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1
Maksuti, Elira. "Imaging and modeling the cardiovascular system." Doctoral thesis, KTH, Medicinsk bildteknik, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-196538.
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Understanding cardiac pumping function is crucial to guiding diagnosis, predicting outcomes of interventions, and designing medical devices that interact with the cardiovascular system. Computer simulations of hemodynamics can show how the complex cardiovascular system is influenced by changes in single or multiple parameters and can be used to test clinical hypotheses. In addition, methods for the quantification of important markers such as elevated arterial stiffness would help reduce the morbidity and mortality related to cardiovascular disease. The general aim of this thesis work was to improve understanding of cardiovascular physiology and develop new methods for assisting clinicians during diagnosis and follow-up of treatment in cardiovascular disease. Both computer simulations and medical imaging were used to reach this goal. In the first study, a cardiac model based on piston-like motions of the atrioventricular plane was developed. In the second study, the presence of the anatomical basis needed to generate hydraulic forces during diastole was assessed in heathy volunteers. In the third study, a previously validated lumped-parameter model was used to quantify the contribution of arterial and cardiac changes to blood pressure during aging. In the fourth study, in-house software that measures arterial stiffness by ultrasound shear wave elastography (SWE) was developed and validated against mechanical testing. The studies showed that longitudinal movements of the atrioventricular plane can well explain cardiac pumping and that the macroscopic geometry of the heart enables the generation of hydraulic forces that aid ventricular filling. Additionally, simulations showed that structural changes in both the heart and the arterial system contribute to the progression of blood pressure with age. Finally, the SWE technique was validated to accurately measure stiffness in arterial phantoms.QC 20161115
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FEVOLA, ELISA. "Boundary conditions estimation techniques for cardiovascular modeling." Doctoral thesis, Politecnico di Torino, 2022. http://hdl.handle.net/11583/2972100.
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Du, Dongping. "Physical-Statistical Modeling and Optimization of Cardiovascular Systems." Scholar Commons, 2002. http://scholarcommons.usf.edu/etd/5875.
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Heart disease remains the No.1 leading cause of death in U.S. and in the world. To improve cardiac care services, there is an urgent need of developing early diagnosis of heart diseases and optimal intervention strategies. As such, it calls upon a better understanding of the pathology of heart diseases.
Computer simulation and modeling have been widely applied to overcome many practical and ethical limitations in in-vivo, ex-vivo, and whole-animal experiments. Computer experiments provide physiologists and cardiologists an indispensable tool to characterize, model and analyze cardiac function both in healthy and in diseased heart. Most importantly, simulation modeling empowers the analysis of causal relationships of cardiac dysfunction from ion channels to the whole heart, which physical experiments alone cannot achieve.
Growing evidences show that aberrant glycosylation have dramatic influence on cardiac and neuronal function. Variable but modest reduction in glycosylation among congenital disorders of glycosylation (CDG) subtypes has multi-system effects leading to a high infant mortality rate. In addition, CDG in all young patients tends to cause Atrial Fibrillation (AF), i.e., the most common sustained cardiac arrhythmia. The mortality rate from AF has been increasing in the past two decades. Due to the increasing healthcare burden of AF, studying the AF mechanisms and developing optimal ablation strategies are now urgently needed.
Very little is known about how glycosylation modulates cardiac electrical signaling. It is also a significant challenge to experimentally connect the changes at one organizational level (e.g.,electrical conduction among cardiac tissue) to measured changes at another organizational level (e.g., ion channels). In this study, we integrate the data from in vitro experiments with in-silico models to simulate the effects of reduced glycosylation on the gating kinetics of cardiac ion channel, i.e., hERG channels, Na+ channels, K+ channels, and to predict the glycosylation modulation dynamics in individual cardiac cells and tissues.
The complex gating kinetics of Na+ channels is modeled with a 9-state Markov model that have voltage-dependent transition rates of exponential forms. The model calibration is quite a challenge as the Markov model is non-linear, non-convex, ill-posed, and has a large parametric space. We developed a new metamodel-based simulation optimization approach for calibrating the model with the in-vitro experimental data. This proposed algorithm is shown to be efficient in learning the Markov model of Na+ model. Moreover, it can be easily transformed and applied to many other optimization problems in computer modeling.
In addition, the understanding of AF initiation and maintenance has remained sketchy at best. One salient problem is the inability to interpret intracardiac recordings, which prevents us from reconstructing the rhythmic mechanisms for AF, due to multiple wavelets' circulating, clashing and continuously changing direction in the atria. We are designing computer experiments to simulate the single/multiple activations on atrial tissues and the corresponding intra-cardiac signals. This research will create a novel computer-aided decision support tool to optimize AF ablation procedures.
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Zamanian, Sam Ahmad. "Modeling and simulating human cardiovascular response to acceleration." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/40536.
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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2007.Includes bibliographical references (p. 95-98).
The human cardiovascular system routinely encounters conditions that cause it to adapt. For example, when an astronaut enters microgravity, his/her cardiovascular system adapts rapidly to the weightless environment with no functional impairment. This adaptation is entirely appropriate while in space. However, it predisposes astronauts to problems when they return. It has been suggested that the regimen for astronauts on long-duration space travel include periods of artificial acceleration via centrifugation, in order to maintain some exposure to a gravitational gradient and thus ameliorate some of the physiological consequences of exposure to microgravity. To design such an intervention, it is desirable to know and understand, as well as to predict the cardiovascular response to centrifugation stress. A reasonably compartmentalized mathematical model of the cardiovascular system that represents these conditions is presented, which will allow for understanding and predicting cardiovascular behavior under such conditions. We validated our simulations against human data and showed that our results closely matched the experimental data. Upon validation, we used our model to predict the response of the cardiovascular system to levels of stress that cannot yet be tested on human subjects.
by Sam Ahmad Zamanian.
S.M.
5
Boilevin-Kayl, Ludovic. "Modeling and numerical simulation of implantable cardiovascular devices." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS039.
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Cette thèse, réalisée dans le cadre du projet Mivana, est consacrée à la modélisation et à la simulation numérique de dispositifs cardiaques implantables. Ce projet est mené par les start-up Kephalios et Epygon, concepteurs de solutions chirurgicales non invasives pour le traitement de la régurgitation mitrale. La conception et la simulation de tels dispositifs nécessitent des méthodes numériques efficaces et précises capables de calculer correctement l’hémodynamique cardiaque. C’est le but principal de cette thèse. Dans la première partie, nous décrivons le système cardiovasculaire et les valves cardiaques avant de présenter quelques éléments de théorie concernant la modélisation mathématique de l’hémodynamique cardiaque. En fonction du degré de complexité adopté pour la modélisation des feuillets de la valve, deux approches sont identifiées : le modèle de surfaces résistives immergées et le modèle complet d’interaction fluide-structure. Dans la deuxième partie, nous étudions la première approche qui consiste à combiner une modélisation réduite de la dynamique des valves avec un découplage cinématique de l’hémodynamique cardiaque et de l’électromécanique. Nous l’enrichissons de données physiologiques externes pour la simulation correcte des phases isovolumétriques, pierres angulaires du battement cardiaque, permettant d’obtenir un modèle relativement précis qui évite la complexité des problèmes entièrement couplés. Ensuite, une série d’essais numériques sur des géométries 3D physiologiques, impliquant la régurgitation mitrale et plusieurs configurations de valves immergées, illustre la performance du modèle proposé. Dans la troisième et dernière partie, des modèles complets d’interaction fluide-structure sont considérés. Ce type de modélisation est nécessaire pour étudier des problèmes plus complexes où la précédente approche n’est plus satisfaisante, comme par exemple le prolapsus de la valve mitrale ou la fermeture d’une valve mécanique. D’un point de vue numérique, le développement de méthodes précises et efficaces est indispensable pour pouvoir simuler de tels cas physiologiques. Nous considérons alors une étude numérique complète dans laquelle plusieurs méthodes de maillages non compatibles sont comparées. Puis, nous présentons un nouveau schéma de couplage explicite dans le cadre d’une méthode de type domaine fictif pour lequel la stabilité inconditionnelle au sens de la norme en énergie est démontrée. Plusieurs exemples numériques en 2D sont proposés afin d’illustrer les propriétés et les performances de ce schéma. Enfin, cette méthode est finalement utilisée pour la simulation numérique 2D et 3D de dispositifs cardiovasculaires implantables dans un modèle complet d’interaction fluide-structureThis thesis, taking place in the context of the Mivana project, is devoted to the modeling and to the numerical simulation of implantable cardiovascular devices. This project is led by the start-up companies Kephalios and Epygon, conceptors of minimally invasive surgical solutions for the treatment of mitral regurgitation. The design and the simulation of such devices call for efficient and accurate numerical methods able to correctly compute cardiac hemodynamics. This is the main purpose of this thesis. In the first part, we describe the cardiovascular system and the cardiac valves before presenting some standard material for the mathematical modeling of cardiac hemodynamics. Based on the degree of complexity adopted for the modeling of the valve leaflets, two approaches are identified: the resistive immersed surfaces model and the complete fluidstructure interaction model. In the second part, we investigate the first approach which consists in combining a reduced modeling of the valves dynamics with a kinematic uncoupling of cardiac hemodynamics and electromechanics. We enhance it with external physiological data for the correct simulation of isovolumetric phases, cornerstones of the heartbeat, resulting in a relatively accurate model which avoids the complexity of fully coupled problems. Then, a series of numerical tests on 3D physiological geometries, involving mitral regurgitation and several configurations of immersed valves, illustrates the performance of the proposed model. In the third and final part, complete fluid-structure interaction models are considered. This type of modeling is necessary when investigating more complex problems where the previous approach is no longer satisfactory, such as mitral valve prolapse or the closing of a mechanical valve. From the numerical point of view, the development of accurate and efficient methods is mandatory to be able to compute such physiological cases. We then consider a complete numerical study in which several unfitted meshes methods are compared. Next, we present a new explicit coupling scheme in the context of the fictitious domain method for which the unconditional stability in the energy norm is proved. Several 2D numerical examples are provided to illustrate the properties and the performance of this scheme. Last, this method is finally used for 2D and 3D numerical simulation of implantable cardiovascular devices in a complete fluid-structure interaction framework
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Wang, Siqi. "NONINVASIVE ASSESSMENT AND MODELING OF DIABETIC CARDIOVASCULAR AUTONOMIC NEUROPATHY." UKnowledge, 2012. http://uknowledge.uky.edu/cbme_etds/5.
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Noninvasive assessment of diabetic cardiovascular autonomic neuropathy (AN): Cardiac and vascular dysfunctions resulting from AN are complications of diabetes, often undiagnosed. Our objectives were to: 1) determine sympathetic and parasympathetic components of compromised blood pressure regulation in patients with polyneuropathy, and 2) rank noninvasive indexes for their sensitivity in diagnosing AN. Continuous 12-lead electrocardiography (ECG), blood pressure (BP), respiration, regional blood flow and bio-impedance were recorded from 12 able-bodied subjects (AB), 7 diabetics without (D0), 7 with possible (D1) and 8 with definite polyneuropathy (D2), during 10 minutes supine control, 30 minutes 70-degree head-up tilt and 5 minutes supine recovery. During the first 3 minutes of tilt, systolic BP decreased in D2 while increased in AB. Parasympathetic control of heart rate, baroreflex sensitivity, and baroreflex effectiveness and sympathetic control of heart rate and vasomotion were reduced in D2, compared with AB. Baroreflex effectiveness index was identified as the most sensitive index to discriminate diabetic AN.
