Ziel dieser Arbeit war es, neue Therapieprinzipien zu entwickeln und zu überprüfen, ob diese geeignet sind, ein Rechtsherzversagen nach Implantation eines LVAD bei Patienten mit terminaler Herzinsuffizienz zu verhindern. Bei Patienten mit chronischem Linksherzversagen erhöht sich der pulmonalvaskuläre Widerstand. Als Ursache wird eine Dysregulation des pulmonalen Gefäßendothels verstanden, die mit einer gestörten Freisetzung von NO und einer erhöhten Expression von Endothelin einhergeht und die bei längerem Bestehen auch strukturelle Veränderungen der Lungenstrombahn nach sich zieht. Bei Patienten mit chronischem Linksherzversagen führt dies zu einer sekundären pulmonalen Hypertonie, die direkt die rechtsventrikuläre Funktion beeinträchtigt und durch eine Vasodilatantientherapie zunächst noch reversibel ist. Nach LVAD-Implantation bei terminaler Herzinsuffizienz steigt häufig der pulmonalvaskuläre Widerstand unter anderem infolge der extrakorporalen Zirkulation weiter an, so daß bei vielen Patienten ein Rechtsherzversagen aufgund der sekundären pulmonalen Hypertonie mit hoher Morbidität und Mortalität auftritt. Weder positiv inotrope Pharmaka noch systemische Vasodilatantien oder gar die sekundäre Implantation eines RVAD konnten das Problem bisher lösen. Einen völlig neuen Therapieansatz stellt die inhalative Verabreichung von NO dar, welches durch die direkte Wirkung auf die glatte Gefäßmuskulatur eine selektive Vasodilatation in der pulmonalen Zirkulation bewirkt und somit konsekutiv die rechtsventrikuläre Nachlast senkt, ohne dabei den systemischen Widerstand zu beeinflussen. Zunächst wurden die klinischen Effekte einer inhalativen NO-Therapie bei Patienten untersucht, die nach Implantation eines LVAD aufgrund einer rechtsventrikulären Dysfunktion bei sekundärer pulmonaler Hypertonie ein postoperatives low-cardiac-output-Syndrom entwickelt hatten. Im ersten Teil der Untersuchungen konnte gezeigt werden, daß die ausgeprägtesten hämodynamischen Wirkungen bei einer individuellen NO-Dosis zwischen 25 und 40 ppm NO erreicht werden. Bis zu 40 ppm nahmen der pulmonalvaskuläre Widerstand und der pulmonalarterielle Mitteldruck progredient ab, während der Cardiac Index dosisabhängig signifikant stieg, ohne daß dabei eine Änderung der systemischen Druck- und Widerstandsverhältnisse zu bemerken war. Die pulmonalvaskuläre Selektivität der inhaltiven NO-Therapie sowie die teils dramatische hämodynamische Verbesserung waren somit bestätigt. Auch unter Dauerapplikation der jeweils individuell ausgetesteten optimalen NO-Dosierung zeigte sich über den gesamten Behandlungszeitraum die oben beschriebene signifikante hämodynamische Verbesserung mit Abnahme der rechtsventrikulären Nachlast bei gleichzeitiger Zunahme des Cardiac Index. Zusätzlich wurde mittels TEE ein stetiger Anstieg der RVEF und ein Abfall des RVEDV dokumentiert. Somit konnte bei den Patienten unter NO-Therapie zunächst die Katecholamingabe deutlich reduziert und die NO-Behandlung ausgeschlichen werden. Im Verlauf der Therapie kam es weder durch eine abrupte Unterbrechung der NO-Zufuhr bei täglich durchgeführten NO-Auslassversuchen noch bei Beendigung der Therapie zu einer hämodynamischen Verschlechterung, was indirekt die Erholung des rechten Ventrikels belegt. Trotz der insgesamt eindrucksvollen hämodynamischen Verbesserung unter Beatmung mit NO gab es einige Patienten, bei denen trotz hochdosierter Katecholamintherapie und adäquatem Volumenersatz die rechtsventrikuläre Dysfunktion persistierte. Dies wurde darauf zurückgeführt, daß durch Zunahme des Cardiac Index und somit des venösen Rückstromes nach LVAD-Implantation eine Erholung der Rechtsherzfunktion nicht möglich war. Um die Erholung der Rechtsherzfunktion über eine Minimierung der rechtsventrikulären Schlagarbeit zu ermöglichen, wurde ein zu sämtlichen anderen Therapiestrategien kontroverses Konzept entwickelt, das sowohl der rechtsventrikulären Vorlast und Nachlast als auch der inotropen Therapie Rechnung trägt. Statt wie bisher einen hohen Cardiac Index anzustreben wurde jetzt untersucht, ob nicht bei einem postoperativ recht niedrigen Cardiac Index von 2.5 L/min/m2 (( 2.3 L/min/m2 und ( 2.8 L/min/m2) mit daraus folgender Verminderung der Schlagarbeit eine Erholung des rechten Ventrikel möglich