Transmural dispersion of repolarization and cardiac remodeling in ventricles of rabbit with right ventricular hypertrophy

Introduction: Recent publications demonstrated that rabbits with right ventricular hypertrophy (RVH) possess high sensitivity and specificity for drug-induced arrhythmias. However, the underlying mechanism has not been elucidated. This study aimed to evaluate RVH induced changes in cardiac remodeling especially the transmural dispersion of repolarization (TDR), epicardial monophasic action potentials (MAP), and hERG mRNA expression in rabbits. Methods: New Zealand White rabbits (n = 13) were divided into 2 groups: sham operated (SHAM, n = 6) and pulmonary artery banding (PAB, n = 7). PAB was induced by narrowing the pulmonary artery. Twenty weeks after surgery, hemodynamic, cardiac function, electrocardiograms, and MAP were obtained from PAB compared with SHAM. After measurement, rabbits were sacrificed to collect ventricular myocardium for histopathological analysis and measurement of hERG mRNA expression by real time PCR. Results: After 20 weeks, the % HW to BW ratio of whole heart and right ventricle (RV) and left and right ventricular free wall thickness was significantly increased in PAB when compared with those in SHAM. PAB has a significant electrical remodeling as demonstrated by lengthening of QT, QTc intervals, and increased Tp-Te duration. PAB also has a significant functional remodeling verified by decreased contractility index of RV and lengthened time constant of relaxation of LV. MAP of RV epicardium was significantly shortened in PAB consistently with increased hERG mRNA expression at the epicardium of RV. Discussion: The rabbit with PAB demonstrates cardiac remodeling diastolic and systolic dysfunctions. These rabbits also demonstrate increased TDR and electrical remodeling related to the change of hERG mRNA expression which may be prone to develop arrhythmias. (C) 2014 Elsevier Inc. All rights reserved.