EMETINE-INDUCED LACTATE-DEHYDROGENASE RELEASE, FUNCTIONAL-CHANGES ANDELECTROCARDIOGRAPHIC CHANGES IN THE RAT-HEART IN-VITRO

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.