scholarly journals Cardiomyocyte Deletion of Bmal1 Exacerbates QT- and RR-Interval Prolongation in Scn5a+/ΔKPQ Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Elizabeth A. Schroder ◽  
Jennifer L. Wayland ◽  
Kaitlyn M. Samuels ◽  
Syed F. Shah ◽  
Don E. Burgess ◽  
...  
Keyword(s):  
Heart Rate ◽  
Circadian Clock ◽  
Qt Interval ◽  
Adult Mouse ◽  
Interval Prolongation ◽  
Rr Interval ◽  
Adult Cardiomyocytes ◽  
Channel Expression ◽  
Cell Type Specific

Circadian rhythms are generated by cell autonomous circadian clocks that perform a ubiquitous cellular time-keeping function and cell type-specific functions important for normal physiology. Studies show inducing the deletion of the core circadian clock transcription factor Bmal1 in adult mouse cardiomyocytes disrupts cardiac circadian clock function, cardiac ion channel expression, slows heart rate, and prolongs the QT-interval at slow heart rates. This study determined how inducing the deletion of Bmal1 in adult cardiomyocytes impacted the in vivo electrophysiological phenotype of a knock-in mouse model for the arrhythmogenic long QT syndrome (Scn5a+/ΔKPQ). Electrocardiographic telemetry showed inducing the deletion of Bmal1 in the cardiomyocytes of mice with or without the ΔKPQ-Scn5a mutation increased the QT-interval at RR-intervals that were ≥130 ms. Inducing the deletion of Bmal1 in the cardiomyocytes of mice with or without the ΔKPQ-Scn5a mutation also increased the day/night rhythm-adjusted mean in the RR-interval, but it did not change the period, phase or amplitude. Compared to mice without the ΔKPQ-Scn5a mutation, mice with the ΔKPQ-Scn5a mutation had reduced heart rate variability (HRV) during the peak of the day/night rhythm in the RR-interval. Inducing the deletion of Bmal1 in cardiomyocytes did not affect HRV in mice without the ΔKPQ-Scn5a mutation, but it did increase HRV in mice with the ΔKPQ-Scn5a mutation. The data demonstrate that deleting Bmal1 in cardiomyocytes exacerbates QT- and RR-interval prolongation in mice with the ΔKPQ-Scn5a mutation.

Effects of probucol, a typical hERG expression inhibitor, on in vivo QT interval prolongation in conscious dogs

2013 ◽  
Vol 720 (1-3) ◽  
pp. 29-37 ◽  
Author(s):  
Hisashi Nogawa ◽  
Tomoyuki Kawai ◽  
Miho Yajima ◽  
Masahiro Miura ◽  
Tetsurou Ogawa ◽  
...  
Keyword(s):  
Qt Interval ◽  
Conscious Dogs ◽  
Interval Prolongation ◽  
Qt Interval Prolongation

Influence of age, the autonomic nervous system and anxiety on QT-interval variability

2001 ◽  
Vol 101 (4) ◽  
pp. 429-438 ◽  
Author(s):  
Gianfranco PICCIRILLO ◽  
Mauro CACCIAFESTA ◽  
Marco LIONETTI ◽  
Marialuce NOCCO ◽  
Vincenza DI GIUSEPPE ◽  
...  
Keyword(s):  
Heart Rate ◽  
Qt Interval ◽  
Spectral Power ◽  
Low Frequency ◽  
Elderly Subjects ◽  
Rr Interval ◽  
T Wave ◽  
Qt Variability ◽  
Qt Interval Variability ◽  
Sympathetic Stress

As QT variability increases and heart rate variability diminishes, the QT variability index (QTVI)-a non-invasive measure of beat-to-beat fluctuations in QT interval on a single ECG lead-shows a trend towards positive values. Increased QT variability is a risk factor for sudden death. Aging lengthens the QT interval and reduces RR-interval variability. In the present study we investigated the influence of aging and the autonomic nervous system on QT-interval variability in healthy subjects. We studied 143healthy subjects, and divided them into two age ranges (younger and older than 65 years). For each subject we measured two QTVIs: from the q wave to the end of the T wave (QTeVI) and to the apex of the T wave (QTaVI). Both indexes were calculated at baseline and after sympathetic stress. In 10 non-elderly subjects, both QTVIs were determined after β-adrenoreceptor blockade induced by intravenous infusion of propranolol or sotalol. The QTVI was higher in elderly than in younger subjects (P < 0.001). QTVIs obtained during sympathetic stress remained unchanged in the elderly, but became more negative in the younger group (P < 0.05). QTeVI and QTaVI at baseline were correlated positively with age (P < 0.01) and anxiety scores (P < 0.05), but inversely with the low-frequency spectral power of RR-interval variability (P < 0.001). QTVIs were higher in subjects with higher anxiety scores. In younger subjects, sotalol infusion increased both QTVIs significantly, whereas propranolol infusion did not. In conclusion, aging increases QT-interval variability. Whether this change is associated with an increased risk of sudden death remains unclear. The association of abnormal QT-interval variability with anxiety and with reduced low-frequency spectral power of heart rate variability merits specific investigation. In healthy non-elderly subjects, acute sympathetic stress (tilt) decreases the QTVI. β-Adrenoreceptor blockade inhibits this negative trend, thus showing its sympathetic origin. Because a negative trend in QTVI induced by sympathetic stress increases only in younger subjects, it could represent a protective mechanism that is lost with aging.

