Abstract 1693: Predominant Vulnerability of the Right Ventricle to Arrhythmias in Aged Mouse Hearts.
Background Reduced excitability and electrical coupling have shown to affect impulse propagation and arrhythmogeneity, preferentially of the RV. We investigated the electrophysiological and tissue characteristics of aged mouse hearts, whether conduction abnormalities are also more dominant in the RV.
Methods Epicardial ventricular activation mapping (247 sites) was performed on 29 old (22 months) and 21 young (3 months) C57B/6 Langendorff perfused mouse hearts. ERP was determined by the extrastimulus method. Arrhythmia inducibility was tested by programmed stimulation (≥3 premature stimuli and burst pacing). Conduction velocity (CV) longitudinal and transversal (CVt) to the fiber orientation and heterogeneity of conduction was determined during pacing at BCL (150 ms). Hearts were processed for Cx43 immunohistochemistry, western blotting and Sirius Red staining of collagen. Cell size of isolated myocytes was measured.
Results Electrophysiological characteristics of the LV did not alter significantly with age. In contrast, in the aged RV, ERP (53.7±5.5 vs. 36.6±2.1 ms p=.008) and CVt (29.1±1.8 vs. 23.5±1.1 cm/s p=.012) decreased. Anisotropic ratio (1.4±0.06 vs. 1.8±0.11 p=.006) and CV heterogeneity (1.53±0.13 vs. 2.15±0.19 cm/s p=.018) increased with age. Arrhythmias were induced in 59% of aged hearts, none in young ones. Ninety percent of the arrhythmias originated from the RV and were due to anisotropic reentry. Cx43 protein levels of RV and LV were equally decreased in old mice. Interstitial fibrosis increased in both aged LV and RV compared to young hearts (p=.001). In addition, heterogeneously distributed patches of replacement fibrosis were present, extending throughout the entire RV myocardium, but only present in mid- and sub-endocardium of the LV. Notably, Cx43 expression in these areas was disrupted. LV myocytes were longer (132.3±4.1 vs. 138.6±2.3 μm p>.05) and broader (20.8±0.8 vs. 22.9±0.6 μm p=.04) than RV myocytes.
Conclusions Widespread presence of replacement fibrosis in the aged RV, together with the associated Cx43 disruption, and the smaller myocyte cell size, potentiate conduction heterogeneity and slowing in the RV. This, in combination with the shorter ERP, yields greater vulnerability of the aged RV to arrhythmias.