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Evaluation of cardiac electrophysiological properties in an experimental model of right ventricular hypertrophy and failure*

Published online by Cambridge University Press:  14 April 2015

Jacob G. Schultz Open the ORCID record for Jacob G. Schultz [Opens in a new window] ,
Stine Andersen ,
Asger Andersen ,
Jens Erik Nielsen-Kudsk  and
Jan M. Nielsen
Jacob G. Schultz*
Affiliation:
Department of Cardiology, Institute of Clinical Medicine, Aarhus University Hospital, Denmark
Stine Andersen
Affiliation:
Department of Cardiology, Institute of Clinical Medicine, Aarhus University Hospital, Denmark
Asger Andersen
Affiliation:
Department of Cardiology, Institute of Clinical Medicine, Aarhus University Hospital, Denmark
Jens Erik Nielsen-Kudsk
Affiliation:
Department of Cardiology, Institute of Clinical Medicine, Aarhus University Hospital, Denmark
Jan M. Nielsen
Affiliation:
Department of Cardiology, Institute of Clinical Medicine, Aarhus University Hospital, Denmark
*
Correspondence to: J. G. Schultz, Department of Cardiology–Research, Aarhus University Hospital, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark. Tel: +4529702879; Fax: +4578452260; E-mail: jacobgschultz@gmail.com
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Abstract

Background

Malignant arrhythmias are a major cause of sudden cardiac death in adults with congenital heart disease. We developed a model to serially investigate electrophysiological properties in an animal model of right ventricular hypertrophy and failure.

Method

We created models of compensated (cHF; n=11) and decompensated (dHF; n=11) right ventricular failure in Wistar rats by pulmonary trunk banding. Healthy controls underwent sham operation (Control; n=13). Surface electrocardiography was recorded from extremities, and inducibility of ventricular tachycardia was evaluated in vivo by programmed stimulation. Isolated right ventricular myocardium was analysed for mRNA expression of selected genes.

Results

Banding caused an increased mRNA expression of both connexin 43 and the voltage-gated sodium channel 1.5, as well as a prolongation of PQ, QRS and QTc intervals. Ventricular tachycardia was induced in the majority of banded animals compared with none in the healthy control group. No differences were found between the two degrees of failure in neither the electrophysiological parameters nor inducibility.

Conclusions

The electrophysiological properties of rat hearts subjected to pulmonary trunk banding were significantly changed with increased susceptibility to ventricular tachycardia, but no differences were found between compensated and decompensated right ventricular failure. Furthermore, we demonstrate that in vivo electrophysiological evaluation is a sensitive method to characterise the cardiac electric phenotype in an experimental rat model.

Keywords

Heart failureventricular tachycardiapulmonary trunk bandingadults with congenital heart diseaseright ventricle
Type
Original Articles
Information
Cardiology in the Young , Volume 26 , Issue 3 , March 2016 , pp. 451 - 458
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Copyright
© Cambridge University Press 2015 

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Footnotes

*

All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

†

Both authors contributed equally.

