한국산(韓國産) 사독(蛇毒)에 관(關)한 실험적(實驗的) 연구(硏究)

Experimental Studies on Korean Snake Venoms

Agkistrodon halys (Crotalidae) is the only species of poisonous snakes in Korea, and is divided into three subspecies; Agkistrodon bromhoffii brevicaudus, Agkistrodon calaginosus and Agkistrodon saxatilis. With the three venoms, the pharmacological actions on the cardiovascular system and intestine as well as some toxicological characteristics were studied. In addition, the precipitin test in an agar gel medium was employed for immunological comparison of the venoms and the sera of envenomed patients. The results obtained were as follows: Lyophilized venoms contained solids of $211{\sim}273mg/ml$, and LD50 to mice were 1.73 and 0.86 mg/kg in venoms of Agkistrodon bromhoffii brevicaudus obtained on July and October respectively, and 0.40 and 0.32 mg/kg in Agkistrodon calaginosus and the venoms of Agkistrodon saxatilis obtained on October was 2.29 mg/kg. Isoelectric focusing of lyophilized snake venoms showed 19 to 22 protein fractions and 2 to 3 isoamylase fractions. Acute irreversible hypotension was caused by the intravenous injection of large doses of venoms in rabbits and cats, but at the small doses, acute hypotension followed by slow recovery. Little changes of cardiac movements by the venom injection despite of marked hypotension were showed except bradycardia and arrhythmia prior the death. Also no changes on the isolated rabbit atria by the snake venoms were noted. The hypotensive effect of the snake venoms was prevented by the bilateral vagotomy or atropine pretreatment (1 mg/kg), but they did not affect when already the hypotension has undergone. In the isolated rabbit duodenum, small doses of venom increased the phasic movement, while large doses decreased after spastic contraction. With the injection of venoms in dog, strong contraction of gall-bladder was caused and it was not blocked by the pretreatment with phenoxybenzamine (10 mg/kg) or atropine (1.4 mg/kg). In the venoms of Agkistrodon bromhoffii brevicaudus and Agkistrodon calaginosus, at least 5 antigenic components were detected, and four of them were shared in common with each other. Polyvalent antivenin (Wyeth Lab. USA) had three common precipitating antibodies with the venom of Agkistrodon bromhoffii brevicaudus and Akistrodon calaginosus. In the serum of envenomed patients, no precipitating antibodies were seen to the venoms and little changes in serum protein, GOT and GPT were observed. In conclusion, the snake venoms obtained in Korea were highly toxic and caused chiefly the vascular collapse leading to death. This vascular collapse was resulted largely by cholinergic effects, and not cardiotoxin of venoms. In human, it is likely that precipitating antibodies to venom were not produced by an envenomed incidence to poisonous snakes.