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Interuniversity Cardiology Institute of the Netherlands, Utrecht, and Department of Medical Physiology, Division of Heart & Lungs, University Medical Center Utrecht, Utrecht, the Netherlands
Department of Medical Physiology, Division of Heart & Lungs, University Medical Center Utrecht, Utrecht, the Netherlands and Department of Cardiology and Angiology, University Hospital Muenster, Muenster, Germany
Department of Medical Physiology, Division of Heart & Lungs, University Medical Center Utrecht, Utrecht, the Netherlands
Interuniversity Cardiology Institute of the Netherlands, Utrecht, Department of Medical Physiology, Division of Heart & Lungs, University Medical Center Utrecht, Utrecht, and Heart Failure Research Center, Academic Medical Center, Amsterdam, the Netherlands
Division of Heart & Lungs, Department of Medical Physiology, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, the Netherlands
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.)
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- Longitudinal arrhythmogenic remodelling in a mouse model of longstanding pressure overload
M. A. Engelen
T. A. B. van Veen
M. A. Vos
J. M. T. de Bakker
H. V. M. van Rijen
- Bohn Stafleu van Loghum