Date of Graduation

5-2019

Document Type

Thesis

Degree Name

Bachelor of Science in Biomedical Engineering

Degree Level

Undergraduate

Department

Biomedical Engineering

Advisor/Mentor

Balachandran, Kartik

Committee Member/Reader

Quinn, Kyle

Abstract

The renin-angiotensin system (RAS) plays a crucial role in the regulation of renal, cardiac, and vascular physiology. This system regulates in vivo blood pressure and fluid balance. As renal blood flow decreases, the kidneys convert prorenin into renin and secrete it into the circulatory system. Renin then converts angiotensinogen into angiotensin I (ang-I). The ang-I is then converted into angiotensin II (ang-II) by the angiotensin-converting enzyme (ACE). Ang-II, a vasoconstrictor, increases blood pressure by causing the blood vessels to narrow. Recent evidence suggests that RAS may be involved in the progression of valve disease, most notably, aortic stenosis.

The first part of this Honors thesis study was focused on the ACE and chymase inhibitors, quinaprilant and chymostatin, respectively. The aims of this study were to determine if ang-I is being converted into ang-II locally within the valve milieu. Results showed that the mechanical characteristics of the tissue were altered when the angiotensin converting enzymes were inhibited while the sample was exposed to ang-I. This suggests that ang-I is being converted into ang-II within the valve tissue. The binding of ang-I and ang-II to the receptors was investigated by inhibiting their respective receptor subtypes. The samples were treated with either ang-II type 1 receptor (AT-1R) inhibitor, losartan, or ang-II type 2 receptor (AT-2R) inhibitor, PD123-319, in combination with ang-I or ang-II. Blocking AT-1R mitigates the effect from ang-II binding while blocking AT-2R allows ang-II to only bind to AT-1R which increases its vasoconstrictive effect. Biaxial tensile testing was used to quantify the mechanical characteristics of the tissue; the mechanical characteristics measured were areal strain and anisotropy alignment of the tissue.

The second half of the study was focused on formulating a constitutive model to fit the data and determining the strain energy of the samples. The constitutive model chosen was the Choi-Vito model since it is commonly used in modeling the non-linear mechanics of anisotropic soft tissue. To test the reliability of the mathematical model, the strain energy density was also analyzed.

Keywords

Biomechanics, Renin-Angiotensin System, Biaxial Tensile Testing, Aortic Valve Leaflets, Constitutive Modeling

Comments

Joshua Fahy’s research was supported by an University of Arkansas Honors College Research Grant.

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