EFFECTS OF PHARMACOLOGICAL INTERVENTIONS ON EMETINE CARDIOTOXICITY INISOLATED-PERFUSED RAT HEARTS

The cardiotoxicity of emetine continues to be a significant clinical p roblem. The purpose of this study was to investigate the effect of sev eral mechanistic interventions, including ICRF-187, an iron-chelating agent which protects against doxorubicin toxicity, atropine, and fruct ose-1,6-bisphosphate (FBP) on the toxicity of emetine in our isolated, perfused rat heart model. The model includes functional, electrocardi ographic, and biochemical determinations in the same preparation. Atro pine and ICRF-187 had no effect on the time needed for emetine to indu ce ventricular asystole, while FBP significantly increased this time. Administration of 47 mu M atropine, 300 mu M FBP, or 1 mM FBP decrease d the release of lactate dehydrogenase (LDH) into the coronary effluen t, while ICRF-187 had no effect. These pharmacological interventions v ariably changed the amplitude of the biphasic response of the coronary flow to emetine. Finally, FBP was very effective in slowing the rate of QRS-waveform degeneration in the perfused hearts. Emetine caused PR - and QRS-prolongation which was not altered by FBP.