Fetal heart computational modeling

Treballs Finals de Grau d'Enginyeria Biomèdica. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona. Curs: 2021-2022. Tutor/Director: Director: Patricia Garcia Cañadilla / Tutor: Fàtima Crispi BrillasAmong infants born with cardiac defects, congenital heart disease (CHD) is the leading congenital abnormality and it origins the majority of newborns death in developed countries. The structural malformations in the heart or great vessels it causes increase the postnatal cardiovascular risk and mortality. In particular, the high incidence of tetralogy of Fallot (ToF) in live births make essential to develop new procedures that enable the study and understanding of this cardiac disorder and the hemodynamic changes it induces. That way, fetal medicine has been constantly evolving in the past years, and computational modeling techniques are becoming more established in the clinical practice and are of growing importance. Nowadays, different 0D lumped parameters models have demonstrated to be useful to evaluate complex cardiac defects in order to aid health workers and find the best management for patients. In this project, a 0D lumped model simulating hemodynamic components and parameters of the fetal heart was developed to study the changes occurring in a ToF heart. Specifically, birth defects of ventricular septal defect (VSD) and pulmonary valve stenosis (PVS) were modeled, allowing the analysis of their effects in fetal circulation. Our results suggested that the designed 0D lumped model can reproduce the blood velocities and pressure waveforms of the fetal heart in healthy conditions after adjusting the values of some model parameters. Despite that, the parameters of the ductus arteriosus (DA) should be better fit since we could not completely reproduce its velocity waveform. Regarding the evaluation of hemodynamic changes of cardiac defects, results suggested that the 0D lumped model can simulate the features present in ToF, such as the right-to-left shunt, characteristic of blood flow in VSD, and the increase of the pressure gradient and peak velocity of the pulmonary artery, indicative of PVS. However, more literature and clinical data of cardiac defects should be used in order to verify these outcomes and ensure their reliability

Nouvelle Théorie Hémodynamique Flux et Rythme Concept et applications précliniques en utilisant des nouveaux dispositifs d'assistance circulatoire Directeur

