Im Rahmen dieser Dissertation wurden anhand eines Ferkelmodells (8-15kg Schweine, 5 Gruppen: „nicht pulsatile HLM“: n=9, „Minozyklin+HLM“: n= 6, „pulsatile HLM“: n=7, „Minozyklin-Kontrolle: n=6, „Kontrolle“: n=8) während einer 120-minütigen extrakorporaler Zirkulation (EKZ) und einer darauffolgenden 90-minütigen Rekonvaleszenzzeit der physikalische Einflussfaktor des pulsatilen Flusses sowie der pharmakologische Effekt von Minozyklin auf die Niere jeweils unabhängig voneinander untersucht. In allen Gruppen wurden HE-Färbungen sowie immunhistochemische Färbungen (HIF-1-α, 3-Nitrotyrosin, PAR, AIF) durchgeführt um pathologische Veränderungen auf zellulärer Ebene zu detektieren. Zusätzlich wurden energiereiche Phosphate und ihre Abbauprodukte mittels High Pressure/Performance Liquid Chromatography (HPLC) bestimmt. Zur Beurteilung der klinischen Funktion der Niere wurden nierenspezifische Blutwerte (Serumkreatinin, Serumharnstoff) und Laktat im arteriellen Blut bestimmt. Mit der pulsatilen Perfusion konnte ein Abfall des O2-Partialdruckes nicht verhindert werden (HIF-1-α), allerdings konnte die ATP-Konzentration aufrecht erhalten werden. Dies spricht dafür, dass die pulsatile Perfusion im Gegensatz zu der nicht pulsatilen Perfusion keinen relevanten O2-Mangel verursachte. Auch die Ergebnisse der Nitrotyrosin-3-Auswertung zeigen, dass die Bildung von Peroxynitrit reduziert und somit der nitrosative Stress auf die Zellen begrenzt wurde. Die DNA wurde jedoch unabhängig vom gewählten Blutflussprofil geschädigt (PAR). Auch anhand der nierenspezifischen Blutparameter (Serumkreatinin, Serumharnstoff) ließ sich eine postoperative Beeinträchtigung der Nierenfunktion feststellen. Im Vergleich zu der nicht pulsatilen EKZ war hier jedoch eine geringfügige Verbesserung zu erkennen (Serumkreatinin). Zusammenfassend kann gesagt werden, dass durch die pulsatile EKZ der Grad der Ischämie beeinflusst werden konnte, allerdings waren insgesamt keine wesentlich positiven Auswirkungen auf zellulärer Ebene und auf die postoperative Nierenfunktion festzustellen. Der Einsatz des technisch anspruchsvollen pulsatilen Perfusionssystems scheint daher in Bezug auf die Niere in der routinemäßigen Herzchirurgie nicht unbedingt erforderlich zu sein. Durch die Gabe von Minozyklin wurde zwar der Grad der Ischämie (HIF-1-α, ATP) nicht beeinflusst, allerdings konnte Minozyklin durch seine antioxidativen bzw. antinitrosativen (3-Nitrotyrosin), PARP-1-hemmenden (PAR) sowie antiapoptotischen (AIF) Wirkmechanismen die Niere offenbar vor den Folgen einer Ischämie schützen. Anhand der nierenspezifischen Blutwerte (Serumkreatinin, Serumharnstoff) wurde erkenntlich, dass Minozyklin die Nierenfunktion positiv beeinflusst, was wiederum die histologischen Befunde bestätigt. Für die Humanmedizin ist somit der Einsatz von Minozyklin während der EKZ eine Möglichkeit die Auswirkungen des Ischämie/Reperfusionsschadens und deren klinische Folgen hinsichtlich der Niere zu begrenzen. Allerdings muss berücksichtigt werden, dass der einmalige Einsatz eines Antibiotikums auch negativen Einfluss auf den Körper ausübt (Resistenzentwicklung, Nebenwirkungen), sodass Minozyklin aufgrund der in dieser Versuchsreihe gezeigten positiven Eigenschaften, insbesondere die PARP-1-Inhibition, lediglich als Modellsubstanz für Weiterentwicklungen genutzt werden kann.

