Incorrectly corrected? QT interval analysis in rats and mice

Mulla, Wesam; Murninkas, Michael; Levi, Or; Etzion, Yoram

doi:10.3389/fphys.2022.1002203

Cited by 13 publications

(15 citation statements)

References 80 publications

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“…We also found that the QT interval was negatively correlated to the heart rate, which is in line with the rate-dependence of the QT interval known in humans and larger mammals (22,23). However, the QT dependence of heart rate in mice is matter of debate, with studies showing either a dependence or no dependence in unanesthetized mouse hearts (24)(25)(26), which resulted in the lack of an accurate QT correction formula for mice.…”

Section: Simultaneous Recording Of Cardiac Mechanical and Electrical ...supporting

confidence: 80%

Simultaneous assessment of mechanical and electrical function in Langendorff-perfused ex-vivo mouse heart

Louradour,

Ottersberg,

Segiser

et al. 2023

Preprint

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Background: The Langendorff-perfused ex-vivo isolated heart model has been extensively used to study cardiac function for many years. However, electrical and mechanical function are often studied separately - despite growing proof of a complex electro-mechanical interaction in cardiac physiology and pathology. Therefore, we developed an isolated mouse heart perfusion system that allows simultaneous recording of electrical and mechanical function. Methods: Isolated mouse hearts were mounted on a Langendorff setup and electrical function was assessed via a pseudo-ECG and an octapolar catheter inserted in the right atrium and ventricle. Mechanical function was simultaneously assessed via a balloon inserted into the left ventricle coupled with pressure determination. Hearts were then submitted to an ischemia-reperfusion protocol. Results: At baseline, heart rate, PR and QT intervals, intra-atrial and intra-ventricular conduction times, as well as ventricular effective refractory period, could be measured as parameters of cardiac electrical function. Left ventricular developed pressure (DP), left ventricular work (DP-heart rate product) and maximal velocities of contraction and relaxation were used to assess cardiac mechanical function. Cardiac arrhythmias were observed with episodes of bigeminy during which DP was significantly increased compared to that of sinus rhythm episodes. In addition, the extrasystole-triggered contraction was only 50% of that of sinus rhythm, recapitulating the pulse deficit phenomenon observed in bigeminy patients. After ischemia, the mechanical function significantly decreased and slowly recovered during reperfusion while most of the electrical parameters remained unchanged. Finally, the same electro-mechanical interaction during episodes of bigeminy at baseline was observed during reperfusion. Conclusion: Our modified Langendorff setup allows simultaneous recording of electrical and mechanical function on a beat-to-beat scale and can be used to study electro-mechanical interaction in isolated mouse hearts.

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Section: Simultaneous Recording Of Cardiac Mechanical and Electrical ...supporting

confidence: 80%

Simultaneous assessment of mechanical and electrical function in Langendorff-perfused ex-vivo mouse heart

Louradour,

Ottersberg,

Segiser

et al. 2023

Preprint

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“…The temperature dependence of the QT interval and daily rhythm in Tb were not considered. Importantly, recent studies show mice have a weak HR adaptation of the QT interval 32,33,48 and applying the QT interval correction leads to overcorrection and errors. We suspected that the daily rhythm in the QT interval used to derive the QT interval correction in mice may have reflected daily rhythms in Tb and not HR.…”

Section: Discussionmentioning

confidence: 99%

“…This concept is consistent with recent studies showing that mice have a weak HR adaptation of the QT interval. (44,45,52) The idea that the daily rhythm in the QT interval in mice primarily reflects Tb is also supported by a study showing that the 24-hour rhythm of the QT interval in mice is independent of the RR interval. (9) Tb was not reported in the study, but the observed change in the amplitude of the daily rhythm in the QT interval (4-5 ms) is consistent with a Tb amplitude typically seen in mice (1 °C).…”

Section: The 24-hour Rhythm In the Qt Depends On Tbmentioning

confidence: 94%

“…Previous studies demonstrate that QT interval duration in mice is independent of RR interval. [32][33][34][35] Therefore, we quantified the linear relation between the hourly QT interval and Tb using data recorded from mice in ALF, initially after starting L-RF, and two weeks after starting L-RF similar to that described for beagles (Figure 5A). 23 We found a strong negative linear relationship, and we used the average slope of linear regression analyses to normalize the QT interval data to a mean Tb of ALF (37 o C) (Figure 5A).…”

Section: L-rf Reveals a Robust Linear Qt-tb Relation In Wt Micementioning

confidence: 99%

“…Unlike larger mammals, studies show that the duration of the QT interval in mice is mainly independent of the RR interval. (9,(44)(45)(46)) Therefore, we quantified the relation between the QT interval and Tb. We identified a strong negative linear relationship between the mean QT interval and Tb recorded from mice in ALF, initially after starting L-RF, and two weeks after starting L-RF (Figure 3A).…”

Section: The 24-hour Rhythm In the Qt Interval Depends On Tbmentioning

confidence: 99%

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Feeding Behavior Modifies the Circadian Variation in RR and QT intervals by Distinct Mechanisms in Mice

Ono,

Burgess,

Johnson

et al. 2023

Preprint

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Circadian rhythms in physiology and behavior are intrinsic ≈24-hour cycles regulated by biological clocks (i.e., circadian clocks) that optimize organismal homeostasis in response to predictable environmental changes. Studies suggest that circadian clock signaling in the suprachiasmatic nucleus of the hypothalamus and cardiomyocytes shape day/night rhythms in cardiac electrophysiology (i.e., RR and QT intervals). However, studies also show that the day/night rhythm of the RR and QT intervals depends on the timing of feeding in mice. This study determined the mechanisms for how feeding impacts day/night rhythms in the RR and QT intervals in mice. Telemetry was used to record electrocardiograms, core body temperature, and activity in mice during ad libitum-fed conditions and after inverting normal feeding behavior by restricting the timing of feeding to the light cycle. Light-cycle restricted feeding caused a simultaneous realignment of RR, QT, and PR intervals and body temperature to the new feeding time. Correcting the QT interval for body temperature eliminated the 24-hour rhythm in the QT interval. Estimating the impact of temperature on RR intervals did not account for the daily change in the RR interval during light-cycle restricted feeding. Cross-correlation analysis suggested daily rhythm in RR intervals correlated with heart rate variability measures but not activity. Injecting mice undergoing light cycle-restricted feeding with propranolol and atropine caused a complete loss in the 24-hour rhythm in the RR interval. We conclude that feeding behavior impacts body temperature and autonomic regulation of the heart to generate 24-hour rhythms in RR and QT intervals.New and NoteworthyOur findings demonstrate that feeding behavior is a critical timekeeper for aligning daily rhythms in cardiac electrophysiology (i.e., RR and QT intervals) in mice. The data suggest that feeding behavior shapes 24-hour rhythms in the RR interval by altering day/night rhythms in core body temperature and autonomic input to the heart. In contrast to the RR interval, the 24-hour rhythms in the QT interval are largely shaped by day/night rhythms in core body temperature.

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