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A brief morning rest period benefits cardiac repair in pressure overload hypertrophy and postmyocardial infarction
Cristine J. Reitz, … , W. Glen Pyle, Tami A. Martino
Cristine J. Reitz, … , W. Glen Pyle, Tami A. Martino
Published October 18, 2022
Citation Information: JCI Insight. 2022;7(22):e164700. https://doi.org/10.1172/jci.insight.164700.
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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 4

Rest reduces cardiac workload through intrinsic effects on the cardiac myofilaments.

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Rest reduces cardiac workload through intrinsic effects on the cardiac m...
(A) Cardiac actomyosin MgATPase activity and (B) EC50 were reduced at 4 weeks after TAC, (C) consistent with pathological cardiac afterload (mean arterial pressure; MAP) in the TAC model (additional cardiac hemodynamics are provided in Supplemental Figure 3). (D) Myofilament activity and (E) EC50 and (F) MAP were normalized in TAC+Rest hearts, consistent with (G) increased myofilament protein phosphorylation. TAC data from A and B are repeated in D and E for comparison. (H) Cardiac actomyosin MgATPase activity was maintained at 4 weeks after MI, (I) with increased EC50, (J) consistent with reduced in vivo cardiac contractility. (K) Extended rest lowered myofilament ATP consumption (L) but not EC50 (M) consistent with better in vivo cardiac contractility and (N) reduced myofilament protein phosphorylation. MI data are repeated in H and I and in K and L for comparison. Murine heart tissue collected at ZT15, 4 weeks after surgery. n = 6/group for ATPase and phosphorylation, n = 4/group for in vivo radiotelemetry, n = 9/group for in vivo pressure-volume hemodynamics. For MgATPase data, *P < 0.005; for all other data, *P < 0.05, by unpaired Student’s t test.

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