Each year all over the world, Millions of patients from infants to adults are diagnosed with heart failure. A limited number of donor hearts available for these patients results in a tremendous demand of mechanical circulatory support (MCS) system, either in the form of total artificial heart (TAH) or a ventricular assist device (VAD). Physiologically MCS are expected to provide heart; a time to rest and potential recovery by unloading the ventricle, while maintaining the adequate peripheral as well as coronary circulation. Existing ventricular assist devices (VAD) have employed either displacement type pulsatile flow pumping systems or continuous flow type centrifugal/rotodynamic pumps systems. Displacement type devices produce a pulsatile outflow, which has significant benefits on vital organ function and end organ recovery. Continuous flow devices are small and can be placed within body using minimal invasive procedures, in addition they reduces infection as well as mechanical failure related complications. Despite availability of success stories for both types of pumping systems, the selection of the either of them is an ongoing debate. This thesis aims to merge the advantages of displacement pumps (pulsatile flow) and axial-flow pumps (continuous flow) into a novel left vertical assist device (LVAD), by designing a novel minimal invasive, miniature axial-flow pump producing pulsating outflow for the patients having early heart failure and myocardial infarction as a Bridge-To-Recovery (BTR) or Bridge-To-Decision (BTD) device. The design of VAD, the experimental setup and dedicated control system were developed for the in vitro evaluation of pulsatile flow. Computational fluid dynamics (CFD) had been employed for the detail investigation of pulsatile flow. In addition, CFD was also applied to optimize the pulse generation for low haemolysis levels. Outcome of the study produces comprehensive understanding for the generation of pulsatile flow using an axial flow pump. Further, it provides the means of generating a controlled pulse that can regulate flow rate for varying heart rate within low haemolysis levels.

This research utilizes CFD to analyze blood flow through pathways representative of central shunts, commonly used as part of the Fontan procedure to treat cyanotic heart disease. In the first part of this research, a parametric study of steady, Newtonian blood flow through parabolic pathways was performed to demonstrate the effect that flow pathway curvature has on wall shear stress distribution and flow energy losses. In the second part, blood flow through two shunts obtained via biplane angiograms is simulated. Pressure boundary conditions were obtained via catheterization. Results showed that wall shear stresses were of sufficient magnitude to initiate platelet activation, a precursor for thrombus formation. Steady results utilizing time-averaged boundary conditions showed excellent agreement with the time-averaged results obtained from pulsatile simulations. For the points of interest in this research, namely wall shear stress distribution and flow energy loss, the Newtonian viscosity model was found to yield acceptable results.

Understanding the mechanisms of cardiovascular disease progression is essential in developing novel therapies to combat this disease that contributes to 1 in 3 deaths in the United States every year. Endothelial dysfunction and its effects on vessel growth and remodeling are key factors in the progression and localization of atherosclerosis. Much of our understanding in this area has come from in-vivo and in-vitro experiments however perfused organ culture systems provide an alternative approach. Organ culture systems can provide a more controlled mechanical and biochemical environment compared to in-vivo models. This study focused on furthering development of this organ culture model by introducing a novel device to produce flow waveforms at the high frequencies and low mean flows seen in the mouse model. The device is capable of monitoring pressure, flow, diameter, and nitric oxide release. Each individual mechanism in the system was integrated via a computer using a custom Labview interface. The performance of the device was characterized by developing physiologic, physiologic-oscillatory, low, low-oscillatory waveforms and sinusoidal waveforms at frequencies ranging from 1-10 Hz. Overall this system provides a robust model to test the effects of flow on various biological markers both in real-time and after culture.

Hemodynamic monitoring is extremely important in the accurate measurement of vital parameters. Current methods are highly invasive or noncontinuous, and require direct access to the patient’s skin. This study intends to explore the modulated magnetic signature of blood method (MMSB) to attain blood flow information. This method uses an applied magnetic field to magnetize the iron in the red blood cells and measures the disturbance to the field with a magnetic sensor [1]. Exploration will be done by experimentally studying in-vitro, as well as simulating in COMSOL the alteration of magnetic fields induced by the flow of a magnetic solution. It was found that the variation in magnetic field is due to a high magnetization of blood during slow flow and low magnetization during rapid flow. The understanding of this phenomenon can be used in order to create a portable, non-invasive, continuous, and accurate sensor to monitor the cardiovascular system.

