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Nonlinear analysis of beat-to-beat variability of action potential time series data identifies dynamic re-entrant substrates in a hypokalaemic mouse model of acquired long QT syndrome
Tools
Tse, Gary, Zhou, Jiandong, Dong, Xiuming, Hao, Guoliang, Lee, Sharen, Leung, Keith Sai Kit, Leung, Fung Ping, Liu, Tong, Du, Yimei, Cheng, Shuk Han and Wong, Wing Tak (2023) Nonlinear analysis of beat-to-beat variability of action potential time series data identifies dynamic re-entrant substrates in a hypokalaemic mouse model of acquired long QT syndrome. International Journal of Arrhythmia, 24 (1). 2. doi:10.1186/s42444-023-00084-4 ISSN 2466-1171.
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Official URL: http://dx.doi.org/10.1186/s42444-023-00084-4
Abstract
Background
Previous studies have quantified repolarization variability using time-domain, frequency-domain and nonlinear 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 modeling 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 may reflect arrhythmic risk in hypokalaemia. Heptanol exerts anti-arrhythmic effects without affecting repolarization variability.
Item Type: | Journal Article | ||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||||
Journal or Publication Title: | International Journal of Arrhythmia | ||||||
Publisher: | Springer | ||||||
ISSN: | 2466-1171 | ||||||
Official Date: | 19 January 2023 | ||||||
Dates: |
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Volume: | 24 | ||||||
Number: | 1 | ||||||
Article Number: | 2 | ||||||
DOI: | 10.1186/s42444-023-00084-4 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Open Access (Creative Commons) |
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