Abstract

Background: Beat-to-beat variability in action potential duration (APD) is an intrinsic property of cardiac tissue and is altered in pro-arrhythmic states. However, it has never been examined in mice.Methods: Left atrial or ventricular monophasic action potentials (MAPs) were recorded from Langendorff-perfused mouse hearts during regular 8 Hz pacing. Time-domain, frequency-domain and non-linear analyses were used to quantify APD variability.Results: Mean atrial APD (90% repolarization) was 23.5 ± 6.3 ms and standard deviation (SD) was 0.9 ± 0.5 ms (n = 6 hearts). Coefficient of variation (CoV) was 4.0 ± 1.9% and root mean square (RMS) of successive differences in APDs was 0.3 ± 0.2 ms. The peaks for low- and high-frequency were 0.7 ± 0.5 and 2.7 ± 0.9 Hz, respectively, with percentage powers of 39.0 ± 20.5 and 59.3 ± 22.9%. Poincaré plots of APDn+1 against APDn revealed ellipsoid shapes. The ratio of the SD along the line-of-identity (SD2) to the SD perpendicular to the line-of-identity (SD1) was 8.28 ± 4.78. Approximate and sample entropy were 0.57 ± 0.12 and 0.57 ± 0.15, respectively. Detrended fluctuation analysis revealed short- and long-term fluctuation slopes of 1.80 ± 0.15 and 0.85 ± 0.29, respectively. When compared to atrial APDs, ventricular APDs were longer (ANOVA, P < 0.05), showed lower mean SD and CoV but similar RMS of successive differences in APDs and showed lower SD2 (P < 0.05). No difference in the remaining parameters was observed.Conclusion: Beat-to-beat variability in APD is observed in mouse hearts during regular pacing. Atrial MAPs showed greater degree of variability than ventricular MAPs. Non-linear techniques offer further insights on short-term and long-term variability and signal complexity.

Highlights

  • Beat-to-beat variations in the repolarization time-course represent an intrinsic property of cardiac electrophysiological function

  • Typical time series of atrial and ventricular action potential durations (APDs) at 90% repolarization (APD90) are shown in Figures 1C,D, respectively and their corresponding histograms are shown in Figures 1E,F, respectively

  • The coefficient of variation (CoV), a measure of relative variability calculated by dividing standard deviation (SD) by the mean and subsequently multiplying by 100%, was 4.0 ± 1.9% (Figure 2C) and the root mean square (RMS) of successive differences in APDs was 0.3 ± 0.2 ms (Figure 2D)

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Summary

Introduction

Beat-to-beat variations in the repolarization time-course represent an intrinsic property of cardiac electrophysiological function. This may be manifested as variability of action potential durations (APDs) at the cellular level (Nanasi et al, 2017), or of QT durations at the organism level (Niemeijer et al, 2014; Phadumdeo and Weinberg, 2018). Beat-to-beat variability in action potential duration (APD) is an intrinsic property of cardiac tissue and is altered in pro-arrhythmic states. It has never been examined in mice

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