The right ventricle (RV) is primarily involved with pulmonary disorders, such as pulmonary artery hypertension (PAH). PAH imposes increased pressure on the RV, causing a pathological growth and remodeling response (hypertrophy), which leads to RV wall thickening, and eventually to RV failure. New techniques are needed to allow clinicians to obtain in vivo measurements of RV function and to input these parameters into a model that can help predict the progression of this disease. Our ultimate goal is to develop a computational growth and remodeling (G&R) model of the RV response to a pressure overload. This model is to be used clinically to predict the progression of RV hypertrophy and to provide a method to evaluate the effectiveness of new treatment methods. A critical first step toward this goal was the creation of an experimental rat model to study PAH by our group and collaborators;now there is a pressing need for an accurate constitutive stress-strain model, a requirement for computational model development. This project is a major next step in this direction. In this work, we will apply an existing theoretical framework in the form of a constitutive stress-strain model of the healthy RV;we will extend the model to capture the growth and remodeling response to PAH and use a rat model to obtain model parameters;and we will validate this model by assessing its predictive capabilities when compared to results from an intervention. These objectives will be achieved in three specific aims: 1. To develop a constitutive (stress-strain) model for the normal, healthy right ventricle myocardium 2. To extend the model to include the time-evolving growth and remodeling adaptation of the myocardium to changes in wall stress 3. To evaluate the predictive capabilities of the model by comparing the results from the normal myocardium to a rat model of treatment (intervention) of pulmonary artery hypertension
The mechanisms underlying the right ventricle's (RV) response to pulmonary artery hypertension (PAH) will be investigated, and the results will be applied towards the development of a constitutive stress-strain model of this pathological response. The new model will greatly aid clinicians and scientists in diagnosing and developing new treatment methods for PAH.
|Avazmohammadi, Reza; Hill, Michael; Simon, Marc et al. (2017) Transmural remodeling of right ventricular myocardium in response to pulmonary arterial hypertension. APL Bioeng 1:|
|Avazmohammadi, Reza; Hill, Michael R; Simon, Marc A et al. (2017) A novel constitutive model for passive right ventricular myocardium: evidence for myofiber-collagen fiber mechanical coupling. Biomech Model Mechanobiol 16:561-581|
|Hill, Michael R; Simon, Marc A; Valdez-Jasso, Daniela et al. (2014) Structural and mechanical adaptations of right ventricle free wall myocardium to pressure overload. Ann Biomed Eng 42:2451-65|