ist, ohne dabei jedoch die Organperfusion zu gefährden. Dies beinhaltete neben einer frühzeitig eingeleiteten NO-Beatmung eine minimale Katecholamintherapie und einen restriktiven Volumenersatz. Deshalb wurde mit der NO-Beatmung bereits intraoperativ bei Abgang vom kardiopulmonalen Bypass begonnen. Ein Cardiac Index von circa2.5 L/min/m2 erwies sich bei den analgosedierten und beatmeten Patienten für eine adäquate Organperfusion als ausreichend und zeigte sich darüber hinaus als geeignet, ein Rechtsherzversagen zu verhindern und eine Restitution der rechtsventrikulären Funktion sicherzustellen. Die inhalative NO-Therapie wurde auch hier bei allen Patienten ohne Auftreten eines Rebound-Phänomen beendet. Bekannt ist, daß Endothelin-1 als potenter endogener Vasokonstriktor (Produktion als auch Elimination hauptsächlich in der Lunge) eine pulmonale Hypertonie auslösen kann und damit als Antagonist zum wichtigsten endothelialen Mediator der pulmonalen Vasodilatation, dem NO, betrachtet wird. Zur Klärung weiterer pathophysiologischer Grundlagen wurden die Plasmaspiegel von ET-1 und Big ET-1 unter NO-Therapie nach LVAD-Implantation gemessen. Die präoperativen ET-1- und Big ET-1-Plasmaspiegel waren, wie bei terminaler Herzinsuffizienz zu erwarten, deutlich erhöht und korrelierten mit dem pulmonalvaskulären Widerstand. Dass die höchsten Plasmakonzentrationen von ET-1 intraoperativ gemessen wurden steht in Einklang mit anderen Untersuchungen und wurde mit einer durch den kardiopulmonalen Bypass ausgelösten endothelialen Dysfunktion erklärt. Unter inhalativer NO-Therapie fielen die Plasmaspiegel von ET-1 und Big ET-1 signifikant ab und waren nach Beendigung der Therapie am niedrigsten. Es bestand eine signifikante, inverse Korrelation zwischen der mittleren inhalativen NO-Dosis und den Plasmaspiegeln von ET-1 und Big ET-1. Simultan mit dem Abfall der Plasmaspiegel der Endotheline verbesserte sich die Hämodynamik. Der Abfall des pulmonalarteriellen Druckes korrelierte mit dem Abfall der ET-1-Plasmaspiegel. Die Ergebnisse lassen darauf schließen, daß eine inhalative NO-Therapie, welche die bei sekundärer pulmonaler Hypertonie pathophysiologisch defiziente endogene NO-Produktion ausgleicht, neben einer pulmonalselektiven Vasodilatation auch zu einer NO-vermittelten Inhibition der Endotheline ET-1 und Big-ET-1 führt. Da auch die Linksherzinsuffizienz durch die mechanische Entlastung mit einem LVAD suffizient behandelt ist, kann sich erneut ein physiologisches Gleichgewicht zwischen den Antagonisten NO und Endothelin in der Lungenstrombahn einstellen, das eine Dysfunktion des pulmonalen Gefäßendothels behebt. Dies erklärt, dass eine NO-Beatmung nur vorübergehend erforderlich ist und nach Beendigung der NO-Inhalation ein Rebound-Phänomen mit Wiederanstieg des pulmonalvaskulären Widerstands und konsekutiver Rechtsherzbelastung ausbleibt. Zur Unterstützung der rechtsventrikulären Funktion nach Implantation eines LVAD wurden folgende Therapieprinzipien etabliert: - Eine inhalative NO-Therapie sollte frühzeitig bereits zum Abgang vom kardiopulmonalen Bypass eingesetzt werden. - Eine intraindividuelle Dosistitration von NO ist sinnvoll um einen optimalen Behandlungseffekt mit der geringst möglichen Dosis zu erzielen. - Die inhalative NO-Therapie senkt selektiv den pulmonalvaskulären Widerstand und verursacht keine systemische Hypotension. Die rechtsventrikuläre Nachlast fällt ab, ohne dass die linksventrikulären Füllungsdrucke pathologisch ansteigen, da der linke Ventrikel durch das LVAD entlastet ist. - Tritt trotz NO-Beatmung eine rechtsventrikuläre Dysfunktion auf, so ist zur weiteren Entlastung des rechten Ventrikels ein niedriger Cardiac Index von circa 2.5 L/min/m2 angezeigt, um den venösen Rückstrom gering zu halten. - Dies ist durch eine minimale Katecholamintherapie und einen restriktiven Volumenersatz zu erzielen. Die Reduktion der rechtsventrikulären Schlagarbeit erlaubt eine Erholung der rechtsventrikulären Funktion. - Die ET-1- und Big-ET-1-Plasmaspiegel fallen um so rascher ab, je langsamer die NO-Dosis reduziert wird, da zwischen den Plasmaspiegeln der Endotheline und der mittleren inhalativen NO-Dosis eine inverse Korrelation gefunden wurde. Daher ist eine schrittweise Entwöhnung der inhalativen NO-Therapie