Assessment of the microcirculation is of major importance in understanding the physiology of the vasculature and in assessing te vascular effects of pathological conditions such as diabetes, hypertension and sepsis. Transdermal iontophoresis can be used to non‐invasively introduce vasoactive drugs into the skin. The response to these drugs of the local cutaneous microvasculature can be measured by laser Doppler flowmetry methods. Although these techniques have been used together for over two decades, there are still important methodological issues to be resolved. This work is aimed at optimizing transdermal iontophoresis as a tool for microvascular assessment by focusing on the main methdological issues: non‐specific vasodilatation, drug delivery protocols and analysis of blood flow data. Non‐specific vasodilatation, an increase blood flow during iontophoresis of non‐vasoactive compounds, is an important problem as it interferes with the response to the administered drug. By investigating this effect in healthy volunteers, we found that the extent of the non‐specific response differs between the positive and negative electrode and that it is dependent on the voltage over the skin andon the ionic strength of the vehicle in which the drug is dissolved. We also found that the extent of the non‐specific response could be reduced by applying local anesthetics and by pre‐treatment with antihistamine drugs. These results suggest that non‐specific effects could be mediated by depolarization or hyperpolarisation of cells, triggering neural and histamine related mechanisms that finally lead to vasodilatation of the local microvasculature. To prevent non‐specific effects from occurring during the experiments, our results show that the current strength and the total electric charge during iontophoresis should be limited to 0.02 mA and12 mC, respectively. Furthermore, drug solutions at physiological ionic strengths should be used. Under these conditions, adequate responses to the most commonly used drugs, acetylcholine (ACh) and sodium nitroprusside (SNP), are obtained while no significant non‐specific vasodilatation occurs. The results of our investigations show that blood responses to ACh and SNP applied by a single iontophoretic pulse can well be escribed by conventional dose‐response models, which enables a more powerful analysis and comparison between drugs or possibly patient groups as compared with conventional aalysis methods. Finally, we have incorporated drug transport and physiological response to the local drug concentration during iontophoresis of vasoactve drugs into a single model. Validation of this model using measured responses to ACh and SNP shows that the commonly used assumption that the local drug concentration during iontophoresis is linearly proportional to the electric charge may not be valid. / Mikrocirkulationen, som inbegriper kroppens minsta blodkärl, transporterar syre och näringsämnen till våra celler. Vissa sjukdomar, som diabetes, hjärt‐kärlsjukdom och akut blodförgiftning leder till förändringar hos mikrocirkulationen. Mekanismerna bakom dessa förändringar är delvis okända. Det finns därför ett stort behov av kliniska mättekniker som kan bedöma mikrocirkulationens funktion. Vid jontofores placeras en elektrod tillsammans med ett läkemedel på huden. När en svag elektrisk ström anbringas transporteras läkemedlet ner genom hudlagren. Effekterna av ett kärlaktivt läkemedel som appliceras på detta sätt kan sedan avläsas non‐invasivt med laser Doppler‐teknik. En stor fördel med jontoforesmetoden, förutom att den är non‐invasiv, är att läkemedelsdoserna som tillförs kroppen är mycket små och därmed ger de inte upphov till några systemiska bi‐effekter. I avhandlingen presenteras forskning, vilkas målsättning är att lösa några av de viktiga frågorna kring transdermal jontofores så att tekniken optimeras för att denskall kunna brukas som ett verktyg vid kliniska undersökningar av mikrocirkulationen. Den första delen ägnas ett fenomen som kallas ospecifik vasodilatation. Det uppstår vid jontofores av substanser som är inte kärlaktiv, som vatten och koksaltlösning. Resultaten från dessa försök indikerar att den ospecifika vasodilatationen beror på framför allt spänningen över huden, vilken i sin tur är relaterad till jon‐koncentrationen hos läkemedelslösningen. Vidare registreras att mekanismen bakom den ospecifika vasodilatationen delvis är neuralt medierad genom att de till stor del år att förhindra med hjälp av lokal bedövning. Dessutom leder förbehandling med anti‐histamina läkemedel till minskade ospecifika reaktioner, vilket också indikerar att lokala inflammatoriska processer är inblandande. Den andra delen av avhandlingen ägnas att optimera försöksprotokollen för jontofores. Till att börja med utvecklas ett protokoll som ger ett adekvat läkemedelssvar samtidigt som ospecifika effekter minimeras. Det visar sig är möjligt genom att begränsa strömstyrkan och den elektriska laddningen under jontoforesen och genom att använd läkemedelslösningar som har en fysiologisk jonstyrka. Resultaten visar också att blodflödesförändringen som registreras under jontofores av acetylkolin och natriumnitroprussid kan eskrivas med hjälp av konventionella dos‐responsmodeller, vilket möjliggör en mer exakt analys av det mikrocirkulatoriska svaret samt underlättar jämförelse mellan olika läkemedel elle patientgrupper. Slutligen presenteras en mekanistisk model för det mikrocirkulatoriska svaret vid jontofores. Modellen beskriver läkemedlets transport från elektroden ner genom huden, clearance i huden vilken beror på diffusion och det lokala blodflödet, samt förändringen i blodflöde som sker på grund av läkemedlet. Modellen valideras genom försök på försökspersoner och resultaten visar att förändringarna i blodflödet åstadkommet av acetylklin och natriumnitroprussid med denna modell kan beskrivas på ett exakt sätt. Vidare visar resultaten att det sker en betydande clearance av läkemedel i huden under jontofores. Detta har väsentlig betydelse när man ska uppskatta den lokala jontoforesdosen. / The author changed surname from Droog to Tesselaar in January 2006.

