The frank-starling mechanism involves deceleration of cross-bridge kinetics and is preserved in failing human right ventricular myocardium

Nima Milani-Nejad, Benjamin D. Canan, Mohammad T. Elnakish, Jonathan P. Davis, Jae Hoon Chung, Vadim V. Fedorov, Philip F. Binkley, Robert S.D. Higgins, Ahmet Kilic, Peter J. Mohler, Paul M.L. Janssen

Research output: Contribution to journalArticle

Abstract

Cross-bridge cycling rate is an important determinant of cardiac output, and its alteration can potentially contribute to reduced output in heart failure patients. Additionally, animal studies suggest that this rate can be regulated by muscle length. The purpose of this study was to investigate cross-bridge cycling rate and its regulation by muscle length under near-physiological conditions in intact right ventricular muscles of nonfailing and failing human hearts. We acquired freshly ex-planted nonfailing (n = 9) and failing (n = 10) human hearts. All experiments were performed on intact right ventricular cardiac trabeculae (n = 40) at physiological temperature and near the normal heart rate range. The failing myocardium showed the typical heart failure phenotype: a negative force-frequency relationship and ß-adrenergic desensitization (P < 0.05), indicating the expected pathological myocardium in the right ventricles. We found that there exists a length-dependent regulation of cross-bridge cycling kinetics in human myocardium. Decreasing muscle length accelerated the rate of cross-bridge reattachment (ktr) in both nonfailing and failing myocardium (P < 0.05) equally; there were no major differences between nonfailing and failing myocardium at each respective length (P > 0.05), indicating that this regulatory mechanism is preserved in heart failure. Length-dependent assessment of twitch kinetics mirrored these findings; normalized dF/dt slowed down with increasing length of the muscle and was virtually identical in diseased tissue. This study shows for the first time that muscle length regulates cross-bridge kinetics in human myocardium under near-physiological conditions and that those kinetics are preserved in the right ventricular tissues of heart failure patients.

Original languageEnglish (US)
Pages (from-to)H2077-H2086
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume309
Issue number12
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Keywords

  • Cross-bridge cycling kinetics
  • Heart failure
  • Muscle length
  • Muscle length
  • Relaxation
  • Trabeculae

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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