Prolonged QT intervals in mice with cardiomyocyte-specific deficiency of the molecular clock

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Prolonged QT intervals in mice with cardiomyocyte-specific deficiency of the molecular clock. / Gottlieb, Lisa A.; Larsen, Karin; Halade, Ganesh; Young, Martin E.; Thomsen, Morten B.

In: Acta Physiologica, Vol. 233, No. 1, e13707, 09.07.2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Gottlieb, LA, Larsen, K, Halade, G, Young, ME & Thomsen, MB 2021, 'Prolonged QT intervals in mice with cardiomyocyte-specific deficiency of the molecular clock', Acta Physiologica, vol. 233, no. 1, e13707. https://doi.org/10.1111/apha.13707

APA

Gottlieb, L. A., Larsen, K., Halade, G., Young, M. E., & Thomsen, M. B. (2021). Prolonged QT intervals in mice with cardiomyocyte-specific deficiency of the molecular clock. Acta Physiologica, 233(1), [e13707]. https://doi.org/10.1111/apha.13707

Vancouver

Gottlieb LA, Larsen K, Halade G, Young ME, Thomsen MB. Prolonged QT intervals in mice with cardiomyocyte-specific deficiency of the molecular clock. Acta Physiologica. 2021 Jul 9;233(1). e13707. https://doi.org/10.1111/apha.13707

Author

Gottlieb, Lisa A. ; Larsen, Karin ; Halade, Ganesh ; Young, Martin E. ; Thomsen, Morten B. / Prolonged QT intervals in mice with cardiomyocyte-specific deficiency of the molecular clock. In: Acta Physiologica. 2021 ; Vol. 233, No. 1.

Bibtex

@article{c12a81729a0d41c3839e492d1e8f767b,
title = "Prolonged QT intervals in mice with cardiomyocyte-specific deficiency of the molecular clock",
abstract = "Aim Cardiac arrhythmias and sudden deaths have diurnal rhythms in humans. The underlying mechanisms are unknown. Mice with cardiomyocyte-specific disruption of the molecular clock genes have lower heart rate than control. Because changes in the QT interval on the electrocardiogram is a clinically used marker of risk of arrhythmias, we sought to test if the biological rhythms of QT intervals are dependent on heart rate and if this dependency is changed when the molecular clock is disrupted. Methods We implanted radio transmitters in male mice with cardiomyocyte-specific Bmal1 knockout (CBK) and in control mice and recorded 24-h ECGs under diurnal and circadian conditions. We obtained left ventricular monophasic action potentials during pacing in hearts ex vivo. Results Both RR and QT intervals were longer in conscious CBK than control mice (RR: 117 +/- 7 vs 110 +/- 9 ms, P < .05; and QT: 53 +/- 4 vs 48 +/- 2 ms, P < .05). The prolonged QT interval was independent of the slow heart rate in CBK mice. The QT interval exhibited diurnal and circadian rhythms in both CBK and control mice. The action potential duration was longer in CBK than in control mice, indicating slower repolarization. Action potential alternans occurred at lower pacing rate in hearts from CBK than control mice (12 +/- 3 vs 16 +/- 2 Hz, respectively, P < .05). Conclusion The bradycardic CBK mice have prolonged ventricular repolarization independent of the heart rate. Diurnal and circadian rhythms in repolarization are preserved in CBK mice and are not a consequence of the 24-h rhythm in heart rate. Arrhythmia vulnerability appears to be increased when the cardiac clock is disrupted.",
keywords = "chronobiology, circadian rhythm, heart rate, mouse model, QT interval, telemetry, HEART-RATE-VARIABILITY, CIRCADIAN GENE-EXPRESSION, CONTRACTILE FUNCTION, K+ CURRENTS, PHYSIOLOGY, RHYTHMS, REPOLARIZATION, CONTRIBUTES, METABOLISM, FAILURE",
author = "Gottlieb, {Lisa A.} and Karin Larsen and Ganesh Halade and Young, {Martin E.} and Thomsen, {Morten B.}",
year = "2021",
month = jul,
day = "9",
doi = "10.1111/apha.13707",
language = "English",
volume = "233",
journal = "Acta Physiologica",
issn = "1748-1708",
publisher = "Wiley-Blackwell",
number = "1",

}

RIS

TY - JOUR

T1 - Prolonged QT intervals in mice with cardiomyocyte-specific deficiency of the molecular clock

AU - Gottlieb, Lisa A.