La utilización práctica del efecto Doppler en la emisión láser fue propuesta desde los inicios del desarrollo de los láseres en los años sesenta. Sólo en los años ochenta la investigación realizada pudo salir del laboratorio y dar lugar a la fabricación de aparatos de medida de velocidad comerciales. A partir de los noventa estos aparatos se popularizaron rápidamente. Actualmente se utilizan medidores de velocidad láser por efecto Doppler en múltiples aplicaciones, entre las que sobresale la medida de velocidad de fluidos, para estudios aéreo e hidrodinámicos. Sus características únicas, como la precisión obtenida en la medida, su alta resolución espacial y el carácter no intrusivo, sólo han comenzado recientemente a tener rivales de consideración, como pueden ser la velocimetría de imagen de partículas (PIV). También la medida de velocidades de móviles sólidos comienza a resultar, con el abaratamiento general de los componentes opto-electrónicos, un objetivo para muchas empresas. Entre las aplicaciones de este tipo se contemplan el control de velocidad de los vehículos en carretera y el control de procesos industriales del ramo textil, papelero y deempresas fabricantes de cables, entre otros. Empresas europeas y americanas, como Dantec Electronik y TSI, por citar las más representativas, comercializan aparatos LDA de propósito general de altas prestaciones. Hasta la fecha estos sistemas sólo podían ser adquiridos por importantes centros de investigación o grandes empresas, debido a su elevado coste. El futuro comercial de la velocimetría láser Doppler exige la fabricación de aparatos más económicos y adaptados a las necesidades del cliente. Muchos de los sistemas actuales son voluminosos,difíciles de manejar y con potencias de trabajo elevadas. Se está llevando a cabo un importante trabajo para conseguir reducir el tamaño y coste de los equipos sin perder sus principales prestaciones. Asimismo la alta velocidad y capacidad de cálculo de los ordenadores personales actuales debe hacer innecesaria la inclusión de procesadores específicos para estos equipos.Presentamos el diseño y construcción de un sistema integral de medida de dos componentes de la velocidad, sistema 2D-LDA, para aplicaciones industriales e hidrodinámicas de baja potencia. Siguiendo la filosofía delineada arriba, el diseño de nuestro sistema LDA fue realizado utilizando únicamente una fuente laser y un módulo detector. Los sistemas LDA de medida de dos componentes de velocidad comercialmente disponibles, por el contrario, emplean dos longitudes de onda óptica y dos fotodetectores independientes. Las emisiones azul y verde típicas de los láseres de ion-Ar son las longitudes de onda a menudo elegidas en este tipo de medidas. Por otra parte, se ha empleado los dos canales de entrada de una tarjeta de adquisición de uso general para realizar el disparo multinivel. Esta configuración permite trabajar en cada momento con la parte de señal burst teóricamente más adecuada, con mayor valor de relación señal a ruido.Este trabajo ha sido financiado por la CICYT Proyecto PETRI 95-0249-OP:REALIZACIÓN DE SISTEMAS LÁSER PORTÁTILES DE MEDIDA DE VELOCIDAD POR EFECTO DOPPLER (LDA-LDV) DE BAJO COSTE PARA APLICACIONES INDUSTRIALES E HIDRODINÁMICAS. / The practical use of the Doppler effect at optical wavelengths was proposed at the early beginning of the development of the laser, in the sixties. However, it was only in the eighties when the results of the experimental work could finally get out of the laboratories, and the first Laser Velocimeters were commercially available. In the nineties this kind of systems became rapidly popular. Nowadays the Laser Velocimeters based on the Doppler frequency shift find a lot of important applications, especially in some industrial processes and in hydrodynamic and aerodynamic research.The unique characteristics of the Laser Doppler Velocimetry (LDV) only recently have encountered a rival technique in the Particle Image Velocimetry (PIV), for applications on fluids. The main features of LDV systems are the accuracy and the speed of the measurements, the high spatial resolution and, of course, the non-intrusive character of the technique. Moreover this kind of systems present advantages not only in fluid applications: actually it can compete with the microwave radar in the estimation of the velocity of solid targets. This becomes possible due to theprogressive reduction of prices of optoelectronic devices and the improvement of its performances. The monitoring of the traffic velocity and the control of machinery in the manufacture of paper, wires and cables or thread can be mentioned among these applications.European an American companies, as Dantek Electronic or TSI, to mention the two most representative, commercialize high performance general-purpose LDV systems. Up to the date these instruments are sizeable and expensive, and its use requires some special training. There is not doubt that the future market of the LDV systems goes through a substantial decrease of prices and, indeed, through the possibility of custom-built designs. The potential number of users would increase then in an important manner. Many efforts are now being devoted by researchers in that direction. Moreover, the important improvement of capabilities of the desktop computers makes unnecessary the special electronic processors that, up to now, have been provided by the manufacturers of LDV systems as a part of them.In this Thesis the design and realization of a complete Laser Doppler Anemometer is presented. The system can measure two components of a fluid velocity (2D-LDA) and originally it was conceived to be used in industrial and hydrodynamics applications.Following the philosophy outlined above, the design of our LDA system was performed with only one laser source and one detector module. The common commercially available LDAs, on the contrary, designed to measure two components of velocity, use two different optical wavelengths and two independent photodiodes.On the other hand, a general-purpose acquisition card with two input channels has been used to implement a multilevel trigger. The configuration performed here permits to work in each moment with the part of the burst having the best signal to noise ratio.This work has been supported by the Spanish Government, CICYT project PETRI 95-0249-OP.

