Effect of Cepharanthin on the lethality and cardiovascular disorder by Mamushi, Agkistrodon halys blomhoffii, snake venom

Effects of Cepharanthin on the lethality to mice and the cardiovascular disorder in rat induced by Mamushi (Agkistrodon halys blomhoffii) snake venom were studied. The LD 50 of Mamushi snake venom was 1. 22 mg/kg in mice by i.p. administration. Cepharanthin activated slightly the lethal activity when it was administered just after injection of the venom. However, this drug was effective against the venom at 4 to 5 times the lethal dose, if it was administered at the optimal interval. Mamushi snake venom and Cepharanthin showed a lethality and dose relationship that were clearly prolonged by Cepharanthin. In rat, Mamushi snake venom administered intraperitoneally produced an irreversible decrease of blood pressure accompanied by capillary hemorrhage. Moreover, it suppressed the heart rate. On the electrocardiogram, prolongation of ventricular contraction, extension of the relative refractory period and reduction of diastole were induced by the venom. These observations show that the venom suppresses cardiac functions inotropically and chronotropically. Cepharanthin shortened the refractory period and prolonged the diastole, indicating that it activated cardiac function. It was able to produce recovery from several cardiac disorders induced by Mamushi snake venom, for example, increase of blood pressure with inhibition of capillary hemorrage, release of heart rate suppression, partial recovery of the amplitudes of P and R waves, and shortening of extensive relative refractory period. These cardiac recoveries by Cepharanthin will be reflected in the suppression of lethality.