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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Physiol. | doi: 10.3389/fphys.2019.01095

Pro-arrhythmic ventricular remodeling is associated with increased respiratory and low frequency oscillations of monophasic action potential duration in the chronic atrioventricular block dog model

 David J. Sprenkeler1*, Jet D. Beekman1,  Alexandre Bossu1, Albert Dunnink1 and  Marc A. Vos1
  • 1University Medical Center Utrecht, Netherlands

In addition to beat-to-beat fluctuations, action potential duration (APD) oscillates at 1.) a respiratory frequency and 2.) a low frequency (< 0.1 Hz), probably caused by bursts of sympathetic nervous system discharge. This study investigates whether ventricular remodeling in the chronic AV block (CAVB) dog alters these oscillations of APD and whether this has consequences for arrhythmogenesis.
We performed a retrospective analysis of 39 dog experiments in sinus rhythm (SR), acute AV block (AAVB) and after 2 weeks of chronic AV block. Spectral analysis of left ventricular monophasic action potential duration (LV MAPD) was done to quantify respiratory frequency (RF) power and low frequency (LF) power. Dofetilide (0.025mg/kg in 5 minutes) was infused to test for inducibility of Torsade de Pointes (TdP) arrhythmias.
RF power was significantly increased at CAVB compared to AAVB and SR (log[RF] of -1.13 ± 1.62 at CAVB versus log[RF] of -2.82 ± 1.24 and -3.29 ± 1.29 at SR and AAVB, respectively, p<0.001). LF power was already significantly increased at AAVB and increased even further at CAVB (-3.91 ± 0.70 at SR, versus -2.52 ± 0.85 at AAVB and -1.14 ± 1.62 at CAVB, p<0.001). In addition, LF power was significantly larger in inducible CAVB dogs (log[LF] -0.6 ± 1.54 in inducible dogs vs. -2.56 ± 0.43 in non-inducible dogs, p < 0.001).
In conclusion, ventricular remodeling in the CAVB dog results in augmentation of respiratory and low frequency oscillations of LV MAPD. Furthermore, TdP-inducible CAVB dogs show increased LF power.

Keywords: chronic AV block dog, electrical remodeling, Respiration, Action potential duration, Low frequency oscillations

Received: 04 Jun 2019; Accepted: 08 Aug 2019.

Edited by:

Peter Taggart, University College London, United Kingdom

Reviewed by:

Gudrun Antoons, Maastricht University, Netherlands
Daniel M. Johnson, University of Birmingham, United Kingdom  

Copyright: © 2019 Sprenkeler, Beekman, Bossu, Dunnink and Vos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. David J. Sprenkeler, University Medical Center Utrecht, Utrecht, Netherlands, djsprenkeler@gmail.com