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A brief morning rest period benefits cardiac repair in pressure overload hypertrophy and postmyocardial infarction
Cristine J. Reitz, Mina Rasouli, Faisal J. Alibhai, Tarak N. Khatua, W. Glen Pyle, Tami A. Martino
Cristine J. Reitz, Mina Rasouli, Faisal J. Alibhai, Tarak N. Khatua, W. Glen Pyle, Tami A. Martino
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Research Article Cardiology

A brief morning rest period benefits cardiac repair in pressure overload hypertrophy and postmyocardial infarction

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Abstract

Rest has long been considered beneficial to patient healing; however, remarkably, there are no evidence-based experimental models determining how it benefits disease outcomes. Here, we created an experimental rest model in mice that briefly extends the morning rest period. We found in 2 major cardiovascular disease conditions (cardiac hypertrophy, myocardial infarction) that imposing a short, extended period of morning rest each day limited cardiac remodeling compared with controls. Mechanistically, rest mitigates autonomic-mediated hemodynamic stress on the cardiovascular system, relaxes myofilament contractility, and attenuates cardiac remodeling genes, consistent with the benefits on cardiac structure and function. These same rest-responsive gene pathways underlie the pathophysiology of many major human cardiovascular conditions, as demonstrated by interrogating open-source transcriptomic data; thus, patients with other conditions may also benefit from a morning rest period in a similar manner. Our findings implicate rest as a key driver of physiology, creating a potentially new field — as broad and important as diet, sleep, or exercise — and provide a strong rationale for investigation of rest-based therapy for major clinical diseases.

Authors

Cristine J. Reitz, Mina Rasouli, Faisal J. Alibhai, Tarak N. Khatua, W. Glen Pyle, Tami A. Martino

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Figure 5

Benefits of rest are not dependent on a functional circadian mechanism.

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Benefits of rest are not dependent on a functional circadian mechanism.
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(A) Representative actigraphy and periodogram, (B) activity quantification, and (C) hours of rest per day in ClockΔ19/Δ19 mutant mice under the rest model (+Rest) versus control. n = 5 mice/group. *P < 0.01, paired Student’s t test. (D) Rest model and cardiac hypertrophy experimental design in ClockΔ19/Δ19 mice: mice underwent baseline echocardiography followed by TAC and were randomized to control conditions versus the rest model for up to 4 weeks. (E) Representative M-mode echocardiography showing that the cardiac benefits of rest persisted in ClockΔ19/Δ19 mice, with (F) smaller LVIDd and LVIDs and better % EF and % FS and (G) smaller HW/BW ratio compared with controls at 4 weeks after TAC. n = 5 sham mice/group and n = 9 TAC mice/group. *P < 0.05, unpaired Student’s t test. (H) Representative images and quantification of cardiomyocyte cross-sectional area at 4 weeks after TAC. n = 5 hearts/group. *P < 0.005, unpaired Student’s t test. Scale bar: 100 μm.

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