This thesis is motivated by the necessity to understand the flow structure of turbulent flows in bends encountered in many technical applications such as heat exchangers, nuclear reactors and internal combustion engines. Flows in bends are characterised by strong secondary motions in terms of counter-rotating vortices (Dean cells) set up by a centrifugal instability. Specifically the thesis deals with turbulent flows in 90° curved pipes of circular cross-section with and without an additional motion, swirling or pulsatile, superposed on the primary flow.  The aim of the present thesis is to study these complex flows in detail by using time-resolved stereoscopic particle image velocimetry to obtain the three-dimensional velocity field, with complementary hot-wire anemometry and laser Doppler velocimetry measurements. In order to analyse the vortical flow field proper orthogonal decomposition (POD) is used. The so called ``swirl-switching'' is identified and it is shown that the vortices instantaneously, ``rock'' between three states, viz. a pair of symmetric vortices or a dominant clockwise or counter-clockwise Dean cell. The most energetic mode exhibits a single cell spanning the whole cross-section and ``rolling'' (counter-)clockwise in time. However, when a honeycomb is mounted at the inlet of the bend, the Dean vortices break down and there is strong indication that the ``swirl-switching'' is hindered. When a swirling motion is superimposed on the incoming flow, the Dean vortices show a tendency to merge into a single cell with increasing swirl intensity. POD analysis show vortices which closely resemble the Dean cells, indicating that these structures co-exist with the swirling motion. In highly pulsating turbulent flow at the exit of a curved pipe, the vortical pattern is diminished or even eliminated during the acceleration phase and then re-established during the deceleration. In order to investigate the effect of pulsations and curvature on the performance of a turbocharger turbine, highly pulsating turbulent flow through a sharp bend is fed into the turbine. Time-resolved pressure and mass-flow rate measurements show that the hysteresis loop in the pressure-ratio-mass-flow plane, may differ significantly between straight and curved inlets, however the mean operating point is only slightly affected. / <p>QC 20140523</p>

Diss. Linköping : University, 2004.

abstract: Aortic pathologies such as coarctation, dissection, and aneurysm represent a particularly emergent class of cardiovascular diseases and account for significant cardiovascular morbidity and mortality worldwide. Computational simulations of aortic flows are growing increasingly important as tools for gaining understanding of these pathologies and for planning their surgical repair. In vitro experiments are required to validate these simulations against real world data, and a pulsatile flow pump system can provide physiologic flow conditions characteristic of the aorta. This dissertation presents improved experimental techniques for in vitro aortic blood flow and the increasingly larger parts of the human cardiovascular system. Specifically, this work develops new flow management and measurement techniques for cardiovascular flow experiments with the aim to improve clinical evaluation and treatment planning of aortic diseases. The hypothesis of this research is that transient flow driven by a step change in volume flux in a piston-based pulsatile flow pump system behaves differently from transient flow driven by a step change in pressure gradient, the development time being substantially reduced in the former. Due to this difference in behavior, the response to a piston-driven pump can be predicted in order to establish inlet velocity and flow waveforms at a downstream phantom model. The main objectives of this dissertation were: 1) to design, construct, and validate a piston-based flow pump system for aortic flow experiments, 2) to characterize temporal and spatial development of start-up flows driven by a piston pump that produces a step change from zero flow to a constant volume flux in realistic (finite) tube geometries for physiologic Reynolds numbers, and 3) to develop a method to predict downstream velocity and flow waveforms at the inlet of an aortic phantom model and determine the input waveform needed to achieve the intended waveform at the test section. Application of these newly improved flow management tools and measurement techniques were then demonstrated through in vitro experiments in patient-specific coarctation of aorta flow phantom models manufactured in-house and compared to computational simulations to inform and execute future experiments and simulations. / Dissertation/Thesis / Doctoral Dissertation Bioengineering 2015