SAMMAMFATTNING Bakgrund: Reaktiv hyperemi definieras som ett övergående ökat blodflöde över det normala efter en tids ischemi. Det kan registreras med laserdopplerteknik. Att registrera reaktiv hyperemi är ett sätt att värdera mikrocirkulationen. Det finns många flödesvariabler att studera varav tid till maxflöde efter ocklusion är en. Det har gjorts studier som undersöker om det finns ett samband mellan reaktiv hyperemi och fysisk aktivitet/syreupptagningsförmåga. Det har inte gjorts någon studie som undersöker tid till maxflöde och fysisk aktivitet. Syftet var att undersöka om det finns ett samband mellan fysisk aktivitet och reaktiv hyperemi med avseende på tid till maxflöde. Material och metod: Testpersoner fick bära en accelerometer en vecka under dygnets alla vakna timmar samt göra en registrering av reaktiv hyperemi med laserdoppler. För statistiska beräkningar användes oparat T-test för att undersöka skillnad mellan olika grad av fysisk aktivitet och tid till maxflöde. Resultat: Ingen statistiskt signifikant skillnad mellan olika aktivitetsgrad och tid till maxflöde kunde observeras. Slutsats: Den här studien visade inte på statistiskt signifikant samband mellan blodflöde och fysisk aktivitet.

