Thesis (Ph.D.)--University of Iowa, 2006. / Includes separate files for thesis supplements. Supervisor: H.S. Udaykumar. Includes bibliographical references (leaves 182-195).

One of the major achievements in cardiac surgery over the past 30 years has been the ability to replace severely diseased heart valves with prosthetic ones. The option of using prosthetic heart valves for the treatment of valvular diseases has improved and prolonged many lives. This is reflected in around 120,000 heart valve replacement operations carried out every year in North America alone to correct the cardiovascular problems of stenosis, insufficiency, regurgitation, etc. The development of artificial heart valves depends on reliable knowledge of the hemodynamic performance and physiology of the cardiovascular system in addition to a sound understanding, at the fundamental level, of the associated fluid mechanics. It is evident from the literature review that noninvasive measurements in a confined area of complex transient geometry, providing critical information relating to valve performance, are indeed scarce. This thesis presents results of an extensive test program aimed at measuring turbulence stresses, steady and transient velocity profiles and their decay downstream of the mitral valve. Three mechanical tilting disc-type heart valves (Björk-Shiley convexo- concave, Björk-Shiley monostrut, and Bicer-Val) and two biological tissue valves (Hancock II and Carpentier-Edwards supraannular) are studied. The investigation was carried out using a sophisticated and versatile cardiac simulator in conjunction with a highly sensitive, noninvasive, two-component three-beam laser doppler anemometer system. The study covers both the steady (valve fully open) and pulsatile (resting heart rate) flow conditions. The continuous monitoring of the parametric time histories revealed useful details of the complex flow as well as helped establish location and timing of the peak parameter values. In addition, orientation experiments are conducted on the mechanical valves in an attempt to reduce stresses by altering the position of the major orifice. The experiments suggest correlation between high stresses and orientation. Based on the the data, the following general conclusions can be made: (i) Hemodynamic test results should be presented in nondimensional form to render them independent of test facilities, flow velocities, size of models, etc. This would facilitate comparison of results by different investigators, using different facilities and test conditions. (ii) The valves tested showed very disturbed flow fields which generated high turbulent stresses presenting a possibility of thromboembolism and, perhaps, haemolysis. (iii) Implantation orientation of the valve significantly affect the mechanical prostheses flow field. The single vortex formation in the posterior orientation results in a reduction in stresses compared to the anterior configuration. (iv) The present results together with the earlier information on pressure drop and regurgitation provide a comprehensive and organized picture of the valve performance. (v) The information is fundamental to the improvement in valve design, and development of guidelines for test methodology and acceptable performance criteria for marketing of the valves. / Applied Science, Faculty of / Mechanical Engineering, Department of / Graduate

Graphene is a 2D material well known for its high intrinsic strength of 100 GPa and Young’s modulus of 1 TPa. Because of its 2D nature, the most promising avenues to utilize graphene as a mechanical material include incorporating it as reinforcement in a nanocomposite and creating free-standing foams and aerogels. However, the current techniques are not well-controlled – the reinforcing graphene particles are often discontinuous and randomly dispersed – making it difficult to accurately model and predict the resulting material properties. Here we aim to develop a framework for a new class of nanocomposites reinforced not by discrete nanoparticles, but by a continuous 3D graphene network. These 3D graphene networks were formed by chemical vapor deposition of graphene on periodic metallic microlattices, thereby providing mechanical reinforcement for the lattices. To assist in the lattice design, analytical models were derived for the mechanical properties of core/shell composite lattices and experimentally validated through compression testing of polymer lattices coated with electroless Ni-P. The models and experiments showed good agreement at lower shell thicknesses, while there was divergence at higher thicknesses, likely due to fabrication imperfections. The analytical models were also applied to hollow metallic lattices coated with graphene and compared to experimental data. The results showed that the models are plausible and suggest that graphene has a significant strengthening effect on the microlattices. These studies represent a paradigm shift in the design and fabrication of nanocomposites as one may now precisely prescribe the placement of the reinforcing nanomaterials. On a broader scale, this work also lays the framework for using a 2D material to span 3D space, enabling further exploration of 2D material properties and applications. One potential application area for a graphene-reinforced polymer composite is in prosthetic heart valves. The tissue of a human heart valve leaflet is heavily reinforced with networks of collagen and elastin fibers. One could similarly incorporate a graphene network as reinforcement within the polymeric leaflets of a prosthetic valve. One promising application of polymeric valves is in growth-accommodating implants for pediatric patients. Here we aim to develop a polymeric valved conduit that can be expanded by transcatheter balloon dilation to match a child’s growth. We designed the valve, characterized and selected materials, fabricated the devices and performed benchtop in vitro testing. The first generation of an expandable biostable valved conduit displayed excellent hydrodynamic performance before and after permanent balloon dilation from 22 to 25 mm. The second generation has shown the potential for a greater dilation from 12 to 24 mm. These results demonstrate concept feasibility and motivate further development of a polymeric balloon-expandable device to replace valves in children and avoid reoperations.