Made available in DSpace on 2014-06-11T19:27:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-26Bitstream added on 2014-06-13T19:14:28Z : No. of bitstreams: 1 cicigliano_ecs_me_ilha.pdf: 2408732 bytes, checksum: 0af63a8f55dcecc2b890effc02c98e0e (MD5) / O presente trabalho propõe-se a modelar, analisar, e comparar os efeitos do escoamento de um fluido dentro de um tubo elástico. Esses efeitos, por sua vez, serão ocasionados por uma variação de pressão nesse fluido. Para tanto, através das propriedades físicas e mecânicas do tubo e do fluido, foi calculado o deslocamento da parede do tubo, vazão e velocidade do fluido. Essa modelagem tem como intenção comparar numericamente um arranjo que visa simular uma pulsação com características próximas as do coração humano. Através da construção de duas geometrias cilíndricas que representam domínios distintos (estrutura e fluido) que foram acoplados em sua interface, foi possível fazer um estudo da interação fluido-estrutura (FSI) utilizando o software comercial ANSYS, obtendo assim um estudo tri-dimensional do problema. Os resultados mostraram que o deslocamento da interface fluido-estrutura ocorreu simultaneamente, confirmando, portanto, a correta aplicação do comando FSIN. O fluido é considerado incompressível e Newtoniano e é governado pelas equações de Navier-Stokes. As paredes da estrutura são modeladas a partir da Lei de Hooke. Por fim, uma solução numérica é desenvolvida utilizando o Método dos Elementos Finitos / This project proposes to model, analyze and compare the effects of fluid flow inside an elastic tube. These effects, in turn, will be caused by a variation of pressure in this fluid. Therefore, through the physical and mechanical properties of the tube and fluid was calculated the displacement of the tube wall, flow and velocity of the fluid. The Modeling intends to compare numerically an arrangement that aims to simulate a heartbeat with characteristics similar to the human heart. Through of building two cylindrical geometries representing different domains (structure and fluid) that were engaged in its interface, it was possible to study the fluid-structure interaction (FSI) using the commercial software ANSYS, thereby obtaining a three-dimensional study. The results showed that the displacement of the interface fluid-structure occurred simultaneously, thereby confirming the correct application of the command FSIN. The fluid is considered incompressible and Newtonian and is governed by the Navier-Stokes equations. The walls of the structure are modeled from the Hooke's Law. Finally, a numerical solution is developed using the Finite Element Method

Resumo: O presente trabalho propõe-se a modelar, analisar, e comparar os efeitos do escoamento de um fluido dentro de um tubo elástico. Esses efeitos, por sua vez, serão ocasionados por uma variação de pressão nesse fluido. Para tanto, através das propriedades físicas e mecânicas do tubo e do fluido, foi calculado o deslocamento da parede do tubo, vazão e velocidade do fluido. Essa modelagem tem como intenção comparar numericamente um arranjo que visa simular uma pulsação com características próximas as do coração humano. Através da construção de duas geometrias cilíndricas que representam domínios distintos (estrutura e fluido) que foram acoplados em sua interface, foi possível fazer um estudo da interação fluido-estrutura (FSI) utilizando o software comercial ANSYS, obtendo assim um estudo tri-dimensional do problema. Os resultados mostraram que o deslocamento da interface fluido-estrutura ocorreu simultaneamente, confirmando, portanto, a correta aplicação do comando FSIN. O fluido é considerado incompressível e Newtoniano e é governado pelas equações de Navier-Stokes. As paredes da estrutura são modeladas a partir da Lei de Hooke. Por fim, uma solução numérica é desenvolvida utilizando o Método dos Elementos Finitos / Abstract: This project proposes to model, analyze and compare the effects of fluid flow inside an elastic tube. These effects, in turn, will be caused by a variation of pressure in this fluid. Therefore, through the physical and mechanical properties of the tube and fluid was calculated the displacement of the tube wall, flow and velocity of the fluid. The Modeling intends to compare numerically an arrangement that aims to simulate a heartbeat with characteristics similar to the human heart. Through of building two cylindrical geometries representing different domains (structure and fluid) that were engaged in its interface, it was possible to study the fluid-structure interaction (FSI) using the commercial software ANSYS, thereby obtaining a three-dimensional study. The results showed that the displacement of the interface fluid-structure occurred simultaneously, thereby confirming the correct application of the command FSIN. The fluid is considered incompressible and Newtonian and is governed by the Navier-Stokes equations. The walls of the structure are modeled from the Hooke's Law. Finally, a numerical solution is developed using the Finite Element Method / Orientador: Gilberto Pechoto de Melo / Coorientador: Amarildo Tabone Paschoalini / Banca: Adyles Arato Junior / Banca: Marcio Higa / Mestre