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.

Synergistic effects of polydatin and vitamin C in inhibiting cardiotoxicity induced by doxorubicin in rats

“…Some studies confirm that urethane in animal anesthesia has minimal effects on autonomic and cardiovascular systems. In the present study, consistent with the literature, cardiac function and structure alteration in DOX group are verified including ECG changes such as QRS, QT, and ST interval prolongation , heart rate reduction , the descents in systolic blood pressure, diastolic blood pressure and pulse pressure , as well as myocardial degeneration, and increased mesenchymal cells. According to ECG results, polydatin, vitamin C, and combination could shorten QRS, ST, and QT intervals, and this shortening effect in combination group was more obvious than in single polydatin group or vitamin C group.…”

Ventricular repolarization in a rat model of global heart failure

“…Second, the ARI prolongation in isoproterenol‐induced heart failure was not uniform. Regional differences in prolongation of ARIs have been observed previously in rats with hypertensive LV hypertrophy and doxorubicin‐induced cardiomyopathy . Third, increasing repolarization heterogeneity was revealed in isoproterenol‐induced heart failure as a result of the non‐uniform ARI prolongation.…”

“…Electrophysiological remodelling of ventricular myocardium in isoproterenol‐induced heart failure was similar to that in doxorubicin‐induced heart failure . In both models of toxic cardiomyopathy, the non‐uniform prolongation of repolarization and increasing repolarization heterogeneity resulted in QT prolongation and T wave flattening; the apex‐to‐base difference in repolarization durations was due to the greatest prolongation of repolarization at the apex of the RV and alterations of ventricular repolarization were not associated with myocardial hypertrophy.…”

Suppression of hERG K+ current and cardiac action potential prolongation by 4-hydroxynonenal via dual mechanisms

“…Previous reports have discovered acquired QT prolongation in oxidative stress-related cardiac disease models and patients; patients with acute myocardial ischemia [26], undergoing balloon angioplasty [27], and patients or animal models of doxorubicin-induced cardiotoxicity [28], [29]. In fact, treatment with antioxidants was protective in the doxorubicin-induced cardiotoxicity model [30].…”