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Development of a Swine Model of Left Bundle Branch Block for Experimental Studies of Cardiac Resynchronization Therapy

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Abstract

Animal models that mimic human electrical and mechanical dyssynchrony often associated with chronic heart failure would provide an essential tool to investigate factors influencing response to cardiac resynchronization therapy. A standardized closed-chest porcine model of left bundle branch block (LBBB) was developed using 16 pigs. Radiofrequency applications were performed to induce LBBB, which was confirmed by QRS widening, a surface electrocardiogram pattern concordant with LBBB, and a prolonged activation time from endocardial. Echocardiography confirmed abnormal motion of the septum, which was not present at the baseline echocardiogram. High susceptibility of pigs to ventricular fibrillation during the endocardial ablation was overcome by applying high-rate pacing during radiofrequency applications. This is the first study to devise a closed-chest porcine model of LBBB that closely reproduces abnormalities found in patients with electrical and mechanical cardiac dyssynchrony, and provides a useful tool to investigate the basic mechanisms underlying cardiac resynchronization therapy benefits in heart failure.

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References

  1. Cleland, J. G., Daubert, J. C., Erdmann, E., Freemantle, N., Gras, D., Kappenberger, L., et al. (2005). The effect of cardiac resynchronization on morbidity and mortality in heart failure. The New England Journal of Medicine, 352(15), 1539–1549.

    Article  PubMed  CAS  Google Scholar 

  2. Solanes, N., Rigol, M., Khabiri, E., Castellà, M., Ramírez, J., Roqué, M., et al. (2005). Effects of cryopreservation on the immunogenicity of porcine arterial allografts in early stages of transplant vasculopathy. Cryobiology, 5, 1130–1141.

    Google Scholar 

  3. Rigol, M., Solanes, N., Sionis, A., Gálvez, C., Martorell, J., Rojo, I., et al. (2008). Effects of cyclosporine, tacrolimus and sirolimus on vascular changes related to immune response. The Journal of Heart and Lung Transplantation, 27, 416–422.

    Article  PubMed  Google Scholar 

  4. Rigol, M., Solanes, N., Farré, J., Roura, S., Roqué, M., Berruezo, A., et al. (2010). Effects of adipose tissue-derived stem cell therapy after myocardial infarction: impact of the route of administration. Journal Cardiac Failure, 16, 357–366.

    Article  CAS  Google Scholar 

  5. Shofti, R., Zaretzki, A., Cohen, E., Engel, A., & Bar-El, Y. (2004). The sheep as a model for coronary artery bypass surgery. Laboratory Animals, 38, 149–157.

    Article  PubMed  CAS  Google Scholar 

  6. Chorro, F. J., Such-Belenguer, L., & López-Merino, V. (2009). Animal models of cardiovascular disease. Revista Española de Cardiología, 62(1), 69–84.

    Article  PubMed  Google Scholar 

  7. Murry, C. E., Field, L. J., & Menasché, P. (2005). Cell-based cardiac repair: reflections at the 10-year point. Circulation, 112(20), 3174–3183.

    Article  PubMed  Google Scholar 

  8. van Deursen, C., van Geldorp, I. E., Rademakers, L. M., van Hunnik, A., Kuiper, M., Klersy, C., et al. (2009). Left ventricular endocardial pacing improves resynchronization therapy in canine left bundle-branch hearts. Circular Arrhythm Electrophysiology, 2(5), 580–587.

    Article  Google Scholar 

  9. Mills, R. W., Cornelussen, R. N., Mulligan, L. J., Strik, M., Rademakers, L. M., Skadsberg, N. D., et al. (2009). Left ventricular septal and left ventricular apical pacing chronically maintain cardiac contractile coordination, pump function and efficiency. Circular Arrhythm Electrophysiology, 2(5), 571–579.

    Article  Google Scholar 

  10. Vernooy, K., Verbeek, X. A., Peschar, M., Crijns, H. J., Arts, T., Cornelussen, R. N., et al. (2005). Left bundle branch block induces ventricular remodelling and functional septal hypoperfusion. European Heart Journal, 26, 91–98.

