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

Abstract

AbstractWe 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.) andE. 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.) andD. siamensis(100 µg/kg, i.v.) venoms caused ‘prolonged hypotension’, characterised by a persistent decrease in blood pressure with recovery.D. russeliivenom (50 mg/kg and 100 mg/kg, i.m.) also caused prolonged hypotension. A priming dose ofP. textilisvenom (2 µg/kg, i.v.) prevented collapse byE. ocellatusvenom (50 µg/kg, i.v.), but had no significant effect on subsequent additionof D. russeliivenom (1 mg/kg, i.v). Two priming doses (1 µg/kg, i.v.) ofE. ocellatusvenom prevented collapse byE. ocellatusvenom (50 µg/kg, i.v.).B. gabonica,C. vegrandisandB. arietans(all at 200 µg/kg, i.v.) induced mild transient hypotension. Artificial respiration preventedD. russeliivenom induced prolonged hypotension but not rapid cardiovascular collapse fromE. ocellatusvenom.D. russeliivenom (0.001–1 μg/ml) caused concentration-dependent relaxation (EC50 = 82.2 ± 15.3 ng/ml, Rmax = 91 ± 1%) in pre-contracted mesenteric arteries. In contrast,E. ocellatusvenom (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.