Browsing by Subject "Heart valves"

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    Experimental studies of flow through deformable silicone and tissue engineered valves.
    (2009-12) Amatya, Devesh M.
    Annually, approximately 250,000 repair/replacement heart valve surgeries are performed world-wide. Currently the two options available for valve replacement are mechanical or bioprosthetic valves. Thrombosis (blood clots) and embolic events (movement of the clots through the blood vessels) have been linked with the mechanical valves, so that life-long anticoagulant therapy is required. Deterioration of the structural integrity, in part due to calcification, has been linked with bioprosthetic valves. The current paradigm is to replace a living, but incompetent valve with a non-living valve, be it mechanical or biological prosthetic. A living prosthetic valve grown with patient donor-based tissue engineering paradigm may be a possible solution. The primary objective of this study was to characterize the in vitro performance of the tissue engineered valve equivalents in a cardiovascular pulse duplicator and assess their potential for clinical use as valve replacement prostheses. A second objective was to conduct experiments under different flow conditions with synthetic silicone polymer valves of various geometries and materials similar in mechanical properties to those of the valve equivalents that are more amenable to experimental measurements of velocity and structural deformation using two-dimensional particle image velocimetry of high spatial resolution, three-dimensional velocimetry of volumetric measurements, and hot film anemometry of high temporal resolution. These measurements are needed to validate computational codes incorporating fluid-structure interaction and may be applied towards tissue engineered heart valve design and optimization. All of the silicone materials tested showed a neo-Hookean material response at engineering strains less than 0.5. The silicone linear elastic modulus was similar in order to the values measured in native aortic valve leaflets. The diaphragm valves with an orifice deformed to a concave shape with respect to the upstream flow for both steady and pulsatile flow conditions, along with orifice expansion at increasing flow rates. The orifice expansion (up to 75% increase in area) led to reduced pressure drops as compared with non-expanding or rigid diaphragm valves. A jet with significant inward radial velocity was present immediately downstream of the deformed diaphragm valves for both steady and pulsatile flows. This inward flow was associated with vena contracta. For low Reynolds number, laminar steady upstream flow conditions, the diaphragm valve supported the formation of relatively large scale vortices with passage frequency of St = 0.34. For pulsating flow, a leading vortex ring followed by a trailing jet was present during forward flow acceleration. Phase-averaged velocity measurements show lower fluctuations during the acceleration phase than during the deceleration phase of the flow. The deformation of the transparent bileaflet silicone valve in the pulsating flow showed leaflets deforming in similar concave state with respect to the upstream forward flow of systole and towards the lower pressures during diastole. The bileaflet silicone valve showed asymmetry in root deformation and a slot-like elliptical jet flow profile through the leaflets unlike the circular profile of the diaphragm valve. Downstream flow stagnation and recirculation were present during systole and areas of recirculation were present both upstream and downstream. These flow features were less organized for the latter during diastole. The tissue engineered valve equivalents harvested after development in the bioreactor and placed within a rigid housing were able to withstand pressures of ~50 mmHg, pressure drops of ~40 mmHg, and flow rates of ~25 L/min throughout the loading of the right ventricular cardiac cycle. The temporal pressures and flow signatures replicated right physiological conditions. The flow downstream indicated an elliptical jet during systole similar to the bileaflet silicone valve. The locations of tissue engineered valve equivalent failures were at the leaflet commissure and Dacron cuff-valve root interface.
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    The Sheep as a Translational Model for Next Generation Valve Replacement Devices: A Multimodal Cardiac Imaging Study
    (2024) Carney, John
    The development of catheter-based cardiac valve replacement devices, or transcatheter valves, has ushered in a new era in the treatment of patients with valvular disease. Prior to clinical study, regulators require comprehensive in vivo safety studies of novel cardiac devices in large animal models. The domestic sheep model has been widely used to evaluate predicate surgically implanted valves, therefore its use to assess valve durability, thromboembolic complications and biocompatibility is well documented and understood. However, the model’s cardiac valvular anatomy and hemodynamics both pre- and postoperatively remains largely unstudied to date, presenting a gap in the knowledge and understanding of the model and the translation of preclinical device findings to clinical use. The purpose of this thesis was to characterize, propose and standardize methods for the use of cardiac computed tomography (CT), echocardiography (echo) and four-dimensional flow magnetic resonance imaging (4D MRI) in assessing naïve and implanted prosthetic valves in the sheep model. Resulting anatomic and hemodynamic data was analyzed statistically and reported to create the first cardiac valve reference intervals for sheep, to be used as comparator data in future studies of next-generation cardiac valve devices in the model. Looking to the future of preclinical in vivo studies, we demonstrate the use of machine learning algorithms and their potential predictive role in determining cardiac anatomy of the sheep model, as well as in-life outcomes to help investigators better assess, interpret, and translate preclinical study outcomes to clinical use. Finally, we present a number of articles documenting our use of the sheep model in next generation cardiac valve replacement studies and background pathology of the model to be used to more effectively interpret study findings. We envision this thesis improving future preclinical research studies of novel cardiac device technology in the sheep through understanding of the model, refinements in animal use, and ultimately interpretation of future study results.