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Updated: Apr 6, 2026
A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy
Published on: November 7, 2017
Arrhythmogenic Remodeling in Murine Models of Deoxycorticosterone Acetate-Salt-Induced and 5/6-Subtotal
Magda S C Fontes1, Diana A Papazova2, Arianne van Koppen2
1Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands.
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.
Insights
Renal failure in mice models leads to cardiac dysfunction, increasing susceptibility to ventricular arrhythmias. Reduced connexin 43 and increased fibrosis contribute to this arrhythmogenic substrate.
Area of Science:
- Cardiovascular Research
- Nephrology
- Electrophysiology
Background:
- Renal failure is linked to cardiac remodeling and sudden cardiac death.
- Mechanisms of cardiac arrhythmogenicity in cardiorenal syndrome remain unclear.
- This study investigates electrophysiological and tissue changes in renal failure models.
Purpose of the Study:
- To characterize electrophysiological and tissue alterations in mouse models of renal failure.
- To correlate these changes with enhanced arrhythmogenicity.
- To elucidate the mechanisms behind cardiorenal syndrome-induced arrhythmias.
Main Methods:
- Two mouse models of renal failure were used: DOCA-salt aged and 5/6 subtotal nephrectomy (SNx)-salt adult.
- Epicardial mapping assessed arrhythmia vulnerability and cardiac conduction velocities (CVs).
- Hearts were analyzed for connexin 43 (Cx43) expression and interstitial fibrosis.
Main Results:
- Both models exhibited renal dysfunction (albuminuria) and high susceptibility to ventricular arrhythmias.
- DOCA-salt mice showed increased heart, lung, and kidney weights.
- Reduced Cx43 expression and increased interstitial fibrosis were observed in both models; CVs were decreased in DOCA-salt mice.
Conclusions:
- Renal dysfunction in these models induces cardiac remodeling and enhances arrhythmogenicity.
- Decreased Cx43 expression and increased fibrosis are key factors in the arrhythmogenic substrate formation.
- These findings provide insights into the cardiorenal syndrome's impact on cardiac electrical stability.
