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Updated: Jun 7, 2026
A Rat Model of Pressure Overload Induced Moderate Remodeling and Systolic Dysfunction as Opposed to Overt Systolic Heart Failure
Published on: April 30, 2020
Longitudinal arrhythmogenic remodelling in a mouse model of longstanding pressure overload
M Boulaksil1, M Noorman, M A Engelen
1Interuniversity Cardiology Institute of the Netherlands, Utrecht, and Department of Medical Physiology, Division of Heart & Lungs, University Medical Center Utrecht, Utrecht, the Netherlands.
Insights
Sudden cardiac death in heart failure is linked to electrical remodelling. In a mouse model, pressure overload caused arrhythmias due to heterogeneous connexin 43 (Cx43) expression, leading to unstable electrical conduction.
Area of Science:
- Cardiovascular Physiology
- Cardiac Electrophysiology
- Heart Failure Research
Background:
- Sudden arrhythmogenic cardiac death is a primary cause of mortality in congestive heart failure patients, often linked to adverse electrical remodelling.
- Investigating the role of abnormal conduction in arrhythmogenic remodelling during advanced heart failure stages is crucial.
Purpose of the Study:
- To monitor functional, structural, and electrical remodelling in a murine model of heart failure induced by chronic pressure overload.
- To determine if abnormal conduction contributes to arrhythmogenic remodelling in progressed heart failure.
Main Methods:
- Mice underwent transverse aortic constriction (TAC) or sham surgery, with biweekly echocardiography and electrocardiography monitoring.
- Epicardial electrical mapping assessed conduction velocity and arrhythmia susceptibility at 16 weeks.
- Tissue analysis included Cx43 expression and fibrosis quantification.
Main Results:
- TAC mice exhibited progressive decreases in fractional shortening and developed significant left ventricular hypertrophy.
- Electrical abnormalities included PQ, QT, and QRS prolongation, alongside slowed right ventricular conduction velocity.
- Polymorphic ventricular tachyarrhythmias occurred in 8/18 TAC hearts, correlated with increased interstitial fibrosis and heterogeneous Cx43 expression.
Conclusions:
- Chronic pressure overload rapidly induces structural and electrical remodelling in the heart.
- Arrhythmias in this model are associated with heterogeneous connexin 43 (Cx43) expression.
- This heterogeneity may cause functional blocks and unstable re-entry, precipitating ventricular tachyarrhythmias.
Introduction:
Sudden arrhythmogenic cardiac death is a major cause of mortality in patients with congestive heart failure due to adverse electrical remodelling. To establish whether abnormal conduction is responsible for arrhythmogenic remodelling in progressed stages of heart failure, we have monitored functional, structural and electrical remodelling in a murine model of heart failure, induced by longstanding pressure overload.
Methods:
Mice were subjected to transverse aortic constriction (TAC; n=18) or sham operated (n=19) and monitored biweekly by echocardiography and electrocardiography. At the 16-week endpoint, electrical mapping was performed to measure epicardial conduction velocity and susceptibility to arrhythmias. Finally, tissue sections were stained for Cx43 and fibrosis.
Results:
In TAC mice, fractional shortening decreased gradually and was significantly lower compared with sham at 16 weeks. Left ventricular hypertrophy was significant after six weeks. TAC mice developed PQ prolongation after 12 weeks, QT prolongation after 16 weeks and QRS prolongation after two weeks. Right ventricular conduction velocity was slowed parallel to fibre orientation. In 8/18 TAC hearts, polymorphic ventricular tachyarrhythmias were provoked and none in sham hearts. TAC mice had more interstitial fibrosis than sham. Immunohistology showed that Cx43 levels were similar but highly heterogeneous in TAC mice. All parameters were comparable in TAC mice with and without arrhythmias, except for Cx43 heterogeneity, which was significantly higher in arrhythmogenic TAC mice. CONCLUSION.: Chronic pressure overload resulted in rapid structural and electrical remodelling. Arrhythmias were related to heterogeneous expression of Cx43. This may lead to functional block and unstable reentry, giving rise to polymorphic ventricular tachyarrhythmias. (Neth Heart J 2010;18:509-15.).
