Effects of pharmacological interventions on emetine cardiotoxicity in isolated perfused rat hearts.
The cardiotoxicity of emetine continues to be a significant clinical problem. The purpose of this study was to investigate the effect of several mechanistic interventions, including ICRF-187, an iron-chelating agent which protects against doxorubicin toxicity, atropine, and fructose-1,6-bisphosphate (FBP) on the toxicity of emetine in our isolated, perfused rat heart model. The model includes functional, electrocardiographic, and biochemical determinations in the same preparation. Atropine and ICRF-187 had no effect on the time needed for emetine to induce ventricular asystole, while FBP significantly increased this time. Administration of 47 microM atropine, 300 microM FBP, or 1 mM FBP decreased the release of lactate dehydrogenase (LDH) into the coronary effluent, while ICRF-187 had no effect. These pharmacological interventions variably 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.
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Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin 78712-1074, USA.
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D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D004562:Electrocardiography; D004640:Emetine / Q000633:toxicity*; D005635:Fructosediphosphates / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D011929:Razoxane / Q000494:pharmacology
D005635:Fructosediphosphates; D011929:Razoxane; D001285:Atropine; D007770:L-Lactate Dehydrogenase; C029063:fructose-1,6-diphosphate; D004640:Emetine