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The effect of enhanced gap junctional conductance on ventricular conduction in explanted hearts from patients with heart failure

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Abstract

Aim

To investigate ventricular conduction and refractoriness before and after application of rotigaptide, an enhancer of gap junctional conductance, to explanted hearts of patients with heart failure (HF).

Methods and results

In six explanted perfused hearts of patients with end-stage HF, activation/repolarization mapping was performed and refractory periods (RPs) and activation recovery intervals (ARIs) were measured before and after application of 50 nM rotigaptide. Rotigaptide caused a decrease of RP from 476 ± 36 to 453 ± 31 ms (P < 0.05), but did not change ARI-dispersion. During premature activation along the fibers rotigaptide decreased the minimal activation time (ATmin) and maximal activation time (ATmax) significantly from 35 ± 12 to 24 ± 9 and from 97 ± 38 to 43 ± 7 ms, respectively. Rotigaptide did not change ATmin and ATmax during activation perpendicular to the fiber direction. After application of rotigaptide conduction curves normalized in five/six recordings when activation was parallel, but destabilized in three/six hearts when activation was perpendicular to fiber direction. The destabilization was associated with local conduction delays rather than with facilitation of conduction.

Conclusion

Rotigaptide applied to hearts of patients with end-stage HF shortened RPs normalized conduction curves and increased conduction parallel to fiber direction. However, in 50% of the hearts local slowing of conduction with destabilization of conduction (curves) occurs at sites close to the stimulation site, when activation is perpendicular to fiber direction.

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Acknowledgments

The authors gratefully acknowledge Zealand Pharma for providing us with rotigaptide for this study and Dr. Anne Louise Kjølbye for her critical comments. We thank Dr. M. G. Hoogendijk and S. C van Amersfoorth for assistance with the histological sections.

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Authors and Affiliations

  1. Experimental Cardiology Group (ECG), Dept. of Experimental Cardiology, Center for Heart Failure Research, Academic Medical Center Rm K2-112, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Rob F. Wiegerinck PhD, Jacques M. T. de Bakker PhD, Tobias Opthof PhD & Ruben Coronel MD, PhD

  2. Dept. of Cardiology, Heart Lung Center, University Medical Center Utrecht, Utrecht, The Netherlands

    Jacques M. T. de Bakker PhD, Nicolaas de Jonge MD, PhD & Hans Kirkels MD, PhD

  3. Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands

    Jacques M. T. de Bakker PhD & Francien J. G. Wilms-Schopman RA

Authors
  1. Rob F. Wiegerinck PhD
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  2. Jacques M. T. de Bakker PhD
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  3. Tobias Opthof PhD
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  4. Nicolaas de Jonge MD, PhD
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  5. Hans Kirkels MD, PhD
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  6. Francien J. G. Wilms-Schopman RA
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  7. Ruben Coronel MD, PhD
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Corresponding author

Correspondence to Ruben Coronel MD, PhD.

Additional information

Returned for 1. Revision: 14 July 2008 1. Revision received: 26 August 2008

Returned for 2. Revision: 19 September 2008 2. Revision received: 31 October 2008

Returned for 3. Revision: 17 November 2008 3. Revision received: 18 November 2008

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Wiegerinck, R.F., de Bakker, J.M.T., Opthof, T. et al. The effect of enhanced gap junctional conductance on ventricular conduction in explanted hearts from patients with heart failure. Basic Res Cardiol 104, 321–332 (2009). https://doi.org/10.1007/s00395-008-0771-7

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  • DOI: https://doi.org/10.1007/s00395-008-0771-7

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