by Dai Kang Sheng. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1989. / Bibliography: leaves 127-130.

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 73-87).

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Extracorporeal circulation damages blood and causes harmful side effects such as stroke and/or systemic inflammatory response in patients. Reactions of blood components to extracorporeal circulation include complement and inflammatory reactions, coagulation and thrombogenesis, frank hemolysis, and platelet activation and adhesion to the extracorporeal circuit. Non-physiologic pressure and flow produced by blood pumps contribute to blood injury. Two pump types, roller and centrifugal, are used for maintaining flow, with various models available from different manufacturers. This study compared the effects of these two pumps in identical, isolated, artificial circuits to a non-pumped control for a period of 24 hours on heparinized porcine blood. Hematology parameters were used to evaluate blood damage. Mean corpuscular volume, mean corpuscular hemoglobin, white blood cell count, platelet count, and mean platelet volume were affected by time of circulation. Mean corpuscular hemoglobin, platelet count, and red cell distribution width were different between circulated and non-circulated blood, however no differences were found between the pumping systems in any parameter. Red blood cell count, total hemoglobin, and hematocrit were not affected by time or treatment. The changes observed in this study have implications for the use of extracorporeal circulation in the clinical setting and in future use of blood as a potential organ perfusion medium. / Master of Science

Over 26 million Americans suffer from pulmonary disease, resulting in more than 150,000 deaths annually. Lung transplantation remains the only definitive treatment for many patients, but has meager survival rates and only approximately 1,700 of the 2,200 patients added to the lung transplant wait list each year are transplanted. Extracorporeal gas exchangers have been used as an alternative to mechanical ventilation in acute respiratory failure and as a bridge to transplantation in chronic respiratory failure. Current gas exchangers are limited by their high resistance and low biocompatibility that lead to patient complications and device clot formation. Therefore, there exists a dire need for improved devices that can act as destination therapy. To accomplish the goal of destination therapy, this dissertation discusses three studies that were performed to pave the way. First, I examined clot formation and failure patterns of two common clinical devices (Maquet’s CardioHelp (CH) and Quadrox (Qx)) to further our understanding of their limitations with respect to long-term support. Overall, it was demonstrated that the Qx devices fail earlier and more frequently than CH devices and result in a significantly greater reduction in platelet count, and that a four-inlet approach is beneficial. Next, I determined the optimal sweep gas nitric oxide (NO) concentration that minimizes platelet binding and activation while ensuring that blood methemoglobin (metHb) concentrations increase less than 5%. Miniature artificial lungs were attached to rabbits in a pumped veno-venous configuration and run for 4 h with NO added to the sweep gases in concentrations of 0, 100, 250, and 500 ppm (n=8 ea.). 100 ppm significantly reduced the amount of platelet consumption (p < 0.05), reduced platelet activation as measured by soluble p-selectin (p < 0.05), and had negligible increases in metHb and will thus be used in future experiments. Last, I tested the Pulmonary Assist Device (PAD) which was designed for long term use as a bridge to transplantation and destination therapy. Benchtop experiments were performed that confirmed that it meets our design and performance goals. From here, we are equipped to commence with 30-day PAD testing in sheep.

L’insuffisance cardiaque aigue est une émergence médicale qui nécessite une prise en charge multidisciplinaire. L’Extracorporeal Life Support (ECLS) peut être envisagé comme option thérapeutique pour les formes d’insuffisance cardiaque aigue réfractaire au traitement conventionnel. L’objectif de ce projet de recherche clinique est de fournir une vue d’ensemble de l’ECLS dans la prise en charge du choc cardiogénique et de l’arrêt cardiaque réfractaire. L’intoxication médicamenteuse et la myocardite sont les meilleures indications à l’implantation de l’ECLS en considération de leur potentiel de récupération myocardique très élevé. La défaillance primaire du greffon après transplantation cardiaque et l’infarctus du myocarde présentent des résultats plus mitigés avec l’ECLS en raison d’une physiopathologie plus complexe. Le choc cardiogénique postcardiotomie après une intervention de chirurgie cardiaque montre des résultats décevants en raison du profile préopératoire des patients. L’arrêt cardiaque aussi exige une prise en charge immédiate et l’ECLS peut être considéré comme une solution thérapeutique de sauvetage. Une meilleure sélection des patients s’impose afin d’améliorer les résultats de l’ECLS pour l’arrêt cardiaque réfractaire intrahospitalier. Les résultats de l’ECLS pour l’arrêt cardiaque réfractaire extrahospitalier sont dictés principalement par le temps de réanimation cardio-pulmonaire et le rythme cardiaque. Les rythmes non choquables pourraient être considérés comme une contre-indication formelle à l’utilisation de l’ECLS autorisant une concentration de nos efforts sur les rythmes choquables où les chances de survie sont plus importantes / Acute heart failure is a clinical situation requiring a prompt multidisciplinary approach. Extracorporeal Life Support (ECLS) could represent a therapeutic option for acute heart failure refractory to standard maximal treatment. The aim of this report is to offer an overview of ECLS in the management of refractory cardiogenic shock and cardiac arrest. Drug intoxication and myocarditis are the best indications of ECLS in consideration of their high potential of myocardial recovery. Primary graft dysfunction after heart transplantation and acute myocardial infarction show reduced survival rates owing to their more complex pathophysiology. Postcardiotomy cardiogenic shock after cardiac surgery operations displays poor outcomes due to the preoperative profile of the patients. ECLS could be also considered as a rescue solution for refractory cardiac arrest. A better selection of in-hospital cardiac arrest patients is mandatory to improve ECLS outcomes. In-hospital cardiac arrest patients with a reversible cause like drug intoxication and acute coronary syndrome should benefit from ECLS whereas end-stage cardiomyopathy and postcardiotomy patients with an unclear cause of cardiac arrest should be contraindicated to avoid futile support. ECLS for refractory out-ofhospital cardiac arrest should be limited in consideration of its poor, especially neurological, outcome and the results are mainly limited by the low-flow duration and cardiac rhythm. Nonshockable rhythms could be considered as a formal contraindication to ECLS for refractory out-of-hospital cardiac arrest allowing a concentration of our efforts on the shockable rhythms, where the chances of success are substantial

