DOCA-salt and SNx-salt treatment in mice induced renal dysfunction, cardiac remodeling, and enhanced arrhythmogenicity associated with reduced Cx43 expression and increased interstitial fibrosis.
Does cardiorenal disease induced by DOCA-salt or SNx-salt treatment increase arrhythmogenicity and structural/electrical cardiac remodeling in mice?
In murine models of cardiorenal disease, renal dysfunction leads to structural and electrical cardiac remodeling, including reduced Cx43 expression and increased fibrosis, which enhances susceptibility to ventricular arrhythmias.
BACKGROUND: Renal failure is associated with adverse cardiac remodeling and sudden cardiac death. The mechanism leading to enhanced arrhythmogenicity in the cardiorenal syndrome is unclear. The aim of this study was to characterize electrophysiological and tissue alterations correlated with enhanced arrhythmogenicity in two distinct mouse models of renal failure. METHODS: Thirty-week-old 129Sv mice received a high-salt diet and deoxycorticosterone acetate (DOCA) for 8 weeks, followed by an additional period of high-salt diet for 27 weeks (DOCA-salt aged model). Adult CD-1 mice were submitted to 5/6-subtotal nephrectomy (SNx) and treated for 11 weeks with a high-salt diet (SNx-salt adult model). Vulnerability to arrhythmia as well as conduction velocities (CVs) of the hearts were determined ex vivo with epicardial mapping. Subsequently, the hearts were characterized for connexin 43 (Cx43) and fibrosis. RESULTS: DOCA-salt and SNx-salt mice developed renal dysfunction characterized by albuminuria. Heart, lung and kidney weights were increased in DOCA-salt mice. Both DOCA-salt and SNx-salt mice were highly susceptible to ventricular arrhythmias. DOCA-salt mice had a significant decrease in both longitudinal and transversal CV in the left ventricle. Histological analysis revealed a significant reduction in Cx43 expression as well as an increase in interstitial fibrosis in both DOCA-salt and SNx-salt mice. CONCLUSION: DOCA-salt and SNx-salt treatment induced renal dysfunction, which resulted in structural and electrical cardiac remodeling and enhanced arrhythmogenicity. The reduced Cx43 expression and increased fibrosis levels in these hearts are likely candidates for the formation of the arrhythmogenic substrate.
Fontes et al. (Thu,) conducted a other in Cardiorenal disease. Deoxycorticosterone acetate (DOCA)-salt and 5/6-subtotal nephrectomy (SNx)-salt was evaluated on Vulnerability to arrhythmia, conduction velocities, connexin 43 expression, and fibrosis. DOCA-salt and SNx-salt treatment in mice induced renal dysfunction, cardiac remodeling, and enhanced arrhythmogenicity associated with reduced Cx43 expression and increased interstitial fibrosis.