Spatial Heterogeneity of Cx43 is an Arrhythmogenic Substrate of Polymorphic Ventricular Tachycardias during Compensated Cardiac Hypertrophy in Rats

• Published in: Frontiers in cardiovascular medicine 2016-03, Vol.3, p.5-5
• Main Authors: Boulaksil, Mohamed, Bierhuizen, Marti F A, Engelen, Markus A, Stein, Mèra, Kok, Bart J M, van Amersfoorth, Shirley C M, Vos, Marc A, van Rijen, Harold V M, de Bakker, Jacques M T, van Veen, Toon A B
• Format: Article
• Language: English
• Subjects: arrhythmia; Cardiovascular Medicine; Electrophysiology; Gap Junctions; Hypertrophy; sudden death
• ISSN: 2297-055X; 2297-055X
• DOI: 10.3389/fcvm.2016.00005

Ventricular remodeling increases the propensity of ventricular tachyarrhythmias and sudden death in patients. We studied the mechanism underlying these fatal arrhythmias, electrical and structural cardiac remodeling, as well as arrhythmogeneity during early, compensated hypertrophy in a rat model of chronic pressure overload. Twenty-six Wistar rats were subjected to transverse aortic constriction (TAC) (n = 13) or sham operation (n = 13). Four weeks postoperative, echo- and electrocardiography was performed. Epicardial (208 or 455 sites) and transmural (30 sites) ventricular activation mapping was performed on Langendorff perfused hearts. Subsequently, hearts were processed for (immuno)histological and molecular analyses. TAC rats showed significant hypertrophy with preserved left ventricular (LV) function. Epicardial conduction velocity (CV) was similar, but more dispersed in TAC. Transmural CV was slowed in TAC (37.6 ± 2.9 cm s(-1)) compared to sham (58.5 ± 3.9 cm s(-1); P