Four-dimensional multiscale modeling of ECG indexes of diabetic autonomic neuropathy: QT interval prolongation which predicts long-term mortality in diabetics with AN, is well known. The mechanism of QT interval prolongation is still unknown, but correlation of regional sympathetic denervation of the heart (revealed by cardiac imaging) with QT interval in 12-lead ECG has been proposed. The goal of this study is to 1) reproduce QT interval prolongation seen in diabetics, and 2) develop a computer model to link QT interval prolongation to regional cardiac sympathetic denervation at the cellular level. From the 12-lead ECG acquired in the study above, heart rate-corrected QT interval (QTc) was computed and a reduced ionic whole heart mathematical model was constructed. Twelve-lead ECG was produced as a forward solution from an equivalent cardiac source. Different patterns of regional denervation in cardiac images of diabetic patients guided the simulation of pathological changes. Minimum QTc interval of lateral leads tended to be longer in D2 than in AB. Prolonging action potential duration in the basal septal region in the model produced ECG and QT interval similar to that of D2 subjects, suggesting sympathetic denervation in this region in patients with definite neuropathy.
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Ojeda, Avellaneda David. "Multi-resolution physiological modeling for the analysis of cardiovascular pathologies." Phd thesis, Université Rennes 1, 2013. http://tel.archives-ouvertes.fr/tel-01056825.
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This thesis presents three main contributions in the context of modeling and simulation of physiological systems. The first one is a formalization of the methodology involved in multi-formalism and multi-resolution modeling. The second one is the presentation and improvement of a modeling and simulation framework integrating a range of tools that help the definition, analysis, usage and sharing of complex mathematical models. The third contribution is the application of this modeling framework to improve diagnostic and therapeutic strategies for clinical applications involving the cardiovascular system: hypertension-based heart failure (HF) and coronary artery disease (CAD). A prospective application in cardiac resynchronization therapy (CRT) is also presented, which also includes a model of the therapy. Finally, a final application is presented for the study of the baroreflex responses in the newborn lamb. These case studies include the integration of a pulsatile heart into a global cardiovascular model that captures the short and long term regulation of the cardiovascular system with the representation of heart failure, the analysis of coronary hemodynamics and collateral circulation of patients with triple-vessel disease enduring a coronary artery bypass graft surgery, the construction of a coupled electrical and mechanical cardiac model for the optimization of atrio ventricular and intraventricular delays of a biventricular pacemaker, and a model-based estimation of sympathetic and vagal responses of premature newborn lambs.
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Parlikar, Tushar Anil 1978. "Modeling and monitoring of cardiovascular dynamics for patients in critical care." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/40859.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2007.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Includes bibliographical references (p. 231-239).
In modern intensive care units (ICUs) a vast and varied amount of physiological data is measured and collected, with the intent of providing clinicians with detailed information about the physiological state of each patient. The data include measurements from the bedside monitors of heavily instrumented patients, imaging studies, laboratory test results, and clinical observations. The clinician's task of integrating and interpreting the data, however, is complicated by the sheer volume of information and the challenges of organizing it appropriately. This task is made even more difficult by ICU patients' frequently-changing physiological state. Although the extensive clinical information collected in ICUs presents a challenge, it also opens up several opportunities. In particular, we believe that physiologically-based computational models and model-based estimation methods can be harnessed to better understand and track patient state. These methods would integrate a patient's hemodynamic data streams by analyzing and interpreting the available information, and presenting resultant pathophysiological hypotheses to the clinical staff in an effcient manner. In this thesis, such a possibility is developed in the context of cardiovascular dynamics. The central results of this thesis concern averaged models of cardiovascular dynamics and a novel estimation method for continuously tracking cardiac output and total peripheral resistance. This method exploits both intra-beat and inter-beat dynamics of arterial blood pressure, and incorporates a parametrized model of arterial compliance. We validated our method with animal data from laboratory experiments and ICU patient data.
(cont.) The resulting root-mean-square-normalized errors -- at most 15% depending on the data set -- are quite low and clinically acceptable. In addition, we describe a novel estimation scheme for continuously monitoring left ventricular ejection fraction and left ventricular end-diastolic volume. We validated this method on an animal data set. Again, the resulting root-mean-square-normalized errors were quite low -- at most 13%. By continuously monitoring cardiac output, total peripheral resistance, left ventricular ejection fraction, left ventricular end-diastolic volume, and arterial blood pressure, one has the basis for distinguishing between cardiogenic, hypovolemic, and septic shock. We hope that the results in this thesis will contribute to the development of a next-generation patient monitoring system.
by Tushar Anil Parlikar.
Ph.D.
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GUALA, ANDREA. "Mathematical modelling of cardiovascular fluid mechanics: physiology, pathology and clinical practice." Doctoral thesis, Politecnico di Torino, 2015. http://hdl.handle.net/11583/2615064.
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The cardiovascular apparatus is a complex dynamical system that
carries oxygen and nutrients to cells, removes carbon dioxide and
wastes and performs several other tasks essential for life. The
physically-based modelling of the cardiovascular system has a long
history, which begins with the simple lumped Windkessel model by
O. Frank in 1899. Since then, the development has been impressive
and a great variety of mathematical models have been proposed.
The purpose of this Thesis is to analyse and develop two different mathematical models of the cardiovascular system able to
(i) shed new light into cardiovascular ageing and atrial fibrillation
and to (ii) be used in clinical practice. To this aim, in-house codes
have been implemented to describe a lumped model of the complete
circulation and a multi-scale (1D/0D) model of the left ventricle
and the arterial system. We then validate each model. The former is validated against literature data, while the latter against
both literature data and numerous in-vivo non-invasive pressure
measurements on a population of six healthy young subjects.
Afterwards, the confirmed effectiveness of the models has been
exploited. The lumped model has been used to analyse the effect
of atrial fibrillation. The multi-scale one has been used to analyse the effect of ageing and to test the feasibility of clinical use
by means of central-pressure blind validation of a parameter setting unambiguously defined with only non-invasive measurements
on a population of 52 healthy young men. All the applications
have been successful, confirming the effectiveness of this approach.
Pathophysiology studies could include mathematical model in their
setting, and clinical use of multi-scale mathematical model is feasible.
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Lindgren, Peter. "Modeling the economics of prevention /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-352-3/.
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Mak, Shiu-kwong Thomas, and 麥肇鑛. "Modeling diabetic cardiomyopathy using embryonic stem cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/193562.
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Diabetic cardiomyopathy (DCM), a disorder of the heart muscle, is one of the major and most rampant culprits claiming thousands and thousands of lives around the globe every year by interfering with the blood circulation and causing the development of heart failure eventually. The progression of the disease is asymptomatic and having a long latent period, and it is characterized functionally by ventricular dilation, diastolic dysfunction, interstitial fibrosis and cardiomyocytes hypertrophy. It was suggested the pathogenesis of the disease and the related complications are related to the effects of hyperglycemia on cardiomyocytes. So understanding the physiology of both the normal and pathological conditions, and the underlying mechanisms involved are of paramount importance to derive therapies to cope with this disease. However, it is difficult, if not impossible, to study the physiology in vivo using a live sample or to build a cellular model with adult cardiomyocytes due to the insufficient number of the cells harvested. This is not until the emergence of Embryonic Stem Cells (ESCs) that a cellular model with clinical sufficient number of cardiomyocytes could be built for investigation and drug screening.
With a view to mimicking the situation of the Diabetic cardiomyopathy of the Type II Diabetes mellitus (DM) patients, mouse ESCs are used to differentiate into cardiomyocytes using the traditional hanging drop method to produce Embryoid body (EB). The cardiomyocytes were then enriched and plated so that different testing conditions could be applied. The effect of high glucose (HG), Insulin and the combination of high glucose and insulin were then analyzed. This was to show the significance of hyperglycemia, hyperinsulinemia due to insulin resistance and the role of insulin in hyperglycemia on cardiomyocytes respectively.
The results agreed with previous findings that high glucose and insulin alone do induce cells apoptosis while the combination of insulin and glucose did decrease the number of apoptosis and while the co-culture of insulin with High dosage of glucose has shown to reduce the effect of hypertrophy.published_or_final_version
Medicine
Master
Master of Medical Sciences
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Randles, Amanda Elizabeth. "Modeling cardiovascular hemodynamics using the lattice Boltzmann method on massively parallel supercomputers." Thesis, Harvard University, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=3567037.
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Accurate and reliable modeling of cardiovascular hemodynamics has the potential to improve understanding of the localization and progression of heart diseases, which are currently the most common cause of death in Western countries. However, building a detailed, realistic model of human blood flow is a formidable mathematical and computational challenge. The simulation must combine the motion of the fluid, the intricate geometry of the blood vessels, continual changes in flow and pressure driven by the heartbeat, and the behavior of suspended bodies such as red blood cells. Such simulations can provide insight into factors like endothelial shear stress that act as triggers for the complex biomechanical events that can lead to atherosclerotic pathologies. Currently, it is not possible to measure endothelial shear stress in vivo, making these simulations a crucial component to understanding and potentially predicting the progression of cardiovascular disease. In this thesis, an approach for efficiently modeling the fluid movement coupled to the cell dynamics in real-patient geometries while accounting for the additional force from the expansion and contraction of the heart will be presented and examined.
First, a novel method to couple a mesoscopic lattice Boltzmann fluid model to the microscopic molecular dynamics model of cell movement is elucidated. A treatment of red blood cells as extended structures, a method to handle highly irregular geometries through topology driven graph partitioning, and an efficient molecular dynamics load balancing scheme are introduced. These result in a large-scale simulation of the cardiovascular system, with a realistic description of the complex human arterial geometry, from centimeters down to the spatial resolution of red-blood cells. The computational methods developed to enable scaling of the application to 294,912 processors are discussed, thus empowering the simulation of a full heartbeat.
Second, further extensions to enable the modeling of fluids in vessels with smaller diameters and a method for introducing the deformational forces exerted on the arterial flows from the movement of the heart by borrowing concepts from cosmodynamics are presented. These additional forces have a great impact on the endothelial shear stress. Third, the fluid model is extended to not only recover Navier-Stokes hydrodynamics, but also a wider range of Knudsen numbers, which is especially important in micro- and nano-scale flows. The tradeoffs of many optimizations methods such as the use of deep halo level ghost cells that, alongside hybrid programming models, reduce the impact of such higher-order models and enable efficient modeling of extreme regimes of computational fluid dynamics are discussed. Fourth, the extension of these models to other research questions like clogging in microfluidic devices and determining the severity of co-arctation of the aorta is presented. Through this work, a validation of these methods by taking real patient data and the measured pressure value before the narrowing of the aorta and predicting the pressure drop across the co-arctation is shown. Comparison with the measured pressure drop in vivo highlights the accuracy and potential impact of such patient specific simulations.
