Bibliography: leaves 184-190 / viii, 190 leaves : ill ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Applied Mathematics, 1987

<p>In the human body, turbulent flow is associated with many complications. Turbulence typically occurs downstream from stenoses and heart valve prostheses and at branch points of arteries. A proper way to study turbulence may enhance the understanding of the effects of stenoses and improve the functional assessment of damaged heart valves and heart valve prostheses.</p><p>The methods of today for studying turbulence in the human body lack in either precision or speed. This thesis exploits a magnetic resonance imaging (MRI) phenomenon referred to as signal loss in order to develop a method for estimating turbulence intensity in blood flow.</p><p>MRI measurements were carried out on an appropriate flow phantom. The turbulence intensity results obtained by means of the proposed method were compared with previously known turbulence intensity results. The comparison indicates that the proposed method has great potential for estimation of turbulence intensity.</p>

In the human body, turbulent flow is associated with many complications. Turbulence typically occurs downstream from stenoses and heart valve prostheses and at branch points of arteries. A proper way to study turbulence may enhance the understanding of the effects of stenoses and improve the functional assessment of damaged heart valves and heart valve prostheses. The methods of today for studying turbulence in the human body lack in either precision or speed. This thesis exploits a magnetic resonance imaging (MRI) phenomenon referred to as signal loss in order to develop a method for estimating turbulence intensity in blood flow. MRI measurements were carried out on an appropriate flow phantom. The turbulence intensity results obtained by means of the proposed method were compared with previously known turbulence intensity results. The comparison indicates that the proposed method has great potential for estimation of turbulence intensity.

Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 275-293).

A number of clinical, in vitro and computational studies have shown the potential for thromboembolic complications in bileaflet mechanical heart valves (BMHV), primarily due to the complex and unsteady flows in the valve hinges. These studies have focused on quantitative and qualitative parameters such as velocity magnitude, turbulent shear stresses, vortex formation and platelet activation to identify potential for blood damage. However, experimental characterization of the whole flow fields within the valve hinges has not yet been conducted. This information can be utilized to investigate instantaneous damage to blood elements and also to validate numerical studies focusing on the hinge’s complex fluid dynamics. The objective of this study was therefore to develop a high-resolution imaging system to characterize the flow fields and global velocity maps in a BMHV hinge. Subsequently, the present study investigated the effect of hinge gap width on flow fields in a St. Jude Medical BMHV. The results from this study suggest that the BMHV hinge design is a delicate balance between reduction of fluid shear stresses and areas of flow stasis during leakage flow, and needs to be optimized to ensure minimal thromboembolic complications. Overall, the current study demonstrates the ability of high-resolution Micro Particle Image Velocimetry to assess the fluid flow fields within the hinges of bileaflet mechanical heart valves, which can be extended to investigate micro-scale flow domains in critical regions of other cardiovascular devices to assess their blood damage potential.

Infective endocarditis (IE) is a rare but complex disease that is fatal if untreated. With a modern combination of antimicrobial therapy and heart valve surgery, mortality is still 10-20 %. The structure of the endocarditis vegetation impedes the penetration of phagocytic cells such as monocytes and granulocytes. This leads to high bacterial counts inside the vegetation and the need for long treatment courses with a combination of intravenously administered bactericidal antibiotics. The aim of this thesis was to study the changes in epidemiology, management, and mortality at our hospital between 1980 and 2001, and to identify prognostic factors associated with mortality. To assess the issue of referral bias, differences between referred episodes and episodes from our local community were studied. Additional aims were to study the occurrence of the pro-chemotactic cytokines IL-8 and TNF-α in heart valves and vegetations during the active phase of IE, and to study the effect of the glycopeptide antibiotic vancomycin in dense staphylococcal cultures in vitro. As it is a rare and complex disease, management of IE is usually complicated for non-specialists. For this reason a computerised decision support system for IE was developed and evaluated. Between 1980 and 2001, the occurrence of Staphylococcus aureus IE and the use of early heart valve surgery increased significantly, regardless of whether the episodes were referred or of local origin. Glycopeptide antibiotics, mainly vancomycin, were used more frequently, especially among referred patients. Referred patients were younger, predominantly male, had more complications, and received surgical treatment more often than patients from our local community. The reason for the lower frequency of female patients in the referral cohort cannot be explained by more comorbidity or fewer complications. The differences between referred and local episodes seen in our study highlight the need for assessment and adjustment for referral bias in IE studies (Paper I). In six patients who needed early heart valve surgery, the largest numbers of IL-8-containing cells, and the greatest amount of inflammation, were seen in patients with short preoperative antimicrobial treatment courses. No such relationships were seen with respect to TNF-α-containing cells. The IL-8-containing cells and the inflammatory cells were predominantly scattered in the heart valve stroma or in the margin of the vegetation (Paper II). The primary effect of IL-8 is to stimulate chemotaxis of polymorphonuclear neutrophil granulocytes. This indicates that there is no deficiency of IL-8 in the area close to the vegetation as a cause of the localised agranulocytosis often present inside the vegetation. Our study revealed a need for computerised decision support systems (DSSs) in the field of IE, but to be used in clinical practice these DSSs need be part of knowledge bases covering larger domains (Paper IV). Some of our initial ideas described in Paper III, especially the use of Internet technology and the combination of rule-based advice and explanatory hypertext, will probably be included in these knowledge bases. In vitro, there is a rapid reduction of free vancomycin in broth containing dense staphylococcal cultures. Consequently, there is a simultaneous increase in broth MICs, particularly in high inocula, which is not caused by a development of resistance (Paper V). These findings need further evaluation in vivo, but indicate that the dosing regimen of vancomycin is of particular importance in staphylococcal infections with dense inocula, e.g. infective endocarditis. Diabetes mellitus and moderate to severe heart failure were independent risk factors for 6-month mortality in left-sided, Duke definite IE episodes, regardless of referral or local origin of the episodes. Early heart valve surgery had a positive impact on the 6-month mortality in the referral cohort of episodes, which may be due to referral bias (Paper VI).

