Les pathologies valvulaires aortiques sont des pathologies plurifactorielles, comportant un déterminisme génétique indiscutable mais peu caractérisé. Ma thèse a pour but d’étudier le rôle du facteur de transcription Krox20 au cours du développement et de la maturation valvulaire à travers l’analyse de modèles murins. Nous avons montré que ce gène est nécessaire au développement et à la maturation de la valve aortique. L’invalidation de Krox20 chez la souris conduit à une hypertrophie des feuillets aortiques dès les stades fœtaux et à des insuffisances aortiques chez l’adulte. Ces anomalies sont associées à des défauts d’organisation de la matrice extracellulaire en partie liée à une régulation directe de l’expression des collagènes de type I et III. 25% des souris déficientes pour Krox20 présentent une bicuspidie de la valve aortique. Nous avons observé une diminution de l’expression de eNos chez ces mutants et pu mettre en évidence une interaction génétique entre Krox20 et eNos. De plus, nous avons identifié une sous population de cellules des crêtes neurales cardiaques impliquées dans l’apparition de la bicuspidie chez les mutants Krox20. Afin d’explorer le rôle de Krox20 dans la calcification de la valve aortique, nous avons étudié les conséquences de la surexpression de ce gène dans un modèle et montré que lcela induisait une activation de gènes pro-fibrotiques et pro-ostéogénique sans conduire à des dépôts calciques. Krox20 est donc un facteur de transcription important pour la valvulogenèse et à l’homéostasie valvulaire chez l’adulte. Mes travaux ont contribué à l’identification de Krox20 comme gène candidat potentiel aux valvulopathies rencontrées chez l’homme. / Long seen as a consequence of aging and mechanical wear of aortic cusps, aortic valve diseases are currently considered multifactorial diseases, with an indisputable genetic determinism but not well characterized. My thesis aims to study the role of the transcription factor Krox20 during development and maturation of the valve through the analysis of mouse models. We have shown that this gene is necessary for the development and maturation of the aortic valve. Indeed, the deletion of Krox20 in the mouse leads to thickened aortic leaflets from the fetal stage and the onset of aortic valve disease in adults. These anomalies are associated with defects in the organization of the extracellular matrix and more particularly to direct regulsation of collagen type I and type III expression. Our analysis showed that 25% Krox20-/- mice have a bicuspid aortic valve. The analysis of this model has allowed us to identify a population of cardiac neural crest cells involved in the occurrence of this phenotype. In addition, we were able to observe a down regulation of eNos in Krox20-/- embryos and show a genetic interaction between Krox20 and eNos. To address the role of Krox20 in the process of calcification of the aortic valve, we have studied the effects of its overexpression. Our preliminary results indicate that this overexpression leads to activation of pro-fibrotic and pro-osteogenic genes, however, this is not sufficient to induce calcification of aortic valve leaflets.Therefore Krox20 is important for valvulogenesis but also for valvular homeostasis in the adult. My work has contributed to the identification of a potential candidate gene involved in human valve diseases.

Master of Science / Department of Clinical Sciences / Barret J. Bulmer / Degenerative valve disease is the most common cardiac affliction facing our canine population. To date, canine research has focused on characterizing the disease itself and the histopathological features. Because of the ability to routinely repair or replace diseased valves in human medicine, research focus in humans has been on perfecting these techniques rather than elucidating etiology. The recent interest in valvular interstitial cells has been primarily due to their capacity to degrade collagen with the knowledge that disorganized collagen is a hallmark characteristic of degenerative valve disease. In this project, an easily reproducible cell culture protocol for canine valvular interstitial cells was developed. These cells were phenotyped by utilization of RT-PCR and immunocytochemistry. The use of these cells in a research project looking at response to endothelin exposure with and without protection of vitamin E is demonstrated as an example of the unlimited possibilities for these cells to elucidate not only the etiology of the disease process but also the response to therapy.

Choosing suitable and safe valve with accessories depends on general specifications for plant. Using valve for on/off, throttling, back-flow prevention, etc., pressure drop is related with Kv value or leakages from piping systems are main factors for properly valve selection. Valve have to resist chemicals and substances that may change the state, temperature and its fluctuation, pressure, corrosion and erosion. This properties determine pressure class, temperature resistance, connection into pipe and sealing material as gland packing, seats, seal between flange etc. This and other specification, listed in this thesis, can help determine suitable type of valve. This thesis deals construction design of valve and accessories as well. The last chapters are focused on calculation of safety valve and selection safe and appropriate control valve with accessories.