Finally, a method to enable the simulation of longer trajectories in time by discretizing both spatially and temporally is presented. In this method, a serial coarse iterator is used to initialize data at discrete time steps for a fine model that runs in parallel. This coarse solver is based on a larger time step and typically a coarser discretization in space. Iterative refinement enables the compute-intensive fine iterator to be modeled with temporal parallelization. The algorithm consists of a series of prediction-corrector iterations completing when the results have converged within a certain tolerance. Combined, these developments allow large fluid models to be simulated for longer time durations than previously possible.
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Trivedi, Dyuti Kishorbhai. "Simulation of a Complete Cardiovascular Loop: Development of a Simulink Based Pressure-Flow Model to Obtain the Origin of the Electrical Impedance Cardiogram." Akron, OH : University of Akron, 2009. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=akron1232729044.
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Thesis (M.S.)--University of Akron, Dept. of Chemical and Biomedical Engineering, 2009."May, 2009." Title from electronic thesis title page (viewed 8/2/2009) Advisor, Bruce C. Taylor; Committee members, Daniel B. Sheffer, Dale H. Mugler; Department Chair, Daniel B. Sheffer; Dean of the College, George K. Haritos; Dean of the Graduate School, George R. Newkome. Includes bibliographical references.
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Everett, Kay Dee Furman. "Mechanisms and Implications of Fracture in Cardiovascular Stents." Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11458.
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Cardiovascular stents are one of the most widely implanted medical devices, with over 1 million implanted each year in the United States alone. While stent failure modes of restenosis and thrombosis have been widely examined, there is an increasing appreciation of the propensity for stents to fracture and break after implantation. It remains unclear however what causes these fractures, which patients and devices are most susceptible, and whether fracture results in failure of device function.Engineering and Applied Sciences
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Dong, Rumei. "Modeling of the cardiovascular system with integrated finite elemant and electrical analog methods /." View online ; access limited to URI, 2006. http://0-wwwlib.umi.com.helin.uri.edu/dissertations/fullcit/3239905.
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Santos, Andreia Esteves. "Modeling and numerical simulation of the flexibility and structural instability of cardiovascular stents." Master's thesis, Universidade de Aveiro, 2018. http://hdl.handle.net/10773/23678.
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Mestrado em Engenharia MecânicaCardiovascular disease is currently one of the major causes of death in developed countries. Atherosclerosis is one of these diseases and results from an unhealthy lifestyle a ecting predominantly medium size arteries, such as the coronary or the carotid artery. It consists on the deployment of layers of fat in the vessel walls, narrowing the blood vessel and limiting the blood ow. Stents are small expandable devices that, when placed inside the artery, allow it to expand almost to its original form. There are two types of stents: ballon expandable stents and self-expanding stents. Self-expanding stents were the ones studied in this Dissertation and their major di erence relies on the material they were made of. Shape memory alloys have been researched for the past decades due to their unique features. They are known for being able to recover their original form after su ering a large deformation, through the application of a stimulus that can either be magnetic or of temperature. The main goal of this Dissertation was to study the shape memory alloys in order to have a better understanding of their behavior and unique properties, so that it can be applied in numerical simulation software (in this case Femap with NX Nastran). Therefore, it was performed a bending test on two commercially available models. Di erent types of analysis and options provided by the software, as well as three di erent mesh sizes, allowed to take di erent conclusions. It was possible to conclude that, for the theoretically more exible model, the obtained results were similar to the ones used as a reference. Nevertheless, for the other model the results were a bit di erent than the ones expected. It was also noted that the mesh size has noticeable in uences on the results.
As doenças cardiovasculares correspondem atualmente a uma das maiores causas de morte nos países desenvolvidos. A aterosclerose é uma destas doenças e resulta, essencialmente, de um estilo de vida pouco saudável afetando predominantemente as artérias de médio calibre: coronárias, carótidas, renais, entre outras, e consiste no acumulamento de gordura no interior do vaso sanguíneo até este ficar completamente obstruído. Os stents são pequenos dispositivos expansíveis que, uma vez colocados na artéria, expandem permitindo assim que este vaso _que desobstruído. Existem essencialmente dois tipos de stents: os que são expandidos através de um balão e os que expandem automaticamente. Estes últimos foram estudados no âmbito da proposta dissertação, estando a sua grande diferença no material de que são feitos. Os materiais com memória de forma têm sido alvo de pesquisa durante as últimas décadas devido às suas características únicas. Distinguem-se por, após terem sofrido uma deformação elevada, conseguirem recuperar a sua forma original apenas através da aplicação de um estímulo, que pode ser magnético ou de temperatura. O âmbito desta dissertação consistiu em estudar os materiais com memória de forma, de modo a perceber o seu comportamento e as suas propriedades bem como a sua aplicação no software de simulação numérica Femap with NX Nastran. Foram então estudados dois modelos disponíveis comercialmente, através da execução de um teste de flexão. Diferentes tipos de análises e opções do software foram testadas, assim como diferentes malhas para o mesmo modelo. Foi possível concluir que, para o modelo teoricamente mais flexível, os resultados foram semelhantes à referência utilizada, enquanto que para o outro modelo foram encontradas algumas diferenças. De notar ainda a influência do tamanho da malha nos resultados obtidos.
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Yilmaz, Neval A. "An Integrated, Dynamic Model For Cardiovascular And Pulmonary Systems." Master's thesis, METU, 2006. http://etd.lib.metu.edu.tr/upload/2/12607650/index.pdf.
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In this thesis an integrated, dynamic model for cardiovascular and respiratory systems has been developed. Models of cardiopulmonary system, airway mechanics and gas exchange that preexisted in literature have been reviewed, modified and combined. Combined model composes the systemic and pulmonary circulations, left/right ventricles, tissue/lung compartments, airway/lung mechanics and gas transportation. Airway resistance is partitioned into three parts (upper, middle, small airways). A collapsible airways segment and a viscoelastic element describing lung tissue dynamics and a static chest wall compliance are included. Frank-Starling Law, Bowditch effect and variable cerebral flow are also employed in the model.
The combined model predictions have been validated by laboratory data collected from two healthy, young, male subjects, by performing dynamic bicycle exercise tests, using Vmax 229 Sensormedics, Cardiopulmonary Exercise Testing Instrument. The transition from rest to exercise under a constant ergometric workload is simulated. The initial anaerobic energy supply, autoregulation and the dilatation of pulmonary vessels are considered. Mean arterial blood pressure and the blood gas concentrations are assumed to be regulated by the controllers of the central nervous system namely, the heart rate and alveolar ventilation. Cardiovascular and respiratory regulation is modeled by a linear feedback control which minimizes a quadratic cost functional.
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Kotiya, Akhilesh A. "Mechanical characterisation and structural analysis of normal and remodeled cardiovascular soft tissue." Texas A&M University, 2008. http://hdl.handle.net/1969.1/85903.
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Characterization of multiaxial mechanical properties of cardiovascular soft tissue
is essential in order to better understand their growth and remodeling in homeostatic
conditions and in response to injury or pathological conditions. Though numerous
phenomenological models have been proposed to characterize such multiaxial
mechanical behavior, the approach has certain drawbacks regarding experimental
determination of the model coefficients. We propose a method that aims to overcome
these drawbacks. The approach makes use of orthogonal polynomials to fit the biaxial
test data and suggests a way to derive the strain energy function from these analytical fits
by way of minimizing the deviation of the behavior from hyperelastic ideal. Using the
proposed method, a strain energy function for a lymphatic vessel is derived and the
method is compared with traditional ones that used non-orthogonal polynomials as
independent variables in the functional form for strain energy. The unique coefficient
values obtained using the proposed method, for the first time gives us an opportunity to
attribute a physical characteristic of the material to the coefficient values. The method
also provides a way to assess two different material behaviors by way of comparing their
deviation from the hyperelastic behavior when a similar test protocol is used to collect
the data, over a similar deformation range and the order of polynomial function is chosen
so as to give a similar error of fit. The behavior of mesenteric lymph vessels from
normal cows, cows subjected to sham surgery and those subjected to 3 days of
edematous conditions by venous occlusion are compared using this method. To be able
to better understand the changes in mechanical behavior, morphological analysis of the
vessels was carried out and the geometric and structural changes in these vessels were
studied. We found that the behavior of bovine mesenteric lymph vessels subjected to a high flow condition shows a small difference in their mechanical behavior as compared
to the vessels from normal a cow and a cow subjected to sham surgery. The geometry
and structure of these vessels also showed marked differences from the other two. The
thickness to radius ratio increased and a rise in percentage of area occupied by smooth
muscle cells and medial collagen was observed. Though not all the differences were
statistically significant, we conclude that the behavior and the morphology are
suggestive of the remodeling of the vessel in response to altered hemodynamic
conditions and require further investigation.
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Qu, Wenlong. "The multiprocessor SAS framework for modeling and cost-effectiveness analysis of treatments for cardiovascular disease." Thesis, University of Ottawa (Canada), 2004. http://hdl.handle.net/10393/26748.
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This thesis provides an economic and mathematical framework, and the computing tools to compare the effects, costs and incremental cost-effectiveness of acute or preventative interventions for cardiovascular disease. A Finite Space Markov Chain Decision Analysis Model is designed by integrating a Decision Trees Model and a Markov Chain Model. The model and Cost-Effectiveness Analysis are implemented by using SAS/IML both on a PC with one processor and on a machine with multiple processors of the High Performance Computing Virtual Laboratory. A sample case with four states and eight intervention policies is studied to illustrate the framework, which is composed of (1) life path simulation, (2) cost and effectiveness estimation, (3) cost-effectiveness analysis, (4) sensitivity analysis, and (5) performance analysis on different platforms. Solution of delay effects, correlation among risk factors, and fluctuation in discount rate are viewed as limitations of the thesis and rewarding areas for further research.
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Subramaniam, Dhananjay Radhakrishnan. "Role of Elasticity in Respiratory and Cardiovascular Flow." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1522054562050044.
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Kimmig, François. "Multi-scale modeling of muscle contraction : From stochastic dynamics of molecular motors to continuum mechanics." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLX071/document.