erforderlich, um ein Rebound-Phänomen zu verhindern. - NO-Auslaßversuche sind geeignet, um in kritischen Fällen die Abhängigkeit von einer NO-Beatmung in der Entwöhnungsphase zu überprüfen. - Da eine Dysfunktion des pulmonalen Gefäßendothels nach Beendigung der inhalativen NO-Therapie offensichtlich nicht mehr fortbesteht, ist im weiteren klinischen Verlauf in der Regel nicht mit einer erneuten Rechtsherzbelastung durch einen Anstieg des pulmonalvaskulären Widerstands zu rechnen. / This thesis aimed to develop and evaluate new therapeutic principles to prevent right ventricular failure following LVAD implantation in patients with end-stage heart failure. Pulmonary vascular resistance increases in patients with chronic left ventricular failure. The mechanism is thought to be a dysregulation of the pulmonary vascular endothelium with an impaired release of NO and increased expression of endothelin, which in the long term leads to structural changes in the pulmonary circulation. In patients with chronic left ventricular failure this causes secondary pulmonary hypertension, directly compromising right ventricular function, but initially this is not fixed and is still reversible by vasodilator therapy. Following LVAD implantation in end-stage heart failure, pulmonary vascular resistance may further increase, partially due to cardiopulmonary bypass, and many patients develop frank right ventricular failure due to aggravation of secondary pulmonary hypertension, which is associated with a high morbidity and mortality. Neither positive inotropic drugs nor systemic vasodilators or even the secondary implantation of a RVAD were able to solve the problem. A novel therapeutic approach is the administration of inhaled NO, which directly acts on vascular smooth muscle cells causing selective pulmonary vasodilation and therefore decreases right ventricular afterload without altering systemic vascular resistance. The clinical effects of NO inhalation therapy were first studied in patients presenting with postoperative low cardiac output syndrome after LVAD implantation due to secondary pulmonary hypertension and right ventricular dysfunction. In this first study the greatest hemodynamic effects were demonstrated at individually titrated doses of 25 to 40 ppm NO. The pulmonary vascular resistance and the mean pulmonary artery pressure progressively decreased with increasing doses up to 40 ppm NO, as the cardiac index significantly increased dependent on dosage and without any noticeable change of the systemic arterial pressure or systemic vascular resistance. Thus a selective pulmonary vasodilating effect of inhaled nitric oxide along with a hemodynamic improvement, which in some patients was dramatic, was demonstrated. During continuous administration with the individually titrated optimal dose significant beneficial effects were shown during the entire treatment period with a decrease of the right ventricular afterload and a consequent increase of the cardiac index. In addition, a steady increase of the RVEF and a decrease of the RVEDV were demonstrated by TEE. This permitted us to first lower the catecholamine dose in these patients and then to wean them of the NO therapy. In the course of NO therapy hemodynamic deterioration was provoked neither by acute interruption of NO administration at daily performed "NO-off-trials", nor after weaning of NO therapy, which indirectly proved regeneration of the right ventricle. Although an overall impressive hemodynamic improvement was demonstrated with NO inhalation there were some patients in whom right ventricular dysfunction persisted despite maximal inotropic support and adequate volume replacement. This was thought to be due to the increase in cardiac index and thereby venous return after LVAD implantation preventing restoration of right ventricular function. To permit improvement of right ventricular function by minimizing right ventricular stroke work, a comprehensive concept contradictory to all other treatment strategies was developed, taking right ventricular preload, afterload and inotropic therapy into account. Instead of the intention being to generate a high cardiac index, it was studied whether a relatively low postoperative cardiac index of 2.5 L/min/m2 (= 2.3 L/min/m2 