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

Porter, B; van Duijvenboden, S; Bishop, MJ; Orini, M; Claridge, S; Gould, J; Sieniewicz, BJ; ... Taggart, P; + view all (2018) Beat-to-beat variability of ventricular action potential duration oscillates at low frequency during sympathetic provocation in humans. Frontiers in Physiology , 9 , Article 147. 10.3389/fphys.2018.00147. Green open access

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Abstract

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 hypothesized that physiologically enhanced sympathetic activity may not only increase BBV of left ventricular APD but also impose a low frequency oscillation which further increases repolarization 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 normalized variability of ARI showed significant increases post Valsalva when compared to control (p = 0.019 and p = 0.032, respectively). The oscillatory behavior was quantified by spectral analysis. Significant increases in low frequency (LF) power (p = 0.002) and normalized LF power (p = 0.019) of ARI were seen following Valsalva. The Valsalva did not induce changes in conduction variability nor the LF oscillatory behavior 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/dt max ). Positive correlations were found between LF-SBP and LF-dP/dt max (r s = 0.933, p < 0.001), LF-ARI and LF-SBP (r s = 0.681, p = 0.001) and between LF-ARI and LF-dP/dt max (rs = 0.623, p = 0.004). There was a strong positive correlation between the variability of ARI and LF power of ARI (rs = 0.679, p < 0.001). CONCLUSIONS: In heart failure patients, physiological sympathetic provocation induced low frequency oscillation (~0.1 Hz) 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.

Type: Article
Title: Beat-to-beat variability of ventricular action potential duration oscillates at low frequency during sympathetic provocation in humans
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fphys.2018.00147
Publisher version: http://dx.doi.org/10.3389/fphys.2018.00147
Language: English
Additional information: © 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.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Clinical Science
URI: https://discovery.ucl.ac.uk/id/eprint/10046997
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