An in vivo examination of the differences between rapid cardiovascular collapse and prolonged hypotension induced by snake venom

• Published in: Scientific reports 2019-12, Vol.9 (1), p.20231-9, Article 20231
• Main Authors: Kakumanu, Rahini, Kemp-Harper, Barbara K., Silva, Anjana, Kuruppu, Sanjaya, Isbister, Geoffrey K., Hodgson, Wayne C.
• Format: Article
• Language: English
• Subjects: 13; 59; 631/443/592; 64; 692/308/1426; Animals; Arterial Pressure - drug effects; Arterial Pressure - physiology; Arteries; Bitis arietans; Bitis gabonica; Blood pressure; Cardiovascular System - drug effects; Cardiovascular System - physiopathology; Crotalus durissus vegrandis; Daboia russelii; Daboia siamensis; Echis ocellatus; Heart Rate - drug effects; Heart Rate - physiology; Humanities and Social Sciences; Hypertension - chemically induced; Hypertension - physiopathology; Hypotension; Male; Mesenteric Arteries - drug effects; Mesenteric Arteries - physiopathology; multidisciplinary; Myography - methods; Pseudonaja textilis; Rats, Sprague-Dawley; Science; Science (multidisciplinary); Snakes; Time Factors; Vasodilation; Vasodilation - drug effects; Venom; Viper Venoms - administration & dosage; Viper Venoms - toxicity
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-56643-0

We investigated the cardiovascular effects of venoms from seven medically important species of snakes: Australian Eastern Brown snake ( Pseudonaja textilis ), Sri Lankan Russell’s viper ( Daboia russelii ), Javanese Russell’s viper ( D. siamensis ), Gaboon viper ( Bitis gabonica ), Uracoan rattlesnake ( Crotalus vegrandis ), Carpet viper ( Echis ocellatus ) and Puff adder ( Bitis arietans ), and identified two distinct patterns of effects: i.e. rapid cardiovascular collapse and prolonged hypotension. P. textilis (5 µg/kg, i.v.) and E. ocellatus (50 µg/kg, i.v.) venoms induced rapid (i.e. within 2 min) cardiovascular collapse in anaesthetised rats. P. textilis (20 mg/kg, i.m.) caused collapse within 10 min. D. russelii (100 µg/kg, i.v.) and D. siamensis (100 µg/kg, i.v.) venoms caused ‘prolonged hypotension’, characterised by a persistent decrease in blood pressure with recovery. D. russelii venom (50 mg/kg and 100 mg/kg, i.m.) also caused prolonged hypotension. A priming dose of P. textilis venom (2 µg/kg, i.v.) prevented collapse by E. ocellatus venom (50 µg/kg, i.v.), but had no significant effect on subsequent addition of D. russelii venom (1 mg/kg, i.v). Two priming doses (1 µg/kg, i.v.) of E. ocellatus venom prevented collapse by E. ocellatus venom (50 µg/kg, i.v.). B. gabonica , C. vegrandis and B. arietans (all at 200 µg/kg, i.v.) induced mild transient hypotension. Artificial respiration prevented D. russelii venom induced prolonged hypotension but not rapid cardiovascular collapse from E. ocellatus venom. D. russelii venom (0.001–1 μg/ml) caused concentration-dependent relaxation (EC 50  = 82.2 ± 15.3 ng/ml, R max  = 91 ± 1%) in pre-contracted mesenteric arteries. In contrast, E. ocellatus venom (1 µg/ml) only produced a maximum relaxant effect of 27 ± 14%, suggesting that rapid cardiovascular collapse is unlikely to be due to peripheral vasodilation. The prevention of rapid cardiovascular collapse, by ‘priming’ doses of venom, supports a role for depletable endogenous mediators in this phenomenon.