Full textAbstract:
L'objectif de cette thèse est la modélisation mathématique des mécanismes de contraction musculaire à l'échelle microscopique dans le but de proposer et d'intégrer ces modèles dans un environnement de simulation cardiaque multi-échelle.Ce travail est réalisé dans le contexte de la médecine numérique, qui propose d'améliorer le traitement des patients par l'utilisation d'outils numériques.La première contribution de cette thèse est une analyse bibliographique des travaux expérimentaux caractérisant l’interaction actine-myosine et ses régulations afin de compiler les informations sous une forme utilisable pour le développement de modèles.Cette étape est une condition préalable essentielle à la modélisation.Nous proposons ensuite une hiérarchie de modèles de contraction musculaire à partir d'un modèle stochastique raffiné existant, mais validé uniquement pour les muscles squelettiques, en appliquant des hypothèses de simplification successives.Les étapes de simplification transforment l'équation différentielle stochastique initiale en une équation aux dérivées partielles avec une description qui fait partie de la famille de modèles dérivée du modèle Huxley'57.Une simplification supplémentaire conduit ensuite à un modèle décrit par un ensemble d'équations différentielles ordinaires.La pertinence des modèles proposés, qui ciblent différentes échelles de temps, est démontrée en les comparant aux données expérimentales obtenues avec des muscles cardiaques, et leur domaine de validité est étudié.Pour intégrer ces descriptions dans un environnement de simulation cardiaque, nous avons étendu ces modèles afin de prendre en compte les mécanismes de régulation de la force qui se produisent in vivo.Cela conduit à de nouvelles équations aux dérivées partielles.Ensuite, nous lions les modèles de contraction microscopiques à un modèle d’organe macroscopique.Nous suivons pour cela une approche fondée sur les principes thermodynamiques pour traiter la nature multi-échelle en temps et en espace du tissu musculaire aux niveaux continu et discret.La validité de cet environnement de simulation est démontrée en présentant sa capacité à reproduire le comportement du coeur et en particulier les caractéristiques essentielles de l'effet Frank-StarlingThis PhD thesis deals with the mathematical description of the micro-scale muscle contraction mechanisms with the aim of proposing and integrating our models into a multiscale heart simulation framework.This research effort is made in the context of digital medicine, which proposes to improve the treatment of patients with the use of numerical tools.The first contribution of this thesis is a literature review of the experimental works characterizing the actin-myosin interaction and its regulations to compile information in a useable form for the development of models.This stage is an essential prerequisite to modeling.We then propose a hierarchy of muscle contraction models starting from a previously proposed refined stochastic model, which was only validated for skeletal muscles, and applying successive simplification assumptions.The simplification stages transform the initial stochastic differential equation into a partial differential equation with a model that is part of the Huxley'57 model family.A further simplification then leads to a description governed by a set of ordinary differential equations.The relevance of these models, targeting different time scales, is demonstrated by comparing them with experimental data obtained with cardiac muscles and their range of validity is investigated.To integrate these microscopic descriptions into a heart simulation framework, we extend the models to take into account the force regulation mechanisms that take place in vivo, leading to the derivation of new partial differential equations.Then, we link the microscopic contraction models to the macroscopic organ model.We follow for that an approach based on the thermodynamical principles to deal with the multi-scale nature in time and space of the muscle tissue at the continuous and at the discrete levels.The validity of this simulation framework is demonstrated by showing its ability to reproduce the heart behavior and in particular to capture the essential features of the Frank-Starling effect
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Gul, Raheem [Verfasser]. "Mathematical Modeling and Sensitivity Analysis of Lumped-Parameter Model of the Human Cardiovascular System / Raheem Gul." Berlin : Freie Universität Berlin, 2016. http://d-nb.info/1082238007/34.
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LI, YUCHEN. "MICROALGAE PEPTIDES IN CARDIOVASCULAR DISEASE PREVENTION: STRUCTURE ELUCIDATION,BIOACTIVITY INVESTIGATION,AND IN SILICO MOLECULAR MODELING ANALYSIS." Doctoral thesis, Università degli Studi di Milano, 2021. http://hdl.handle.net/2434/850789.
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Bioactive food-derived peptides have been increasingly studied and the multiple health benefits they provide have been acknowledged. Since the most investigated sources of bioactive peptides are eggs, meat, fish, soybean, wheat, milk, and their derivatives or byproducts. More recently, some attention is being paid to microalgae, a promising unconventional protein source. On this basis, the PhD thesis was focused on the evaluation of the potential of microalgae to generate peptides with cardiovascular-promoting effects, especially hypotensive and antidiabetic activities, by targeting two therapeutic agents – angiotensin I converting enzyme (ACE) and peptidyl-peptidase IV (DPP-IV), respectively. To achieve this objective, multidisciplinary approaches were employed, involving peptidomic techniques to profile the peptide sequences, biochemical tools to analyze the bioactivity, and emerging molecular modelling methods to predict potentially bioactive peptides as well as to explore their possible mechanism of action.
Briefly, the results showed that the protein hydrolysates from spirulina, PBP and chlorella generally presented significant ACE and/or DPP-IV inhibitory activities. By comparison, peptic hydrolysate of spirulina protein showed the best in vitro inhibiting effect on ACE with IC50 value of 0.1 ± 0.04 mg/mL while the tryptic hydrolysate of PBP stands out with the lowest IC50 value of DPP-IV inhibition (0.5 – 1.0 mg/mL). Noticeably, when working on the intestinal Caco-2 cells, all the hydrolysates turned to be less bioactive than in vitro, indicating their susceptibility to metabolic degradation by intestinal cells. This is further in line with the kinetics of DPP-IV inhibition of PBP tryptic hydrolysate working on the intestinal cells, which showed the decreasing trend of its bioactivity after incubation with Caco-2 cells for 3 h. This reflects the issue of peptide bioavailability, which could be stressed in further studies. Moreover, peptides Pep2 (FLKPLGSGK), Pep7 (QIYTMGK), Pep8 (FLFVAEAIYK), and Pep10 (QHAGTKAK) were screened from hydrolysates of chlorella protein by peptidomics combined with docking and MD. The modelling results indicated that they may block the important domain of both ACE and DPP-IV and generate dynamically stable peptide-ACE/DPP-IV complexes. Based on this theoretical evidence, further study will focus on the verification of their actual bioactivity by biochemical approaches.
In conclusion, the bioactivity investigation of microalgae protein hydrolysates provides new evidence that microalgae protein are great sources to produce peptides with health-promoting properties. The exclusive data of peptide characterization makes a foundation to isolate single bioactive peptides as well as offers useful structural and functional implications for food ingredient formulation or pharmacological use.
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Restrepo, Pelaez Maria. "Development of a coupled geometrical multiscale solver and application to single ventricle surgical planning." Diss., Georgia Institute of Technology, 2015. http://hdl.handle.net/1853/54832.
Full textAbstract:
Single ventricle heart defects are present in two of every 1000 live births in the US. In this condition the systemic and pulmonary blood flow mix in the functioning ventricle, resulting in insufficient blood oxygenation to sustain life. As part of the palliation of these defects, the staged surgical procedure, known as the Fontan procedure, is performed. Here, the venous returns are directed to the pulmonary arteries, bypassing the right heart and forming the Total Cavopulmonary Connection (TCPC). Even though the palliation improves life expectancy, there are numerous long-term complications that become more prevalent as patients reach adulthood. Many of these complications have been related to the function of the single ventricle circulation, especially to the abnormal TCPC hemodynamics, for which this has been the focus of research throughout the years. Recent progress has been made with the availability of improved medical imaging techniques and computational modeling tools; however, there is limited information on how these evolve in time.
In order to improve the Fontan palliation, image-based surgical planning has been used in the most complex cases to prospectively design the TCPC, aiming to improve the hemodynamics. Even though this paradigm has shown promising results, improvement is needed to provide more realistic predictions of the post-operative outcomes. To address this, in this thesis we have developed a novel surgical planning framework that allows us to: (i) model the interaction of the TCPC and global circulation hemodynamics, and (ii) assess the robustness of the surgical option proposed. Here, the single ventricle circulation is modeled using a lumped parameter model, coupled to a computational fluid solver to describe the local TCPC hemodynamics. With this framework, we can predict the immediate post-operative state, model various physiological scenarios, and assess the impact on the local hemodynamics and global circulation. This will allow us to provide information on the effect on the global hemodynamics to the clinical team. In addition to the surgical planning advancements obtained in this thesis, we have performed the largest longitudinal Fontan study to date in which we have evaluated the evolution of the Fontan physiology in time and the effect it has on the energy efficiency of the TCPC.
In this thesis, we have studied the short and long-term effects that geometrical and physiological changes have on the Fontan hemodynamics. With this, we have improved the understanding of the Fontan physiology in terms of the short-term effects of Fontan palliation and the long-term deterioration of the changing single ventricle physiology.
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Hemasilpin, Nat. "Toward Optimal Adaptive Control of Hemodialysis." University of Cincinnati / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1378112378.
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Leoce, Nicole M. "Prognostic Modeling in the Presence of Competing Risks| An Application to Cardiovascular and Cancer Mortality in Breast Cancer Survivors." Thesis, Columbia University, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=10110945.
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Currently, there are an estimated 2.8 million breast cancer survivors in the United States. Due to modern screening practices and raised awareness, the majority of these cases will be diagnosed in the early stages of disease where highly effective treatment options are available, leading a large proportion of these patients to fail from causes other than breast cancer. The primary cause of death in the United States today is cardiovascular disease, which can be delayed or prevented with interventions such as lifestyle modifications or medications. In order to identify individuals who may be at high risk for a cardiovascular event or cardiovascular mortality, a number of prognostic models have been developed. The majority of these models were developed on populations free of comorbid conditions, utilizing statistical methods that did not account for the competing risks of death from other causes, therefore it is unclear whether they will be generalizable to a cancer population remaining at an increased risk of death from cancer and other causes.
Consequently, the purpose of this work is multi-fold. We will first summarize the major statistical methods available for analyzing competing risk data and include a simulation study comparing them. This will be used to inform the interpretation of the real data analysis, which will be conducted on a large, contemporary cohort of breast cancer survivors. For these women, we will categorize the major causes of death, hypothesizing that it will include cardiovascular failure. Next, we will evaluate the existing cardiovascular disease risk models in our population of cancer survivors, and then propose a new model to simultaneously predict a survivor's risk of death due to her breast cancer or due to cardiovascular disease, while accounting for additional competing causes of death. Lastly, model predicted outcomes will be calculated for the cohort, and evaluation methods will be applied to determine the clinical utility of such a model.
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Lonardoni, José Augusto Calvo. "Desenvolvimento de um simulador da mecânica cardiovascular humana controlada pelo mecanismo reflexo baroceptor." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/3/3152/tde-11122006-130030/.