and = 2.8 L/min/m2) which decreases stroke work, enables the right ventricle to regenerate without compromising perfusion to vital organs. This meant early administration of inhaled NO, minimal catecholamine support and restrictive volume replacement. NO inhalation was initiated intraoperatively as soon as weaning from cardiopulmonary bypass had taken place. A cardiac index of 2.5 L/min/m2 proved to be sufficient in the analgosedated and ventilated patients to ensure sufficient organ perfusion and in addition proved to be successful in preventing right ventricular failure and permitting restitution of right ventricular function. Inhaled NO therapy was weaned successfully without rebound phenomena. The potent endogenous vasoconstrictor endothelin-1 (produced and eliminated primarily in the lungs) has been shown to cause pulmonary hypertension and is an antagonist of the most important endothelial mediator of pulmonary vasodilation, NO. To further elucidate the pathophysiology, plasma levels of ET-1 and big ET-1 were measured during NO therapy following LVAD implantation. As expected in end-stage heart failure, the preoperative ET-1 and big ET-1 plasma levels were considerably increased and correlated with the pulmonary vascular resistance. The highest plasma concentrations of ET-1 were measured intraoperatively, which is in keeping with other studies and has been explained by an endothelial dysfunction triggered by cardiopulmonary bypass. Plasma levels of ET-1 and big ET-1 fell significantly during NO therapy and were lowest after termination of inhaled NO. A significant inverse correlation was found between the mean inhaled NO dose and the ET-1 and big ET-1 plasma levels. Hemodynamics improved simultaneously with the drop in plasma levels of the endothelins. The decrease of the pulmonary artery pressures correlated with the decrease of the ET-1 plasma levels. It can be derived from the results that inhaled NO not only induces pulmonary selective vasodilation by replacing a deficient endogenous NO production in secondary pulmonary hypertension, but inhaled NO also inhibits the endothelins ET-1 and big ET-1. In addition, left ventricular failure is effectively treated by mechanical unloading through the LVAD, thus permitting a new physiologic balance to develop between the antagonists NO and endothelin in the pulmonary circulation and ameliorating dysfunction of the pulmonary vascular endothelium. This explains why NO inhalation is needed only as an intermediate therapy and the fact that a rebound phenomenon with increases in pulmonary vascular resistance and consecutive right ventricular constraint does not occur. To support right ventricular function after LVAD implantation, the following therapeutic principles have been established: - Inhaled NO therapy should be started early on weaning from cardiopulmonary bypass. - Intraindividual dose titration is useful to ensure maximal effects with minimal doses. - Inhaled NO selectively decreases pulmonary vascular resistance without inducing systemic hypotension. Right ventricular afterload decreases without pathologically increased left ventricular filling pressures, as the left ventricle is unloaded by the LVAD. - If right ventricular dysfunction presents despite NO inhalation, venous return should be lowered to relieve the right ventricle, by keeping the cardiac index low at around 2.5 L/min/m2. - This is accomplished by minimal inotropic support and restrictive volume replacement. Regeneration of right ventricular function is made possible by a reduction of right ventricular stroke work. - The slower the inhaled NO dose was lowered, the faster the ET-1 and big ET-1 plasma levels fell, as an inverse correlation was found between the plasma levels of the endothelins and the mean inhaled NO dose. Therefore stepwise weaning of inhaled NO therapy is essential in preventing rebound phenomena. - "NO-off-trials" are useful to monitor inhaled NO dependency during weaning from NO therapy in critical cases. - As dysfunction of the pulmonary vascular endothelium obviously does not persist after cessation of inhaled NO therapy, as a rule right ventricular compromise due to an increase in pulmonary vascular resistance does not occur during the further clinical course.