Experimental aeroacoustic research was conducted on a wind turbine specific airfoil at low Reynolds numbers. The goal of this thesis was to study trailing edge noise generation from the airfoil and investigate correlations between the noise and the flow field. Before experiments were performed the current wind tunnel had to be modified in order to make it more suitable for aeroacoustic tests. Sound absorbing foam was added to the inside of the tunnel to lower the background noise levels and turbulence reduction screens were added which lowered the turbulence. An S822 airfoil was chosen because it is designed for low Reynolds flows attainable in the wind tunnel which are on the order of 104. Smoke wire flow visualization was used to gain insight into the airfoil wake development and oil film flow visualization was used to qualitatively assess the boundary layer development. Laser Doppler anemometry (LDA) was used to measure two components of velocity at high data rates in the airfoil wake. Wake profiles were measured in addition to single point measurements to determine the velocity spectrum. A microphone was mounted inside the test section in order to measure the trailing edge noise. Initial plans included measuring the trailing edge noise with a microphone array capable of quantifying and locating noise sources. Although an array was built and beamforming code was written it was only used in preliminary monopole source tests. Oil film results showed the behaviour of the boundary layer to be consistent with previous low Reynolds number experiments. LDA results revealed sharp peaks in the velocity spectra at 1100 Hz from U0 = 15–24 m/s, and 3100 and 3800 Hz, from U0 = 25–35 m/s, which were inconsistent with vortex shedding results of previous researchers. Also present were a series of broad peaks in the spectra that increase from 1200–1700 Hz in the U0 = 25–35 m/s range. The shedding frequency from the smoke wire flow visualization was calculated to be 1250 Hz at U0 = 26 m/s. These sharp peaks were also present in the acoustic spectrum. It was reasoned that these peaks are due to wind tunnel resonance which is a common occurrence in hard wall wind tunnels. In particular the tone at 1100 Hz is due to a standing wave with a wavelength equal to half the tunnel width. The shedding frequency from the smoke wire flow visualization was calculated to be 1100 Hz at U0 = 20 m/s. These tones exhibited a “ladder-like” relationship with freestream velocity, another aspect indicative of wind tunnel resonance. It was reasoned that the wind tunnel resonance was forcing the shedding frequency of the airfoil in the U0 = 15–24 m/s range, and in the U0 = 25–35 m/s range, the shedding frequency corresponded to the broad peaks in the LDA spectra.

The impact of swirl (i.e., flow with axial and azimuthal velocity components) on the turbulent flow in a pipe is studied using two-component laser-Doppler velocimetry (LDV). There are practical motivations for the flow geometry. For example, previous studies demonstrate that introducing swirl in the tube bank of a paper machine headbox can significantly increase mixing, and hence increase fiber dispersion and orientation isotropy in the finished paper product. The flow characteristics in a pipe downstream of a single straight tapered fin, a single fin with 180??ist but otherwise identical geometry, and four twisted fins were therefore studied at a pipe-based Reynolds number of 80,000. Radial profiles of the mean and rms fluctuations of the streamwise and azimuthal velocity components are measured; results for the straight and twisted single fin are compared to determine the effects of fin geometry and swirl on the turbulent wake downstream of the fin. From a practical viewpoint, it is also desirable to have adjustable swirl, where swirl can either be turned on or off depending upon the type of paper product being produced. The next generation swirler concept consists of fins fabricated from two-way shape memory alloys. Using the two-way memory effect, the fins will be in their straight configuration when cold and twisted configuration (hence acting as a swirler) when hot. This study is the initial phase in developing new active control mechanisms, known as the Vortigen concept, for increasing productivity, and hence reducing wasted raw material and energy, in the pulp and paper industry.