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Nos últimos anos, o ensino de fisiologia tem sido fortemente beneficiado pelo desenvolvimento de modelos matemáticos e simuladores de paciente capazes de reproduzir com segurança partes específicas ou sistemas fisiológicos completos. Estudos mostram que aulas teóricas aliadas a simulações conseguem potencializar o nível de compreensão dos conceitos envolvidos. O principal objetivo deste trabalho consiste no desenvolvimento de um simulador do sistema cardiovascular, capaz de representar de forma didática a dinâmica do ciclo cardíaco. A disponibilidade de simuladores deste tipo é reduzida, e limitada a modelos simplificados ou interfaces pouco amigáveis. De modo a conseguir maior flexibilidade nas situações simuladas e um adequado grau de proximidade com o sistema real, decidiu-se pela utilização de um modelo matemático da fisiologia cardiovascular para o cálculo das variáveis e parâmetros atuantes no plano de fundo do simulador. O desenvolvimento deste modelo constitui o segundo objetivo deste trabalho. Devido ao grau de complexidade desejado, optou-se pela utilização de um modelo existente na literatura, acrescido dos parâmetros que fossem considerados ausentes. O resultado foi um modelo com oito compartimentos vasculares e quatro compartimentos representando as câmaras do coração, todas com atividade pulsátil, controlados pelo mecanismo reflexo baroceptor, controle de curto prazo que atua na regulação da pressão arterial. O simulador (desenvolvido em Visual C# com interface em Macromedia Flash) permite a alteração individual dos parâmetros vasculares e a simulação de hemorragias, bem como a visualização de gráficos de pressão, fluxo e volume em qualquer compartimento, e a construção de alças pressão-volume para os átrios e ventrículos. Além disso, o aplicativo resultante possibilita a inclusão futura de novos recursos e ferramentas, como tutoriais e simulação de patologias.During the last years, physiology learning has been strongly favored by the development of mathematical models and patient simulators capable of safely reproduce specific parts or complete physiological systems. Studies show that traditional classes together with simulations are able to in-crease the comprehension of concepts involved. The main objective of this work is to develop a simu-lator of the cardiovascular system capable of representing the cardiac cycle dynamics in a didactic fashion. There are just a few available simulators of this kind, and the existing ones are based on simplified models or unfriendly interfaces. In order to achieve high flexibility in simulated scenarios and an adequate level of realism, we decided to use a mathematical model of the cardiovascular physiology to calculate variables and parameters acting in the background of the application. The development of this model constitutes the second objective of the present work. Due to the desired level of complexity, we decided to use an existing model found in the literature, improved with addi-tional parameters we found necessary. The result is a model with eight vascular compartments and all four cardiac chambers, with pulsatile behavior, controlled by the baroreflex mechanism, a short term control that regulates arterial pressure. The simulator (developed in Visual C# with an interface built in Macromedia Flash) allows the user to change individual parameters and simulate blood losses, as well as visualize press, flow and volume graphs from any compartment and also pressure-volume loops from the cardiac chambers. Moreover, the resulting application is open to future inclusion of new resources and tools, such as tutorials and pathology simulation.
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Heimbigner, Stephen Matthew. "Implications in Using Monte Carlo Simulation in Predicting Cardiovascular Risk Factors among Overweight Children and Adolescents." Digital Archive @ GSU, 2007. http://digitalarchive.gsu.edu/iph_theses/11.
Full textAbstract:
The prevalence of overweight and obesity among children and adolescents has increased considerably over the last few decades. As a result, increasing numbers of American children are developing multiple risk factors for cardiovascular disease, type II diabetes, hyperinsulinemia, hypertension, dyslipidemia and hepatic steatosis. This thesis examines the use of Monte Carlo computer simulation for understanding risk factors associated with childhood overweight. A computer model is presented for predicting cardiovascular risk factors among overweight children and adolescents based on BMI levels. The computer model utilizes probabilities from the 1999 Bogalusa Heart Study authored by David S. Freedman, William H. Dietz, Sathanur R. Srinivasan and Gerald S. Berenson. The thesis examines strengths, weaknesses and opportunities associated with the developed model. Utilizing this approach, organizations can insert their own probabilities and customized algorithms for predicting future events.
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Ylönen, R. (Riikka). "Characterization of the function of type XIII collagen in mice; specific roles during cardiovascular development and posnatally in bone modeling." Doctoral thesis, University of Oulu, 2005. http://urn.fi/urn:isbn:9514279441.
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Abstract
Type XIII collagen is a type II transmembrane protein which is expressed in many tissues throughout development and adult life. It is located in focal adhesions of cultured cells and in the adhesive structures of tissues such as the myotendinous junctions in muscle, intercalated discs in the heart and the cell-basement membrane interphases. To further characterize the function of this protein, we generated transgenic mice overexpressing it in normal and mutant forms.
A large in-frame deletion in the COL2 domain of type XIII collagen led to synthesis of truncated α1(XIII) chains in transgenic mice, disrupting the assembly of normal type XIII collagen trimers. Fibroblasts derived from the mutant mice expressed shortened α1(XIII) chains, and no intracellular accumulation of the mutant protein was detected, suggesting that the mutant molecules were expressed on the cell surface. Transgene expression led to an embryonally lethal phenotype in offspring from heterozygous mating at two distinct stages of development. The early phenotype fetuses died due to the lack of chorioallantoic fusion and functioning placenta at 10.5 dpc, while the death of the late phenotype fetuses was caused by cardiac and placental defects around 13.5 dpc. The phenotype resembles closely several other cell adhesion molecule mutants, indicating that type XIII collagen has an essential role in certain adhesive interactions that are necessary for normal development.
Mice overexpressing type XIII collagen with or without a point mutation developed postnatally an unexpected skeletal phenotype marked by a massive increase in bone mass. The cortical bone cross-sectional area and volumetric bone mineral density were highly increased, but trabecular bone volume was not significantly altered. The bone formation rate was several times higher in the mutant mice than in their normal littermates, while the osteoclast number and resorption activity were normal. Type XIII collagen was expressed highly in primary osteoblasts derived from the transgenic mice. Overexpression of type XIII collagen in osteoblasts enhanced both cell proliferation and differentiation while lack of it had opposite effects. Furthermore, mutant cells responded to mechanical strain differently than wild-type cells. The findings suggest that type XIII collagen has an important role in bone modeling, and it may in particular have a function in coupling the regulation of bone mass to mechanical usage.
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Rahman, Roussel. "Analysis and Sensitivity Study of Zero-Dimensional Modeling of Human Blood Circulation Network." Wright State University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=wright1494769445938849.
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da, Silva Soares Joao Filipe. "Constitutive modeling for biodegradable polymers for application in endovascular stents." Texas A&M University, 2008. http://hdl.handle.net/1969.1/85939.
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Percutaneous transluminal balloon angioplasty followed by drug-eluting stent
implantation has been of great benefit in coronary applications, whereas in peripheral
applications, success rates remain low. Analysis of healing patterns in successful
deployments shows that six months after implantation the artery has reorganized itself to
accommodate the increase in caliber and there is no purpose for the stent to remain,
potentially provoking inflammation and foreign body reaction. Thus, a fully
biodegradable polymeric stent that fulfills the mission and steps away is of great benefit.
Biodegradable polymers have a widespread usage in the biomedical field, such as
sutures, scaffolds and implants. Degradation refers to bond scission process that breaks
polymeric chains down to oligomers and monomers. Extensive degradation leads to
erosion, which is the process of mass loss from the polymer bulk. The prevailing
mechanism of biodegradation of aliphatic polyesters (the main class of biodegradable
polymers used in biomedical applications) is random scission by passive hydrolysis and
results in molecular weight reduction and softening.
In order to understand the applicability and efficacy of biodegradable polymers, a
two pronged approach involving experiments and theory is necessary. A constitutive
model involving degradation and its impact on mechanical properties was developed
through an extension of a material which response depends on the history of the motion
and on a scalar parameter reflecting the local extent of degradation and depreciates the
mechanical properties. A rate equation describing the chain scission process confers
characteristics of stress relaxation, creep and hysteresis to the material, arising due to the entropy-producing nature of degradation and markedly different from their viscoelastic
counterparts.
Several initial and boundary value problems such as inflation and extension of
cylinders were solved and the impacts of the constitutive model analyzed. In vitro
degradation of poly(L-lactic acid) fibers under tensile load was performed and
degradation and reduction in mechanical properties was dependent on the mechanical
environment. Mechanical testing of degraded fibers allowed the proper choice of
constitutive model and its evolution. Analysis of real stent geometries was made possible
with the constitutive model integration into finite element setting and stent deformation
patterns in response to pressurization changed dramatically as degradation proceeded.
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Lane, Kevin J. "The community assessment of freeway exposure and health study: modeling personal exposures to ultrafine particles and effects on biomarkers of cardiovascular health." Thesis, Boston University, 2014. https://hdl.handle.net/2144/12142.
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Thesis (Ph.D.)--Boston UniversityApproximately 45 million people in the United States live, work, or attend schools within 300 feet of a major road, airport or railroad, and approximately 11% of US households reside within lOOm of highways making exposure to TRAPs a major public health concern (EPA, 2014; Brugge et al., 2007). Vehicle emissions are the primary source by which people are exposed to ultrafine particles (particles <100 nm in aerodynamic diameter, UFP), but there are substantial limitations that impede the Environmental Protection Agency's (EPA) ability to adequately monitor and develop a UFP standard. UFPs constitute a developing area of exposure and epidemiological research that requires novel modeling approaches to deal with bias stemming from the high spatial and temporal variability of this pollutant. This dissertation aids in filling the UFP research gap through an examination of the association between UFP and biomarkers of cardiovascular health. During the dissertation I have designed, validated and tested a novel geocoding methodology and implemented a time-activity exposure assignment model as a way to deal with error from various sources that lead to exposure misclassification. This dissertation demonstrates: 1) that epidemiological studies focusing on proximity to major roadways could have reduced ability to detect true association with adverse health effects due to inaccurate geocoding and the effects of population mobility; 2) that inclusion of time-activity in the assignment of personal exposure to UFPs produce more accurate beta estimates during health analysis; 3) positive associations between UFP measured as particle number concentration (PNC) and hsCRP, IL-6 and TNFRll that were evident after adjusting for other cardiovascular disease risk factors. To our knowledge, this is the first study to examine the association between chronic exposure to UFP and biomarkers of systemic inflammation and coagulation.
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Tisminetzky, Mayra. "Modeling Co-Occurring Depression and Anxiety in Patients with an Acute Coronary Syndrome: A Dissertation." eScholarship@UMMS, 2009. https://escholarship.umassmed.edu/gsbs_diss/421.
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The purpose of the current project is to illustrate the application of advanced statistical techniques to address research questions about depression and anxiety in patients with an acute coronary syndrome (ACS). The first study, using data from 100 patients who were randomized into a clinical trial of cognitive behavioral therapy, used bivariate mixed models to determine trajectories of depression and anxiety after an ACS, to examine the effects of cognitive behavioral therapy (CBT) on depression and anxiety, and to determine if anxiety and depression symptoms change at the same rate with CBT treatment as indicated by joint modeling of these two psychiatric disorders. The findings suggest that depression and anxiety are highly correlated and persistent in patients with an ACS both at baseline and over time. The intervention used in the present investigation does not appear to uncouple the association between anxiety and depression, suggesting that CBT has comparable effects on both psychiatric disorders.
The second study used latent transition analysis to identify symptomatology profiles of depression, anxiety, and functional impairment in patients with an ACS, describe changes over time (two, three and six-month follow-up) in patient’s acute symptom profiles, and determine if patients receiving CBT showed signs of remission in depression, anxiety and impaired function earlier than patients that received usual care. A three-class model was selected to identify and describe these acute symptom profiles. One class was characterized by patients with both psychiatric disorders and impaired function, the second by patients with psychiatric disorders but normal function, and the third by patients with anxiety but without depression, and having normal function. There was moderate improvement in depression, anxiety and functional status for control patients, but this improvement was less evident than in the treatment group. Women showed a better response to CBT than men.