Pump thrombosis is the epitome of left ventricular assist device dysfunction for end-stage heart failure patients. With the increased utilization of implantable, long-term, left ventricular assist devices (LVADs), understanding the implications associated with device orientation and interaction with the body is exceedingly important. Components associated with pump thrombosis in the Thoratec© HeartMate II™ (HMII) and the HeartWare© HVAD® devices include the inflow cannula, the outflow graft, and the pump elements as well as pump pocket depth for the HMII specifically. Several studies have been conducted to analyze these interactions with the HMII, however there is minimal to no data available analyzing how the device orientation of the HeartWare HVAD affects hemodynamics and a patient’s risk for developing pump thrombosis. Therefore, the purpose of this pilot study is the simulate the hemodynamic implications associated with Sub-optimal cannula angulation of the HVAD. Using Solidworks 2016 Ed., a simplified, hemo-static model of the left side of the heart was created. Dimensions for the atria, ventricle, and mitral valve were determined through the combination of Trans-Esophageal Echo cardiogram data as well as literature references. Three different inflow cannula angle scenarios were developed including a Control, a Clinically Optimal, and a Sub-optimal. Assumptions included body temperature, no accumulation within the ventricle, and no ejection or contraction. The model consists of static continuous flow set to 5 liters per minute with the assumption that the HeartWare HVAD is completely supporting the left ventricle. The results include both qualitative and quantitative data. Flow trajectory plots for each cannula scenario depict the hemodynamic flow patterns for different time points. Results show visible changes in the Sub-optimal orientation when compared to both the Control and the Clinically Optimal scenario. Additionally, it was determined that there were no statistically significant differences in the velocity vectors for any of the scenarios however, the shear stress values were determined to be significantly different for all time points, p < 0.001 for all scenarios when compared to Control. Though there are several limitations of this study, with sub-optimal inflow cannula angulation, there is a potential increased risk of hemolysis due to increased shear stress.

Background: Right ventricular failure is a serious complication after left ventricular assist device placement. Case Presentation: A 70-year-old male in decompensated heart failure with right ventricular failure after the placement of a left ventricular assist device. A single dual-lumen PROTEKDuo cannula was inserted percutaneously via the internal jugular vein to draw blood from the right atrium and return into the pulmonary artery using the CentriMag system, by passing the failing ventricle. The patient was successfully weaned from right ventricular assist device. Conclusions: In comparison to two-cannula conventional procedures, this right ventrivular assist device system improves patient rehabilitation and minimizes blood loss and risk of infection, while shortening procedure time and improving clinical outcomes in right ventricular failure.

Background: Aortic valve insufficiency (AI) at the time of left ventricular assist device (LVAD) insertion needs to be corrected, however there is little known about how to manage bioprosthetic valvular AI. Case presentation: A 55-year-old female with dilated cardiomyopathy who previously had a bioprosthetic aortic valve replacement needed a LVAD as a bridge to transplant. Her left ventricular ejection fraction was 10% and had mild to moderate transvalvular AI. She underwent a HeartWare HVAD insertion along with aortic valvular coaptation stitch repair (Park's stitch) to the bioprosthetic valve. Conclusion: Her AI improved to trivial with minimal ejection through the bioprosthetic valve. She was transplanted 6 months following the surgery. A Park's stitch to the bioprosthetic aortic valve with more than mild AI might be a good option for bridge to transplant patient.

Heart transplant is often considered the best treatment for prolonged left ventricular failure. However due to limited donor hearts and ineligibility of some patients to get a transplant, heart assist devices are considered a short/long term option to assist the failing ventricle. Numerous in vitro and animal trials are conducted to study the flow fields in artificial ventricles to avoid hemolysis and thrombosis but the effects of flow fields corresponding to the angle of LVAD insertion into the aorta are often neglected. This experiment uses 30, 60 and 90 degree glass models to signify different angles of the surgical end to side anastomosis. Particle Image Velocimetry is used to study the flow fields at the interface and determine optimum angle amongst the three to avoid blood trauma. Use of a 30 degree glass interface minimizes stagnation zone, recirculation patterns, flow reversal, high shear region and other flow irregularities which may lead to reduced hemolysis, thrombosis and blood trauma in a clinical setting.

Foi desenvolvido um diafragma de elevada vida útil e biocompatibilidade a ser utilizado em um dispositivo de assistência ventricular esquerda(DAV) eletromecânico de dimensões reduzidas e totalmente implantável. Foi realizado teste de resistência do diafragma de poliuretana com superfície texturizada. O teste avaliou sua resistência para experimentos In Vivo de até quinze dias com o DAV implantado em bezerro. Uma superfície de endotélio natural tem excelente tromboresistência. A quantidade e as características da neointima formada em um DAV são determinadas pela superfície do material, hemodinâmica e condições físico-patológicas. O implante de patch na aorta abdominal de porco isola as variáveis que normalmente estão presentes durante a utilização do DAV e que interferem na hemocompatibilidade do material. A avaliação das características do material foi obtida com o seu implante na parede da aorta descendente em contato com o fluxo sanguíneo. Diferentes tipos de superfície de contato foram avaliadas em sete experimentos In Vivo. Este estudo está voltado para as reações de interface sangue / material. Um estudo histológico foi realizado ao final de cada experimento para analisar as interações entre o sangue e o material, quantificando e qualificando a intima neo formada sobre a superfície de contato, calcificação e deposições de elementos constituintes do sangue / It has been developed a high lifetime and biocompatible diaphragm to be used in a Left Ventricle Assist Device (LVAD) that is a reduced dimension totally implantable electromechanical device. It has been performed an endurance test on a textured diaphragm made of polyurethane. This test has evaluated the diaphragm resistance to be used in In Vivo tests with the LVAD implanted for fifteen days in calves. A natural endothelial cell surface has excellent thromboresistant characteristics. The quantity and the characteristics of the neointima formed into LVAD are determined by the material surface, hemodynamics of the blood through the device, and the physico-pathological conditions. The patch implantation into the abdominal aorta of pigs has isolated some normal variables that usually are present during LVAD utilization and that may interfere on the material biocompatibility. The evaluation of the material’s characteristics has been enhanced through its implantation at the descending aorta wall in contact with blood flow. Different kinds of contact surfaces of specific polyurethane are tested in seven In Vivo experiments. This study is totally focused in the reaction of the blood-material interface. A histogical study is performed in the end of every animal experiment to analyze the interactions between blood and biomaterial. It’s emphasized the quantification and qualification of the neointima over the blood contact surface, calcification, and blood depositions

Ageing is linked to a decrease in mobility, which affects the quality of life of many elderly individuals. This is a growing challenge in industrialised societies since the proportion of elderly individuals is becoming larger. One potential solution that would keep these individuals active and independent is the use of mobility assist devices. These devices are designed to reduce the energy demand of the user with the use of electric motors providing torques at joints of the lower limb. Although promising, these devices have a problem: they become uncomfortable after prolonged usage. This is especially true for devices designed to produce substantial assistance. The research goal consisted of quantifying the performance of the physical interfaces, or points of attachments, of an experimental device with multiple interface adjustments. The device was fabricated with design criteria similar to active assist devices to simulate the mechanical behaviour of these particular devices. This analysis provided design recommendations that could ultimately enhance the performance of assist devices available on the market and thus the quality of life of many individuals. This research used force mapping and motion capture to quantify the kinetic and the kinematic compatibility of the device. Experimental results have shown that the position, shape and other parameters of the interfaces had an effect on the relative movement of the brace, or the brace performance. The device interface migration was greater when the interfaces were positioned furthest away form the joint. An increasing level of assistance showed more relative movement between the brace and the user. Interface geometry had a noticeable effect on force distribution over the interface. The results and methodology of this research offers an in depth understanding of the mechanical behavior of the physical interfaces of the developed assist device. Nevertheless, further research and development in the field of human machine interactions are needed in order to develop a physical human-machine interface that will ensure the success of powered assist devices in the future.

