Stanford Advisors

All Publications

  • Strain-dependent stress relaxation behavior of healthy right ventricular free wall ACTA BIOMATERIALIA Liu, W., Labus, K. M., Ahern, M., LeBar, K., Avazmohammadi, R., Puttlitz, C. M., Wang, Z. 2022; 152: 290-299


    The increasing evidence of stress-strain hysteresis in large animal or human myocardium calls for extensive characterizations of the passive viscoelastic behavior of the myocardium. Several recent studies have investigated and modeled the viscoelasticity of the left ventricle while the right ventricle (RV) viscoelasticity remains poorly understood. Our goal was to characterize the biaxial viscoelastic behavior of RV free wall (RVFW) using two modeling approaches. We applied both quasi-linear viscoelastic (QLV) and nonlinear viscoelastic (NLV) theories to experimental stress relaxation data from healthy adult ovine. A three-term Prony series relaxation function combined with an Ogden strain energy density function was used in the QLV modeling, while a power-law formulation was adopted in the NLV approach. The ovine RVFW exhibited an anisotropic and strain-dependent viscoelastic behavior relative to anatomical coordinates, and the NLV model showed a higher capacity in predicting strain-dependent stress relaxation than the QLV model. From the QLV fitting, the relaxation term associated with the largest time constant played the dominant role in the overall relaxation behavior at most strains from early to late diastole, whereas the term associated with the smallest time constant was pronounced only at low strains at early diastole. From the NLV fitting, the parameters showed a nonlinear dependence on the strain. Overall, our study characterized the anisotropic, nonlinear viscoelasticity to capture the elastic and viscous resistances of the RVFW during diastole. These findings deepen our understanding of RV myocardium dynamic mechanical properties. STATEMENT OF SIGNIFICANCE: Although significant progress has been made to understand the passive elastic behavior of the right ventricle free wall (RVFW), its viscoelastic behavior remains poorly understood. In this study, we originally applied both quasi-linear viscoelastic (QLV) and nonlinear viscoelastic (NLV) models to published experimental data from healthy ovine RVFW. Our results revealed an anisotropic and strain-dependent viscoelastic behavior of the RVFW. The parameters from the NLV fitting showed nonlinear relationships with the strain, and the NLV model showed a higher capacity in predicting strain-dependent stress relaxation than the QLV model. These findings characterize the anisotropic, nonlinear viscoelasticity of RVFW to fully capture the total (elastic and viscous) resistance that is critical to diastolic function.

    View details for DOI 10.1016/j.actbio.2022.08.043

    View details for Web of Science ID 000870033300005

    View details for PubMedID 36030049

  • Multiscale Contrasts Between the Right and Left Ventricle Biomechanics in Healthy Adult Sheep and Translational Implications. Frontiers in bioengineering and biotechnology Liu, W., Nguyen-Truong, M., LeBar, K., Labus, K. M., Gray, E., Ahern, M., Neelakantan, S., Avazmohammadi, R., McGilvray, K. C., Puttlitz, C. M., Wang, Z. 2022; 10: 857638


    Cardiac biomechanics play a significant role in the progression of structural heart diseases (SHDs). SHDs alter baseline myocardial biomechanics leading to single or bi-ventricular dysfunction. But therapies for left ventricle (LV) failure patients do not always work well for right ventricle (RV) failure patients. This is partly because the basic knowledge of baseline contrasts between the RV and LV biomechanics remains elusive with limited discrepant findings. The aim of the study was to investigate the multiscale contrasts between LV and RV biomechanics in large animal species. We hypothesize that the adult healthy LV and RV have distinct passive anisotropic biomechanical properties. Ex vivo biaxial tests were performed in fresh sheep hearts. Histology and immunohistochemistry were performed to measure tissue collagen. The experimental data were then fitted to a Fung type model and a structurally informed model, separately. We found that the LV was stiffer in the longitudinal (outflow tract) than circumferential direction, whereas the RV showed the opposite anisotropic behavior. The anisotropic parameter K from the Fung type model accurately captured contrasting anisotropic behaviors in the LV and RV. When comparing the elasticity in the same direction, the LV was stiffer than the RV longitudinally and the RV was stiffer than the LV circumferentially, suggesting different filling patterns of these ventricles during diastole. Results from the structurally informed model suggest potentially stiffer collagen fibers in the LV than RV, demanding further investigation. Finally, type III collagen content was correlated with the low-strain elastic moduli in both ventricles. In summary, our findings provide fundamental biomechanical differences between the chambers. These results provide valuable insights for guiding cardiac tissue engineering and regenerative studies to implement chamber-specific matrix mechanics, which is particularly critical for identifying biomechanical mechanisms of diseases or mechanical regulation of therapeutic responses. In addition, our results serve as a benchmark for image-based inverse modeling technologies to non-invasively estimate myocardial properties in the RV and LV.

    View details for DOI 10.3389/fbioe.2022.857638

    View details for PubMedID 35528212

    View details for PubMedCentralID PMC9068898

  • Different Passive Viscoelastic Properties Between the Left and Right Ventricles in Healthy Adult Ovine JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME Liu, W., Nguyen-Truong, M., Ahern, M., Labus, K. M., Puttlitz, C. M., Wang, Z. 2021; 143 (12)