The third study used latent class and latent transition analysis to determine symptom profiles of depression and anxiety in patients with an ACS using the Hospital Anxiety Depression Scale; a secondary study goal was to examine the effects of age and gender on these symptom patterns. A two-class model was selected to describe depression and anxiety symptomatology profiles. Class I (76% of patients at baseline) was labeled as “severe depression and some anxiety” whereas Class II (24% of patients at baseline) was labeled as “mild depression and distress anxiety”. More than 70% of older patients continued to have severe depression and anxiety at follow-up and a large proportion of these patients who reported mild depression and anxiety at baseline showed worsening of symptoms at follow-up. The current study demonstrates that patients with depression and anxiety after an ACS can be identified on the basis of the symptoms that they present. This is particularly important to identifying individuals at potential risk for developing clinical complications after an ACS.
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Yan, Huan. "Statistical adjustment, calibration, and uncertainty quantification of complex computer models." Diss., Georgia Institute of Technology, 2014. http://hdl.handle.net/1853/52290.
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This thesis consists of three chapters on the statistical adjustment, calibration, and uncertainty quantification of complex computer models with applications in engineering. The first chapter systematically develops an engineering-driven statistical adjustment and calibration framework, the second chapter deals with the calibration of potassium current model in a cardiac cell, and the third chapter develops an emulator-based approach for propagating input parameter uncertainty in a solid end milling process.
Engineering model development involves several simplifying assumptions for the purpose of mathematical tractability which are often not realistic in practice. This leads to discrepancies in the model predictions. A commonly used statistical approach to overcome this problem is to build a statistical model for the discrepancies between the engineering model and observed data. In contrast, an engineering approach would be to find the causes of discrepancy and fix the engineering model using first principles. However, the engineering approach is time consuming, whereas the statistical approach is fast. The drawback of the statistical approach is that it treats the engineering model as a black box and therefore, the statistically adjusted models lack physical interpretability. In the first chapter, we propose a new framework for model calibration and statistical adjustment. It tries to open up the black box using simple main effects analysis and graphical plots and introduces statistical models inside the engineering model. This approach leads to simpler adjustment models that are physically more interpretable. The approach is illustrated using a model for predicting the cutting forces in a laser-assisted mechanical micromachining process and a model for predicting the temperature of outlet air in a fluidized-bed process.
The second chapter studies the calibration of a computer model of potassium currents in a cardiac cell. The computer model is expensive to evaluate and contains twenty-four unknown parameters, which makes the calibration challenging for the traditional methods using kriging. Another difficulty with this problem is the presence of large cell-to-cell variation, which is modeled through random effects. We propose physics-driven strategies for the approximation of the computer model and an efficient method for the identification and estimation of parameters in this high-dimensional nonlinear mixed-effects statistical model.
Traditional sampling-based approaches to uncertainty quantification can be slow if the computer model is computationally expensive. In such cases, an easy-to-evaluate emulator can be used to replace the computer model to improve the computational efficiency. However, the traditional technique using kriging is found to perform poorly for the solid end milling process. In chapter three, we develop a new emulator, in which a base function is used to capture the general trend of the output. We propose optimal experimental design strategies for fitting the emulator. We call our proposed emulator local base emulator. Using the solid end milling example, we show that the local base emulator is an efficient and accurate technique for uncertainty quantification and has advantages over the other traditional tools.
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Ebrahimi, Pegah. "Patient-specific design of the right ventricle to pulmonary artery conduit via computational analysis." Thesis, The University of Sydney, 2019. http://hdl.handle.net/2123/20381.
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Cardiovascular prostheses are routinely used in surgical procedures to address congenital malformations, for example establishing a pathway from the right ventricle to the pulmonary arteries (RV-PA) in pulmonary atresia and truncus arteriosus. Currently available options are fixed size and have limited durability. Hence, multiple re-operations are required to match the patients’ growth and address structural deterioration of the conduit. Moreover, the pre-set shape of these implants increases the complexity of operation to accommodate patient specific anatomy. The goal of the research group is to address these limitations by 3D printing geometrically customised implants with growth capacity. In this study, patient-specific geometrical models of the heart were constructed by segmenting MRI data of patients using Mimics inPrint 2.0. Computational Fluid Dynamics (CFD) analysis was performed, using ANSYS CFX, to design customised geometries with better haemodynamic performance. CFD simulations showed that customisation of a replacement RV-PA conduit can improve its performance. For instance, mechanical energy dissipation and wall shear stress can be significantly reduced. Finite Element modelling also allowed prediction of the suitable thickness of a synthetic material to replicate the behaviour of pulmonary artery wall under arterial pressures. Hence, eliminating costly and time-consuming experiments based on trial-and-error. In conclusion, it is shown that patient-specific design is feasible, and these designs are likely to improve the flow dynamics of the RV-PA connection. Modelling also provides information for optimisation of biomaterial. In time, 3D printing a customised implant may simplify replacement procedures and potentially reduce the number of operations required over a life time, bringing substantial improvements in quality of life to the patients
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Deng, Yangyang. "A Study of the Relationship between Childhood Body Size and Adult Blood Pressure, Cardiovascular Structure and Function." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3408.
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BACKGROUND: Little is known of the effects of obesity, body size and body composition, and blood pressure (BP) in childhood on hypertension (HBP) and cardiac structure and function in adulthood due to the lack of long-term serial data on these parameters from childhood into adulthood. In the present study, we are poised to analyze these serial data from the Fels Longitudinal Study (FLS) to evaluate the extent to which body size during childhood determines HBP and cardiac structure and function in the same individuals in adulthood through mathematical modeling. METHODS: The data were from 412 males and 403 females in the FLS. Stature and BMI parameters were estimated using the Preeze-Baines model and the third degree polynomial model to describe the timing, velocity and duration of these measure from 2 to 25 years of age. The biological parameters were related to adult BP and echocardiographic (Echo-) measurements using Generalized Linear Models (GLM). RESULTS: The parameters of stature and BMI were compared between male and female to their overall goodness of fit and their capabilities to quantify the timing, rate of increase, and duration of the growth events. For stature parameters, the age at onset and peak velocity was earlier for girls; but the peak velocity was greater in boys; the velocity at onset was about the same for boys and girls; and stature at onset, peak velocity and adult was greater for boys. For BMI parameters, boys tended to have larger BMI values than girls, but the rates of change in BMI were almost the same; there was no sex difference in the timing of BMI rebound, but there was for the age of the peak velocity of BMI and maximum BMI, both of which were earlier in girls than in boys. CONCLUSIONS: Changes in childhood stature and BMI parameters were related to adult BP and Echo-measurements more so in females than males. Also the relationship of the adult BP measurements with corresponding childhood biological parameters was stronger than the relationship for adult Echo-measurements.
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Dodhy, Sami C. "AGE-DEPENDENT CHANGES IN OXYGEN SUPPLY AND DEMAND OF RAT SPINOTRAPEZIUS MUSCLE." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5670.
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Because of the aerobic nature of cellular metabolism in mammalian organisms, a continuous supply of oxygen is necessary to maintain normal physiological function. As organisms age, their metabolic rates generally decline and there are accompanying alterations in the structure and function of the microcirculation, as this part of the cardiovascular system is especially important for oxygen exchange. The overall Oxygen Transport System can be considered as being composed of two complementary components: one for Oxygen Demand and one for Oxygen Supply. The purpose of the current work is to describe the age-dependent changes in both oxygen demand and oxygen supply at the level of the microcirculation, using intravital microscopic observations of the rat spinotrapezius muscle, along with optical techniques to delineate the structural, hemodynamic and oxygenation variables needed to characterize the Oxygen Transport System in this tissue. A summary of the findings is that basal oxygen consumption gradually declined with age (from 2 to 12 months) and there were corresponding decreases in tissue blood flow, blood hemoglobin concentration and capillary surface area for oxygen exchange, so that oxygen supply and demand were generally well-matched.
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Calvo, Gonźalez Mireia. "Analysis of the cardiovascular response to autonomic nervous system modulation in Brugada syndrome patients." Thesis, Rennes 1, 2017. http://www.theses.fr/2017REN1S056/document.