Introdução: A utilização de dispositivos de assistência ventricular esquerda (DAVE) proporciona melhor manejo dos pacientes que necessitam de métodos alternativos como ponte para o transplante cardíaco. Parcela significativa dos pacientes sob uso de DAVE desenvolve falência de ventrículo direito (VD), com elevada mortalidade. Propusemos estudo experimental para desenvolvimento de método de descompressão do VD em pacientes sob assistência mecânica esquerda e disfunção biventricular. Método: Foi realizado estudo experimental em cães adultos, com disfunção biventricular em fibrilação ventricular, mantidos em uso de DAVE com bomba centrífuga. Os animais foram divididos em dois grupos. No Grupo A, foi realizada descompressão do VD através de anastomose cavo-pulmonar, com anastomose da veia cava superior na artéria pulmonar direita. No grupo B, não foi realizado o \"shunt\". Após o preparo inicial foi iniciada assistência circulatória átrio esquerdo-aorta. Foram realizadas medidas hemodinâmicas e laboratoriais no momento inicial e aos 30, 60 e 90 minutos de assistência nos dois grupos. Resultados: Os dados hemodinâmicos e laboratoriais iniciais foram semelhantes nos dois grupos. No Grupo A, houve melhora da pressão arterial media (p<0,0001) durante a assistência. O fluxo pulmonar também foi maior no grupo A (p<0,0001), resultando em maior fluxo na bomba centrífuga, principalmente aos 90 min(1,2L/min X 0,5L/min, p<0,0001). A dosagem de lactato sérico no último momento de estudo foi menor no grupo A (27,6mg/dL versus 47,6mg/dL, p<0,05). Conclusão: Concluímos que a anastomose cavo-pulmonar promove descompressão do VD em modelo de disfunção bi-ventricular aguda sob assistência circulatória isolada do ventrículo esquerdo. A descompressão do VD leva a aumento do fluxo pulmonar e melhor desempenho hemodinâmico da assistência ao ventrículo esquerdo. / Introduction: The use of Left Ventricular Assist Devices promotes better clinical handling of patients in the need of alternative methods as bridge to heart transplant. A significant part of them develop right ventricle failure, leading to high death incidence. We have proposed an experimental study for the development of a method to decompress the right ventricle in biventricular failure patients under Left Ventricular Assist Devices . Method: Experimental study with adult dogs with acute biventricular failure in ventricular fibrillation under left assist device by centrifugal pump. The animals were divided in 2 groups. In Group A decompression of RV was made by cavo-pulmonary anastomosis between superior vena cava and right pulmonary artery. In Group B the anastomosis was not performed. After initial preparation left atrium-aorta circulatory support begun. Hemodinamic and laboratory measures were taken at start time and at 30, 60 and 90 minutes of circulatory support. Results: Initial laboratory and haemodinamic data were similar in both groups. Group A had better mean arterial pressure during support(p<0,0001). Pulmonary blood flow was higher in Group A resulting in higher pump flow, mainly at 90 minutes(1,2L/minX0,5L/min, p<0,0001). Serum lactate was lower at 90 minutes in Group A(27,6mg/dL x 47,6mg/dL, p<0,05). Conclusion: We conclude that the cavo-pulmonary anastomosis led to right ventricle decompression in an experimental model of acute biventricular failure under isolated left ventricle circulatory support. The right ventricle decompression generated enhancement in pulmonary blood flow and better circulatory support performance.

