This research paper highlights the significance of mock circulatory loops in aiding the development and testing of left ventricle assist devices (LVADs). Heart disease is the leading cause of death in America, and LVAD offers an effective solution to patients with severe coronary artery disease who are not eligible for heart transplants. However, before testing LVADs in-vivo, extensive performance and reliability testing is required as per Food and Drug Administration guidelines. Mock circulatory loops are useful for simulating the cardiac cycle and capturing pressure and flow meter readings. The research focused on developing and testing a mock circulatory loop that accurately captures pressure and flow meter readings. The team experimented with various silicone elastomers and a urethane-based material, ClearFlex 30, to create a transparent phantom. The report highlights the importance of surface roughness for optical clarity, with an average surface roughness of 0.186 μ being ideal for optimal clarity achieved with 800-grit sandpaper. The impact of pressure differences between the aortic and mitral inlet/outlets was also studied, and it was found that the loop's resistance can be modified to achieve elevated pressure in the aortic outlet. The report further emphasized the importance of refractive index matching to perform particle image velocity. Matching the refractive index of the phantom with the medium is critical to avoid distortion and refraction of the light. Glycerol water was found to be an effective medium for refractive index matching. Overall, the successful testing of the mock circulatory loop provides valuable insights into the flow structure within the heart, aiding in the development of future LVADs. This research is significant in advancing the cardiology field and will potentially benefit many patients suffering from heart disease. / Master of Science / This research paper focuses on developing and testing left ventricle assist devices (LVADs) using a mock circulatory loop tool. Heart disease is a leading cause of death in America, and LVADs provide an effective solution for patients with severe coronary artery disease who are not eligible for heart transplants. However, before testing LVADs on humans, extensive performance and reliability testing is required as per Food and Drug Administration guidelines. Mock circulatory loops are a tool that helps simulate the cardiac cycle and capture pressure and flow meter readings. The researchers developed and tested a mock circulatory loop that could accurately capture pressure and flow meter readings. They used various materials to create a transparent phantom that allowed them to see inside the loop. The researchers found that the surface roughness of the phantom was important for optical clarity, and they achieved optimal clarity using 800-grit sandpaper. They also studied the impact of pressure differences between the aortic and mitral inlet/outlets. They found that the loop's resistance can be modified to achieve elevated pressure in the aortic outlet. To study the flow structure within the heart, the researchers used a technique called particle image velocity. They emphasized the importance of refractive index matching, which helps avoid distortion and refraction of light. The researchers found that glycerol water was an effective medium for refractive index matching. Overall, the successful testing of the mock circulatory loop provides valuable insights into the flow structure within the heart, aiding in the development of future LVADs. This research has significant implications for advancing the cardiology field and potentially benefitting many patients suffering from heart disease.

Congestive heart failure (CHF) is a debilitating condition that afflicts 4.8 million Americans with an increasing incidence. Each year, there are an estimated 400,000 new cases. The incidence is on the rise as the age of the population is increasing and because most people are surviving their first heart attack. Pharmacological therapies are improving, yet many patients still reach end-stage heart failure and there are too few donor hearts available. This thesis is presented as a first small step in a long process in the design and development of a novel cardiac assist device that would ultimately heal a diseased heart by the process of ventricular recovery. The device acts to restore the kinematics of a diseased heart by modulating the extra ventricular displacements. The first surgery / trial were conducted on a bovine at the Veterinary School at Texas A&M University. Main objectives of the surgery were to test the method of attachment of the device and power requirements of the device. Details regarding the design and construction of the device have been presented in the thesis.

This thesis project examined the interactive fluid dynamics between a blood pump and the univentricular Fontan circulation. 2-D particle image velocimetry (PIV) measurements were conducted on an idealized total cavopulmonary connection (TCPC) with an axial pump prototype in the inferior vena cava (IVC). Fluid velocity profiles were examined under various physiologic conditions for Fontan patients. The velocity profiles for all cases demonstrated the shunting of flow from the IVC toward the right pulmonary artery. A rotational component in the pump outflow was observed forcing flow to the periphery as compared to the flow profile without a pump present in the IVC. The inclusion of the pump provides a pressure rise of 3 to 9 mmHg. These results demonstrate the ability of the intravascular blood pump to support a Fontan circulation and support the continued optimization and development of the pump.

Este trabalho apresenta a implementação de um sistema de velocimetria de imagens de partícula (VIP) para estudo do escoamento do sangue em um dispositivo de assistência ventricular para uso pediátrico (DAVP). O sistema VIP implementado é constituído por uma fonte de iluminação composta por um par de lasers de Nd:YAG (pulso de aproximadamente 18mJ de energia e duração de 5ns), um sistema óptico contendo duas lentes convergentes, uma câmera CCD e uma câmara para visualização. O DAVP estudado foi construído em acrílico transparente e é constituído de uma câmara de sangue e uma câmara pneumática, divididas por uma membrana flexível. A câmara sanguínea possui dois orifícios dotados de válvulas de tecido biológico para a entrada e saída de sangue. A câmara pneumática é conectada a um gerador de pulsos de pressão positiva. O fluido foi semeado com esferas de poliestireno (10 \"mu\" de diâmetro). Foram determinadas as distribuições de velocidades instantâneas nas freqüências de batimento de 80, 100 e 120 bpm em três campos (65 mm x 65mm) da câmara paralelos à membrana e um campo situado no canal de entrada do DAVP, usando correlação cruzada com base na transformada rápida de Fourier. Um gerador de pulsos foi utilizado para sincronizar a detecção das imagens pelo sistema VIP com as fases de interesse no ciclo de bombeamento. Na freqüência de batimentos de 80 bpm as velocidades máximas foram de 1,94 m/s no canal de entrada durante o período de enchimento e 1,66 m/s nas regiões próximas à membrana durante o período de ejeção. Em 100 bpm, as velocidades máximas foram de 1,68 m/s no canal de entrada e 1,15 m/s nas regiões próximas a membrana. As distribuições de velocidades instantâneas mostram a ocorrência de pequenos vórtices, principalmente durante a fase de enchimento. Estes vórtices apresentam grande variabilidade ciclo-a-ciclo produzindo turbulências no fluxo e tensões de Reynolds elevadas. No ciclo a 80 bpm, ) parte da energia cinética turbulenta é dissipada devido à desaceleração do fluxo na câmara sanguínea antes do inicio da fase de ejeção. Isto ocorre para as freqüências de 100 e 120 bpm. A máxima tensão de Reynolds foi observada no canal de entrada do DAVP no valor de 222 N/m2 durante o enchimento, persistindo por 25 ms. No plano da membrana a maior tensão encontrada foi igual a 250 N/m2 durante o enchimento, persistindo por 25 ms. O campo de velocidades media contém vórtices permanentes durante a fase de enchimento que influenciam significativamente o fluxo na câmara e cujo numero aumenta com a freqüência de batimentos, provocando aumento de turbulências. Estes resultados indicam que existe maior possibilidade de ocorrer o processo de hemólise durante o enchimento do que durante a ejeção. Vetores com baixas velocidades foram observados na região compreendida entre os canais de entrada e saída do fluxo na câmara sanguínea no período de ejeção, sugerindo a possibilidade de ocorrer à formação de trombos nesta. / --

The objectives of the present body of work were 1) to evaluate the Personal Lift-Assist Device (PLAD) in terms of its effect on lifting technique, interjoint coordination, and whether sex modulates these effects and 2) to explore the use of principal component analysis (PCA) as a method to investigate lifting waveforms. Thirty participants (15M, 15F) completed a freestyle, symmetrical lifting protocol during which three-dimensional kinematics of the ankle, knee, hip, and lumbar and thoracic spine were collected using a two-camera Optotrak 3020 system. There were four testing conditions: a) with and b) without wearing the PLAD; and c) 0% load and d) 10% of maximum back strength load. All data were evaluated using PCA. In the first analysis, the relationship between the PLAD and lifting technique under a loaded condition was explored. Results showed that 8 PCs were significantly different between the PLAD/No PLAD conditions yet there were no significant effects of sex on any of the PCs. It was concluded that wearing the PLAD encourages a lifting technique that is reflective of a squat lift, independent of sex. In the second analysis, the PLAD’s effect on interjoint coordination patterns under both loaded and unloaded conditions was examined using the relative phase angle (RPA). It was found that there were no significant differences between device, sex, or load conditions on any of the PCs retained in the model. A novel approach to enhance interpretability of PCs was developed during this study. Finally, when the PLAD was not worn, male and female differences were further investigated under loaded and unloaded conditions. It was determined that when the load is individualized to personal strength characteristics, sex differences in lifting technique are negligible. This is a contradictory finding from previous research. Overall, the major contributions of this research are: support for the use of the PLAD in industry; the recommendation that load be selected based on individual strength characteristics for lifting research experimental design; the use of PCA as a method to effectively evaluate lifting waveforms; and the development of a novel approach to aid in the interpretation of principal components. / Thesis (Master, Kinesiology & Health Studies) -- Queen's University, 2010-08-18 09:35:19.142

Implantation of a left ventricular assist device (LVAD) is a potential treatment in terminal heart failure. Right ventricular (RV) failure is a severe complication in these patients and sometimes requires additional placement of a right ventricular assist device (RVAD). RVAD implantation, however, is an invasive treatment associated with both increased mortality and morbidity. The aim of this thesis was to study whether partial volume exclusion of the RV through a modified Glenn shunt or cavoaortic shunt could treat severe RV failure. The ultimate goal would be to use it as an alternative to a RVAD in RV failure during LVAD therapy. Swine were used as the model animal in all studies. In Study I, experimental RV failure was induced by ischemia, and verified by hemodynamic measurements and genetic expression. Treatment with a modified Glenn shunt reduced venous stasis and improved hemodynamics in general. In Study II, experimental RV failure was induced by the same method as in Study I. Treatment with a cavoaortic shunt in addition to LVAD therapy proved to reduce venous stasis and improved hemodynamics in general, which was feasible with preserved oxygen delivery despite cyanotic shunting. In Study III, experimental RV failure was induced by pulmonary banding, and verified by hemodynamic measurements and genetic expression. Treatment with a modified Glenn shunt reduced venous stasis but did not improve hemodynamics in general compared with a control group. In Study IV, the effects of LVAD therapy and subsequent treatment with a modified Glenn shunt on the normal RV function were studied. It demonstrated that LVAD therapy can put strain on the RV by increasing stroke work and end-diastolic volume, and that these effects can be reversed by treatment with a modified Glenn shunt during LVAD therapy. In conclusion, partial volume exclusion through a modified Glenn shunt or cavoaortic shunt is a feasible treatment of experimental RV failure. Thus, it could potentially be used as an alternative treatment to a RVAD in severe RV failure during LVAD therapy.

At an annual cost of over thirty billion dollars annually, the diagnosis and management of heart failure is one of the most significant public health concerns of the twenty first century, as nearly twenty percent of Americans will develop some form of heart failure in their lifetime. The incidence of newly diagnosed heart failure has remained stable over the last several years at approximately 650,000 diagnoses per year; however, due to several contributing factors the prevalence has continued to rise despite substantial advancements in interventional therapies. The three most significant contributing factors to the rising heart failure prevalence have been identified as 1) significant advancements in technology and medical intervention have dramatically improved the survival rate of those experiencing acute coronary events. This has resulted in a greater number of patients who then progress to chronic heart failure. 2) The management of those with chronic heart failure has been dramatically improved which has allowed those with the disease to live longer and 3) heart failure is in large part a disease associated with advancing age. As the population in the United States and other developed countries continue to grow, such a strong association will inevitably result in a rapidly increasing prevalence. Current clinically therapies for managing heart failure can be categorized into three major groups: pharmaceutical therapy, mechanical circulatory support, or cell-based therapy. Pharmaceutical therapies are used in the earlier stages of disease progression or to manage symptoms and comorbidities of later stage heart failure. Mechanical circulatory support is often implemented when the disease progresses to a more severe state, where volume and / or pressure overload of the ventricles is present. Many modalities of mechanical circulatory support serve as a bridge to transplant, as the only long-term treatment of advanced decompensated heart failure is cardiac transplantation. The third category of treatments for HF is cell-based or stem cell therapies. These therapies are still in their infancies but hold significant potential of cardiac regeneration and reversal of the pathologic remodeling associated with heart failure. While the management of the early stages of heart failure have improves, addressing end-stage failure remains a significant obstacle in resolving the U.S. of the heart failure epidemic. The use of ventricular assist devices (VADs) has improved the management of end-stage failure over the last few decades, but VADs serve mostly as a bridge to transplant, so eventually a donor organ and cardiac transplantation is required. As the population continues to grow, the number of patients in need of a donor heart will increase, leading to an even larger discrepancy between the number of donor organs available and those in severe need. While advancements in VAD technology have reduced potential complications and increased the duration and effectiveness of the mechanical circulatory support, a long-term permanent treatment is still very much in need. Cell-based cardiac therapy or cardiac stem cell therapy holds the greatest potential to solving this age-old problem. The ability to not only regenerate dead or damaged tissue in the heart but also reverse pathologic remodeling due to heart failure could cure millions of patients of heart failure, returning them to a healthy, fully functioning state. The last decade has shed much light on the potential of stem cell therapies, but also has illuminated significant barriers to creating a clinically acceptable treatment. While these barriers seem tall, it is crucial that much time and resources be invested into stem cell therapies for cardiac applications as they hold the greatest potential to being able to effectively treat, rather than manage, those with heart failure. In addition to regenerating dead of damaged myocardium, stem cell technology has the potential to grow an entire organ that is patient specific in its origin, and would fully alleviate having to wait for an available donor organ. The ability to grow an entire organ in the lab, which can later be transplanted, would forever change the way medicine is practiced, while saving millions if not billions of lives worldwide.

Este trabalho apresenta a implementação de um sistema de velocimetria de imagens de partícula (VIP) para estudo do escoamento do sangue em um dispositivo de assistência ventricular para uso pediátrico (DAVP). O sistema VIP implementado é constituído por uma fonte de iluminação composta por um par de lasers de Nd:YAG (pulso de aproximadamente 18mJ de energia e duração de 5ns), um sistema óptico contendo duas lentes convergentes, uma câmera CCD e uma câmara para visualização. O DAVP estudado foi construído em acrílico transparente e é constituído de uma câmara de sangue e uma câmara pneumática, divididas por uma membrana flexível. A câmara sanguínea possui dois orifícios dotados de válvulas de tecido biológico para a entrada e saída de sangue. A câmara pneumática é conectada a um gerador de pulsos de pressão positiva. O fluido foi semeado com esferas de poliestireno (10 \"mu\" de diâmetro). Foram determinadas as distribuições de velocidades instantâneas nas freqüências de batimento de 80, 100 e 120 bpm em três campos (65 mm x 65mm) da câmara paralelos à membrana e um campo situado no canal de entrada do DAVP, usando correlação cruzada com base na transformada rápida de Fourier. Um gerador de pulsos foi utilizado para sincronizar a detecção das imagens pelo sistema VIP com as fases de interesse no ciclo de bombeamento. Na freqüência de batimentos de 80 bpm as velocidades máximas foram de 1,94 m/s no canal de entrada durante o período de enchimento e 1,66 m/s nas regiões próximas à membrana durante o período de ejeção. Em 100 bpm, as velocidades máximas foram de 1,68 m/s no canal de entrada e 1,15 m/s nas regiões próximas a membrana. As distribuições de velocidades instantâneas mostram a ocorrência de pequenos vórtices, principalmente durante a fase de enchimento. Estes vórtices apresentam grande variabilidade ciclo-a-ciclo produzindo turbulências no fluxo e tensões de Reynolds elevadas. No ciclo a 80 bpm, ) parte da energia cinética turbulenta é dissipada devido à desaceleração do fluxo na câmara sanguínea antes do inicio da fase de ejeção. Isto ocorre para as freqüências de 100 e 120 bpm. A máxima tensão de Reynolds foi observada no canal de entrada do DAVP no valor de 222 N/m2 durante o enchimento, persistindo por 25 ms. No plano da membrana a maior tensão encontrada foi igual a 250 N/m2 durante o enchimento, persistindo por 25 ms. O campo de velocidades media contém vórtices permanentes durante a fase de enchimento que influenciam significativamente o fluxo na câmara e cujo numero aumenta com a freqüência de batimentos, provocando aumento de turbulências. Estes resultados indicam que existe maior possibilidade de ocorrer o processo de hemólise durante o enchimento do que durante a ejeção. Vetores com baixas velocidades foram observados na região compreendida entre os canais de entrada e saída do fluxo na câmara sanguínea no período de ejeção, sugerindo a possibilidade de ocorrer à formação de trombos nesta. / --