The cellular mechanical environment, including the elasticity of the extracellular matrix, profoundly affects cellular mechanical and biological responses. This responsiveness depends on and may influence the inherent mechanical properties of the cell and the nucleus. In this thesis, the local and global elastic moduli of valve interstitial cells (VICs) cultured on substrates of varying stiffness were characterized using atomic force microscopy (AFM). A novel AFM technique used to directly determine nuclear elastic moduli in situ was also tested and preliminary results for VIC nuclear elasticity and isolated VIC nuclei elasticity were presented. This study confirmed that both local and global elasticity of VICs were sensitive to substrate compliance, and demonstrated that the nucleus was consistently two to four times stiffer than the cytoplasm and that isolated VIC nuclei were significantly softer than the intact nuclei in situ. It also provides practical guidelines for efficient AFM-based measurement of cell mechanical properties.

The tendency of aortic bileaflet mechanical heart valves (BiMHVs) to promote thrombosis has been well documented in the literature. The relationship of thrombosis to valve fluid dynamics has prompted numerous studies of aortic BiMHV flow. In this study, steady flow was investigated downstream of a model Carbomedics No. 25 BiMHV in an axisymmetric aortic sinus using stereoscopic particle image velocimetry (SPIV). The Reynolds number based on inlet diameter was 7600, and the measurement plane was perpendicular to the leaflet axes at the centerline of the aortic sinus. The typical formation of three jets was observed: the upper and lower lateral orifice jets, and the central jet. Flow separation from the valve ring was seen, and large scale vortices were identified in both the upper and lower sinus regions. An asymmetry in the reverse flow was found, and possible causes were discussed. All three jets were seen to decay similarly to free rectangular jets, with zero decay initially, followed by a 'linear' decay rate in which Umax^2~X. The central jet was also seen to be self similar in the linear decay region. Analysis of the out-of-plane velocity yielded two alternate explanations of streamwise vortex (i.e. Wx) structure, with either a four-cell or an eight-cell streamwise vortex structure being present in the mean velocity field. Organization of large scale three dimensional flow structures was thus apparent. Calculation of in-plane Reynolds stresses showed that values were highest in the outer shear layers of the lateral orifice jets. Elevated Reynolds shear stress values were also found in the leaflet wake regions, and the shear layers of the central jet.

The tendency of aortic bileaflet mechanical heart valves (BiMHVs) to promote thrombosis has been well documented in the literature. The relationship of thrombosis to valve fluid dynamics has prompted numerous studies of aortic BiMHV flow. In this study, steady flow was investigated downstream of a model Carbomedics No. 25 BiMHV in an axisymmetric aortic sinus using stereoscopic particle image velocimetry (SPIV). The Reynolds number based on inlet diameter was 7600, and the measurement plane was perpendicular to the leaflet axes at the centerline of the aortic sinus. The typical formation of three jets was observed: the upper and lower lateral orifice jets, and the central jet. Flow separation from the valve ring was seen, and large scale vortices were identified in both the upper and lower sinus regions. An asymmetry in the reverse flow was found, and possible causes were discussed. All three jets were seen to decay similarly to free rectangular jets, with zero decay initially, followed by a 'linear' decay rate in which Umax^2~X. The central jet was also seen to be self similar in the linear decay region. Analysis of the out-of-plane velocity yielded two alternate explanations of streamwise vortex (i.e. Wx) structure, with either a four-cell or an eight-cell streamwise vortex structure being present in the mean velocity field. Organization of large scale three dimensional flow structures was thus apparent. Calculation of in-plane Reynolds stresses showed that values were highest in the outer shear layers of the lateral orifice jets. Elevated Reynolds shear stress values were also found in the leaflet wake regions, and the shear layers of the central jet.

The cellular mechanical environment, including the elasticity of the extracellular matrix, profoundly affects cellular mechanical and biological responses. This responsiveness depends on and may influence the inherent mechanical properties of the cell and the nucleus. In this thesis, the local and global elastic moduli of valve interstitial cells (VICs) cultured on substrates of varying stiffness were characterized using atomic force microscopy (AFM). A novel AFM technique used to directly determine nuclear elastic moduli in situ was also tested and preliminary results for VIC nuclear elasticity and isolated VIC nuclei elasticity were presented. This study confirmed that both local and global elasticity of VICs were sensitive to substrate compliance, and demonstrated that the nucleus was consistently two to four times stiffer than the cytoplasm and that isolated VIC nuclei were significantly softer than the intact nuclei in situ. It also provides practical guidelines for efficient AFM-based measurement of cell mechanical properties.