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Tesla valve applications for passive flow enhancement in micro fluidic applications are promising, because of its design of no-moving-parts. The effectiveness of the valve (measured via its pressure and thermal diodicity) can be increased by creating a multi-staged Tesla valve. Present study investigates the effect of varying Reynolds number (25-200) on flow rectification and thermal enhancement capability of a Tesla valve. Gamboa Morris Forster (GMF) design with a cross-section of 1mm2 and constant valve-to-valve distance (1mm) was utilized for this research. An arbitrary fluid with constant properties at a reference temperature was used as the working fluid. Periodicity in flow and thermal distribution are noticed in the latter part of MSTV. Average friction factor and pressure diodicity decreased with increasing Reynolds number whereas average Nusselt number and thermal diodicity increased. Correlations for friction factor, pressure diodicity, Nusselt number, and thermal diodicity were derived by fitting a non-linear curve fit model.

With increasing effects of global warming, efforts are made to make transportation in general more fuel efficient. When it comes to internal combustion engines, the most common way to improve fuel efficiency is through ‘downsizing’. Downsizing means that a smaller engine (with lower losses and less weight) performs the task of a larger engine. This is accomplished by fitting the smaller engine with a turbocharger, to recover some of the energy in the hot exhaust gases. Such engine systems need careful optimization and when designing an engine system it is common to use simplified flow models of the complex geometries involved. The exhaust valves and ports are usually modelled as straight pipe flows with a corresponding discharge or loss coefficient, typically determined through steady-flow experiments with a fixed valve and at low pressure ratios across the valve. This means that the flow is assumed to be independent of pressure ratio and quasi-steady. In the present work these two assumptions have been experimentally tested by comparing measurements of discharge coefficient under steady and dynamic conditions. The steady flow experiments were performed in a flow bench, with a maximum mass flow of 0.5 kg/s at pressures up to 500 kPa. The dynamic measurements were performed on a pressurized, 2 litre, fixed volume cylinder with one or two moving valves. Since the volume of the cylinder is fixed, the experiments were only concerned with the blowdown phase, i.e. the initial part of the exhaustion process. Initially in the experiments the valve was closed and the cylinder was pressurized. Once the desired initial pressure (typically in the range 300-500 kPa) was reached, the valve was opened using an electromagnetic linear motor, with a lift profile corresponding to different equivalent engine speeds (in the range 800-1350 rpm). The results of this investigation show that neither the quasi-steady assumption nor the assumption of pressure-ratio independence holds. This means that if simulations of the exhaustion process is made, the discharge coefficient needs to be determined using dynamic experiments with realistic pressure ratios. Also a measure of the quasi-steadiness has been defined, relating the change in upstream conditions to the valve motion, i.e. the change in flow restriction, and this measure has been used to explain why the process cannot be regarded as quasi-steady. / <p>QC 20170306</p>

IntroductionThe young adult patients with aortic valve insufficiency undergo aortic valve replacement (AVR) and are forced to take anticoagulation medications for the rest of life due to prosthetic valve. This leads to many post-operative complications and drastic outcomes. Whereas, the in-vogue alternative of aortic valve repair (AVr) is available and a lot more beneficial as well.Especially considering the surgeon’s skills for selected repair procedure, selectively chosen patient with mild to moderate grades of aortic valve insufficiency and no significant comorbidities present for at least five (5) years or longer time. AimThe aim of this study was to affirm ‘if all kind of outcomes of aortic valve repair are beneficial alternative to aortic valve replacement (AVR) for the patients suffering from aortic valve insufficiency for at least five (5) years or longer time. Material and MethodsInternet search using standard key words of ‘Aortic Valve Repair and Outcomes’ was used to find both white literature (officially published literature) and grey literature (unpublished or ongoing study/literature) with human, adult, English language and studies published after January 1st 2007 as limitations. Inclusion criteria was adult patients with aortic insufficiency with aortic valve repair as intervention with outcomes at least greater than five (5) years were considered. All the data was extracted using Microsoft excel for windows and was analyzed using GraphPad Prisma. Results20 studies comprising of 5369 patients were included in this systemic review, which included 2 randomized control trails, 7 clinical prospective studies, 8 retrospective studies and 3 observational studies. ConclusionThis study suggests that aortic valve repair is a beneficial alternative available for younger adults suffering from aortic valve insufficiency in longer time.