Native heart valves that have limited functionality due to cardiovascular disease or congenital birth defects are commonly replaced by prosthetic heart valves. Bileaflet mechanical heart valves (BMHV) are the most commonly implanted valve design due to their long-term durability. However, their unnatural hemodynamics promote thrombosis and thromboembolic events. Clinical reports and in vitro experiments suggest that the thrombogenic complications in bileaflet valves are related to the stress imposed on blood by the valves during the closing phase. Additionally, animal and clinical studies have shown that BMHV in the aortic position demonstrate reduced failure rates compared to identical valves in the mitral position. The present study aimed to investigate the leakage, hinge, and near hinge flow fields of two BMHV under simulated physiologic aortic flow conditions and to compare these results with previous findings in the mitral position to better understand how the implant location influences the valve performance and the subsequent risk of blood damage. Two and three-component Laser Doppler Velocimetry techniques were used to quantify the velocity and turbulent shear stress fields in both the hinge and the upstream leakage flow regions. The study focused on the 23 mm St. Jude Medical Regent (SJM) and the 23 mm CarboMedics (CM) valves. Although they were tested under similar physiologic conditions, shape and location of the leakage jets were dependent on valve design. Nevertheless, turbulent shear stress levels recorded within all jets were well above the threshold shear stress for the onset of blood cell damage. Within the hinge region, the flow fields were complex and unsteady. The angulated hinge recess of the CM valve appeared to promote blood damage while the streamlined geometry of the SJM valve contributed to better washout of the hinge region. Animations of the velocity flow fields are given in QuickTime or MPEG format. Comparison of the present findings with previously published results for the mitral position suggests that the superior clinical results of the mechanical valves in the aortic position may be due to less severe leakage flow upon valve closure as well as to enhanced hinge washout during the forward flow phase.

The objective of this research is to determine the longitudinal stress in rails by using the polarization of Rayleigh waves. Analytical models are developed to describe the effect of applied stress on wave speed and on the polarization of Rayleigh waves. A numerical simulation is performed to find the effect of applied stress on wave velocity and Rayleigh wave polarization. The effect of uncertainties in material properties on wave velocity and polarization of Rayleigh wave is also examined in the simulation. The experiment uses a laser Doppler vibrometer (LDV) to measure the particle velocities. The in-plane and out-of-plane velocity components are obtained from the measured particle velocities. The polarization of Rayleigh wave, which is defined as the ratio between the in-plane and out-of-plane displacements, is calculated. Furthermore, the polarization of the Rayleigh wave is considered as a measure to identify applied stress. The experiment is performed on unstressed and stressed rail specimen. Thus, Rayleigh wave polarization is obtained as a function of applied stress. The experimental results are compared with the analytical model. The result shows a good agreement with the theoretical values for unstressed rail.

名古屋大学博士学位論文 学位の種類 : 博士(医学)(論文) 学位授与年月日:平成8年3月8日 辻井洋一郎氏の博士論文として提出された

Reproduction de : Thèse de doctorat : Énergétique et transferts : Toulouse, INPT : 2005. / Titre provenant de l'écran-titre. Bibliogr. 109 réf.

Thèse de doctorat : Sciences. Turbomachines : Ecole Centrale de Lyon : 2003. / 73 réf.