Preprint Article Version 1 This version is not peer-reviewed

Nonlinear Analysis of Beat-To-Beat Variability of Action Potential Time Series Data Identifies Dynamic Reentrant Substrates in a Hypokalaemic Mouse Model of Acquired Long QT Syndrome

Version 1 : Received: 5 May 2022 / Approved: 13 May 2022 / Online: 13 May 2022 (10:44:15 CEST)

How to cite: Tse, G.; Zhou, J.; Dong, X.; Hao, G.; Lee, S.; Leung, K.S.K.; Liu, T.; Du, Y.; Cheng, S.H.; Wong, W.T. Nonlinear Analysis of Beat-To-Beat Variability of Action Potential Time Series Data Identifies Dynamic Reentrant Substrates in a Hypokalaemic Mouse Model of Acquired Long QT Syndrome. Preprints 2022, 2022050191 (doi: 10.20944/preprints202205.0191.v1). Tse, G.; Zhou, J.; Dong, X.; Hao, G.; Lee, S.; Leung, K.S.K.; Liu, T.; Du, Y.; Cheng, S.H.; Wong, W.T. Nonlinear Analysis of Beat-To-Beat Variability of Action Potential Time Series Data Identifies Dynamic Reentrant Substrates in a Hypokalaemic Mouse Model of Acquired Long QT Syndrome. Preprints 2022, 2022050191 (doi: 10.20944/preprints202205.0191.v1).

Abstract

Previous studies have quantified repolarization variability using time-domain, frequency-domain and non-linear analysis in mouse hearts. Here, we investigated the relationship between these parameters and ventricular arrhythmogenicity in a hypokalaemia model of acquired long QT syndrome. Methods: Left ventricular monophasic action potentials (MAPs) were recorded during right ventricular regular 8 Hz pacing during normokalaemia (5.2 mM [K+]), hypokalaemia modelling LQTS (3 mM [K+]) or hypokalaemia with 0.1 mM heptanol in Langendorff-perfused mouse hearts. Results: During normokalaemia, mean APD was 33.5±3.7 ms. Standard deviation (SD) of APDs was 0.63±0.33 ms, coefficient of variation was 1.9±1.0% and the root mean square (RMS) of successive differences in APDs was 0.3±0.1 ms. Low- and high-frequency peaks were 0.6±0.5 and 2.3±0.7 Hz, respectively, with percentage powers of 38±22 and 61±23%. Poincaré plots of APDn+1 against APDn revealed ellipsoid morphologies with SD along the line-of-identity (SD2) to SD perpendicular to the line-of-identity (SD1) ratio of 4.6±1.1. Approximate and sample entropy were 0.49±0.12 and 0.64±0.29, respectively. Detrended fluctuation analysis revealed short- and long-term fluctuation slopes of 1.62±0.27 and 0.60±0.18, respectively. Hypokalaemia provoked ventricular tachycardia in six of seven hearts, prolonged APDs (51.2±7.9 ms), decreased SD2/SD1 ratio (3.1±1.0), increased approximate and sample entropy (0.68±0.08 and 1.02±0.33) and decreased short-term fluctuation slope (1.23 ± 0.20) (ANOVA, P<0.05). Heptanol prevented VT in all hearts studied without further altering the above repolarization parameters observed during hypokalaemia. Conclusion: Reduced SD2/SD1, increased entropy and decreased short-term fluctuation slope are associated with ventricular arrhythmogenesis in hypokalaemia. Heptanol exerts anti-arrhythmic effects without affecting repolarization variability.

Keywords

repolarization variability; beat-to-beat; entropy; delayed repolarization; long QT

Subject

BIOLOGY, Physiology

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