Browsing by Author "Wang, Zhijie, advisor"

Now showing 1 - 4 of 4

Open Access
Characterization of the unique biomechanical behavior of right ventricle using experimental and constitutive modeling approaches
(Colorado State University. Libraries, 2022) Liu, Wenqiang, author; Wang, Zhijie, advisor; Puttlitz, Christian, committee member; Bark, David, committee member; Chicco, Adam, committee member
Ventricle dysfunction leads to high morbidity and mortality in heart failure patients. It is known that right and left ventricles (RV&LV) are distinct in their embryologic origins, anatomies and functions, as well as the pathophysiology of ventricular failure. However, how exactly the RV is distinct from the LV in their biomechanical properties remains incompletely understood. Furthermore, the prevalence of RV failure is significantly increased in the later stages of diseases such as pulmonary hypertension (PH) and heart failure with preserved ejection fraction, and the clinical management and treatment of RV failure are persistently challenging. This calls for a further understanding of the mechanisms of RV failure including the biomechanical mechanism. In addition, ventricular tissues are viscoelastic, which means both energy storage (originated from elasticity) and energy loss (originated from viscosity) are present during the deformation. However, the investigation of ventricular tissue viscoelasticity is much less than that of the elasticity, and it is largely unknown how the RV viscoelastic behavior changes during RV failure progression and impacts on the physiological function of the chamber. To fill these knowledge gaps, the overall goal of my study was to investigate the unique biomechanical properties of the RV in its physiological and pathological functions using experimental and constitutive modeling approaches. The Specific Aims are: 1) Develop the experimental protocols and characterize ventricular tissue passive static and dynamic mechanical properties in both large and small animals; 2) Adapted and performed constitutive modeling of ventricular tissue static and dynamic mechanical behaviors; 3) Quantify the changes in RV biomechanics during the maladaptive remodeling induced by pulmonary hypertension. At the completion of my study, I established the ex vivo testing protocols and provided fundamental data regarding static and dynamic mechanical differences between the healthy left and right chambers to delineate the unique biomechanical properties of the RV. I also adapted the constitutive models to capture static and dynamic mechanical behaviors of the RV. Finally, I quantified the biomechanical changes of the RV during the RV failure development and offered new insights in the contributions of the RV tissue biomechanics to the organ function. The findings were obtained from both large and small animals' species, which are translational to human diseases and a strong addition to the current literature of RV failure. More importantly, the investigation on the viscoelastic (dynamic) mechanical properties of the RV and the changes of viscoelasticity in RV failure progression is highly novel. The constitutive modeling of the RV biaxial viscoelastic behavior is pioneering and unique in the computational study of the RV. In summary, this study will deepen the understanding of the biomechanical mechanisms of RV failure and assist with the development of new computational tools for diagnosis and treatment strategies.
Open Access
Establishment of biaxial testing system for characterization of small animal ventricle viscoelasticity under physiological loadings
(Colorado State University. Libraries, 2022) Roth, Kellan, author; Wang, Zhijie, advisor; Garrity, Deborah, committee member; McGilvray, Kirk, committee member
Ventricular dysfunction is a leading cause of heart failure. It is known that the mechanical behavior of both the left and right ventricles contribute to the function and changes during heart failure development. The ventricle tissue is viscoelastic meaning it is a stretch rate dependent material that exhibits both elastic and viscous behavior. The elasticity of the passive ventricular wall has been extensively investigated in cardiac research, but the viscous behavior is poorly understood. Moreover, as viscoelastic behavior is dependent on strain rate, characterizing the ventricle viscoelasticity under physiological loadings will invoke clinically relevant information. The objective of this thesis is to establish a biaxial testing system that can characterize rodent ventricle viscoelasticity under physiological loadings. The new tester was validated using polydimethylsiloxane (PDMS) sheets. The results from the biaxial tester's viscoelastic measurement of PDMS confirm that the tester is functioning properly for the measurement of viscoelastic soft tissue properties in small animal species under sinusoidal deformation at physiological stretch rates. Finally, rat right ventricular (RV) free walls in healthy and diseased specimens were characterized under physiological loadings. Significant alterations in viscoelastic properties and tissue anisotropy between the healthy and diseased tissues were observed. The rat RV study provides novel insight into the frequency-dependent and anisotropic viscoelasticity of the rat RV during heart failure development.