scholarly journals Measurements of blood pressure and electrocardiogram in conscious freely moving guineapigs: a model for screening QT interval prolongation effects

2007 ◽  
Vol 41 (4) ◽  
pp. 470-480 ◽  
Author(s):  
P Hess ◽  
M Rey ◽  
D Wanner ◽  
B Steiner ◽  
M Clozel
Keyword(s):  
Blood Pressure ◽  
Qt Interval ◽  
Abdominal Cavity ◽  
Good Alternative ◽  
Suitable Model ◽  
Interval Prolongation ◽  
Qt Interval Prolongation ◽  
Freely Moving ◽  
Electrocardiographic Intervals

The pro-arrhythmic risk inherent to a new drug must be assessed at an early preclinical stage. Telemetry system implantation is a method widely used in vivo in various species. The present study was designed to assess whether conscious freely moving guineapigs can be used to predict QT prolongation in vivo. The guineapig has three advantages over the dog and the primate. First, it has specific ion channels similar to man; second, a smaller amount of test article is required for the investigation and third, its housing is less expensive. Under sterile conditions and isoflurane anaesthesia, telemetry transmitters were implanted intraperitoneally in male Dunkin Hartley guineapigs. Blood pressure, heart rate and electrocardiographic intervals were measured from two days up to eight months. Chronic implantation of the telemetry device did not lead to anatomic or macroscopic alterations in the abdominal cavity and no inflammation of the peritoneum or infection was observed. Four reference compounds were used: three positive (sotalol, terfenadine and dofetilide) and one negative reference (enalapril). Single oral administration of all three positive references dose-dependently induced bradycardia and QT corrected (QTc) prolongation. In contrast, neither enalapril nor its vehicle prolonged the QTc. These results demonstrate that the guineapig is both a suitable model and a good alternative to dogs or primates to assess the potential of compounds for QT interval prolongation in the early stages of drug development.

scholarly journals IL-6 (Interleukin 6) Blockade and Heart Rate Corrected QT Interval Prolongation in COVID-19

2020 ◽  
Vol 13 (9) ◽  
Author(s):  
Pietro Enea Lazzerini ◽  
Franco Laghi-Pasini ◽  
Maurizio Acampa ◽  
Mohamed Boutjdir ◽  
Pier Leopoldo Capecchi
Keyword(s):  
Heart Rate ◽  
Interleukin 6 ◽  
Qt Interval ◽  
Interval Prolongation ◽  
Corrected Qt Interval ◽  
Qt Interval Prolongation

scholarly journals Comparison of the Effect of Continuous and Interval Aerobic Training on Electrocardiogram of Active Young Girls

2020 ◽  
Vol 26 (3) ◽  
pp. 298-315
Author(s):  
Hawzhin Azizi ◽  
◽  
Fatah Moradi ◽  
Saman Pashaei ◽  
◽  
...  
Keyword(s):  
Heart Rate ◽  
Qt Interval ◽  
Aerobic Training ◽  
Interval Training ◽  
Training Group ◽  
Repeated Measurements ◽  
Young Girls ◽  
Rr Interval ◽  
Training Interval ◽  
Quasi Experimental

Aims: Few studies have examined the effects of various models of aerobic training on electrocardiogram (ECG). The purpose of this study was to compare the effect of continuous and interval aerobic training on ECG of active young girls.  Methods & Materials: The research method was quasi-experimental and 30 active young girls were selected from among physical education students (age=17.0±0.4 y) and were randomly asPned to three groups of continuous aerobic training, interval aerobic training and control (each group was 10). The protocol of the trainings (eight weeks, three sessions per week) included 20-35 minutes of running per session, with an intensity of 60%-75% of the maximum heart rate. Before and after the training, general characteristics of subjects were measured and their ECGs were recorded. To analyze the data, analysis of variance with repeated measurements was used at the Pnificant level of P<0.05.  Findings: Eight-week continuous and interval aerobic training had no Pnificant effect on amplitudes of P, R, and T waves, PR interval and duration of ST segment (P>0.05), whereas both types of training similarly increased QT interval (continuous: P=0.001, interval: P=0.027) and reduced heart rate (continuous: P=0.002, interval: P=0.013). Only in the interval training group RR interval showed a Pnificant increase (continuous: P=0.079, interval: P=0.007). Conclusion: Eight weeks of continuous and interval aerobic training appears to similarly decrease heart rate and increase QT interval in active young girls, whereas only interval aerobic training results in increased RR interval.

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