    Ventricle dysfunction is the most common cause of heart failure, which leads to high mortality and morbidity. The mechanical behavior of the ventricle is critical to its physiological function. It is known that the ventricle is anisotropic and viscoelastic. However, the understanding of ventricular viscoelasticity is much less than that of its elasticity. Moreover, the left and right ventricles (LV&RV) are different in embryologic origin, anatomy, and function, but whether they distinguish in viscoelastic properties is unclear. We hypothesized that passive viscoelasticity is different between healthy LVs and RVs. Ex vivo cyclic biaxial tensile mechanical tests (1, 0.1, 0.01 Hz) and stress relaxation (strain of 3, 6, 9, 12, 15%) were performed for ventricles from healthy adult sheep. Outflow track direction was defined as the longitudinal direction. Hysteresis stress-strain loops and stress relaxation curves were obtained to quantify the viscoelastic properties. We found that the RV had more pronounced frequency-dependent viscoelastic changes than the LV. Under the physiological frequency (1 Hz), the LV was more anisotropic in the elasticity and stiffer than the RV in both directions, whereas the RV was more anisotropic in the viscosity and more viscous than the LV in the longitudinal direction. The LV was quasi-linear viscoelastic in the longitudinal but not circumferential direction, and the RV was nonlinear viscoelastic in both directions. This study is the first to investigate passive viscoelastic differences in healthy LVs and RVs, and the findings will deepen the understanding of biomechanical mechanisms of ventricular function.

    View details for DOI 10.1115/1.4052004

    View details for Web of Science ID 000721743500006

    View details for PubMedID 34350934

  • The Interventricular Septum Is Biomechanically Distinct from the Ventricular Free Walls BIOENGINEERING-BASEL Nguyen-Truong, M., Liu, W., Doherty, C., LeBar, K., Labus, K. M., Puttlitz, C. M., Easley, J., Monnet, E., Chicco, A., Wang, Z. 2021; 8 (12)


    The interventricular septum contributes to the pumping function of both ventricles. However, unlike the ventricular wall, its mechanical behavior remains largely unknown. To fill the knowledge gap, this study aims to characterize the biaxial and transmural variation of the mechanical properties of the septum and compare it to the free walls of the left and right ventricles (LV/RV). Fresh hearts were obtained from healthy, adult sheep. The septal wall was sliced along the mid-line into two septal sides and compared to the epicardial layers of the LV- and RV-free walls. Biaxial tensile mechanical tests and constitutive modeling were performed to obtain the passive mechanical properties of the LV- and RV-side of the septum and ventricular walls. We found that both sides of the septum were significantly softer than the respective ventricular walls, and that the septum presented significantly less collagen than the ventricular walls. At low strains, we observed the symmetric distribution of the fiber orientations and a similar anisotropic behavior between the LV-side and RV-side of the septum, with a stiffer material property in the longitudinal direction, rather than the circumferential direction. At high strains, both sides showed isotropic behavior. Both septal sides had similar intrinsic elasticity, as evidenced by experimental data and constitutive modeling. These new findings offer important knowledge of the biomechanics of the septum wall, which may deepen the understanding of heart physiology.

    View details for DOI 10.3390/bioengineering8120216

    View details for Web of Science ID 000735939400001

    View details for PubMedID 34940369

    View details for PubMedCentralID PMC8698618

  • Establishment of adult right ventricle failure in ovine using a graded, animal-specific pulmonary artery constriction model ANIMAL MODELS AND EXPERIMENTAL MEDICINE Nguyen-Truong, M., Liu, W., Boon, J., Nelson, B., Easley, J., Monnet, E., Wang, Z. 2020; 3 (2): 182-192


    Right ventricle failure (RVF) is associated with serious cardiac and pulmonary diseases that contribute significantly to the morbidity and mortality of patients. Currently, the mechanisms of RVF are not fully understood and it is partly due to the lack of large animal models in adult RVF. In this study, we aim to establish a model of RVF in adult ovine and examine the structure and function relations in the RV.RV pressure overload was induced in adult male sheep by revised pulmonary artery constriction (PAC). Briefly, an adjustable hydraulic occluder was placed around the main pulmonary artery trunk. Then, repeated saline injection was performed at weeks 0, 1, and 4, where the amount of saline was determined in an animal-specific manner. Healthy, age-matched male sheep were used as additional controls. Echocardiography was performed bi-weekly and on week 11 post-PAC, hemodynamic and biological measurements were obtained.This PAC methodology resulted in a marked increase in RV systolic pressure and decreases in stroke volume and tricuspid annular plane systolic excursion, indicating signs of RVF. Significant increases in RV chamber size, wall thickness, and Fulton's index were observed. Cardiomyocyte hypertrophy and collagen accumulation (particularly type III collagen) were evident, and these structural changes were correlated with RV dysfunction.In summary, the animal-specific, repeated PAC provided a robust approach to induce adult RVF, and this ovine model will offer a useful tool to study the progression and treatment of adult RVF that is translatable to human diseases.

    View details for DOI 10.1002/ame2.12124

    View details for Web of Science ID 000681668600008

    View details for PubMedID 32613177

    View details for PubMedCentralID PMC7323700

  • Current Understanding of the Biomechanics of Ventricular Tissues in Heart Failure BIOENGINEERING-BASEL Liu, W., Wang, Z. 2020; 7 (1)


    Heart failure is the leading cause of death worldwide, and the most common cause of heart failure is ventricular dysfunction. It is well known that the ventricles are anisotropic and viscoelastic tissues and their mechanical properties change in diseased states. The tissue mechanical behavior is an important determinant of the function of ventricles. The aim of this paper is to review the current understanding of the biomechanics of ventricular tissues as well as the clinical significance. We present the common methods of the mechanical measurement of ventricles, the known ventricular mechanical properties including the viscoelasticity of the tissue, the existing computational models, and the clinical relevance of the ventricular mechanical properties. Lastly, we suggest some future research directions to elucidate the roles of the ventricular biomechanics in the ventricular dysfunction to inspire new therapies for heart failure patients.

    View details for DOI 10.3390/bioengineering7010002

    View details for Web of Science ID 000523493300027

    View details for PubMedID 31861916

    View details for PubMedCentralID PMC7175293