Mechanical Characterization of the Pulmonary Vasculature in an Animal Model of Pulmonary Arterial Hypertension
- Harimani, Vaishali
- Advisor(s): Valdez-Jasso, Daniela
Abstract
Pulmonary arterial hypertension (PAH) is a progressive lung vasculature disorder that results in elevated mean pulmonary arterial pressure due to extensive pulmonary vascular remodeling While the origins of the disease may be idiopathic or familial, the narrowing of vasculature and remodeling of the distal pulmonary arterioles contribute to heightened pressure and right ventricle afterload. The increased afterload in the right ventricle leads to RV dysfunction, and death. The female sex is a risk factor for PAH, with females having a greater incidence of the diseases, and yet, they have better survival than men. There is no cure for PAH, and current treatment strategies only aim to alleviate the immediate symptoms but do not undo the vascular remodeling. We aim to establish the mechanical properties of the large pulmonary arteries in the sugen-hypoxia animal model, and hypothesize that the remodeling is affected by ovarian hormones. In order to better understand the remodeling of pulmonary vasculature, rats were inducted with PAH through a combination of Sugen 5416, a vascular endothelial growth factor receptor blocker, and hypoxia, to obtain an animal model of the disease. Through the utilization of a tubular biaxial system, this study probed the passive mechanical attributes of pulmonary arteries. The Quasilinear viscoelastic model, employing both Kelvin and sigmoid functions, facilitated the characterization of these mechanical properties. The research extensively examined the differences in these properties across males, females, and ovariectomized females, revealing significant variations among the groups. Hypertensive female rats showed the greatest vascular remodeling and had significantly higher values of stiffness compared to males and OVX females. The left and right sides of the pulmonary arteries showed little difference in their remodeling and mechanical properties. The results suggest the possible role of ovarian hormones in affecting severity of PAH in the pulmonary arteries.