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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 1

Rest benefits outcomes in pressure overload–induced cardiac hypertrophy (TAC model).

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Rest benefits outcomes in pressure overload–induced cardiac hypertrophy ...
(A) Rest model and cardiac hypertrophy experimental design: mice underwent baseline echocardiography followed by transverse aortic constriction (TAC) and were randomized to control conditions (12 hour-light/12-hour dark cycle; LD 12:12) versus the rest model (12-hour light/4-hour blue light/8-hour dark; LBD 12:4:8) for up to 4 weeks. (B) Representative M-mode echocardiography at 4 weeks after TAC, showing (C) smaller left ventricular internal dimensions at diastole (LVIDd) and systole (LVIDs) and better % ejection fraction (EF) and fractional shortening (FS) in mice under the rest model. n = 11 mice/group. ***P < 0.001, unpaired, 2-tailed Student’s t test. (D) Representative images and (E) quantification of heart weight (HW) and HW/BW at 4 weeks after TAC. n = 11 mice/group. ***P < 0.001, unpaired Student’s t test. (F) Representative images and quantification of cardiomyocyte cross-sectional area at 4 weeks after TAC. n = 3 sham hearts/group, n = 5 TAC hearts/group. **P < 0.01, unpaired Student’s t test. Scale bar: 100 μm.

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