Our long term objective is to quantitively define the varying hemodynamic forces which act on the human thoracoabdominal aorta resulting in biomechanical stresses and strains in the vessel wall which may over time result in mechanical failure of the aortic wall and aneurysmal enlargement. Since the infrarenal abdominal aorta is particularly prone to aneurysm formation and the thoracic aorta is resistant, we will compare the two segments of aorta to determine predisposing factors for aneurysm formation. Our hypothesis is that hemodynamic forces and cumulative biomechanical stresses and strains, along with genetic susceptibility and superimposed atherogenic and humoral factors combine to result in aortic wall tissue failure and aneurysm formation. These factors, coincide, and are magnified in the abdominal aorta making it more prone to AAA. We will characterize and contrast the structural, compositional and biomechanical properties of the abdominal and thoracic aorta in humans and determine age related changes of the aortic wall. Utilizing MR imaging techniques, we will noninvasively assess thoracic and abdominal aortic blood flow in young (20-35 year old) and old (60-75 year old) normal adults as well as in patients with AAA. We will determine the 3 dimensional pulstaile flow field and quantitate differences in aortic wall strain between the abdominal and thoracic aorta. Physical models and in vivo animal experiments will be used to validate MR measurements and to develop and validate computational methods to model and predict biomechanical stress and strain of the aortic wall. These data will be used to construct a computational model of the human thoracoabdominal aorta which characterizes the 3 D pulsatile flow environment under a wide variation of conditions, such as changes in exercise states, cardiac output and blood pressure and quantify the real time aortic wall stress and strain pattern. Similarly, we will construct a computational biomechanical model of a human abdominal aortic aneurysm which will enable calculation of cumulative aortic wall stress loads over time. This will be used for predictive modeling of tissue failure and aneurysm enlargement and will be useful to evaluate strategies for therapies aimed at altering aortic wall tissue characteristics and matrix structure as well as in evaluating treatment strategies such as aortic stent grafts and open repair of the abdominal aortic aneurysms.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL064327-02
Application #
6184781
Study Section
Special Emphasis Panel (ZHL1-CSR-K (S1))
Project Start
1999-09-30
Project End
2003-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
2
Fiscal Year
2000
Total Cost
$277,375
Indirect Cost
Name
Stanford University
Department
Surgery
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Figueroa, C Alberto; Taylor, Charles A; Yeh, Victoria et al. (2010) Preliminary 3D computational analysis of the relationship between aortic displacement force and direction of endograft movement. J Vasc Surg 51:1488-97; discussion 1497
Figueroa, C Alberto; Taylor, Charles A; Yeh, Victoria et al. (2009) Effect of curvature on displacement forces acting on aortic endografts: a 3-dimensional computational analysis. J Endovasc Ther 16:284-94
Morrison, Tina M; Choi, Gilwoo; Zarins, Christopher K et al. (2009) Circumferential and longitudinal cyclic strain of the human thoracic aorta: age-related changes. J Vasc Surg 49:1029-36
Figueroa, C Alberto; Taylor, Charles A; Chiou, Allen J et al. (2009) Magnitude and direction of pulsatile displacement forces acting on thoracic aortic endografts. J Endovasc Ther 16:350-8
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Goergen, Craig J; Johnson, Bonnie L; Greve, Joan M et al. (2007) Increased anterior abdominal aortic wall motion: possible role in aneurysm pathogenesis and design of endovascular devices. J Endovasc Ther 14:574-84
Draney, Mary T; Arko, Frank R; Alley, Marcus T et al. (2004) Quantification of vessel wall motion and cyclic strain using cine phase contrast MRI: in vivo validation in the porcine aorta. Magn Reson Med 52:286-95
Xu, Chengpei; Zarins, Christopher K; Glagov, Seymour (2002) Biphasic response of tropoelastin at the poststenotic dilation segment of the rabbit aorta. J Vasc Surg 36:605-12
Xu, Chengpei; Lee, Sheila; Shu, Chang et al. (2002) Expression of TGF-beta1 and beta3 but not apoptosis factors relates to flow-induced aortic enlargement. BMC Cardiovasc Disord 2:11
Xu, Chengpei; Zarins, Christopher K; Glagov, Seymour (2002) Gene expression of tropoelastin is enhanced in the aorta proximal to the coarctation in rabbits. Exp Mol Pathol 72:115-23

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