title: Remodeling of ventricular repolarization in a chronic doxorubicin cardiotoxicity rat model.
abstract: Doxorubicin, one of the most effective anticancer drugs, is characterized by severe cardiotoxic effects, which induce cardiac remodeling and congestive heart failure. The aim of the study was to evaluate remodeling of ventricular repolarization heterogeneity in chronic doxorubicin cardiotoxicity in rats. Doxorubicin cardiotoxicity was produced by six equal intraperitoneal injections of the drug in a cumulative dose of 15 mg/kg in a 2-week period. Electrophysiological mapping of the ventricular epicardium in situ was performed 6 weeks after the last injection of doxorubicin. Activation-recovery intervals (ARIs) were used for the evaluation of the heterogeneity in repolarization durations. The major findings were as follows: (1) ARIs on the ventricular epicardium of both ventricles were significantly prolonged in the doxorubicin group and (2) this inhomogeneous prolongation of ARIs on the ventricular epicardium resulted in (i) the increase in the dispersion of repolarization across the ventricular epicardium and (ii) the inhomogeneous alterations of the regional ARI gradients on the ventricular epicardium. These changes in repolarization could explain the electrocardiographic alterations, that is, the prolongation of the QT interval and flattening of the T wave.
authors.affiliation: Laboratory of Cardiac Physiology, Institute of Physiology, Komi Science Centre, Ural Branch, Russian Academy of Sciences, 50, Pervomayskaya st., Syktyvkar, Komi Republic 167000, Russia. s.kharin@mail.ru
authors.forename: Sergey
authors.initials: S
authors.lastname: Kharin
authors.forename: Valeria
authors.initials: V
authors.lastname: Krandycheva
authors.forename: Alena
authors.initials: A
authors.lastname: Tsvetkova
authors.forename: Marina
authors.initials: M
authors.lastname: Strelkova
authors.forename: Dmitry
authors.initials: D
authors.lastname: Shmakov
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D004317:Doxorubicin / Q000633:toxicity*; D004562:Electrocardiography / Q000379:methods; D005260:Female; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced*; D006352:Heart Ventricles / Q000187:drug effects; D010496:Pericardium / Q000187:drug effects*; D051381:Rats; D016276:Ventricular Function / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin