Afin d’apporter les soins adéquats aux victimes d'arrêt cardiaque extrahospitalier, l'évaluation de leur état hémodynamique est primordiale. La prise de pouls manuelle ne permet pas une identification fiable de l'arrêt cardiaque par les profanes ou une discrimination des rythmes organisés par les premiers intervenants. Dans ce contexte, l'entreprise Schiller Médical a cherché à intégrer dans sa gamme de défibrillateurs un module de détection de l'hémodynamique systémique par analyse de l'électrocardiogramme et des variations d'impédance transthoracique recueillis via les électrodes de défibrillation. Ce travail de recherche mené en partenariat entre l'entreprise Schiller Médical et l'Institut Pluridisciplinaire Hubert Curien de l’Université de Strasbourg a consisté dans un premier temps a recherché, lors d'arrêt cardiaque induit électriquement chez l'homme, des descripteurs des variations d'impédance transthoracique marqueurs de l’hémodynamique systémique. L’identification des descripteurs les plus pertinents a par la suite permis de construire des modèles prédictifs des défaillances circulatoires. Nous avons mis en lumière des limites à l’utilisation des variations d’impédance transthoracique. Elles sont prises en considération pour la documentation des interventions extrahospitalières destinée à l’apprentissage des algorithmes de classification des rythmes perfusants et rythmes sans pouls. / Providing suitable emergency care during out of hospital cardiac arrest requires the diagnostic of the circulatory status. Manual pulse check does not provide a reliable way for laypersons to identify cardiac arrest or for first responders to discriminate organized rhythms. Thus, Schiller Medical sought to embed an hemodynamic sensor in its external defibrillators by analyzing the electrocardiogram and transthoracic impedance recorded via the defibrillation pads. This thesis work stemmed from a partnership between Schiller Medical and the Institut Pluridisciplinaire Hubert Curien of the Université de Strasbourg. We first identified transthoracic impedance featureslinked with the circulatory status by studying clinically induced cardiac arrest. The most relevant features were later selected to form predictive models of hemodynamic collapse. We uncovered restrictions to the use of transthoracic impedance. We took them into account for the annotation of out of hospital cardiac arrests aimed at training algorithms for the classification of pulseless electrical activity and pulsatile rhythms.

Heart valve tissue engineering (HVTE) stands as a potential intervention that could reduce the prevalence of congenital heart valve disease in juvenile patients. Prior studies in our laboratory have utilized mechanobiological testing to quantify the forces involved in the development of heart valve tissue, utilizing a Flow-Stretch-Flexure (FSF) bioreactor to condition bone marrow stem cells (BMSCs)-derived valve tissue. Simulations have demonstrated that certain sets of flow conditions can introduce specific levels of oscillatory shear stress (OSS)-induced stimuli, augmenting the growth of engineered valves as well as influencing collagen formation, extracellular matrix (ECM) composition and gene expression. The computational findings discussed in this thesis outline the methods in which flow conditions, when physiologically relevant, induce specific oscillatory shear stresses which could not only lead to an optimized valve tissue phenotype (at 0.18≤ OSI≤ 0.23), but could identify native valve tissue remodeling indicative of aortic valve disease.

In the first part of this dissertation, the phenomenon of self-sustained pressure os-cillations due to the flow past a circular, axisymmetric cavity, associated with inline gate valves, was investigated. In many engineering applications, such as flows through open gate valves, there exists potential for coupling between the vortex shedding from the up-stream edge of the cavity and a diametral mode of the acoustic pressure fluctuations. The effects of the internal pipe geometry immediately upstream and downstream of the shal-low cavity on the characteristics of partially trapped diametral acoustic modes were in-vestigated numerically and experimentally on a scaled model of a gate valve mounted in a pipeline that contained convergence-divergence sections in the vicinity of the valve. The resonant response of the system corresponded to the second acoustic diametral mode of the cavity. Excitation of the dominant acoustic mode was accompanied by pressure oscillations, and, in addition to that, as the angle of the converging-diverging section of the main pipeline in the vicinity of the cavity increased, the trapped behavior of the acoustic diametral modes diminished, and additional antinodes of the acoustic pressure wave were observed in the main pipeline. In addition to that, the effect of shallow chamfers, introduced at the upstream and/or downstream cavity edges, was investigated in the experimental system that con-tained a deep, circular, axisymmetric cavity. Through the measurements of unsteady pressure and associated acoustic mode shapes, which were calculated numerically for several representative cases of the internal cavity geometry, it was possible to identify the configuration that corresponded to the most efficient noise suppression. This arrangement also allowed calculation of the azimuthal orientation of the acoustic modes, which were classified as stationary, partially spinning or spinning. Introduction of shallow chamfers at the upstream and the downstream edges of the cavity resulted in changes of azimuthal orientation and spinning behaviour of the acoustic modes. In addition, introduction of splitter plates in the cavity led to pronounced change in the spatial orientation and the spinning behaviour of the acoustic modes. The short splitter plates changed the behaviour of the dominant acoustic modes from partially spinning to stationary, while the long split-ter plates enforced the stationary behaviour across all resonant acoustic modes. Finally, the evolution of fully turbulent, acoustically coupled shear layers that form across deep, axisymmetric cavities and the effects of geometric modifications of the cavity edges on the separated flow structure were investigated using digital particle image velocimetry (PIV). Instantaneous, time- and phase-averaged patterns of vorticity pro-vided insight into the flow physics during flow tone generation and noise suppression by the geometric modifications. In particular, the first mode of the shear layer oscillations was significantly affected by shallow chamfers located at the upstream and, to a lesser degree, the downstream edges of the cavity. In the second part of the dissertation, the performance of aortic heart valve pros-thesis was assessed in geometries of the aortic root associated with certain types of valve diseases, such as aortic valve stenosis and aortic valve insufficiency. The control case that corresponds to the aortic root of a patient without valve disease was used as a reference. By varying the aortic root geometry, it was possible to investigate corresponding changes in the levels of Reynolds shear stress and establish the possibility of platelet activation and, as a result of that, the formation of blood clots. / Graduate / 0541 / 0546 / 0548 / 0986 / alexbn024@gmail.com

In the first part of this dissertation, the phenomenon of self-sustained pressure os-cillations due to the flow past a circular, axisymmetric cavity, associated with inline gate valves, was investigated. In many engineering applications, such as flows through open gate valves, there exists potential for coupling between the vortex shedding from the up-stream edge of the cavity and a diametral mode of the acoustic pressure fluctuations. The effects of the internal pipe geometry immediately upstream and downstream of the shal-low cavity on the characteristics of partially trapped diametral acoustic modes were in-vestigated numerically and experimentally on a scaled model of a gate valve mounted in a pipeline that contained convergence-divergence sections in the vicinity of the valve. The resonant response of the system corresponded to the second acoustic diametral mode of the cavity. Excitation of the dominant acoustic mode was accompanied by pressure oscillations, and, in addition to that, as the angle of the converging-diverging section of the main pipeline in the vicinity of the cavity increased, the trapped behavior of the acoustic diametral modes diminished, and additional antinodes of the acoustic pressure wave were observed in the main pipeline. In addition to that, the effect of shallow chamfers, introduced at the upstream and/or downstream cavity edges, was investigated in the experimental system that con-tained a deep, circular, axisymmetric cavity. Through the measurements of unsteady pressure and associated acoustic mode shapes, which were calculated numerically for several representative cases of the internal cavity geometry, it was possible to identify the configuration that corresponded to the most efficient noise suppression. This arrangement also allowed calculation of the azimuthal orientation of the acoustic modes, which were classified as stationary, partially spinning or spinning. Introduction of shallow chamfers at the upstream and the downstream edges of the cavity resulted in changes of azimuthal orientation and spinning behaviour of the acoustic modes. In addition, introduction of splitter plates in the cavity led to pronounced change in the spatial orientation and the spinning behaviour of the acoustic modes. The short splitter plates changed the behaviour of the dominant acoustic modes from partially spinning to stationary, while the long split-ter plates enforced the stationary behaviour across all resonant acoustic modes. Finally, the evolution of fully turbulent, acoustically coupled shear layers that form across deep, axisymmetric cavities and the effects of geometric modifications of the cavity edges on the separated flow structure were investigated using digital particle image velocimetry (PIV). Instantaneous, time- and phase-averaged patterns of vorticity pro-vided insight into the flow physics during flow tone generation and noise suppression by the geometric modifications. In particular, the first mode of the shear layer oscillations was significantly affected by shallow chamfers located at the upstream and, to a lesser degree, the downstream edges of the cavity. In the second part of the dissertation, the performance of aortic heart valve pros-thesis was assessed in geometries of the aortic root associated with certain types of valve diseases, such as aortic valve stenosis and aortic valve insufficiency. The control case that corresponds to the aortic root of a patient without valve disease was used as a reference. By varying the aortic root geometry, it was possible to investigate corresponding changes in the levels of Reynolds shear stress and establish the possibility of platelet activation and, as a result of that, the formation of blood clots. / Graduate / 0541 / 0546 / 0548 / 0986 / alexbn024@gmail.com

Οι καρδιαγγειακές παθήσεις αποτελούν την κύρια αιτία θανάτου στις αναπτυγμένες χώρες. Η στένωση σε μία αρτηρία, είτε αυτή προκαλείται από μία πάθηση όπως το ανεύρυσμα, είτε προκαλείται από μία περίδεση, όπως στις περιπτώσεις των συγγενών καρδιοπαθειών, μπορεί να μεταβάλλει σε σημαντικό βαθμό τα χαρακτηριστικά της ροής του αίματος. Η μελέτη της φυσιολογικής παλλόμενης ροής μέσα από στένωση είναι ιδιαίτερα σημαντική για τη διάγνωση και αντιμετώπιση των αγγειακών νόσων. Το ιατρικό πρόβλημα το οποίο εξετάζουμε στην παρούσα εργασία, είναι η στένωση της πνευμονικής αρτηρίας από περίδεση. Η περίδεση γίνεται προφανώς για να μειωθεί η υψηλή αρτηριακή πίεση και τελικά η ροή του αίματος προς τους πνεύμονες. Πρόκειται για μία χειρουργική μέθοδο αντιμετώπισης συγγενών καρδιοπαθειών. Η περίδεση της πνευμονικής αρτηρίας (pulmonary artery banding - PAB) είτε με συμβατικό τρόπο, ή με την πλέον σύγχρονη μέθοδο μέσω της συσκευής FloWatchTM προκαλεί τη στένωσή της. Με τον συμβατικό τρόπο η στένωση μπορεί να θεωρηθεί αξονικά συμμετρική, ωστόσο με τη χρήση του FloWatchTM είναι μη αξονικά συμμετρική. Έχει αποδειχθεί ότι τόσο η αξονικά συμμετρική, όσο και η μη συμμετρική περίδεση δημιουργεί διαφόρου βαθμού ίνωση του τοιχώματος της πνευμονικής αρτηρίας. Η αναδόμηση της πνευμονικής αρτηρίας είναι πολύ ηπιότερη στην περίπτωση της περίδεσης με το FloWatchTM. Η διαφοροποίηση αυτή έγκειται κυρίως στο ότι η συμβατική περίδεση προκαλεί για συγκεκριμένη μείωση της διατομής ισχυρότερη μείωση της περιμέτρου της διατομής από εκείνης της περίδεσης με το FloWatchTM. Στην παρούσα εργασία γίνεται αναφορά και ανάλυση των διαφόρων περιπτώσεων ροής σε στενώσεις αρτηριών, των συγγενών καρδιοπαθειών και των τεχνικών περίδεσης της πνευμονικής αρτηρίας. Επιπρόσθετα, μελετήθηκαν και υπολογίστηκαν η μόνιμη και η παλλόμενη ροή σε αξονικά συμμετρική 25% στένωση προκαλούμενη από συμβατική περίδεση, καθώς και η μόνιμη και παλλόμενη ροή σε μη συμμετρική 25% στένωση της πνευμονικής αρτηρίας όπως προκαλείται από το FloWatchTM, μέσω των πακέτων Fluent και Gambit. Η υπολογιστική μελέτη του πεδίου ροής περιλαμβάνει την κατανομή ταχυτήτων, τον προσδιορισμό των περιοχών ανακυκλοφορίας, την κατανομή των πιέσεων και την σύγκριση των παραπάνω μεγεθών με τα αντίστοιχα αποτελέσματα της βιβλιογραφίας. Τέλος, με βάση τα αποτελέσματα γίνεται η σύγκριση των δύο μελετούμενων μεθόδων περίδεσης. Αριθμητικά ρεαλιστικά δεδομένα ελήφθησαν από την καρδιοχειρουργική κλινική του νοσοκομείου Παίδων «Αγία Σοφία». / Cardiovascular diseases are the leading cause of death in developed countries. A stenosis in an artery , caused either by a disease such as an aneurism or by a banding (such as in congenital diseases) can change the characteristics of the blood flow very seriously. The study of the physiological pulsatile flow through a stenosis is very important for the diagnosis and treatment of the arterial diseases. The medical problem which is examined in this study is pulmonary artery stenosis caused by a banding. The banding takes place to reduce the high arterial pressure and finally the blood flow from the heart to the lungs. It is a surgical method used for treatment of congenital heart diseases. The pulmonary artery banding either with the use of the conventional method or the most modern with the use of the FloWatchTM technology causes stenosis of the artery. With the conventional method, stenosis can be considered axially symmetrical while with the use of FloWatchTM it is asymmetrical. It has been proven that both the axially symmetrical and asymmetrical banding cause fibrosis of the pulmonary artery walls of different degrees. The reconstruction of the pulmonary artery is milder where there is banding with FloWatchTM. This differentiation is based mainly on the fact that the conventional banding causes, for a specific decrease of the cross-section, a decrease in the perimeter of the cross-section higher than that of banding with FloWatchTM. In this assignment there is a report of different cases of flow in arterial stenosis, in congenital heart diseases and pulmonary banding techniques. In addition what was studied and appreciated was the steady and pulsatile flow in axially symmetrical 25% stenosis caused by the conventional banding, as well as the steady and pulsatile flow in asymmetrical 25% stenosis of pulmonary artery caused by FloWatchTM with the use of Fluent and Gambit. The numerical study of flow distribution includes velocity distribution, designation of back flow area, distribution of pressure and comparison of these quantities with the results in bibliography. Finally, based on the results, there is a comparison of the two banding methods under study. The numerical realistic data were received from the cardio-surgical clinic of children’s hospital “Aghia Sophia”.

Indiana University-Purdue University Indianapolis (IUPUI) / With the recent advancement of computation and imaging technology, Image-based computational fluid dynamics (ICFD) has emerged as a great non-invasive capability to study biomedical flows. These modern technologies increase the potential of computation-aided diagnostics and therapeutics in a patient-specific environment. I studied three components of this image-based computational fluid dynamics process in this work. To ensure accurate medical assessment, realistic computational analysis is needed, for which patient-specific image segmentation of the diseased vessel is of paramount importance. In this work, image segmentation of several human arteries, veins, capillaries, and organs was conducted to use them for further hemodynamic simulations. To accomplish these, several open-source and commercial software packages were implemented. This study incorporates a new computational platform, called InVascular, to quantify the 4D velocity field in image-based pulsatile flows using the Volumetric Lattice Boltzmann Method (VLBM). We also conducted several parametric studies on an idealized case of a 3-D pipe with the dimensions of a human renal artery. We investigated the relationship between stenosis severity and Resistive index (RI). We also explored how pulsatile parameters like heart rate or pulsatile pressure gradient affect RI. As the process of ICFD analysis is based on imaging and other hemodynamic data, it is often time-consuming due to the extensive data processing time. For clinicians to make fast medical decisions regarding their patients, we need rapid and accurate ICFD results. To achieve that, we also developed surrogate models to show the potential of supervised machine learning methods in constructing efficient and precise surrogate models for Hagen-Poiseuille and Womersley flows.

In the past decades, stricter legislation has been imposed to improve fuel economy and to reduce tail-end emissions of automotive vehicles worldwide. One of the important and effective technologies adopted by the automobile manufacturers to fulfill legislation requirements is the turbocharger technology. As unavoidable large temperature gradients exists in an automotive turbocharger, heat transfer is prominent. However, the effects of heat loss on the turbocharger turbine performance is unclear, i.e. there is no consensus about its effects among researchers. Therefore, the objective of the licentiate thesis is to investigate the effects of heat transfer on an automotive turbocharger radial turbine performance. Furthermore, the thesis also aims to quantify the heat transfer related losses in a turbocharger turbine. Both gas stand (continuous flow) and engine-like (pulsating flow) conditions are considered. By using Detached Eddy Simulation (DES), the flow field of the targeted turbocharger turbine is computed under adiabatic and non-adiabatic conditions. Energy balance and exergy concept are then applied to the simulations data to study the effects of heat loss on performance and to quantify the heat transfer related losses. The main findings of the licentiate thesis are 1) Pressure ratio drop in turbine is less sensitive to heat loss as compared with turbine power. Hence there is a risk of making wrong conclusions about the heat transfer effects on the turbine performance by just comparing the measured pressure ratio under adiabatic and non-adiabatic scenarios; 2) It is possible to quantify heat transfer related losses in a turbocharger turbine. This quantification allows understanding on how well the turbine system utilizes the available energy, and assisting identification of the system component that is sensitive to heat transfer; 3) Heat loss has insignificant effect on turbine power under the investigated engine-like pulsating flow condition; and 4) Even under unavoidable non-adiabatic conditions, much of the exergy discharged out to the environment and more effort could be done to recover the wasted exergy as useful turbine work in the current turbine system. The outcomes of the licentiate thesis naturally lead to the main focus of future work, i.e. exploring different exhaust valve strategies to minimize losses and to optimize flow exergy extraction as useful turbine work for better exhaust gas exergy utilization. / Under de senaste decennierna har allt strängare lagstiftning införts för att förbättra bränsleekonomin och minska avgasutsläppen från motorfordon världen över. En av de viktigaste och mest effektiva tekniker som införts av biltillverkarna för att kunna uppfylla lagkraven är turboladdartekniken. Eftersom stora temperaturgradienter existerar i en fordonsturboladdare, spelar värmeöverföring en framträdande roll. Emellertid är effekterna av värmeförluster på turboturbinprestanda oklar, dvs det finns ingen konsensus bland forskare om dess effekter. Syftet med denna licentiatavhandling är därför att undersöka effekterna av värmeöverföring på prestanda för radialturbinen i en fordonsturboladdare. Vidare syftar avhandlingen till att kvantifiera värmeöverföringsrelaterade förluster i en turboladdares turbin. Både fall med kontinuerligt gas flöde och motorliknande, pulserande flöde beaktas. Strömningsfältet i den utvalda turboladdarens turbin beräknas med en metod kallad Detached Eddy Simulation (DES) under adiabatiska och icke adiabatiska förhållanden. Energi- och exergibalanser för simuleringsresultaten analyseras sedan för att studera effekterna av värmeförluster på prestanda och kvantifiera värmeöverföringsrelaterade förluster. De viktigaste resultaten av licentiatuppsatsen är 1) Tryckförhållandet över turbinen är mindre känsligt för värmeförluster jämfört med turbineffekten. Därmed finns det en risk för att felaktiga slutsatser dras beträffande effekterna av värmeöverföring på turbinprestanda genom att enbart jämföra det uppmätta tryckförhållandet under adiabatiska och icke adiabatiska förhållanden; 2) Det är möjligt att kvantifiera värmeöverföringsrelaterade förluster i en turboladdares turbin. Denna kvantifiering ger förståelse för hur väl turbinsystemet utnyttjar den tillgängliga energin, och bistår med identifiering av systemkomponenter som är känsliga för värmeöverföring; 3) Värmeförluster har en obetydlig inverkan på turbineffekten för det undersökta motorliknande, pulserande flödesförhållandet; och 4) Under oundvikliga, icke-adiabatiska förhållanden, släpps även en stor del av exergin ut till omgivningen och det finns utrymme för förbättringar gällande exergiutnyttjandet i det aktuella turbinsystemet. Baserat på resultaten av licentiatavhandlingen kommer det fortsatta arbetet att fokusera på att utforska olika avgasventilstrategier för att minimera förluster och optimera omvandling av flödesexergi till användbart turbinarbete för bättre avgasexergiutnyttjande. / <p>QC 20161213</p> / KTH CCGEx HOTSIDE project

Les troubles cognitifs postopératoires sont fréquents après une chirurgie cardiaque, variant entre 26 % à 70 %. Bien que diverses hypothèses expliquent leur pathogenèse, la congestion veineuse représente une hypothèse prometteuse. Des études ont associé le délirium à des signes échographiques de congestion veineuse tels que la pulsatilité du Doppler de la veine porte et rénale. Détecter la congestion veineuse pourrait potentiellement prédire le trouble cognitif, facilitant ainsi sa gestion. Une technique prometteuse, mais peu explorée, est l’évaluation de la congestion veineuse par le Doppler de la veine fémorale. Les objectifs de ce mémoire sont : (1) synthétiser les évidences sur la relation entre le Doppler de la veine fémorale et la congestion veineuse chez les adultes ; et (2) caractériser l’existence d’une association entre les trouble cognitifs et le Doppler pulsatile de la veine fémorale après une chirurgie cardiaque. Afin d’atteindre ces objectifs, nous avons effectué une revue rapide de littérature portant sur la corrélation entre le Doppler de la veine fémorale et la congestion veineuse. De plus, nous avons complété une étude (NCT05038267) dont l’objectif secondaire était de déterminer la corrélation entre un Doppler anormal de la veine fémorale et le délirium. Les résultats ont montré une association entre la congestion veineuse et Doppler pulsatile de la veine fémorale, ainsi qu’entre les troubles cognitifs et le Doppler anormal de la veine fémorale. Toutefois, des études approfondies sont nécessaires. En conclusion, un lien entre le Doppler de la veine fémorale, la congestion veineuse, et les troubles cognitifs après une chirurgie cardiaque a été démontré. Ces observations ouvrent la voie à des recherches approfondies sur ce lien et à de potentielles applications cliniques et thérapeutiques. / Postoperative cognitive disorders are common after cardiac surgery, ranging from 26% to 70%. While various hypotheses explain their pathogenesis, venous congestion emerges as a promising hypothesis. Studies have linked delirium to ultrasound signs of venous congestion, such as pulsatility in the Doppler of the portal and renal veins. Detecting venous congestion could potentially predict cognitive disorders, thus facilitating their management. A promising yet underexplored technique is the assessment of venous congestion using the Doppler of the femoral vein. The objectives of this thesis are: (1) to synthesize evidence on the relationship between FV Doppler characteristics and venous congestion in adults; and (2) to characterize the existence of an association between cognitive disorders and pulsatility in femoral vein Doppler after cardiac surgery. To achieve these objectives, we conducted a rapid literature review focusing on the correlation between femoral vein Doppler and venous congestion. Additionally, we completed a study (NCT05038267) with the secondary objective of determining the correlation between abnormal femoral vein Doppler and delirium. The results showed an association between venous congestion and pulsatility in the FV Doppler, as well as between cognitive disorders and abnormal FV Doppler. However, in-depth studies are needed. In conclusion a connection has been demonstrated between femoral vein Doppler, venous congestion, and cognitive disorders after cardiac surgery. These findings open the way for in-depth research on this link and potential clinical and therapeutic applications.

Die vorliegende Untersuchung stellt sich die folgenden Fragen: Welchen Stand hat die Entwicklung von mechanischen Kreislaufunterstützungssystemen für Kinder, worin unterscheiden sich die eingesetzten Verfahren? Wie beeinflusst der Blutkontakt mit Fremdmaterial das Kapillarleck beim Kind? Welche Erfahrungen gibt es mit dem pulsatilen Ventrikelunterstützungssystem Berlin Heart beim Kind, welche Schwierigkeiten und Nebenwirkungen sind für das Kindesalter spezifisch? Wann profitieren Kinder von einer mechanischen Kreislaufunterstützung? Die bei Kindern am häufigsten eingesetzten Verfahren, Herzlungenmaschine (HLM), extrakorporale Membranoxygenierung (ECMO) und pneumatisch pulsatiles ventrikuläres Assist device (VAD) unterscheiden sich in Technik, Indikation, Nebenwirkung und möglicher Einsatzdauer erheblich. Die HLM dient der intraoperativen Kreislaufunterstützung. ECMO haben wir seit 1990 zur mittelfristigen Kreislaufunterstützung bei mehr als 70 Kindern für eine Dauer von ein bis zwei, selten bis zu drei Wochen eingesetzt. Mit VAD''s haben wir seit 1990 bei 56 Kindern die Herzfunktion teils monatelang ersetzt. Es bestehen multiple Unterschiede bei dem Einsatz von VAD zwischen Säuglingen, Kindern und Erwachsenen sowohl in der Indikation, Physiologie, Technik, Antikoagulation, der Familienbetreuung und hinsichtlich der Komplikationen. Bei jeder mechanischen Kreislaufunterstützung aktiviert der Fremdflächenkontakt des Blutes das Kontaktsystem, zu dem Gerinnungs- und Komplementsystem gehören. Klinische Äquivalente sind Thrombosen, Thrombozytenverlust und Kapillarleck. Insbesondere Säuglinge neigen zu diesen Komplikationen, weil das Verhältnis von Blutvolumen zu Fremdfläche ungünstig ist und der kontaktabhängige alternative Weg der Komplementaktivierung im jungen Alter vorherrscht. - Wir untersuchten prospektiv den prä- und postoperativen Verlauf von Kontakt- und Komplementsystem (C1q, C3, C4, C1-Inhibitor, Faktor B, Faktor XIIa) bei 11 herzoperierten Säuglingen ohne und 24 Säuglingen mit HLM. Es konnte nachgewiesen werden, dass obwohl bei allen Kindern eine Komplementaktivierung vorhanden war, diese signifikant ausgeprägter in der HLM-Gruppe stattfand. Die Kontaktaktivierung (Faktor XIIa, Präkallikrein) ließ sich nur in der HLM-Gruppe nachweisen, so dass belegt war, dass es nicht die Anästhesie oder die Operation an sich, sondern die HLM ist, die die inflammatorische Reaktion hervorruft. - Bei 27 mit HLM operierten Säuglingen untersuchten wir prospektiv die CLS-Entstehung und die Komplement- und Kontaktaktivierung. Bei den 10 Kindern, die im späteren Verlauf ein Kapillarlecksyndrom (CLS) entwickelten, waren bereits 30 Minuten nach HLM-Beginn die C1-INH-Konzentration und -Aktivität niedriger und Faktor XIIa, C3a und C5a höher als bei den 17 Kindern, die später kein CLS entwickelten. Die Aktivierung korrelierte mit dem Alter der Kinder und der HLM-Zeit, nicht mit der Tiefe der Hypothermie. - Retrospektiv untersuchten wir 28 Kinder (6 Tage - 16 Jahre alt), bei denen im terminalen Herzversagen nach Reanimation die Herzfunktion mit dem parakorporalen pneumatischen VAD Berlin Heart 1-98 Tage lang unterstützt wurde. Zwölf dieser Kinder wurden unter laufender Reanimation mit Herzdruckmassage in den Operationssaal gebracht. 13 Patienten erreichten eine Herztransplantation, 3 Kinder wurden mit dem eigenen Herzen vom System entwöhnt. 12 Kinder starben am System, Todesursachen waren Schock, Multiorganversagen, Sepsis und Blutungen. - Bei 95 herztransplantierten Kindern untersuchten wir retrospektiv die Verläufe in Abhängigkeit davon, ob die Kinder (I) vor der Transplantation in relativ stabilem Zustand zuhause waren (n=33), ob sie (II) kritisch krank hospitalisiert waren (n= 44), oder ob sie (III) nach Reanimation mit einem VAD kreislaufunterstützt wurden (n=18, Dauer 4-111 Tage). Die Überlebensraten nach 1Mo/1J/5J betrugen in Gruppe I 88/88/80 %, Gruppe II 88/82/79 %, Gruppe III 72/72/72 %. Der frühpostoperative Verlauf nach Transplantation war bei Gruppe III nur wenig komplizierter, was den Erfolg der Transplantation nicht minderte. - Retrospektiv untersuchten wir den Verlauf von 4 Kindern mit schwerer Myokarditis, die bei kardiogenem Schock mit biventrikulärem VAD kreislaufunterstützt wurden. Das schockbedingte Multiorganversagen und die Thrombozytopenie bildete sich während der Unterstützung mit dem VAD zurück. Drei Kinder konnten nach Erholung des Myokards vom VAD entwöhnt werden, eines wurde erfolgreich transplantiert. - Ausserdem untersuchten wir den Verlauf von 84 Kindern, die wegen Kardiomyopathie auf der Intensivstation behandelt wurden. Von den 69 (= 82 %), bei denen eine kreislaufstützende medikamentöse Therapie ausreichend war, konnten 32 herztransplantiert werden, 36 besserten sich und wurden nach Hause entlassen und ein Kind verstarb akut. Fünfzehn der 84 Kinder (= 18 %) ließen sich nicht stabilisieren und erhielten nach Reanimation eine mechanische Kreislaufunterstützung mit VAD (Dauer 1 – 98 Tage). Von diesen konnten 12 transplantiert werden. Die in dieser Habilitationsschrift ausgeführten Arbeiten haben weiterführende Fragestellungen und Grenzbereiche des mechanischen Kreislaufersatzes im Kindesalter aufgezeigt und neue Therapiestrategien dargestellt. Dadurch ist es möglich, die Überlebenschancen von Kindern mit terminalem Herzversagen erheblich zu verbessern. Sei es durch Zeitgewinn bis zur Erholung des Myokards oder zum Organangebot auf der HTx-Warteliste. Durch den Zeitgewinn, den die VAD`s den zur HTx gelisteten Kindern bieten, brauchen zur Transplantation freigegebene Kinderherzen seltener verworfen werden, mehr Kinder können überleben und die Ausnutzung der angebotenen Organe gelingt besser. / This scientific work addresses the following questions: what is the state of the art in mechanical circulatory support (MCS) in infants and children? How do the different techniques differ? How does mechanical circulatory support influence the systemic inflammatory response after cardiac surgery? What are the indications for use of the pneumatic pulsatile ventricular support system Berlin Heart in children and what do our experience and the results of its use show? The MCS systems most often used for children of all ages are cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), centrifugal pumps and the pneumatic pulsatile ventricular assist device (VAD). These systems vary in indications, results, side effects and potential supporting time. CPB is used to replace the circulation during cardiac surgery. ECMO has been used in our hospital since 1990 for circulatory support in cases of cardiac failure and of pulmonary failure and has been applied in more than 70 children over a period of 1 to 3 weeks. The VAD (Berlin Heart) has been used since 1990 in 56 children for long-term support, when the heart function had to be supported for up to several months. In VAD use there are multiple differences in indication, physiology, underlying disease, technique, anticoagulation and complications between infants, children and adults. In every case of MCS there is contact and complement activation as a reaction of the blood to foreign surfaces, resulting in capillary leak and activation of coagulation and anticoagulation systems with the risk of thrombosis or bleeding. In particular, young infants are prone to systemic inflammatory response in the form of capillary leak. In a prospective study we compared the complement activation after cardiac operations with or without CPB in 35 infants and measured serially the complement function and concentrations or activity of C1q, C3, C4, C1 esterase inhibitor, factor B, the activated split product C3a, prekallikrein and factor XIIa of the contact system. We found that complement activation occurs in all infants but is significantly higher in the group with CPB. Contact activation occurred only in patients who undergo CPB. Thus, the inflammatory response is caused by the use of a CPB circuit and to a lesser degree by surgical procedures and anesthesia. In 27 infants with CPB surgery we prospectively investigated the early clinical parameters that predict the development of capillary leak syndrome (CLS) and examined the relationship between CLS and complement and contact activation and C1 esterase inhibitor during and after bypass. We found that contact and complement activation occurs during CPB and contributes to CLS more frequently in infants of a younger age and with a prolonged bypass time. This activation and decrease in C1 esterase inhibitor was strongly expressed in the CLS group. Although MCS in intractable heart failure in children has normally been limited to centrifugal pumps and ECMO, we implanted 28 children with the pediatric sized pulsatile air-driven Berlin Heart VAD. Our aim was to keep the children alive and allow recovery from shock sequeale until later transplantation or myocardial recovery. Twelve children were brought to the operating room under cardiac massage. In total 12 children died on the system, but thirteen children were transplanted and three were sucessfully weaned from the system. Acute myocarditis appears to be a promising precondition for complete recovery during VAD support and in patients with cardiomyopathy support until transplantation is the goal for the future. We reviewed the course of 95 children who had undergone heart transplantation in our center to investigate whether previous VAD support has an impact on long-term outcome after transplantation. Three groups were compared and we found that bridging to transplantation with a pulsatile pneumatic VAD is a safe procedure in pediatric patients. After transplantation the overall survival rate is 86 % at 1 month, 82 % at 1 year and 75 % at 5 years. The survival of children previously supported with a VAD is similar to that of patients who were bridged with inotropes or who awaited heart transplantation electively. In 4 children with fulminant myocarditis and cardiogenic shock in whom all aggressive medical treatment failed