Diss.--Medizinischen Fakultät--Berlin--Humboldt-Universität, 1992. / Bibliogr. p. 85-93.

Effective diagnosis of COA hinges on quantifications of the global hemodynamics (heart function metrics and workload), and the local hemodynamics (3-dimensional flow dynamics in COA). In this study, we developed an image-based framework that can quantify local and global hemodynamics for COA diagnosis. The proposed framework uses lattice Boltzmann method and lumped-parameter modeling that only needs routine non-invasive clinical patient data. The computational framework was validated against clinical cardiac catheterization data and Doppler echocardiographic measurements. One of the complicating factors of COA is its common association with mixed valvular diseases (MVD), which include varying combinations of aortic and mitral valve pathologies. Treatment strategies for these patients are quite unclear and differ from patient to patient. In order to evaluate risk factors and create guidelines for intervention aimed at minimizing the progression of cardiovascular disease, the impact of COA and MVD on aortic fluid dynamics in patients with COA and MVD was investigated in this thesis. Our results show that interaction of MVD with COA fluid dynamics may amplify adverse hemodynamic effects especially downstream of COA and may contribute to speed up the progression of the disease. The results suggest that some more aggressive surgical approaches may be required as regularly chosen current surgical techniques may not be optimal for patients with both COA and MVD. The appropriate surgical technique for COA repair often remains unclear for adult patients. Extra-anatomical bypass grafting has been recommended in some of the COA cases. To effectively evaluate risk status and create guidelines for intervention, precise quantification of aortic fluid dynamics and hemodynamics is required. We used a patient-specific numerical framework to investigate the impact of bypass grafts on aortic fluid dynamics in patients with COA. This study can partially explain the complications associated in patients with COA who underwent bypass grafting. / Dissertation / Doctor of Philosophy (PhD) / Coarctation of the aorta is a congenital narrowing of the proximal descending aorta which coexists with other cardiovascular diseases. Although accurate and early diagnosis of coarctation hinges on blood flow quantification, proper diagnostic methods for coarctation still lack because fluid-dynamics methods that can be used for accurate flow quantification are not well developed yet. We developed an image-based patient-specific computational framework that can quantify hemodynamics in patients with coarctation. Moreover, we investigated the impact of coarctation coexisting with other diseases and its interventions on hemodynamics to answer clinical questions.

Calcified atheromatous aortic lesion causing significant narrowing of the aorta is an uncommon clinical entity. This calcified atheroma leads to obstruction of the lumen of the aorta simulating acquired coarctation of aorta causing impaired perfusion of lower limbs, visceral ischemia, and hypertension. We report a case of 58-year-old patient who presented with dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, 25-lb weight gain, lower extremity edema, and chest pain. Extensive workup including computed tomography and magnetic resonance imaging revealed a large calcific mass in the aortic arch causing his presenting symptoms. After surgical correction his symptoms resolved. Any patient presenting with heart failure symptoms in the setting of uncontrolled renovascular hypertension, intermittent claudication symptoms, or visceral ischemia with normal ejection fraction but moderate to severe left ventricular hypertrophy should be in high suspicion for acquired coarctation of aorta. The routine thorough examination of pulses in bilateral upper and lower extremities in all hypertensive patients is a very simple and useful clinical tool to diagnose acquired aortic coarctation.

Coarctation of the aorta (CoA) is a congenital heart disease in which the aorta witnesses localized obstruction. CoA can be fatal if left untreated. Endovascular stenting of CoA is an attractive treatment of choice in adolescents and adults; however, it can be associated with problems like stent malapposition and inappropriate stent expansion. The main objective of this study is to investigate the effects of stent implantation on the hemodynamic factors in a patient with mild coarctation. Computational fluid dynamics was utilized to illustrate the hemodynamic factors like velocity distribution, wall shear stress, and trans-coarctation pressure drop in pre- and post-intervention states. These factors were used to assess the success of stent deployment in this patient. Large Eddy Simulation (LES) model is employed in this work to provide detailed information on hemodynamics in patient-specific preand post-intervention geometries of the aorta. The results of an in-house lumped parameter code, in which its input parameters are obtained from patient-specific clinical data, were applied as the boundary conditions in this study. / Thesis / Master of Applied Science (MASc)

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Vascular reactivity to vasopressin and phenylephrine is potentiated by constrictor prostanoids (CP) in normotensive female (F) but not male (M) rat aorta and CP function is estrogen-dependent. This study investigated the effects of estrogen on CP function and arterial blood pressure (MAP) during development of aortic coarctation-induced hypertension (HT). M and F rats, (15-18 wks.) in four groups: normotensive (NT), hypertensive (HT), ovariectomized (OVX), and OVX estrogen-replaced (OE), underwent abdominal aortic coarctation or sham surgery (NT). At 14 days, SQ 29,548 (SQ, Thromboxane A2 (TXA2) receptor antagonist) was given i.v. to the groups. In another experiment, rats received Ridogrel (TXA2 receptor antagonist+TXA2 synthase (TXS) inhibitor) or vehicle (methyl cellulose) daily, for 14 days. Thoracic aortae were analyzed for morphology, incubated in Kreb’s Henseleit Buffer (KHB) ± angiotensin II (ANG II), or underwent continuous pulsatile flow and pressure experiments (PFP) with KHB ± ANG II. Perfusate was analyzed for thromboxane B2 (TXB2) and prostaglandin F1α (PGF1α). RT-PCR and immunohistochemistry were performed for TXS. MAP was higher in F-HT than in M-HT after 14 days. SQ infusion reduced MAP substantially more in F-HT and OE-HT than in others. Ridogrel prevented increases in MAP in F/OE-HT rats, but not M/OVX-HT. Basal release of TXB2 and PGF1α increased to a greater extent in F-HT than in M-HT relative to their controls. ANG II-stimulated TXB2 and PGF1α release increased to a greater extent in F-HT than in M-HT. With or without ANG II, TXB2 production in HT during PFP increased with estrogen. PGF1α increased during PFP with estrogen, however not with ANG II. Pressurization resulted in less diameter change in F and OE-HT than in OVX-HT. Elastin increased with HT (inhibited by Ridogrel) in all but M. Collagen increased in HT with estrogen (inhibited by Ridogrel). Neither OVX-HT nor Ridogrel had any effect on morphology. Estrogen increased TXS with HT. Estrogen enhanced vascular CP and MAP in F-HT by increased expression of TXS and collagen density in the vasculature indicating that in aortic coarctation-induced HT, CP are upregulated by estrogen. Specific forms of HT in human beings may involve estrogen-induced vascular CP upregulation.