Heart valve dysfunction is a relatively common condition in the population, whereas significant heart valve disease is more unusual. The cause of different types of heart valve disease depends on which valve is concerned. Rheumatic heart valve disease, has for a long time been considered to constitute a post-inflammatory condition. During the 1990s it was also shown that the so-called non-rheumatic or degenerative tricuspid aortic stenosis, comprised signs of inflammation. In this study, 118 patients (the VOCIN study group) referred to the University Hospital for preoperative investigation due to significant heart valve disease, were examined regarding signs of inflammation. Twenty-nine aortic valves from patients with significant aortic stenosis were divided into tricuspid and bicuspid aortic valves. The bicuspid aortic stenotic valves revealed signs of inflammation to a similar extent as the tricuspid valves. However, the tricuspid and bicuspid valves differed regarding distribution of calcification. In contrast, inflammation was not a predominant feature in 15 aortic and mitral valves from patients with significant heart valve regurgitation. Gross valvular pathology consistent with rheumatic aortic stenosis was found in 10 patients. These valves revealed a somewhat lower degree of inflammatory cell infiltration, but on the whole, there were no substantial differences when compared to non-rheumatic aortic stenotic valves. They did, however, reveal a similar distribution of calcification as the bicuspid, non-rheumatic aortic valves. The VOCIN study group was compared to an age- and gender matched control group with regard to history and signs of rheumatic disease. There was not any increased prevalence of clinical manifestations of non-cardiac inflammatory disease in patients with significant heart valve disease, when compared to healthy control subjects. However, patients with heart valve disease had significantly increased serum levels of inflammatory markers compared to controls. The increase in inflammatory markers remained significant even in the subgroup of non-rheumatic aortic stenosis devoid of coronary artery disease. These results indicate that a systemic inflammatory component is associated with stenotic, non-rheumatic heart valve disease. The similarities between different forms of calcific aortic valve disease indicate a similar pathogenesis. The question is raised whether aortic stenosis is one disease, mainly caused by a general and non-specific response to dynamic tissue stress due to an underlying malformation of the valve.

In vitro and in vivo models were proposed to evaluate the effects of ischemic mitral regurgitation and surgical repair on the function and mechanics of the heart’s mitral valve. In specific aim 1, a novel transducer was developed to measure the radially directed forces that may act on devices implanted to the mitral annulus. In an ovine model, radial forces were found to statistically increase with left ventricular pressure and were reduced in the setting of ischemic mitral regurgitation. In specific aim 2, the suture forces required to constrain true-sized and undersized annuloplasty rings to the mitral annulus of ovine animals was evaluated. Suture forces were observed to be larger on the anterior aspect of the rings and were elevated with annular undersizing. In specific aim 3, an in vitro simulator’s ability to mimic healthy and ischemic mitral regurgitation ovine mitral valve function was evaluated. After understanding the accuracy of the model, the in vitro ischemic mitral regurgitation model was used to evaluate the progressive effects of annuloplasty on strut and intermediary chordal tethering. The generated data and knowledge will contribute to the development of more durable devices and techniques to assess the significant clinical burden known as ischemic mitral regurgitation.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 6 uppsatser.

Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (p. 123-133).

No description available.

