title: Emetine-induced lactate dehydrogenase release, functional changes and electrocardiographic changes in the rat heart in vitro.
abstract: Emetine is an old drug which is used primarily as a emetic in ipecac syrup 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 mechanical activity and electrocardiograms, and biochemical assays were performed on male Sprague-Dawley rat hearts perfused by the Langendorff technique. Emetine was perfused constantly at concentrations of 19 or 37 mum for 10 min. All of the effects of emetine were concentration dependent. The most significant toxicological effect was the large amounts of LDH which appeared in the coronary effluent. A significant degree of injury to the cardiac plasma membrane is indicated by this observation, since LDH normally is an intracellular enzyme. Such damage to the membrane might accumulate and lead to the chronic, cumulative cardiotoxicity observed clinically with emetine. The pharmacological effects of emetine perfusion included decreased contractility which occurred concurrently with P-R interval prolongation, QRS duration prolongation, and degeneration of the QRS waveform. Coronary flow increased early during emetine perfusion, but then dropped to below control levels. The atria were more delayed in their response to emetine and in their recovery following emetine than were the ventricles. The simultaneous measurement of several parameters is a useful technique for the study of cardiac toxicity.
authors.affiliation: Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712-1074, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Pan
authors.forename: A B
authors.initials: AB
authors.lastname: Combs