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Le syndrome de Brugada (BS) est une maladie génétique responsable de troubles du rythme cardiaque. En raison de la nature complexe et multifactorielle de cette pathologie, la stratification du risque peut s’avérer particulièrement difficile et il est nécessaire de pouvoir définir de nouveaux marqueurs avec des valeurs prédictives élevées afin d’identifier les patients à haut risque. Les événements arythmiques dans cette population étant souvent liés à des modifications de fonctionnement du système nerveux autonome (SNA), l’objectif de la thèse est l’évaluation et comparaison de la réponse cardiovasculaire aux modulations du SNA pendant la nuit, ainsi qu'en réponse à des manœuvres normalisées, telles que l'épreuve d'effort ou le test d'orthostatisme, chez une série de patients BS présentant différents niveaux de risque (sujets symptomatiques et asymptomatiques). Une première partie du travail de thèse est dédiée à l’application de méthodes d'analyse de complexité cardiaque, de sensibilité baroréflexe et de variabilité non-stationnaire du rythme cardiaque, jamais étudiées dans le cadre des patients BS. Dans une deuxième partie, afin d'aborder la nature multifactorielle de la maladie, une approche multivariée basée sur une méthode de machine learning est introduite. En employant des marqueurs extraits à l'analyse du traitement du signal précédent, des classificateurs robustes capables de distinguer les patients à différents niveaux de risque sont proposés. Dans la troisième partie de ce travail, deux modèles mathématiques de connaissances ont été proposés et analysés, afin d'étudier les réponses autonomiques et hémodynamiques au test d’orthostatisme et à l’épreuve d’effort. Enfin, une application prospective d’une approche multivariée intégrant les paramètres extraits à l'étape de modélisation est également présentée. L’ensemble des résultats de la thèse permet une meilleure caractérisation des profils autonomiques des patients BS et laisse envisager une amélioration de la sélection des patients pour implantation d'un défibrillateur implantableBrugada syndrome (BS) is a genetic arrhythmogenic disease characterized by a distinctive electrocardiographic pattern, associated with a high risk for sudden cardiac death. Its complex and multifactorial nature turns risk stratification into a major challenge. Although variations in autonomic modulation are commonly related to arrhythmic events in this population, novel markers with higher predictive values are still needed so as to identify those patients at high risk. Since the autonomic function can be better characterized through the application of standardized maneuvers stimulating the autonomic nervous system (ANS), the main objective of this thesis is to evaluate and compare the cardiovascular response to ANS modulations overnight, as well as in response to exercise and HUT testing, on a series of BS patients with different levels of risk (symptomatic and asymptomatic subjects). In a first part of this work, we apply previously described methods for the analysis of heart rate complexity, baroreflex sensitivity, and non-stationary heart rate variability, never before studied in the context of BS patients. In a second part, in order to address the multifactorial nature of the disease, a multivariate approach based on a step-based machine learning method is introduced. By employing markers extracted at signal-processing analysis, robust classifiers capable of distinguishing patients at different levels of risk are proposed. The third part of this work has been focused on the proposal of novel mathematical models and the associated model analysis methods, so as to study the autonomic and hemodynamic responses to exercise and HUT testing. Finally, a prospective application of a multivariate approach integrating parameters extracted at the model-based stage is also presented. Overall, the obtained results provide new insights into the underlying autonomic mechanisms regulating the cardiovascular system in BS, improving physiopathology and prognosis interpretation. The proposed approach may be used as an instrument for the identification of those asymptomatic patients at high risk who may benefit from a cardioverter defibrillator implantation
El síndrome de Brugada (SB) es una enfermedad genética asociada a un patrón electrocardiográfico característico y a un elevado riesgo de muerte súbita cardíaca (MSC), causada por fibrilación ventricular (FV) en ausencia de cardiopatías estructurales. Debido a su naturaleza compleja y multifactorial, la estratificación del riesgo supone, en la actualidad, uno de los aspectos más controvertidos. Ciertas alteraciones en la modulación del sistema nervioso autónomo (SNA) se han relacionado con eventos arrítmicos en esta población; no obstante, nuevos marcadores con valores predictivos más elevados que permitan identificar a aquellos pacientes con un alto riesgo de sufrir MSC son todavía necesarios. El uso de maniobras estandarizadas con el objetivo de estimular el SNA permite una mejor caracterización de la función autonómica. El principal objetivo de esta tesis doctoral es, por tanto, la evaluación exhaustiva de la respuesta cardiovascular a la modulación del SNA en una serie de pacientes con SB y diferentes niveles de riesgo (sujetos sintomáticos y asintomáticos), a través de diferentes maniobras autonómicas, con la finalidad de identificar nuevos marcadores potencialmente útiles para la estratificación de riesgo en esta población. En este contexto, la evaluación de la función autonómica se llevó a cabo mediante tres estrategias principales. En primer lugar, se caracterizaron y compararon la variabilidad y complejidad del ritmo cardíaco, así como la sensibilidad barorrefleja, en pacientes sintomáticos y asintomáticos, con el objetivo de identificar nuevos marcadores capaces de distinguir entre grupos de pacientes. Los resultados mostraron, en el grupo sintomático, una menor variabilidad y complejidad durante la noche, así como un mayor tono vagal y una menor actividad simpática tanto durante el ejercicio como en respuesta a la prueba de mesa inclinada. En un segundo análisis, se abordó la etiología multifactorial del síndrome mediante un enfoque multivariado basado en un método de aprendizaje automático por etapas. A partir de marcadores extraídos en la etapa anterior, se propusieron modelos predictivos capaces de clasificar pacientes diagnosticados con SB en función de su nivel de riesgo. El mejor clasificador (AUC = 95%) fue diseñado a partir de marcadores autonómicos obtenidos durante la noche, superando modelos predictivos previamente descritos para la estratificación del riesgo en el SB a partir de la combinación de parámetros no invasivos. Finalmente, se analizaron las interacciones entre las funciones mecánica, circulatoria y autonómica de estos pacientes a partir de modelos fisiológicos. En primer lugar, mediante la implementación y evaluación de un modelo computacional integrando la dinámica del sistema cardiovascular y su respuesta autonómica a la prueba de mesa inclinada. Asimismo, se propuso la identificación recursiva de un modelo implementado para el análisis de la evolución temporal de las contribuciones simpática y parasimpática del SNA durante una prueba de esfuerzo. Los resultados mostraron una menor contractilidad, así como una actividad parasimpática significativamente mayor durante el ejercicio, en pacientes sintomáticos. Con el objetivo de combinar características extraídas del modelado fisiológico, un último estudio prospectivo propuso el diseño de un clasificador multivariado integrando los parámetros estimados en esta última etapa. Los resultados obtenidos indican importantes tendencias de relevancia clínica que aportan nuevos conocimientos sobre los mecanismos autonómicos encargados de regular el sistema cardiovascular en el SB. Su interpretación permite mejorar la estratificación del riesgo en estos pacientes y, por tanto, optimizar las estrategias terapéuticas aplicadas. La metodología propuesta se presenta como un instrumento para la identificación de aquellos pacientes con alto riesgo de MSC que podrían beneficiarse de la implantación de desfibriladores automáticos
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Zhang, Xia. "Endothelial HSPA12B is a Novel Protein for the Preservation of Cardiovascular Function in Polymicrobial Sepsis via Exosome MiR-126." Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/etd/3129.
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Sepsis is the most frequent cause of mortality in most intensive care units. Cardiovascular dysfunction is a major complication associated with sepsis, with high mortality rates up to 70%. Currently, there is no effective treatment approach for sepsis.
The integrity of the endothelium is fundamental for the homeostasis of the cardiovascular system. Sepsis induces endothelial cell injury which is the key factor for multiple organ failure. The increased expression of adhesion molecules and chemokines in endothelial cell promotes leukocytes infiltration into the tissue. The loss of tight junction proteins and increased permeability of the endothelial cells will provoke tissue hypoxia and subsequent organ failure. Therefore, preservation of endothelial function is a critical approach for improving sepsis-induced outcome.
Here, we showed that endothelial specific protein HSPA12B plays a critical role in the preservation of cardiovascular function in polymicrobial sepsis. HSPA12B is the newest member of HSP70 family which predominantly expresses in endothelial cells. We observed that HSPA12B deficiency (HSPA12B-/-) exaggerated polymicrobial sepsis-induced endothelial dysfunction, leading to worse cardiac dysfunction. HSPA12B-/- significantly increases the expression of adhesion molecules, decreases tight junction protein levels and enhances vascular permeability. HSPA12B-/- alsomarkedly promotes the infiltration of inflammatory cells into the myocardium and inflammatory cytokine production.
We investigated the cardioprotective mechanisms of HSPA12B in sepsis induced cardiovascular dysfunction. Exosomes play a critical role in intercellular communication. Exosome is a natural vehicle of microRNAs. We found that exosomes isolated from HSPA12B-/- septic mice induced more expression of adhesion molecules in endothelial cells and inflammation in macrophages. Interestingly, the levels of miR-126 in serum exosomes isolated from HSPA12B-/- septic mice were significantly lowers than in WT septic mice. Importantly, delivery of miR-126 carried exosomes significantly improved cardiac function, suppressed the expression of adhesion molecules, reduced immune cell infiltration in the myocardium, and improved vascular permeability in HSPA12B-/- septic mice. The data suggests that HSPA12B is essential for endothelial function in sepsis and that miR-126 containing exosomes plays a critical role in cardiovascular-protective mechanisms of endothelial HSPA12B in polymicrobial sepsis.
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Shandilya, Sharad. "ASSESSMENT AND PREDICTION OF CARDIOVASCULAR STATUS DURING CARDIAC ARREST THROUGH MACHINE LEARNING AND DYNAMICAL TIME-SERIES ANALYSIS." VCU Scholars Compass, 2013. http://scholarscompass.vcu.edu/etd/3198.
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In this work, new methods of feature extraction, feature selection, stochastic data characterization/modeling, variance reduction and measures for parametric discrimination are proposed. These methods have implications for data mining, machine learning, and information theory. A novel decision-support system is developed in order to guide intervention during cardiac arrest. The models are built upon knowledge extracted with signal-processing, non-linear dynamic and machine-learning methods. The proposed ECG characterization, combined with information extracted from PetCO2 signals, shows viability for decision-support in clinical settings. The approach, which focuses on integration of multiple features through machine learning techniques, suits well to inclusion of multiple physiologic signals. Ventricular Fibrillation (VF) is a common presenting dysrhythmia in the setting of cardiac arrest whose main treatment is defibrillation through direct current countershock to achieve return of spontaneous circulation. However, often defibrillation is unsuccessful and may even lead to the transition of VF to more nefarious rhythms such as asystole or pulseless electrical activity. Multiple methods have been proposed for predicting defibrillation success based on examination of the VF waveform. To date, however, no analytical technique has been widely accepted. For a given desired sensitivity, the proposed model provides a significantly higher accuracy and specificity as compared to the state-of-the-art. Notably, within the range of 80-90% of sensitivity, the method provides about 40% higher specificity. This means that when trained to have the same level of sensitivity, the model will yield far fewer false positives (unnecessary shocks). Also introduced is a new model that predicts recurrence of arrest after a successful countershock is delivered. To date, no other work has sought to build such a model. I validate the method by reporting multiple performance metrics calculated on (blind) test sets.
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Liu, Zhanqiu. "BIVENTRICULAR FINITE ELEMENT MODELING AND QUANTIFICATION OF 3D LANGRAGIAN STRAINS AND TORSION USING DENSE MRI." UKnowledge, 2016. http://uknowledge.uky.edu/me_etds/80.
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Statistical data suggests that increased use of evidence-based medical therapies has largely contributed to the decrease in American death rate caused by heart disease. And my studies are about two applications of magnetic resonance imaging (MRI) as a non-invasive approach in evidence-based health care research. In my first study, the achievement of a pulmonary valve replacement surgery was assessed on a patient with tetralogy of Fallot (TOF). In order to evaluate the remodeling of right ventricle, two biventricular finite element models were built up for pre-surgical images and post-surgical images. In my second study, 3D Lagrangian strains and torsion in the left ventricle of ten rats were investigated using Displacement ENcoding with Stimulated Echoes (DENSE) cardiac magnetic resonance (CMR) images. Tools written in MATLAB were developed for 2D contouring, 3D modeling, strain and torsion computations, and statistical comparison across subjects.
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Rodriguez, Polo Ignacio [Verfasser], Rüdiger [Akademischer Betreuer] Behr, Rüdiger [Gutachter] Behr, Gregor [Gutachter] Bucher, and Wolfram-Hubertus [Gutachter] Zimmermann. "Non-human primate iPS cells for cell replacement therapies and human cardiovascular disease modeling / Ignacio Rodriguez Polo ; Gutachter: Rüdiger Behr, Gregor Bucher, Wolfram-Hubertus Zimmermann ; Betreuer: Rüdiger Behr." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2019. http://d-nb.info/1201161096/34.
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Gibb, Matthew Michael James. "Myocardial microstructure and its role in propagation dynamics." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:69a1a65e-9a71-422c-86e8-c347cfabf21a.
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Computational modelling and simulation, in close interaction with experiments, has provided invaluable insight into the biochemical, mechanical and electrophysiological function and dysfunction of the heart. However, limitations in imaging techniques and computing resources have precluded the analysis of tissue architecture near the cellular scale and the effect of this architecture on cardiac function. It is the wider aim of this thesis to develop a framework to characterise cardiac microstructure and to investigate the role of microstructure in cardiac propagation dynamics and arrhythmogenesis. An initial modelling study elucidates the effect of blood vessels in sustaining arrhythmic episodes, and how the accurate modelling of fibre direction in the vicinity of the vessels mitigates this detrimental mechanism. A mathematical model of fibre orientation in a simple geometry around blood vessels has been developed, based on information obtained from highly detailed histological and MRI datasets. A simulation regime was chosen, guided by the vasculature extracted from whole heart MRI images, to analyse ventricular wavefront propagation for different orientations and positions of blood vessels. Our results demonstrate not only that the presence of the blood vessels encourages curvature in the activation wavefront around the blood vessels, but further that vessels act to restrict and prolong phase singularities. When compared to a more simplistic implementation of fibre orientation, the model is shown to weaken wavefront curvature and reduce phase singularity anchoring. Having established the importance of microstructural detail in computational models, it seems expedient to generate accurate data in this regard. An automated registration toolchain is developed to reconstruct histological slices based on coherent block face volumes, in order to present the first 3-D sub-cellular resolution images of cardiac tissue. Although mesoscopic geometry is faithfully reproduced throughout much of the dataset, low levels of transformational noise obfuscate tissue microstructure. These distortions are all but eradicated by a novel transformational diffusion algorithm, with characteristics that outperform any previous method in the literature in this domain, with respect to robustness, conservation of geometry and extent of information transfer. Progress is made towards extracting microstructural models from the resultant histological volumes, with a view to incorporating this detail into simulations and yielding a deeper understanding of the role of microstructure in arrhythmia.
