Sj. Pan et Ab. Combs, EMETINE-INDUCED LACTATE-DEHYDROGENASE RELEASE, FUNCTIONAL-CHANGES ANDELECTROCARDIOGRAPHIC CHANGES IN THE RAT-HEART IN-VITRO, Toxicology in vitro, 9(3), 1995, pp. 219-229
Emetine is an old drug which is used primarily as a emetic in ipecac s
yrup and as an alternative amoebicide. The major problem with emetine
is that chronic use causes severe cardiotoxicity. In order to explore
the mechanism of emetine cardiotoxicity, simultaneous recordings of me
chanical activity and electrocardiograms, and biochemical assays were
performed on male Sprague-Dawley rat hearts perfused by the Langendorf
f technique. Emetine was perfused constantly at concentrations of 19 o
r 37 mu M for 10 min. All of the effects of emetine were concentration
dependent. The most significant toxicological effect was the large am
ounts of LDH which appeared in the coronary effluent. A significant de
gree of injury to the cardiac plasma membrane is indicated by this obs
ervation, since LDH normally is an intracellular enzyme. Such damage t
o the membrane might accumulate and lead to the chronic, cumulative ca
rdiotoxicity observed clinically with emetine. The pharmacological eff
ects of emetine perfusion included decreased contractility which occur
red concurrently with P-R interval prolongation, QRS duration prolonga
tion, and degeneration of the QRS waveform. Coronary flow increased ea
rly during emetine perfusion, but then dropped to below control levels
. The atria were more delayed in their response to emetine and in thei
r recovery following emetine than were the ventricles. The simultaneou
s measurement of several parameters is a useful technique for the stud
y of cardiac toxicity.