    Article  PubMed  Google Scholar 

  11. Kerckhoffs, R. C. P., Lumens, J., Vernooy, K., Omens, J. H., Mulligan, L. J., Delhaas, T., et al. (2008). Cardiac resynchronization: insight from experimental and computational models. Progress in Biophysics and Molecular Biology, 97(2–3), 543–561.

    Article  PubMed  CAS  Google Scholar 

  12. Marrouche, N. F., Pavia, S. V., Zhuang, S., et al. (2002). Nonexcitatory stimulus delivery improves left ventricular function in hearts with left bundle branch block. Journal of Cardiovascular Electrophysiology, 13, 691–695.

    Article  PubMed  Google Scholar 

  13. Parsai, C., Bijnens, B., Sutherland, G. R., Kim, Y. J., Tabata, T., Wallick, D., et al. (2009). Toward understanding response to cardiac resynchronization therapy: left ventricular dyssynchrony is only one of multiple mechanisms. European Heart Journal, 30, 940–949.

    Article  PubMed  Google Scholar 

  14. Olgin, J. E., & Zipes, D. P. (2007). Specific Arrhythmias: Diagnosis and Treatment. In P. Libby, R. O. Bonow, D. L. Mann, & D. P. Zipes (Eds.), Braunwald’s heart disease: a textbook of cardiovascular medicine (8th ed.). Philadelphia: Saunders Elsevier. Chap 35.

    Google Scholar 

  15. Thomas, G., Gurung, I. S., Killeen, M. J., Hakim, P., Goddard, C. A., Mahaut-Smith, M. P., et al. (2007). Effects of L-type Ca2+ channel antagonism on ventricular arrhythmogenesis in murine hearts containing a modification in the Scn5a gene modelling human long QT syndrome 3. The Journal of Physiology, 578(Pt 1), 85–97.

    PubMed  CAS  Google Scholar 

  16. Bordachar, P., Grenz, N., Jais, P., Ritter, P., Leclercq, C., Morgan, J. M., et al. (2012). Left ventricular endocardial or triventricular pacing to optimize cardiac resynchronization therapy in a chronic canine model of ischemic heart failure. American Journal of Physiology - Heart and Circulatory Physiology, 303(2), H207–H215.

    Article  PubMed  CAS  Google Scholar 

  17. Liu, L., Tockman, B., Girouard, S., Pastore, J., Walcott, G., KenKnight, B., et al. (2002). Left ventricular resynchronization therapy in a canine model of left bundle branch block. American Journal of Physiology - Heart and Circulatory Physiology, 282, H2238–H2244.

    PubMed  CAS  Google Scholar 

  18. Vernooy, K., Cornelussen, R. N. M., Verbeek, X. A., Vanagt, W. Y., van Hunnik, A., Kuiper, M., et al. (2007). Cardiac resynchronization therapy cures dyssynchronopathy in canine left bundle-branch block hearts. European Heart Journal, 28, 2148–2155.

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors are grateful to the Universitat de Barcelona facilities, Neus Portella (Hospital Clínic, Barcelona, Spain) for assistance, and Elaine Lilly, Ph.D. for English editing. They also acknowledge David Andreu (Hospital Clínic, Barcelona, Spain) and Daniel Traver (Biosense Webster, Barcelona, Spain) for their support on the electroanatomic mapping and ablation devices.

Funding

This study was supported in part by grants from the CENIT program of the Centro de Desarrollo Tecnológico Industrial (cvREMOD project; CEN-20091044), and the Spanish Government, REDINSCOR RD06/0003/0008. A Doltra received a personal grant from Fundació Clinic.

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Correspondence to Montserrat Rigol.

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Montserrat Rigol and Núria Solanes contributed equally to this study.

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Rigol, M., Solanes, N., Fernandez-Armenta, J. et al. Development of a Swine Model of Left Bundle Branch Block for Experimental Studies of Cardiac Resynchronization Therapy. J. of Cardiovasc. Trans. Res. 6, 616–622 (2013). https://doi.org/10.1007/s12265-013-9464-1

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  • DOI: https://doi.org/10.1007/s12265-013-9464-1

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