Background “valve-in-valve” TAVR (VIV-TAVR) is established and provides good initial clinical and hemodynamic outcomes. Lacking long-term durability data baffle the expand to lower risk patients. For those purposes, the present study adds a hemodynamic 3-years follow-up. Methods A total of 77 patients underwent VIV-TAVR for failing aortic bioprosthesis during a 7-years period. Predominant mode of failure was stenosis in 87.0%. Patients had a mean age of 79.4 ± 5.8 years and a logistic EuroSCORE of 30.8 ± 15.7%. The Society of Thoracic Surgeons-PROM averaged 5.79 ± 2.63%. Clinical results and hemodynamic outcomes are reported for 30-days, 1-, 2-, and 3-years. Completeness of follow-up was 100% with 44 patients at risk after 3-years. Follow-up ranged up to 7.1 years. Results Majority of the surgical valves were stented (94.8%) with a mean labeled size of 23.1 ± 2.3 mm and true-ID of 20.4 ± 2.6 mm. A true-ID ≤21 mm had 58.4% of the patients. Self-expanding valves were implanted in 68.8% (mean labeled size 24.1 ± 1.8 mm) and balloon-expanded in 31.2% (mean size 24.1 ± 1.8 mm). No patient died intraoperatively. Hospital mortality was 1.3% and three-years survival 57.1%. All patients experienced an initial significant dPmean-reduction to 16.8 ± 7.1 mmHg. After 3-years mean dPmean raised to 26.0 ± 12.2 mmHg. This observation was independent from true-ID or type of transcatheter aortic valve replacement (TAVR)-prosthesis. Patients with a true-ID ≤21 mm had a higher initial (18.3 ± 5.3 vs. 14.9 ± 7.1 mmHg; p = .005) and dPmean after 1-year (29.2 ± 8.2 vs. 13.0 ± 6.7 mmHg; p = .004). There were no significant differences in survival. Conclusions VIV-TAVR is safe and effective in the early period. In surgical valves with a true-ID ≤21 mm inferior hemodynamic and survival outcomes must be expected. Nonetheless, also patients with larger true-IDs showed steadily increasing transvalvular gradients. This raises concern about durability.

Thesis (MScEng (Mechanical and Mechatronic Engineering))--Stellenbosch University, 2008. / Aortic valve replacements are frequently performed during heart surgery. However, since this is quite a stressful procedure, many patients are turned down for medical reasons. Stented valves, designed and manufactured for percutaneous insertion, eliminate many of the risks involved in open-heart surgery, thus providing a solution to patients not deemed strong enough for open-chest aortic valve replacements. The aortic valve is a complex structure, and therefore numerical simulation is necessary to obtain flow and stress data to support the design of a prosthetic heart valve in the absence of viable physical measuring methods. To aid in the design of a prosthetic heart valve, various finite element valve models were created, and the fluid structure interaction (FSI) between the valves and the blood was simulated using commercial finite element software. The effect of the geometry of the leaflets on the haemodynamic behaviour over the cardiac cycle was investigated. It was found that leaflet dimensions should be chosen judiciously, because of their considerable effect on the stress distribution and performance of the valve. A simple leaflet geometry optimisation was done for a 20 mm and 26 mm valve, respectively, by means of existing geometry relationships found in the literature. Simulations were done to obtain the maximum leaflet attachment forces that can be used by a stent designer for fatigue loading, or to investigate the structural strength of the stent. These simulations were numerically validated. The effect of leaflet thickness and stiffness on resistance to opening, stress distribution and strain were investigated. Results showed that leaflet thickness has a greater effect on the performance of the valve than leaflet stiffness, and thereby validated the results of similar tests contained in the literature. After simulating over-, as well as under-dilation of a stented valve, it was found that problems associated with over-dilation can be minimised to a certain extent by increasing the coaptation1 region of the leaflets. A simple pulse duplicator was designed based on a four-element Windkessel model. The pulse duplicator was used to study the performance of the prototype valves by means of high-speed photography, the results of which were fed into one of the numerical finite element models and compared to real valve performance. Some of the prototype valves showed efficiencies of 88%.