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Sensi, C. "LCAT MOLECULAR MODELING:APPLICATIONS TO STRUCTURE-FUNCTION RELATIONSHIPS AND TO INHIBITOR DISCOVERY." Doctoral thesis, Università degli Studi di Milano, 2013. http://hdl.handle.net/2434/216122.
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A series of large population studies have revealed the existence of a strong inverse correlation between plasma levels of high-density lipoprotein cholesterol (HDL-C) and cardiovascular risk. Accordingly, HDL has become a major target for the development of novel therapies for the treatment of atherosclerotic cardiovascular disease.
LCAT catalyzes cholesteryl ester synthesis and plays a central role in HDL structure and metabolism. Also, LCAT promotes the reverse cholesterol transport, and mediates its atheroprotective effects. Recent studies demonstrated that decreasing LCAT activity possibly has positive effects on HDL structure/function, and may represent a novel therapeutic strategy to reduce cardiovascular risk. To exploit LCAT therapeutic prospects, the availability of new potent and selective LCAT modulators is mandatory. With the present work, we identified molecules able to inhibit LCAT enzymatic activity implementing an in silico strategy.
The computational approach can be deployed in two different ways: i) the availability of large chemical databases, and the computational power of the new computers allow a very efficient in silico high-throughput screening starting from the target structure and independently of any pharmacophoric hypothesis; ii) the knowledge of the active site and of the catalytic mechanism of a target can be exploited for ab initio computer-aided drug design.
We have designed, through a de novo approach, an irreversible inhibitor, which is the first specific LCAT inhibitor known, and can be considered as a lead compound for the identification of new active molecules belonging to the same chemical family.
In parallel, the high-throughput screening carried out on LCAT identified some very potent reversible inhibitors, which can be of interest in further drug development steps.
Globally, this project produced innovative pharmacological entities to be further developed for a completely new therapeutic approach to the treatment of atherosclerotic cardiovascular diseases.
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D'Arienzo, Maria Pia. "Cardiovascular System: Modelling and Optimization." Doctoral thesis, Universita degli studi di Salerno, 2016. http://hdl.handle.net/10556/2224.
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2014 - 2015A conservation law is a partial di_erential equation, in which the variable is a quantity which remains constant in time, that is it cannot be created and destroyed. Thanks to the conservation laws it is possible to de_ne models able to describe real systems in which something is stored. Fluid dynamic models, which are based on them, have a wide range of applications, because they can be used to describe blood ows, tra_c evolution on street networks of big cities or on motorways of big states, data ows on telecommunication networks, ows of goods on supply chains, electric networks, etc. ... [edited by author]
XIV n.s.
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Xi, Jiahe. "Cardiac mechanical model personalisation and its clinical applications." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:0db4cf52-4f64-4ee0-8933-3fb49d64aee6.
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An increasingly important research area within the field of cardiac modelling is the development and study of methods of model-based parameter estimation from clinical measurements of cardiac function. This provides a powerful approach for the quantification of cardiac function, with the potential to ultimately lead to the improved stratification and treatment of individuals with pathological myocardial mechanics. In particular, the diastolic function (i.e., blood filling) of left ventricle (LV) is affected by its capacity for relaxation, or the decay in residual active tension (AT) whose inhibition limits the relaxation of the LV chamber, which in turn affects its compliance (or its reciprocal, stiffness). The clinical determination of these two factors, corresponding to the diastolic residual AT and passive constitutive parameters (stiffness) in the cardiac mechanical model, is thus essential for assessing LV diastolic function. However these parameters are difficult to be assessed in vivo, and the traditional criterion to diagnose diastolic dysfunction is subject to many limitations and controversies. In this context, the objective of this study is to develop model-based applicable methodologies to estimate in vivo, from 4D imaging measurements and LV cavity pressure recordings, these clinically relevant parameters (passive stiffness and active diastolic residual tension) in computational cardiac mechanical models, which enable the quantification of key clinical indices characterising cardiac diastolic dysfunction. Firstly, a sequential data assimilation framework has been developed, covering various types of existing Kalman filters, outlined in chapter 3. Based on these developments, chapter 4 demonstrates that the novel reduced-order unscented Kalman filter can accurately retrieve the homogeneous and regionally varying constitutive parameters from the synthetic noisy motion measurements. This work has been published in Xi et al. 2011a. Secondly, this thesis has investigated the development of methods that can be applied to clinical practise, which has, in turn, introduced additional difficulties and opportunities. This thesis has presented the first study, to our best knowledge, in literature estimating human constitutive parameters using clinical data, and demonstrated, for the first time, that while an end-diastolic MR measurement does not constrain the mechanical parameters uniquely, it does provide a potentially robust indicator of myocardial stiffness. This work has been published in Xi et al. 2011b. However, an unresolved issue in patients with diastolic dysfunction is that the estimation of myocardial stiffness cannot be decoupled from diastolic residual AT because of the impaired ventricular relaxation during diastole. To further address this problem, chapter 6 presents the first study to estimate diastolic parameters of the left ventricle (LV) from cine and tagged MRI measurements and LV cavity pressure recordings, separating the passive myocardial constitutive properties and diastolic residual AT. We apply this framework to three clinical cases, and the results show that the estimated constitutive parameters and residual active tension appear to be a promising candidate to delineate healthy and pathological cases. This work has been published in Xi et al. 2012a. Nevertheless, the need to invasively acquire LV pressure measurement limits the wide application of this approach. Chapter 7 addresses this issue by analysing the feasibility of using two kinds of non-invasively available pressure measurements for the purpose of inverse parameter estimation. The work has been submitted for publication in Xi et al. 2012b.
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Vargas, JoseÌ Juan SuaÌrez. "Physical modelling of the cardiovascular system." Thesis, Lancaster University, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.444643.
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Wu, Congqing. "THE ROLE OF ANGIOTENSINOGEN IN ATHEROSCLEROSIS AND OBESITY." UKnowledge, 2014. http://uknowledge.uky.edu/nutrisci_etds/16.
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Angiotensinogen is the only known precursor in the renin-angiotensin system, a hormonal system best known as an essential regulator of blood pressure and fluid homeostasis. Angiotensinogen is sequentially cleaved by renin and angiotensin- converting enzyme to generate angiotensin II. As the major effector peptide, angiotensin II mainly function through angiotensin type 1 receptor.
Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and more recently renin inhibitors are widely known as the 3 classic renin-angiotensin system inhibitory drugs against hypertension and atherosclerosis. Here, we developed an array of regents to explore the effects of angiotensinogen inhibition. First, we demonstrated that genetic deficiency of angiotensinogen not only protected against hypercholesterolemia- induced atherosclerosis but also prevented diet-induced obesity. Then we found weekly intraperitoneal injection of antisense oligonucleotides against angiotensinogen remarkably surpressed body weight gain in mice fed a western diet, which was absent from classic renin-angiotensin system inhibition. The suppressed body weight gain was attributable to diminished body fat mass gain and enhanced energy expenditure. More excitingly, angiotensinogen antisense oligonucleotides regressed body weight gain on obese mice. Together, our findings revealed a unique feature of angiotensinogen inhibition beyond classic renin angiotensin inhibition and demonstrated therapeutic potentials of angiotensinogen antisense oligonucleotides against hypertension, atherosclerosis, and obesity.
We also developed an in vivo system to explore the functional consequences of disrupting a conserved Cys18-Cys137 disulfide bridge in angiotensinogen. The formation of this disulfide bridge could trigger conformational changes in angiotensinogen, thereby facilitating renin cleavage of angiotensinogen. It was predicted that the redox-sensitive disulfide bridge might change the efficiency of angiotensinogen/renin reaction to release angiotensin II, thus modulate angiotensin II-dependent functions. We determined effects of the presence and absence of the disulfide bridge on angiotensin II concentrations and responses in mice expressing either native angiotensinogen or Cys18Ser, Cys137Ser mutated angiotensinogen in liver via adeno-associated viral vectors. Contrary to the prediction, disruption of Cys18-Cys137 disulfide bridge in angiotensinogen had no discernible effects on angiotensin II production and angiotensin II-dependent functions in mice.
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Baker, Shannon. "Examination of Strain-Dependent Differences in S. sanguinis Virulence and Growth." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5707.
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Streptococcus sanguinis, an abundant and benign inhabitant of the oral cavity, is an important etiologic agent of infective endocarditis, particularly in people with pre-disposing cardiac valvular damage. Although commonly isolated from patients with IE, little is known about the factors that make any particular S. sanguinis isolate more virulent than another or, indeed, whether significant differences in virulence exist among isolates. To investigate the virulence of multiple isolates, a variation of the Bar-seq (barcode sequencing) method was employed. A conserved chromosomal site was identified for subsequent insertion of a barcode identifier, unique for each strain. Barcode insertion did not affect growth in vitro or in a rabbit model of endocarditis. Pooling of these strains and inoculation into rabbits demonstrated that all strains were capable of causing disease; however, virulence varied widely among strains. Genomic comparisons of the more virulent strains versus less virulent strains failed to conclusively identify any single gene responsible for virulence. Given this result, we continued our examination of the manganese transport system SsaACB, which is present in every strain of S. sanguinis examined. Although its contribution to virulence has not been confirmed in any strain other than SK36, it has been shown to be required for virulence in multiple species of streptococci, making it a candidate for emerging targeted therapies. In S. sanguinis strain SK36, previous studies have confirmed that loss of the manganese transport protein SsaB is tantamount to loss of virulence. Moreover, ssaB-deficient mutants are deficient for serum growth—a phenotype we have previously found to be associated with virulence. Our in vitro studies of manganese transporter-deficient strain SK36 supported this, but also revealed the emergence of suppressor mutants. In each suppressor mutant that was isolated, mutations were identified that mapped to a common gene, SSA_0696. Deletion of SSA_0696 resulted in restored in vitro growth in the ssaACB-deficient background, unearthing a novel mechanism for bacterial growth under manganese limitation. Fortunately, the suppressor mutant phenotype was not maintained in vivo; however, the combined results of these experiments suggest the efficacy of future therapeutics may require consideration of virulence at the species level and the incorporation of multiple targets.
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Ibinson, James W. "The study of pain with blood oxygen level dependant functional magnetic resonance imaging." The Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=osu1092705600.
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