References

1. Walsh, EP, Cecchin, F. Arrhythmias in adult patients with congenital heart disease. Circulation 2007; 115: 534–545.Google Scholar
2. Walsh, EP. Sudden death in adult congenital heart disease: risk stratification in 2014. Heart Rhythm 2014; 11: 1735–1742.CrossRefGoogle ScholarPubMed
3. Gatzoulis, MA, Walters, J, McLaughlin, PR, Merchant, N, Webb, GD, Liu, P. Late arrhythmia in adults with the mustard procedure for transposition of great arteries: a surrogate marker for right ventricular dysfunction? Heart 2000; 84: 409–415.Google Scholar
4. Roche, L, Redington, AN. The failing right ventricle in congenital heart disease. Can J Cardiol 2013; 29: 768–778.Google Scholar
5. Daliento, L, Rizzoli, G, Menti, L, et al. Accuracy of electrocardiographic and echocardiographic indices in predicting life threatening ventricular arrhythmias in patients operated for tetralogy of Fallot. Heart 1999; 81: 650–655.Google Scholar
6. Valente, AM, Gauvreau, K, Assenza, GE, et al. Contemporary predictors of death and sustained ventricular tachycardia in patients with repaired tetralogy of Fallot enrolled in the INDICATOR cohort. Heart 2014; 100: 247–253.CrossRefGoogle ScholarPubMed
7. Park, SJ, On, YK, Kim, JS, et al. Relation of fragmented QRS complex to right ventricular fibrosis detected by late gadolinium enhancement cardiac magnetic resonance in adults with repaired tetralogy of Fallot. Am. J. Cardiol 2012; 109: 110–115.Google Scholar
8. Gatzoulis, MA, Till, JA, Somerville, J, Redington, AN. Mechanoelectrical interaction in tetralogy of Fallot. QRS prolongation relates to right ventricular size and predicts malignant ventricular arrhythmias and sudden death. Circulation 1995; 92: 231–237.CrossRefGoogle ScholarPubMed
9. Andersen, S, Schultz, JG, Andersen, A, et al. Effects of bisoprolol and losartan treatment in the hypertrophic and failing right heart. J Card Fail 2014; 20: 864–873.Google Scholar
10. Rosker, C, Salvarani, N, Schmutz, S, Grand, T, Rohr, S. Abolishing myofibroblast arrhythmogeneicity by pharmacological ablation of smooth muscle actin containing stress fibers. Circ Res 2011; 109: 1120–1131.CrossRefGoogle ScholarPubMed
11. Bishop, JE, Rhodes, S, Laurent, GJ, Low, RB, Stirewalt, WS. Increased collagen synthesis and decreased collagen degradation in right ventricular hypertrophy induced by pressure overload. Cardiovasc Res 1994; 28: 1581–1585.CrossRefGoogle ScholarPubMed
12. Braun, MU, Szalai, P, Strasser, RH, Borst, MM. Right ventricular hypertrophy and apoptosis after pulmonary artery banding: regulation of PKC isozymes. Cardiovasc Res 2003; 59: 658–667.Google Scholar
13. Tanaka, Y, Takase, B, Yao, T, Ishihara, M. Right ventricular electrical remodeling and arrhythmogenic substrate in rat pulmonary hypertension. Am J Respir Cell Mol Biol 2013; 49: 426–436.Google Scholar
14. Akhavein, F, St-Michel, EJ, Seifert, E, Rohlicek, CV. Decreased left ventricular function, myocarditis, and coronary arteriolar medial thickening following monocrotaline administration in adult rats. J Appl Physiol 2007; 103: 287–295.Google Scholar
15. Rich, JD, Thenappan, T, Freed, B, et al. QTc prolongation is associated with impaired right ventricular function and predicts mortality in pulmonary hypertension. Int J Cardiol 2013; 167: 669–676.Google Scholar
16. Khairy, P, Landzberg, MJ, Gatzoulis, MA, et al. Value of programmed ventricular stimulation after tetralogy of Fallot repair: a multicenter study. Circulation 2004; 109: 1994–2000.Google Scholar
17. Burstein, B, Nattel, S. Atrial fibrosis: mechanisms and clinical relevance in atrial fibrillation. J Am Coll Cardiol 2008; 51: 802–809.Google Scholar
18. Kantharia, BK. Cardiac arrhythmias in congestive heart failure. Expert Rev Cardiovasc Ther 2010; 8: 137–140.Google Scholar
19. Uzzaman, M, Honjo, H, Takagishi, Y, et al. Remodeling of gap junctional coupling in hypertrophied right ventricles of rats with monocrotaline-induced pulmonary hypertension. Circ Res 2000; 86: 871–878.CrossRefGoogle ScholarPubMed
20. Shang, LL, Pfahnl, AE, Sanyal, S, et al. Human heart failure is associated with abnormal C-terminal splicing variants in the cardiac sodium channel. Circ Res 2007; 101: 1146–1154.CrossRefGoogle ScholarPubMed
21. Shryock, JC, Song, Y, Rajamani, S, Antzelevitch, C, Belardinelli, L. The arrhythmogenic consequences of increasing late INa in the cardiomyocyte. Cardiovasc Res 2013; 99: 600–611.Google Scholar
22. Wickenden, AD, Kaprielian, R, Kassiri, Z, et al. The role of action potential prolongation and altered intracellular calcium handling in the pathogenesis of heart failure. Cardiovasc Res 1998; 37: 312–323.Google Scholar