Reduced repolarization reserve due to anthracycline therapy facilitates torsade de pointes induced by IKr blockers

• Published in: Basic research in cardiology 2007-01, Vol.102 (1), p.42-51
• Main Authors: Milberg, Peter, Fleischer, Dirk, Stypmann, Jörg, Osada, Nani, Mönnig, Gerold, Engelen, Markus A, Bruch, Christian, Breithardt, Günter, Haverkamp, Wilhelm, Eckardt, Lars
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Animals; Antibiotics, Antineoplastic - adverse effects; Delayed Rectifier Potassium Channels - antagonists & inhibitors; Dose-Response Relationship, Drug; Doxorubicin - adverse effects; Electrocardiography; Erythromycin - adverse effects; Heart Conduction System - drug effects; In Vitro Techniques; Male; Rabbits; Stroke Volume - drug effects; Torsades de Pointes - chemically induced
• ISSN: 0300-8428; 1435-1803
• DOI: 10.1007/s00395-006-0609-0

Cytostatic agents such as anthracyclines may cause changes in the electrophysiologic properties of the heart. We hypothesized that anthracyclines facilitate life-threatening proarrhythmic side effects of cardiovascular and non-cardiovascular repolarization prolonging drugs. The electrophysiologic effects of chronic administration of doxorubicin (Dox) were studied in ten rabbits, which were treated with Dox twice a week (1.5 mg/kg i.v.). A control group (11 rabbits) was given NaCl solution. Two of ten Dox rabbits died suddenly, the remaining animals showed mild clinical signs of heart failure after a period of six weeks. Echocardiography demonstrated a decrease in ejection fraction (pre treatment: 74 +/- 23% to post treatment: 63 +/- 16% (p