Force-dependent recruitment from myosin OFF-state increases end-systolic pressure–volume relationship in left ventricle

Charles K. Mann, Lik Chuan Lee, Kenneth S. Campbell, Jonathan F. Wenk

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Finite element (FE) modeling is becoming increasingly prevalent in the world of cardiac mechanics; however, many existing FE models are phenomenological and thus do not capture cellular-level mechanics. This work implements a cellular-level contraction scheme into an existing nonlinear FE code to model ventricular contraction. Specifically, this contraction model incorporates three myosin states: OFF-, ON-, and an attached force-generating state. It has been speculated that force-dependent transitions from the OFF- to ON-state may contribute to length-dependent activation at the cellular level. The current work investigates the contribution of force-dependent recruitment out of the OFF-state to ventricular-level function, specifically the Frank–Starling relationship, as seen through the end-systolic pressure–volume relationship (ESPVR). Five FE models were constructed using geometries of rat left ventricles obtained via cardiac magnetic resonance imaging. FE simulations were conducted to optimize parameters for the cellular contraction model such that the differences between FE predicted ventricular pressures for the models and experimentally measured pressures were minimized. The models were further validated by comparing FE predicted end-systolic strain to experimentally measured strain. Simulations mimicking vena cava occlusion generated descending pressure volume loops from which ESPVRs were calculated. In simulations with the inclusion of the OFF-state, using a force-dependent transition to the ON-state, the ESPVR calculated was steeper than in simulations excluding the OFF-state. Furthermore, the ESPVR was also steeper when compared to models that included the OFF-state without a force-dependent transition. This suggests that the force-dependent recruitment of thick filament heads from the OFF-state at the cellular level contributes to the Frank–Starling relationship observed at the organ level.

Original languageEnglish
Pages (from-to)2683-2692
Number of pages10
JournalBiomechanics and Modeling in Mechanobiology
Volume19
Issue number6
DOIs
StatePublished - Dec 1 2020

Bibliographical note

Funding Information:
This study was supported by grants from the National Institutes of Health (U01HL133359 and S10RR029541), as well the Halcomb Fellowship in Medicine and Engineering from the University of Kentucky.

Publisher Copyright:
© 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

Keywords

  • Contraction
  • Finite element
  • Multi-scale model
  • Three-state model

ASJC Scopus subject areas

  • Biotechnology
  • Modeling and Simulation
  • Mechanical Engineering

Fingerprint

Dive into the research topics of 'Force-dependent recruitment from myosin OFF-state increases end-systolic pressure–volume relationship in left ventricle'. Together they form a unique fingerprint.

Cite this