we found that artificial replacement of the heart with complete unloading was followed by total recovery; 3 patients were successfully weaned from the device. No patient died and heart transplantation was necessary in only one child. Retrospectively we examined the course of 84 children who were treated at the ICU, presenting severe cardiac failure due to cardiomyopathy. In 15 of them medical treatment failed and the disease progressed so rapidly that they would have died during the waiting period before a suitable donor organ was found. After resuscitation these 15 children were supported with a VAD. Only 3 died during the waiting period and 12 (80%) underwent later heart transplantation. Progress has been rapid towards individualized choice of mechanical circulatory support systems for children of different ages and with different indications. With the Berlin Heart VAD prolonged circulatory support until myocardial recovery or until heart transplantation is effective in children and infants. It offers time to restore organ function, allows extubation, mobilization and neurological examination and increases the chances for successful transplantation. It can be used with low device-related morbidity and satisfactory results especially in the myocarditis and the cardiomyopathy groups. Complete recovery from secondary organ dysfunction should be achieved before heart transplantation is considered. We expect not only that children with end-stage heart failure will benefit from long-term VAD support, but also that fewer organs from young donors will be lost. Of particular importance is our experience with myocardial recovery in children with acute myocarditis in whom the devices could be explanted.

L’intervention de Fontan est une chirurgie palliative pour les cardiopathies congénitales univentriculaire. A long terme, la défaillance cardiaque, l’hypertension artérielle pulmonaire(HTAP) et l’entéropathie exsudative peuvent mener à l’échec tardif du Fontan.Une mise au point clinique a été realisée en se focalisant secondairement sur les patients adultes.L’intérêt de la cavo bipulmonaire (CBP), étape intermédiaire au Fontan, dans certains cas de retours veineux pulmonaires anormaux totaux a été décrite. Afin d’affiner de futures études cliniques, nous avons discuté de l’intérêt du Brain NatriureticPeptide en post opératoire de Fontan. Nous avons démontré la fiabilité d’une nouvelle technologiede l’oxyme´trie de pouls chez des enfants cyanosés et la non fiabilité d’un nouveau dispositifd’impédancemétrie pour le monitorage non invasif du de´bit cardiaque en comparaison avecun cathéter artériel pulmonaire.Un modèle animal viable et chronique de la CBP a été développé. Il a montré que le flux pulsatileantérograde empêche la formation de fistules artério-veineuses pulmonaires (FAVP), améliorel’hématose et atténue le développement de l’HTAP soutenant cliniquement le maintien de ce fluxlors de la création d’une CBP. Par ailleurs, la perte de pulsatilité, en diminuant le contrainte de cisaillement, entraîne unediminution de l’eNOS synthase et une réponse altérée vaso-relaxante dépendante de l'endothélium artérielle pulmonaire. La micropulsatilité limite ces effets délétères. Ces résultats impliquent desthérapies potentielles contre l’HTAP du Fontan, en maintenant un débit pulmonaire accessoire et la modulation pharmaceutique vaso-relaxante non endothélium-dépendante / The Fontan surgery is a palliative surgery for univentricular congenital heart disease. On the longterm, heart failure, pulmonary arterial hypertension (PAH) and exudative enteropathy may lead tothe Fontan failure.A clinical adjustment has been realized by focusing secondarily on adult patients. The advantage, insome cases of total anomalous pulmonary venous return, of the bidirectional cavopulmonary (BCP),which is an intermediate stage of Fontan, has been described.In order to prepare future clinical studies, we have discussed about Brain Natriuretic Peptide inpostoperative Fontan surgery. We have demonstrated the reliability of a new technology of pulseoxymetry in cyanotic children and the unreliability of a new device of impedance for non-invasivemonitoring of cardiac outpout in comparison with pulmonary arterial catheter.A viable chronic animal model of bidirectional cavo-pulmonary (BCP) has been developed. Itshowed that the antegrade pulsatile flow prevents the formation of pulmonary arteriovenous fistulas(PAVMs) ,improves hematosis and attenuates the development of PAH clinically supporting themaintenance of this flow when creating a BCP.Moreover, the loss of pulsatility while reducing the shear stress causes a decrease in e-NOSsynthase and a dependent vaso-relaxing altered response of the pulmonary arterial endothelium. Themicropulsatility limits these deleterious effects. These results imply potential therapies against thePAH of Fontan surgery, maintaining an accessory pulmonary blood flow and the pharmaceuticalvaso-relaxing non-endothelium dependent modulation.