586 8th Wofkl COI)IplMI on .Animml: ~ ~ llb~Cl.

ob~ TOXJ~I
CORONARY V ~ P A S MAS THE PRIMARY CAUSE OF DEATH DUE TO EQDINATOXINe
. A TOXIC. PROTEIN FROM .ACTINIA EOOIN&
C. Y. LEE | , S . Y . L~E L, Y . M . CHENI,----~.~ . ~ and I. Ferlan3.
Depts of Pharmacology" and Clinical Pathology-, College of Medicine,
National Ta~wan University, Talpe2, Talwan, R.O.C. and Dept of
Biochemistry ", J. Stefan Institute, University of LjublJana, LJublJana,
Yugoslavia.
The main cause of death due to equinatoxln purified from the
tentacles of Actinla equina has been attributed to circulatory failure,
resulting from its cardiotoxic effects (Sket et al., 1974; Lee et al.,
1983). The effects of equinatoxin on the rat heart were further studied
using both isolated atrial and Langendorff preparations. A dose as low
as 0.3 pg of the toxin injected into the perfusion system produced a
marked coronary vasospasm and a decrease in both contractility and
ventrlcular rate In the Langendorff preparation, whereas no deleterious
effect was found in the atrial preparation at a concentration as high as
10 pg/ml. In the latter preparation, a transient decrease followed by an
increase in the contractility lasting for a few minutes was observed.
The negative Inotroplsm was attenuated by atropine (0.3)~g/ml), while the
positive Inotropism was largely antagonized by Indomethacin 43 pg/ml),
suggesting release of acetylcholine as well as prostaglandins by the
toxin. The coronary vasospasm was not antagonized by papaverine (10
)~g/ml), nitroglycerin (10 ~g/ml), dipyrldamole 40.3 )ig/ml}, Indomethacln
(I yg/ml), FPL-55712 (0.1)Jg/ml), v ~ a p a m l l (0.1 ~g/ml), and low Ca ~+
(0.8 mM) but largely attenuated in Ca -free medium. It is concluded
that the cardlotoxlc effect of equlnatoxln observed in anesthetized rats
and mice is due to myocardial anoxla caused by coronary vasospasm.

REFERENCES
Lee, C.Y., Lee, S.Y., Chen, Y.M. and Ferlan, I. 41983} Toxlcol. letters,
18 (suppl. I), 118.
Sket, D., Draslar, K., Ferlan, I. and Lebez, D. (1974) Toxicon 12, 63.
KEY WORDS
Equlnatoxln; Actlnla equina; coronary vasospasm

ON THE CAUSES OF DEATH DUE TO TOXIC P ~ P R O L I P A S E S A 2 FRGII S N J U [ E V ~

C. ¥. LEE I, S. ¥. LEE 2, Y. M. CHEN I AND W. W. LIN I

Depts of Pharmacology I and Clinical Pathology 2, College of Medicine,

National Taiwan University, Talpei, Taiwan, R.O.C.

The causes of death due to toxic phospholipases A 2 (PLA~) isolated

from elapld ( B -bungarotoxin, talpoxln, CM-I, CM~II and CM-III from NaJa
m. mossambica) and vlperld venoms (k and ~o from Vipera ammodytes) were
studied on anesthetized mice. Th~ carotid arterial blood pressure
(B.P.), ECG and respiratory movements were recorded and immediately after
respiratory arrest, artificial respiration (A.R.) was applied. According
to the length of A.R. that can maintain B.P., in addition to ECG changes
observed, these toxic PLA2s may be classified into the following three
categories:
(I) The cause of death is paralysis of respiratory muscles and B.P. can
be maintained by A.R. for a long period (more than 2 hrs). Most
presynaptlc neurotoxins, such as B-bungarotoxln, talpoxin and V.
ammodytes ~2 belong to this category. 42) The primary cause of death is
circulatory failure, and B.P. cannot be maintained by A.R. Myonecrotic
PLA~s, such as CM-I, CM-II and CM-III from N. m. mossambica belong to
thig category. Various ECG changes observed in mice appear to be due to
pulmonary edema and hyperkalemla rather than direct cardiotoxic effects,
since no deleterious effect was observed in the rat atrlaI preparation
up to 30 pg/ml of these PLAgs. (3) The primary cause of death is
respiratory paralysis but clr~ulatory failure resulting from pulmonary
edema ~ay also contribute to the cause of death. In this case, B.P. can
be maintained by A.R. only for a short period (leas than 30 mln). V_~
-mmodytes ~I belongs to this category.
WORDS
Toxic phoapholipase A2; ~bungarotoxln; talpoxln; NaSa m. mossamblca.