Preterm infants are at risk for respiratory distress syndrome (RDS) due to immature lungs, leading to notable neonatal mortality. About 10% of US births are premature. While mechanical ventilation is a common RDS treatment, it can cause complications. If it fails, extracorporeal membrane oxygenation (ECMO) is employed, but standard ECMO devices are not suited for preterm babies. The limitations of hollow fiber membrane oxygenators used in ECMO have spurred interest in an artificial placenta that connects to the umbilical cord and supports lung growth. Microfluidic blood oxygenators, with their biomimetic designs, have being explored for this purpose. This thesis advances microfabrication techniques for Lung Assist Devices (LADs), focusing on two main objectives: I. Improving Throughput for Elevated Blood Flow Rates: This section delves into refining Microfluidic Blood Oxygenators (MBOs) to accommodate greater blood flow rates. By combining parallel units, we increased throughput and optimized LAD designs. Newly designed MBOs, with an expanded gas exchange surface area, can manage blood flow rates up to 60 mL/min. Using these enhanced MBOs, we constructed a novel LAD achieving superior oxygenation compared to predecessors. Our in vitro tests confirmed that this LAD can sustain blood flow rates of up to 150 ml/min, elevating oxygen saturation by approximately 20%—equivalent to an oxygen transfer of 7.48 mL/min, a leading figure for AP-type devices. II. Hierarchically Designed Microchannels: The second objective revolves around developing microchannels with a hierarchical layout to mitigate stagnation and high shear stress regions. Traditional photolithography poses challenges at channel intersections, inducing clotting risks. We pioneered alternative microfabrication methods, yielding diverse microchannels and intricate hierarchical designs that emulate natural vascular networks devoid of dead zones. These advancements have propelled the microfabrication domain for artificial placenta-like LADs. Utilizing our method, we produced channels varying from hundreds to a few microns in height with a single exposure and an opal diffuser. Thin membranes (~60 µm top and ~45 µm bottom) were amalgamated, culminating in a total depth of about 200 µm. Such oxygenators excel in oxygenating blood even at intense flow rates of up to 15 mL/min per unit. Leveraging these hierarchically designed MBOs, we crafted a LAD supporting a flow rate of 100 mL/min, offering an oxygen transfer of 5.21 mL/min. Both LADs developed in this research proficiently support premature neonates weighing up to 2 kg. Notably, the priming volume of the LAD using the enhanced MBOs has been substantially minimized, underscoring its advancements over earlier models. Realizing these objectives can transform neonatal care, addressing respiratory challenges in premature neonates and bolstering their chances for a healthier life. / Thesis / Master of Science (MSc)

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.