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. SacksEmail author


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.


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




Right ventricle


RV free wall


Pulmonary artery

Hemodynamic Parameters


RV end-systolic pressure


RV end-diastolic volume


Stroke volume


Stroke work

Maximum dP/dt

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


RV diastolic time constant (a measure of diastolic function)


RV elastance (a measure of contractility)


PA elastance (a measure of afterload)


RV–PA coupling

Constitutive Model Measures and Parameters


Green’s strain in longitudinal direction


Green’s strain in circumferential direction


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


2nd PK stress in circumferential direction


Model scaling parameter


Model parameter, representing longitudinal stiffness


Model parameter, representing circumferential stiffness


Model parameter, representing coupling, between longitudinal and circumferential response


Combined myofiber-collagen effective fiber ensemble stress


Combined myofiber-collagen effective fiber ensemble strain


Mass fraction of myofibers


Mass fraction of collagen fibers


Intrinsic myofiber modulus

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

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


Lower bound on recruitment strain for the collagen fiber ensemble


Upper bound on recruitment strain for the collagen fiber ensemble


Post-transition tangent modulus



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
    Email author
  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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