Tissue engineered heart valve (TEHV) is believed to be a promising candidate for curative heart valve replacements. Collagen, elastin and chondroitin-4-sulfate (C4S) comprise the extra-cellular matrix (ECM) of native heart valves and therefore are suitable materials for TEHV scaffolds. Freeze-drying technique was able to produce scaffolds with relative densities of 0.3%-2.0% and pore sizes of 33.2µm-201.5µm, without having any major effects on the ultra-structures on the scaffold materials. Subsequent dehydrothermal (DHT) treatment and ultra-violet (UV) irradiation introduced inter- or intra-molecular crosslinks in the scaffolds in forms of ester and amide bonds, as well as the accompanying denaturation of the proteins (i.e. ultra-structure transition from helices to random coils). The collagen-based scaffolds had tensile, compressive and effective bending moduli ranging from 39.8kPa to 1082kPa, from 2.4kPa to 213.9kPa, and from 11.0kPa to 415.8kPa, respectively. The different behaviours of the wall stretching and the wall buckling in the individual pores of the scaffolds contributed to the different tensile, compressive and bending moduli. The mechanical properties could be tailored through controlling the freezing temperature, the relative density and the composition of the scaffolds. A lower freezing temperature might lead to lower mechanical properties because different pore structures were introduced. When the the relative density of the scaffold increased, the values of the moduli increased exponentially, with an exponential dependence factor larger for the compressive modulus than for the tensile modulus. Adding elastin or C4S into the collagen scaffolds lowered the mechanical properties due to the decrease in the collagen content. Layered structures that combined collagen-rich layers with elastin-rich and/or C4S -rich layers allowed the scaffolds to make use of the different mechanical properties of different layers, and hence to show anisotropic bending behaviour depending on the loading directions. The lower effective bending modulus (9.6 to 25.0kPa) in the with curvature (WC) direction than that (18.1kPa to 39.3kPa) in the against curvature (AC) direction mimicked the characteristic behaviour of the native heart valves and would be beneficial for a mechanically desirable TEHV. The DHT treatment and UV irradiation were able to increase the mechanical properties of the scaffolds to up to 2.5 times of the original values, by reinforcing the scaffold materials with more crosslinks. In the hydrated status, the hydrophilic C4S improved the water uptake ability of the scaffold and the hydrophobic elastin reduced it. The hydrated layered scaffolds still exhibited bending anisotropy despite much lower effective bending modulus. Finite element models of the scaffolds produced results that were in agreement with the experiments, and enabled us to perform distributed loading and internal stress analysis on the scaffolds. The collagen-based scaffolds were seeded with cardiosphere-derived cells (CDCs), and they attached to the scaffolds and showed visible cell division, proliferation and migration. The CDCs exhibited preferred proliferation behaviours on the collagen-C4S scaffolds to that on the collagen-elastin scaffolds because of the cell affinity to the C4S, as well as the elastin-induced contractile cell phenotype and scaffold volume shrinkage. This difference seemed to be less evident in the layered scaffolds due to the cell communication between the layers. The crosslinking process also had effects on the cell proliferation in the ways that it induced ultra-structure changes or volume shrinkage in the scaffolds. The layered scaffold-cell constructs designed and produced in this study served as a forwarding step towards a mechanically desirable and biologically active TEHV.

Congenital heart valve disease is one of the most common abnormalities in children, with common valve defects being aortic stenosis, mitral stenosis, and valvular regurgitation. Although adult sized mechanical heart valve (MHV) replacements are widely studied and utilized, there are currently no FDA approved prosthetic heart valves available for the pediatric population. This is due to a variety of reasons such as a limited patient pool for clinical trials, limited valve sizes, and complex health histories in children. Much like adult sized mechanical heart valves, potential complications with pediatric heart valve replacements include thrombosis, blood damage due to high shear stresses, and cavitation. Due to pediatric sized MHVs being much smaller in size than adult MHVs, different fluid dynamic conditions and associated complications are expected. In order to accelerate the approval of pediatric sized heart valves for clinical use, it is important to first characterize and assess the fluid dynamics across pediatric sized heart valves. By understanding the hemodynamic performance of the valve, connections can be made concerning potential valve complications such as thrombosis and cavitation. The overall objective of this study is to better characterize and assess the flow field characteristics of a pediatric sized mechanical heart valve using flow visualization techniques in a mock circulatory loop. The mechanical heart valve chosen for this research was a size 17 mm Bjork-Shiley tilting disc valve, as this is a common size valve used for younger patients with smaller cardiovascular anatomy. The mock circulatory loop used in this research was designed to provide realistic pediatric physiological flow conditions, consisting of a Harvard Apparatus Pulsatile blood pump, venous reservoir, and a heart valve testing chamber. In order to expose the valve to realistic pediatric flow conditions, six unique pump operating conditions were tested that involved pre-determined heart rate and stroke volume combinations. In addition, a modified aortic root model was used to hold the mechanical heart valve in place within the loop and to provide more realistic aortic root geometry. This heart valve chamber was made from a transparent acrylic material, allowing for fluid flow visualization. A traditional Particle Image Velocimetry (PIV) experimental set up was used in order to illuminate the particles seeded within the fluid path, and thus allowing for the capture of sequential images using a high speed camera. The data collected throughout this study consisted of flow rate measurements using an ultrasonic flow meter, and the sequential PIV images obtained from the camera in order to analyze general flow characteristics across the pediatric valve. Such information regarding the flow profile across the valve allowed for conclusions to be made regarding the valve performance, such as average flow velocities and regions of regurgitant flow. By gaining a better understanding of the fluid dynamic profile across a pediatric sized heart valve, this may aid in the eventual approval of pediatric sized mechanical heart valves for future clinical use.