Myocardial Relaxation Is Accelerated by Fast Stretch, Not Reduced Afterload

Authors

Charles S. Chung, University of KentuckyFollow
Charles W. Hoopes, The University of Alabama at Birmingham
Kenneth S. Campbell, University of KentuckyFollow

Abstract

Fast relaxation of cross-bridge generated force in the myocardium facilitates efficient diastolic function. Recently published research studying mechanisms that modulate the relaxation rate has focused on molecular factors. Mechanical factors have received less attention since the 1980s when seminal work established the theory that reducing afterload accelerates the relaxation rate. Clinical trials using afterload reducing drugs, partially based on this theory, have thus far failed to improve outcomes for patients with diastolic dysfunction. Therefore, we reevaluated the protocols that suggest reducing afterload accelerates the relaxation rate and identified that myocardial relengthening was a potential confounding factor. We hypothesized that the speed of myocardial relengthening at end systole (end systolic strain rate), and not afterload, modulates relaxation rate and tested this hypothesis using electrically-stimulated trabeculae from mice, rats, and humans. We used load-clamp techniques to vary afterload and end systolic strain rate independently. Our data show that the rate of relaxation increases monotonically with end systolic strain rate but is not altered by afterload. Computer simulations mimic this behavior and suggest that fast relengthening quickens relaxation by accelerating the detachment of cross-bridges. The relationship between relaxation rate and strain rate is novel and upends the prevailing theory that afterload modifies relaxation. In conclusion, myocardial relaxation is mechanically modified by the rate of stretch at end systole. The rate of myocardial relengthening at end systole may be a new diagnostic indicator or target for treatment of diastolic dysfunction.

Document Type

Article

Publication Date

2-2017

Notes/Citation Information

Published in Journal of Molecular and Cellular Cardiology, v. 103, p. 65-73.

© 2017 Elsevier Ltd. All rights reserved.

This manuscript version is made available under the CC‐BY‐NC‐ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/.

The document available for download is the author's post-peer-review final draft of the article.

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.yjmcc.2017.01.004

Funding Information

Supported by a Scientist Development Grant from the American Heart Association (14SDG20100063) to CSC and the National Institutes of Health R01 HL090749 to KSC and CTSA UL1TR000117.

Related Content

Refer to Web version on PubMed Central for supplementary material.

Repository Citation

Chung, Charles S.; Hoopes, Charles W.; and Campbell, Kenneth S., "Myocardial Relaxation Is Accelerated by Fast Stretch, Not Reduced Afterload" (2017). Physiology Faculty Publications. 137.
https://uknowledge.uky.edu/physiology_facpub/137