Embargo
Role of right ventricular anisotropic viscoelasticity in pathophysiology of RV failure
(Colorado State University. Libraries, 2024) LeBar, Kristen, author; James, Susan, advisor; Wang, Zhijie, advisor; McGilvray, Kirk, committee member; Chicco, Adam J., committee member; Popat, Ketul, committee member
Right ventricular (RV) failure is a key contributor to the mortality and morbidity of multiple cardiovascular diseases, such as congenital heart disease, heart failure with preserved ejection fraction, and pulmonary hypertension (PH). There has still, though, been a lack of treatment for such patients, due largely to a lack of understanding of the pathology and physiology of RV failure. Right ventricular passive stiffness is significantly increased in disease progression, and this change in mechanical behavior have been shown to markedly contribute to RV diastolic and systolic function. However, the myocardium is viscoelastic, and there is both energy storage (elasticity) and dissipation (viscosity) involved in the dynamic deformation within each cardiac cycle. Therefore, the long-ignored viscous component and its impact on organ performance must be investigated. Understanding of the impact of RV viscoelasticity in RV performance will fill a key knowledge gap in RV pathophysiology. Furthermore, the microtubule (MT), a cytoskeletal component of the cardiomyocyte (CM), is known to significantly contribute to the pathophysiology of multiple cardiovascular diseases. In the pressure-overloaded RV, MT density increases, leading to a stiffening of the CM and thus potentially the entire ventricular wall. Moreover, recent cell studies have shown that the pharmaceutical removal of the MT network reduces CM viscoelasticity and increases the extent of shortening, indicating a key role of the MT network myocardial viscoelasticity and contractile function. These findings suggest a regulation of myocardial viscoelasticity and organ contractility via the MT network. Therefore, the overall goal of my study is to determine the contribution of right ventricular anisotropic viscoelasticity to organ function during PH progression. The three specific aims of my dissertation research are: determine the alterations of RV anisotropic viscoelasticity in PH; delineate the contribution of the microtubules network to RV anisotropic viscoelasticity; explore the impact of the RV viscoelasticity on organ function using experimental and computational approaches.
Open Access
The right ventricle—the forgotten chamber that deserves more love
(Colorado State University. Libraries, 2022) Nguyen-Truong, Michael, author; Wang, Zhijie, advisor; Chicco, Adam, committee member; Li, Yan Vivian, committee member; McGilvray, Kirk, committee member; Popat, Ketul, committee member
Right ventricle failure (RVF) is associated with serious cardiac and pulmonary diseases that contribute significantly to the morbidity and mortality of patients. The prevalence of RVF is significantly increased in the later stages of pulmonary hypertension, congenital heart disease, and left heart failure with preserved ejection fraction. Moreover, the mortality rate of these patients has not improved with currently limited treatment options. The persistent clinical challenge is mainly due to an incomplete understanding of the structure-function relationships of the RV, partly attributed to the lack of large animal models, as well as the lack of RV-specific therapies. Therefore, the overall goal of the study is to fill knowledge gaps in the biomechanics of right ventricle failure secondary to pressure overload and in the regenerative potential of mesenchymal stromal cells (MSCs) regulated by RV mechanics. The specific aims are: 1. Assess the unique ex vivo biomechanics of the RV free wall in contrast to the LV free wall. 2. Assess the ex vivo biomechanics of the "significant other" of the RV chamber – the septum wall. 3. Establish a novel ovine model of RV failure and investigate RV biomechanical changes during RV failure progression. 4. Investigate the pro-angiogenic paracrine effect in the context of mesenchymal stromal cell mechanobiology to ultimately improve RV therapy. From ovine models, there was distinct anisotropic mechanical behavior of the RV compared to the left side in healthy adults, and the low-strain mechanical behavior was correlated to collagen III. Multiscale computational model indicated softer collagen fibers in the RV. The investigation on the septal wall originally revealed transmural biomechanical changes and a significantly more compliant wall than the ventricular free walls. A new adult RV failure was established, and there was stiffening of the RV in the outflow tract direction and altered tissue anisotropy with RV failure progression. Finally, from prior and our own RV mechanical data, biomimetic scaffolds that represent healthy and diseased RV mechanics were fabricated for the first time. The pro-angiogenic potentials of MSCs on these scaffolds were assessed by cytokine production and neovessel formation. There were synergistic effects of matrix stiffness and anisotropy on MSC pro-angiogenic functionality.