AU - Larsen, Karin

AU - Halade, Ganesh

AU - Young, Martin E.

AU - Thomsen, Morten B.

PY - 2021/7/9

Y1 - 2021/7/9

N2 - Aim Cardiac arrhythmias and sudden deaths have diurnal rhythms in humans. The underlying mechanisms are unknown. Mice with cardiomyocyte-specific disruption of the molecular clock genes have lower heart rate than control. Because changes in the QT interval on the electrocardiogram is a clinically used marker of risk of arrhythmias, we sought to test if the biological rhythms of QT intervals are dependent on heart rate and if this dependency is changed when the molecular clock is disrupted. Methods We implanted radio transmitters in male mice with cardiomyocyte-specific Bmal1 knockout (CBK) and in control mice and recorded 24-h ECGs under diurnal and circadian conditions. We obtained left ventricular monophasic action potentials during pacing in hearts ex vivo. Results Both RR and QT intervals were longer in conscious CBK than control mice (RR: 117 +/- 7 vs 110 +/- 9 ms, P < .05; and QT: 53 +/- 4 vs 48 +/- 2 ms, P < .05). The prolonged QT interval was independent of the slow heart rate in CBK mice. The QT interval exhibited diurnal and circadian rhythms in both CBK and control mice. The action potential duration was longer in CBK than in control mice, indicating slower repolarization. Action potential alternans occurred at lower pacing rate in hearts from CBK than control mice (12 +/- 3 vs 16 +/- 2 Hz, respectively, P < .05). Conclusion The bradycardic CBK mice have prolonged ventricular repolarization independent of the heart rate. Diurnal and circadian rhythms in repolarization are preserved in CBK mice and are not a consequence of the 24-h rhythm in heart rate. Arrhythmia vulnerability appears to be increased when the cardiac clock is disrupted.

AB - Aim Cardiac arrhythmias and sudden deaths have diurnal rhythms in humans. The underlying mechanisms are unknown. Mice with cardiomyocyte-specific disruption of the molecular clock genes have lower heart rate than control. Because changes in the QT interval on the electrocardiogram is a clinically used marker of risk of arrhythmias, we sought to test if the biological rhythms of QT intervals are dependent on heart rate and if this dependency is changed when the molecular clock is disrupted. Methods We implanted radio transmitters in male mice with cardiomyocyte-specific Bmal1 knockout (CBK) and in control mice and recorded 24-h ECGs under diurnal and circadian conditions. We obtained left ventricular monophasic action potentials during pacing in hearts ex vivo. Results Both RR and QT intervals were longer in conscious CBK than control mice (RR: 117 +/- 7 vs 110 +/- 9 ms, P < .05; and QT: 53 +/- 4 vs 48 +/- 2 ms, P < .05). The prolonged QT interval was independent of the slow heart rate in CBK mice. The QT interval exhibited diurnal and circadian rhythms in both CBK and control mice. The action potential duration was longer in CBK than in control mice, indicating slower repolarization. Action potential alternans occurred at lower pacing rate in hearts from CBK than control mice (12 +/- 3 vs 16 +/- 2 Hz, respectively, P < .05). Conclusion The bradycardic CBK mice have prolonged ventricular repolarization independent of the heart rate. Diurnal and circadian rhythms in repolarization are preserved in CBK mice and are not a consequence of the 24-h rhythm in heart rate. Arrhythmia vulnerability appears to be increased when the cardiac clock is disrupted.

KW - chronobiology

KW - circadian rhythm

KW - heart rate

KW - mouse model

KW - QT interval

KW - telemetry

KW - HEART-RATE-VARIABILITY

KW - CIRCADIAN GENE-EXPRESSION

KW - CONTRACTILE FUNCTION

KW - K+ CURRENTS

KW - PHYSIOLOGY

KW - RHYTHMS

KW - REPOLARIZATION

KW - CONTRIBUTES

KW - METABOLISM

KW - FAILURE

U2 - 10.1111/apha.13707

DO - 10.1111/apha.13707

M3 - Journal article

C2 - 34176211

VL - 233

JO - Acta Physiologica

JF - Acta Physiologica

SN - 1748-1708

IS - 1

M1 - e13707

ER -

ID: 274431317