Le coeur et les vaisseaux sanguins sont directement issus de l'endothélium et dépendent de sa fonction. Le coeur ne représente pas la seule force motrice de notre système circulatoire, la plupart des stratégies thérapeutiques actuelles des maladies cardiovasculaires sont encore focalisées sur le coeur, négligeant l'ensemble du système circulatoire et le système endothélial. Par exemple, le développement de Dispositifs d'Assistance Cardiaque (DAC) est influencé par le coeur, conçu pour suivre,obéir et doit être synchronisé avec un organe malade.De nombreux signaux de nature différente sont capables d activer les cellules endothéliales : les forces de cisaillement créées par le flux sanguin parallèle à la surface de la paroi des vaisseaux, mais également les forces perpendiculaires provoquées par l étirement de la paroi artérielle par les variations de la pression et la qualité cyclique de ces forces. L activation de cellules endothéliales est due à la pulsatilité du flux mais aussi à l action de substances vasoactives et des médiateurs de l inflammation.Dans notre travail de thèse, nous proposons une nouvelle approche thérapeutique,basée sur une révision fondamentale de l'ensemble du système circulatoire: exposer les défauts de la gestion courante des maladies cardiovasculaires (MCV). Notre nouveau concept se concentre sur la dynamique des flux sanguins pour stimuler,restaurer et maintenir la fonction endothéliale, et compris le coeur lui-même. Nous avons développé et évalué une nouvelle génération de DAC pulsatiles, testée in vitro et in vivo.Pendant le déroulement de cette thèse nous avons effectué les études suivantes:1. Etude d un prototype de cathéter pulsatile. Il est testé de manière isolée dans un modèle expérimental d ischémie aiguë du myocarde et dans un modèle d hypertension pulmonaire aiguë.2. Etude d un prototype de tube pulsatile à double lumière. Il est testé in-vitro dans un circuit de circulation extracorporelle, et in vivo comme assistance ventriculaire gauche.73. Etude d un prototype de combinaison pulsatile. Il est testé sur un modèle animal présentant une défaillance aiguë du ventricule droit. Des prototypes de masques et de pantalons pulsatiles sont en développement.En conclusion, notre approche est basée sur l activation de la fonction endothéliale plutôt qu en une assistance cardiaque directe. Ce concept permet une meilleure gestion thérapeutique des maladies circulatoires et cardio-pulmonaires.The Heart is still considered as the main organ to be dealt with, in case ofcardiovascular disease. Nevertheless, the heart is not the only driving force in ourcirculatory system. In fact, the heart and blood vessels are the direct issues of theendothelium and depend on its function. Moreover, almost all current therapeuticstrategies are still focusing on the heart and neglecting the entire circulatoryendothelialsystem. For example, development of cardiac assist devices (CAD) is stillrestrained by the heart, designed to follow, obey and must be synchronized with adiseased organ.Many "signals" of different nature are capable of activating endothelial cells: the shearforces created by the blood flow parallel to the surface of the vessel wall, but alsoforces caused by stretching perpendicular to the artery wall by the cyclic pressuregradient and the quality of these forces. The activation of endothelial cells is due tothat pressurized flow dynamic forces, but also to the action of vasoactive substancesand inflammatory mediators.In this thesis we are proposing a new therapeutic approach, based on a fundamentalrevision of the entire systems: exposing those defects of current management ofcardiovascular diseases (CVD). A concept that focuses on flow dynamics to stimulate,restore and maintain endothelial function including the heart itself. This includespreliminary results of new generations of pulsatile CAD that promote endothelial shearstress (ESS) enhancement. Devices prototypes were tested.During this thesis, pulsatile devices prototypes were tested in vivo, in vitro as well aswith pre-clinical volunteers as follow:1. A pulsatile catheter prototype was tested in 2 pediatric animal models (piglets) of:acute myocardial ischemia; and acute pulmonary arterial hypertension.2. A pulstile tube prototype was tested in vitro (mock circuit) and in vivo (piglets) as aleft ventricular assist device (ongoing).3. Pulsatile suit prototypes were tested: in vivo (piglets) for acute right ventricularfailure treatment. Prototypes of pulsatile mask and trousers are currently in plannedfor pre-clinical studies.9Conclusion, Think endothelial instead of cardiac is our policy for better management ofCVD.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

In vitro expanded human CD4+CD25+ regulatory T cells suppress effector T cell proliferation.

Regulatory T cells (Tregs) have been shown to be critical in the balance between autoimmunity and tolerance and have been implicated in several human autoimmune diseases. However, the small number of Tregs in peripheral blood limits their therapeutic potential. Therefore, we developed a protocol that would allow for the expansion of Tregs while retaining their suppressive activity. We isolated CD4+CD25 hi cells from human peripheral blood and expanded them in vitro in the presence of anti-CD3 and anti-CD28 magnetic Xcyte Dynabeads and high concentrations of exogenous Interleukin (IL)-2. Tregs were effectively expanded up to 200-fold while maintaining surface expression of CD25 and other markers of Tregs: CD62L, HLA-DR, CCR6, and FOXP3. The expanded Tregs suppressed proliferation and cytokine secretion of responder PBMCs in co-cultures stimulated with anti-CD3 or alloantigen. Treg expansion is a critical first step before consideration of Tregs as a therapeutic intervention in patients with autoimmune or graft-versus-host disease

Front Lines of Thoracic Surgery

Front Lines of Thoracic Surgery collects up-to-date contributions on some of the most debated topics in today's clinical practice of cardiac, aortic, and general thoracic surgery,and anesthesia as viewed by authors personally involved in their evolution. The strong and genuine enthusiasm of the authors was clearly perceptible in all their contributions and I'm sure that will further stimulate the reader to understand their messages. Moreover, the strict adhesion of the authors' original observations and findings to the evidence base proves that facts are the best guarantee of scientific value. This is not a standard textbook where the whole discipline is organically presented, but authors' contributions are simply listed in their pertaining subclasses of Thoracic Surgery. I'm sure that this original and very promising editorial format which has and free availability at its core further increases this book's value and it will be of interest to healthcare professionals and scientists dedicated to this field