups III and IV showed significantly increased of UMb, PLDH and PCPK after Invenomation. In group V animals, there were no significant changes of the MAP, PCV and TPR throughout periods of study whereas the HR increased significantly at 60 minutes (P<0.05). PP, CO and SV significantly decreased at 60 minutes (P<0.01). In group VI, there were no significant changes of SV and TPR throughout periods of study while MAP significantly increased at 120 minutes (P<0.05) but PP and CO significantly decreased at 60 minutes (P<0.05). HR and PCV significantly decreased at 120 (P<0.05) and 180 minutes (P<0.05). No changes in ERPF, ERBF and FF were apparent in group V dogs, whereas V, GFR and RVR significantly increased at 120 and 180 minutes (P<0.05). In group VI dogs showed no significant changes in GFR, ERBF, ERBF and RVR whereas V and FF significantly increased at 120 minutes (P<0.05). In both groups of V and VI, marked elevation of UMb, PLDH and PCPK appeared at 60 and 180 minutes P<0.05). The present results indicate that infusion of NaHCO3 for alkalinuric conditions either before or after SSV administration has a protective role against dysfunction of renal functions.