The fluid shear stress environment of the normal and congenital bicuspid aortic valve and the implications on valve calcification

Yap, Choon Hwai

Title:

The fluid shear stress environment of the normal and congenital bicuspid aortic valve and the implications on valve calcification

dc.contributor.advisor	Yoganathan, Ajit P.
dc.contributor.author	Yap, Choon Hwai	en_US
dc.contributor.committeeMember	Giddens, Don P.
dc.contributor.committeeMember	Gleason, Rudolph L. Jr.
dc.contributor.committeeMember	Glezer, Ari
dc.contributor.committeeMember	Jo, Hanjoong
dc.contributor.committeeMember	Taylor, W. Robert
dc.contributor.department	Biomedical Engineering	en_US
dc.date.accessioned	2013-01-17T20:47:35Z
dc.date.available	2013-01-17T20:47:35Z
dc.date.issued	2011-08-18	en_US
dc.description.abstract	Calcific aortic valve disease is highly prevalent, especially in the elderly. Currently, the exact mechanism of the calcification process is not completely understood, limiting our ability to prevent or cure the disease. Ex vivo investigations, however, have provided evidence that the aortic valve's biological response is sensitive to mechanical forces, including fluid shear stresses, leading to the hypothesis that adverse fluid shear stress environment play a role in leading to valve calcification. This thesis seeks to investigate this hypothesis. A method for performing experimental measurement of time-varying shear stress on aortic valve leaflets under physiologic flow conditions was first developed, based on the Laser Doppler Velocimetry technique, and was systematically validated. This method was then applied to both the aortic surface and the ventricular surface of a normal tricuspid the aortic valve, and then on a congenital bicuspid aortic valve, using suitable in vitro valve models and an in vitro pulsatile flow loop. It was found that in the tricuspid valve, the peak shear stress on the aortic surface under adult resting condition was approximately 15-19 dyn/cm². Aortic surface shear stresses were elevated during mid- to late-systole, with the development of the sinus vortex, and were low during all other instances. Aortic surface shear stresses were observed to increase with increasing stroke volume and with decreasing heart rate. On the ventricular surface, shear stresses had a systolic peak of approximately 64-71 dyn/cm² under adult resting conditions. During late systole, due to the Womersley effect, shear stresses were observed to reverse in direction to a substantial magnitude for a substantial period of time. Further, it was found that a moderately stenotic bicuspid aortic valve can experience excessive unsteadiness in shear stress experienced by its leaflets, most likely due to the turbulent forward flow resulting from the stenosis, and due to the skewed forward flow. To demonstrate that the measured shear stresses can have an effect on the aortic valve biology, ex vivo experiments were performed in specific to determine the effects of these various shear stress characteristics on the biological response of porcine aortic valve leaflets, using the cone and plate bioreactor. It was found that unsteady shear stress measured in the bicuspid valve resulted in increased calcium accumulation. Further, it was found that low shear stresses and high frequency shear stresses resulted in increased calcium accumulation. Thus, shear stress was found to affect aortic valve pathology, and low and unsteady fluid shear stresses can enhance pathology.	en_US
dc.description.degree	PhD	en_US
dc.identifier.uri	http://hdl.handle.net/1853/45742
dc.publisher	Georgia Institute of Technology	en_US
dc.subject	Bicuspid aortic valve	en_US
dc.subject	Laser doppler velocimetry	en_US
dc.subject	Cone and plate bioreactor	en_US
dc.subject	Shear stress	en_US
dc.subject	Fluid mechanics	en_US
dc.subject	Aortic valve	en_US
dc.subject	Aortic valve calcification disease	en_US
dc.subject.lcsh	Aortic valve Diseases
dc.subject.lcsh	Aortic valve insufficiency
dc.subject.lcsh	Aortic valve Stenosis
dc.subject.lcsh	Mitral valve
dc.title	The fluid shear stress environment of the normal and congenital bicuspid aortic valve and the implications on valve calcification	en_US
dc.type	Text
dc.type.genre	Dissertation
dspace.entity.type	Publication
local.contributor.advisor	Yoganathan, Ajit P.
local.contributor.corporatename	Wallace H. Coulter Department of Biomedical Engineering
local.contributor.corporatename	College of Engineering
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