Vascular reactivity to vasopressin and phenylephrine is potentiated by constrictor prostanoids (CP) in normotensive female (F) but not male (M) rat aorta and CP function is estrogen-dependent. This study investigated the effects of estrogen on CP function and arterial blood pressure (MAP) during development of aortic coarctation-induced hypertension (HT). M and F rats, (15-18 wks.) in four groups: normotensive (NT), hypertensive (HT), ovariectomized (OVX), and OVX estrogen-replaced (OE), underwent abdominal aortic coarctation or sham surgery (NT). At 14 days, SQ 29,548 (SQ, Thromboxane A2 (TXA2) receptor antagonist) was given i.v. to the groups. In another experiment, rats received Ridogrel (TXA2 receptor antagonist+TXA2 synthase (TXS) inhibitor) or vehicle (methyl cellulose) daily, for 14 days. Thoracic aortae were analyzed for morphology, incubated in Kreb’s Henseleit Buffer (KHB) ± angiotensin II (ANG II), or underwent continuous pulsatile flow and pressure experiments (PFP) with KHB ± ANG II. Perfusate was analyzed for thromboxane B2 (TXB2) and prostaglandin F1α (PGF1α). RT-PCR and immunohistochemistry were performed for TXS. MAP was higher in F-HT than in M-HT after 14 days. SQ infusion reduced MAP substantially more in F-HT and OE-HT than in others. Ridogrel prevented increases in MAP in F/OE-HT rats, but not M/OVX-HT. Basal release of TXB2 and PGF1α increased to a greater extent in F-HT than in M-HT relative to their controls. ANG II-stimulated TXB2 and PGF1α release increased to a greater extent in F-HT than in M-HT. With or without ANG II, TXB2 production in HT during PFP increased with estrogen. PGF1α increased during PFP with estrogen, however not with ANG II. Pressurization resulted in less diameter change in F and OE-HT than in OVX-HT. Elastin increased with HT (inhibited by Ridogrel) in all but M. Collagen increased in HT with estrogen (inhibited by Ridogrel). Neither OVX-HT nor Ridogrel had any effect on morphology. Estrogen increased TXS with HT. Estrogen enhanced vascular CP and MAP in F-HT by increased expression of TXS and collagen density in the vasculature indicating that in aortic coarctation-induced HT, CP are upregulated by estrogen. Specific forms of HT in human beings may involve estrogen-induced vascular CP upregulation.

Thesis (Ph. D.)--Ohio State University, 2009. / Title from first page of PDF file. Includes vita. Includes bibliographical references (p. 113-121).

Hypertension is a risk factor for many cardiovascular and cerebrovascular diseases such as atherosclerosis and stroke. It is therefore important to understand the effect of hypertension on temporal growth and remodeling of arteries. In this study, experimental hypertension was induced in the mini-pig by aortic coarctation. Basilar arteries and aortas were collected for analysis over an eight week period of hypertension with specimens from normotensive animals serving as controls. Changes in mechanical properties of the basilar artery were evaluated by in vitro pressure-diameter tests on intact cylindrical segments at their in situ length. The basilar arteries from hypertensive animals became less distensible, reflecting increases in both structural and material stiffness, compared to their normotensive counterparts. The circumferential stress rapidly returned toward its homeostatic value by increasing the wall thickness within two weeks. Immunohistochemistry, which is capable of illustrating the localization and distribution of protein expression, was performed to examine changes in wall constituents in the aorta. The increased medial thickness observed in hypertensive pigs compared to normotensive pigs was due to hyperplasia of smooth muscle cells (SMCs) and accumulation of extracellular matrix proteins, which were accompanied by the phenotypic modulation of SMCs. The increased interlamellar thickness, collagen fibers, and the thickness of elastic lamina found in the inner media of hypertensive animal may be associated with the gradient of stress decreasing into the outer media. SMC proliferation, if any, was found evenly distributed across the media, however. In cases showing increased proliferation and matrix protein synthesis, the SMC contractile markers were down-regulated whereas the SMC synthetic markers were up-regulated. While the aortic intima appeared normal in the normotensive animals, neointima formation, which may predispose the vessel to atheroma formation, was found in the hypertensive animals. Immunohistochemistry of Hsp47 and procollagen revealed that the endothelial cells (ECs) may produce collagen, specifically type I collagen in response to hypertension and contribute to the thickened intima. In addition, lectin staining for ECs markers and immunostaining for eNOS suggested that endothelial cells may transdifferentiate into intimal SMCs. These findings suggested an alternative role that ECs may play in hypertension-induced atherogenesis.

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