Foi desenvolvido um diafragma de elevada vida útil e biocompatibilidade a ser utilizado em um dispositivo de assistência ventricular esquerda(DAV) eletromecânico de dimensões reduzidas e totalmente implantável. Foi realizado teste de resistência do diafragma de poliuretana com superfície texturizada. O teste avaliou sua resistência para experimentos In Vivo de até quinze dias com o DAV implantado em bezerro. Uma superfície de endotélio natural tem excelente tromboresistência. A quantidade e as características da neointima formada em um DAV são determinadas pela superfície do material, hemodinâmica e condições físico-patológicas. O implante de patch na aorta abdominal de porco isola as variáveis que normalmente estão presentes durante a utilização do DAV e que interferem na hemocompatibilidade do material. A avaliação das características do material foi obtida com o seu implante na parede da aorta descendente em contato com o fluxo sanguíneo. Diferentes tipos de superfície de contato foram avaliadas em sete experimentos In Vivo. Este estudo está voltado para as reações de interface sangue / material. Um estudo histológico foi realizado ao final de cada experimento para analisar as interações entre o sangue e o material, quantificando e qualificando a intima neo formada sobre a superfície de contato, calcificação e deposições de elementos constituintes do sangue / It has been developed a high lifetime and biocompatible diaphragm to be used in a Left Ventricle Assist Device (LVAD) that is a reduced dimension totally implantable electromechanical device. It has been performed an endurance test on a textured diaphragm made of polyurethane. This test has evaluated the diaphragm resistance to be used in In Vivo tests with the LVAD implanted for fifteen days in calves. A natural endothelial cell surface has excellent thromboresistant characteristics. The quantity and the characteristics of the neointima formed into LVAD are determined by the material surface, hemodynamics of the blood through the device, and the physico-pathological conditions. The patch implantation into the abdominal aorta of pigs has isolated some normal variables that usually are present during LVAD utilization and that may interfere on the material biocompatibility. The evaluation of the material’s characteristics has been enhanced through its implantation at the descending aorta wall in contact with blood flow. Different kinds of contact surfaces of specific polyurethane are tested in seven In Vivo experiments. This study is totally focused in the reaction of the blood-material interface. A histogical study is performed in the end of every animal experiment to analyze the interactions between blood and biomaterial. It’s emphasized the quantification and qualification of the neointima over the blood contact surface, calcification, and blood depositions

Heart failure is a progressive condition that affects over 5.7 million Americans and costs associated with heart failure account for 2-3 % of the national health care budget. The high rates of morbidity and mortality along with increased costs from readmissions associated with advanced heart failure have led to the exploration of advanced treatments such as left ventricular assist devices (LVADs). LVADS have demonstrated morbidity and mortality benefit but cost remains extensive with costs per quality-adjusted years > $400,000. With this in mind, it is important to identify those who are most likely to benefit from an LVAD to avoid unfavorable outcomes and cost. Although general guidelines and criteria for patient eligibility have been established, choosing patients for LVAD implantation remains challenging. A new focus on patient selection involves the presence of frailty. While frailty has been studied in the elderly population and in patients undergoing cardiac surgery, frailty in patients undergoing left ventricular assist device (LVAD) remains controversial. The purpose of this dissertation was to examine measures of frailty in patients undergoing LVAD implantation. The specific aims of this dissertation were to: (1) identify a feasible frailty measure in adults with end-stage heart failure who underwent LVAD implantation by testing the hypothesis that frailty would predict 30 day rehospitalization rates using Fried’s criteria, Short Physical Performance Battery test, handgrip strength, serum albumin and six minute walk test (2) Determine whether frailty measures improve 3 months post LVAD implantation (3) compare sensitivity of these three measures to change in frailty. Surgical approaches, including heart transplantation and LVAD implantation, for patients with end-stage heart failure was discussed in this dissertation. Data from two subsets of participants who underwent LVADS at the University of Kentucky between 2014 and 2017 were included in the analysis for this dissertation. In the first study, we found that none of the measures are good predictors of frailty in patients with advanced heart failure who undergo LVAD implantation. Handgrip was the only marker of frailty that predicted 30 day readmission but the relationship was a negative association. In the second study, six-minute walk and low serum albumin levels reflect short-term improvement in frailty. These simple measures may be used to determine those patients who are responsive to LVAD implantation. The findings of these studies filled some gaps in our understanding of markers of frailty in patients undergoing LVADs. We gained a better understanding of which markers of frailty are likely to improve in most people after LVAD implantation and thus frailty should not preclude candidate selection for an LVAD. Subsequently, more research is needed to investigate these markers and outcomes.