Myocardial relaxation is accelerated by fast stretch, not reduced afterload

Charles S. Chung, Charles W. Hoopes, Kenneth S. Campbell

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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.

Original languageEnglish
Pages (from-to)65-73
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
StatePublished - Feb 1 2017

Bibliographical note

Funding Information:
Supported by from the American Heart Association 14SDG20100063 to CSC and 15GRNT25460003 to KSC and the National Institutes of Health R01 HL090749 to KSC and CTSA UL1TR000117.

Publisher Copyright:
© 2017 Elsevier Ltd


  • Afterload
  • Cross-bridge
  • Diastole
  • Myocardium
  • Relaxation
  • Strain rate

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine


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