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Annals of Biomedical Engineering

, Volume 42, Issue 12, pp 2451–2465 | Cite as

Structural and Mechanical Adaptations of Right Ventricle Free Wall Myocardium to Pressure Overload

  • Michael R. Hill
  • Marc A. Simon
  • Daniela Valdez-Jasso
  • Will Zhang
  • Hunter C. Champion
  • Michael S. Sacks
Article

Abstract

Right ventricular (RV) failure in response to pulmonary hypertension (PH) is a severe disease that remains poorly understood. PH-induced pressure overload leads to changes in the RV free wall (RVFW) that eventually results in RV failure. While the development of computational models can benefit our understanding of the onset and progression of PH-induced pressure overload, detailed knowledge of the underlying structural and biomechanical events remains limited. The goal of the present study was to elucidate the structural and biomechanical adaptations of RV myocardium subjected to sustained pressure overload in a rat model. Hemodynamically confirmed severe chronic RV pressure overload was induced in Sprague–Dawley rats via pulmonary artery banding. Extensive tissue-level biaxial mechanical and histomorphological analyses were conducted to assess the remodeling response in the RV free wall. Simultaneous myofiber hypertrophy and longitudinal re-orientation of myo- and collagen fibers were observed, with both fiber types becoming more highly aligned. Transmural myo- and collagen fiber orientations were co-aligned in both the normal and diseased state. The overall tissue stiffness increased, with larger increases in longitudinal vs. circumferential stiffness. The latter was attributed to longitudinal fiber re-orientation, which increased the degree of anisotropy. Increased mechanical coupling between the two axes was attributed to the increased fiber alignment. Interestingly, estimated myofiber stiffness increased while the collagen fiber stiffness remained unchanged. The increased myofiber stiffness was consistent with clinical results showing titin-associated increased sarcomeric stiffening observed in PH patients. These results further our understanding of the underlying adaptive and maladaptive remodeling mechanisms and may lead to improved techniques for prognosis, diagnosis, and treatment for PH.

Keywords

Hypertrophy Tissue-level biomechanics Pulmonary hypertension Myofiber orientation Collagen fiber orientation 

Abbreviation

Anatomy

RV

Right ventricle

RVFW

RV free wall

PA

Pulmonary artery

Hemodynamic Parameters

RVESP

RV end-systolic pressure

RVEDV

RV end-diastolic volume

SV

Stroke volume

SW

Stroke work

Maximum dP/dt

Maximal first time-derivative of pressure (a measure of systolic function)

Tau

RV diastolic time constant (a measure of diastolic function)

Ees

RV elastance (a measure of contractility)

Ea

PA elastance (a measure of afterload)

Ees/Ea

RV–PA coupling

Constitutive Model Measures and Parameters

ELL

Green’s strain in longitudinal direction

ECC

Green’s strain in circumferential direction

SLL

2nd Piola–Kirchhoff (PK) stress in longitudinal direction

SCC

2nd PK stress in circumferential direction

b0

Model scaling parameter

bL

Model parameter, representing longitudinal stiffness

bC

Model parameter, representing circumferential stiffness

bLC

Model parameter, representing coupling, between longitudinal and circumferential response

Sens

Combined myofiber-collagen effective fiber ensemble stress

Eens

Combined myofiber-collagen effective fiber ensemble strain

\(\Phi_{\text{m}}\)

Mass fraction of myofibers

\(\Phi_{\text{c}}\)

Mass fraction of collagen fibers

\(\eta_{\text{m}}\)

Intrinsic myofiber modulus

\(\bar{\eta }_{\text{c}}\)

Intrinsic collagen fiber modulus, that accounts for the effects of gradual fiber recruitment

Elb

Lower bound on recruitment strain for the collagen fiber ensemble

Eub

Upper bound on recruitment strain for the collagen fiber ensemble

PTTM

Post-transition tangent modulus

Notes

Acknowledgments

This work was supported by the U.S. National Institutes of Health [1F32 HL117535 to M.R.H., P01 HL103455 and U01 HL108642-01 to H.C.C.]; the American Heart Association [13POST14720047 to M.R.H., 11POST6950004 to D.V-J., 10BGIA3790022 to M.A.S.]; and The Pittsburgh Foundation [M2010-0052 to M.A.S. and M.S.S.]. We’d like to thank Sunaina Rustagi, Andrea Sebastiani, and Samantha Carter at the University of Pittsburgh (Pitt) for performing the biomechanical testing; Jeffrey J. Baust at Pitt for performing pulmonary artery banding procedures; Sruti Shiva at Pitt for performing the tissue viability study; Simone Siegel, Michelle Atkins, and John Lesicko at the University of Texas at Austin (UT-Austin) for performing the histomorphological analysis.

Conflict of Interest

No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

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Copyright information

© Biomedical Engineering Society 2014

Authors and Affiliations

  • Michael R. Hill
    • 1
  • Marc A. Simon
    • 2
  • Daniela Valdez-Jasso
    • 3
  • Will Zhang
    • 1
  • Hunter C. Champion
    • 4
  • Michael S. Sacks
    • 1
  1. 1.Center for Cardiovascular Simulation, Institute for Computational Engineering and Sciences, Department of Biomedical EngineeringThe University of Texas at AustinAustinUSA
  2. 2.Departments of Cardiology and Bioengineering, Heart and Vascular InstituteUniversity of PittsburghPittsburghUSA
  3. 3.Department of BioengineeringUniversity of Illinois at ChicagoChicagoUSA
  4. 4.Southeastern Cardiology AssociatesColumbusUSA

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