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Front. Physiol. | doi: 10.3389/fphys.2018.00147

Beat-to-beat variability of ventricular action potential duration oscillates at low frequency during sympathetic provocation in humans

 Bradley Porter1,  Stefan Van Duijvenboden2,  Martin Bishop1, Michele Orini2, Simon Claridge1, Justin Gould1, Benjamin Sieniewicz1, Baldeep Sidhu1, Reza Razavi1, Christopher A. Rinaldi3,  Jaswinder S. Gill3 and Peter Taggart2*
  • 1King's College London, United Kingdom
  • 2University College London, United Kingdom
  • 3Guy's and St Thomas' NHS Foundation Trust, United Kingdom

Background: The temporal pattern of ventricular repolarization is of critical importance in arrhythmogenesis. Enhanced beat-to-beat variability (BBV) of ventricular action potential duration (APD) is pro-arrhythmic and is increased during sympathetic provocation. Since sympathetic nerve activity characteristically exhibits burst patterning in the low frequency range, we hypothesised that physiologically enhanced sympathetic activity may not only increase BBV of left ventricular APD but also impose a low frequency oscillation which further increases repolarisation instability in humans.
Methods and Results: Heart failure patients with cardiac resynchronization therapy defibrillator devices (n=11) had activation recovery intervals (ARI, surrogate for APD) recorded from left ventricular epicardial electrodes alongside simultaneous non-invasive blood pressure and respiratory recordings. Fixed cycle length was achieved by right ventricular pacing. Recordings took place during resting conditions and following an autonomic stimulus (Valsalva). The variability of ARI and the normalised variability of ARI showed significant increases post Valsalva when compared to control (p=0.019 and p=0.032 respectively). The oscillatory behaviour was quantified by spectral analysis. Significant increases in low frequency (LF) power (p=0.002) and normalised LF power (p=0.019) of ARI were seen following Valsalva. The Valsalva did not induce changes in conduction variability nor the LF oscillatory behaviour of conduction. However, increases in the LF power of ARI were accompanied by increases in the LF power of systolic blood pressure (SBP) and the rate of systolic pressure increase (dP/dtmax). Positive correlations were found between LF-SBP and LF-dP/dtmax (rs=.933, p<0.001), LF-ARI and LF-SBP (rs=.681, p=0.001) and between LF-ARI and LF-dP/dtmax (rs=.623, p=0.004). There was a strong positive correlation between the variability of ARI and LF power of ARI (rs=.679, p<0.001).
Conclusions: In heart failure patients, physiological sympathetic provocation induced low frequency oscillation (approx. 0.1Hz) of left ventricular APD with a strong positive correlation between the LF power of APD and the BBV of APD. These findings may be of importance in mechanisms underlying stability/instability of repolarization and arrhythmogenesis in humans.

Keywords: arrhythmia, Sympathetic Nervous System, oscillations, action potential duration variability, activation recovery interval

Received: 17 Nov 2017; Accepted: 13 Feb 2018.

Edited by:

Tobias Opthof, Academic Medical Center (AMC), Netherlands

Reviewed by:

Alexey V. Glukhov, University of Wisconsin System, United States
Jason D. Bayer, Université de Bordeaux, France  

Copyright: © 2018 Porter, Van Duijvenboden, Bishop, Orini, Claridge, Gould, Sieniewicz, Sidhu, Razavi, Rinaldi, Gill and Taggart. 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 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: Prof. Peter Taggart, University College London, London, United Kingdom,