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Review
. 2023 Jan 1;324(1):H1-H13.
doi: 10.1152/ajpheart.00611.2022. Epub 2022 Nov 18.

Cardiac function, structural, and electrical remodeling by microgravity exposure

Mary R Sy  1   2 , Joshua A Keefe  1   2 , Jeffrey P Sutton  3   4 , Xander H T Wehrens  1   2   3   4   5   6
Affiliations
Review

Cardiac function, structural, and electrical remodeling by microgravity exposure

Mary R Sy et al. Am J Physiol Heart Circ Physiol. .

Abstract

Space medicine is key to the human exploration of outer space and pushes the boundaries of science, technology, and medicine. Because of harsh environmental conditions related to microgravity and other factors and hazards in outer space, astronauts and spaceflight participants face unique health and medical challenges, including those related to the heart. In this review, we summarize the literature regarding the effects of spaceflight on cardiac structure and function. We also provide an in-depth review of the literature regarding the effects of microgravity on cardiac calcium handling. Our review can inform future mechanistic and therapeutic studies and is applicable to other physiological states similar to microgravity such as prolonged horizontal bed rest and immobilization.

Keywords: arrhythmia; calcium; microgravity; ryanodine receptor; space.

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Conflict of interest statement

X.H.T.W. is a founding partner of Elex Biotech, a start-up company that developed drug molecules to target ryanodine receptors to treat cardiac arrhythmias. The remaining authors have nothing to disclose.

Figures

Figure 1.
Figure 1.
Microgravity-related effects on cardiac structure and function. A: microgravity leads to selective upper extremity vasodilation because of release of vasodilatory peptides such as atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP). B: microgravity results in deceased left ventricular (LV) and right ventricular (RV) ejection fraction (EF) with biventricular dilation and atrophy. C: microgravity results in increased fibrosis and autophagy. D: microgravity results in no changes in myosin structure but increased long N2BA titin isoform with greater titin phosphorylation.
Figure 2.
Figure 2.
Microgravity-related changes within the cardiomyocyte. Microgravity leads to attenuated cardiac function because of decreased nitric oxide synthase (NOS) activity, predisposing L-type calcium channels (LTCCs) to oxidative damage, and ryanodine receptor 2 (RyR2) Ca2+ leak, secondary to increased calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylation at serine-2814. Increased phosphorylation of CaMKII at threonine-287 and histone deacetylase 4 (HDAC4) at serine-632 results in greater RyR2 activity and cardiac remodeling, respectively. Decreased sarco(endo)plasmic reticulum calcium ATPase 2a (SERCA2a) activity results in decreased sarcoplasmic reticulum (SR) Ca2+ content. These changes contribute to the presence of premature ventricular contraction (PVCs) and prolonged QT interval on electrocardiogram (ECG).
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