Circulating neutrophil activation occurs during cardiac surgery with extracorporeal circulation (ECC) and is implicated in the pathophysiology of inflammatory tissue injury and peri-operative organ dysfunction. However, neutrophil directed antiinflammatory strategies have failed to demonstrate consistent therapeutic benefit indicating that the nature and significance of peri-operative circulating neutrophil activation remains incompletely defined. In particular, conformational activation of the b2 integrin Mac-1 (CD11b/CD18), which is required for neutrophil adhesion competence and facilitation of effector functions, has not previously been investigated during cardiac surgery, and the relative contribution of cellular activation and bone marrow neutrophil recruitment to peri-operative changes in circulating neutrophil phenotype and function is unknown. A novel whole blood flow cytometric technique was used to analyze circulating neutrophil phenotype (total Mac-1, conformationally-active CD11b, CD10, CD16, L-selectin and P-selectin glycoprotein ligand-1) and function in cardiac surgery patients to characterize the nature of changes in Mac-1 expression and activation status, and the effects of relative neutrophil immaturity on circulating neutrophil phenotype and function. The effect of heparin, a known CD11b ligand, on Mac-1 epitope expression was also investigated. Circulating neutrophil numbers observed during ECC were mathematically modeled to determine the acute response of the bone marrow neutrophil reserve to an inflammatory stimulus. Plasma cytokine, chemokine and acute phase mediators were measured in cardiac and lung surgery patients to determine potential regulators of systemic neutrophil recruitment. Neutrophils newlyemergent from the bone marrow were characterized as CD10-/CD16low and exhibited distinct changes in cell surface markers and enhanced functional responses, relative to their more mature CD10+ counterparts. Conformational activation of CD11b occurred peri-operatively and provided a more sensitive measure of circulating neutrophil activation status than changes in total Mac-1 or L-selectin expression, although detection of Mac-1 epitopes was reduced in the presence of heparin. Modeling of circulating neutrophil numbers predicted that post-mitotic maturation time was acutely abbreviated by 8.4 hours during 71 minutes of ECC. Systemic chemokine release occurred with cardiac but not non-cardiac thoracic surgery indicating some specificity of the acute inflammatory response. These findings expand the understanding of peri-operative circulating neutrophil activation and recruitment, and identify potential therapeutic targets to limit neutrophil injurious potential during cardiac surgery with ECC.

With the high development of society and economy, the rising level of national education, and the awareness of consumer rights in Taiwan, consumers¡¦ demands for medical and health care is increasing. The role of consumers has transformed to actively select and require medical and health care. The implementation of the National Health Insurance leads to the role change of the medical provider from a price maker to a price receiver, which benefits hospitals with mass product and cost control. Therefore, price-drive medical consumers become quality¡Vdriven ones, which benefits hospitals with good faculty, facilities and service. Nowadays, the hospital business environment is becoming more and more competitive. It is vital not only for hospital substantial business to create customer value of service and quality but also for hospital competitiveness to satisfy customer needs. The business strategy of hospitals is to greatly strengthen internal management and actively seek for the interaction with the external environment to keep survival and growth. Besides, hospitals apply CRM in order to attract new customers, retain old customers and to increase the profits of the customer contribution. Because of the limit of cost and budget tight policy, large hospitals are increasing their scale and the limited resource /number of customers. In this case, it is necessary for hospital¡¦s business strategy to focus on both quality and cost effectiveness. Hospitals build the tight relationship with customers so that they are willing to be diagnosed. Thus, Customer Relationship Management is the core competitive advantage for hospitals. Nevertheless, hospitals are less willing to purchase extracorporeal shock wave lithotripsy machines for the sake of the tight finance budget. As far as medical device suppliers are concerned, they have to adopt BOT approach in order to maintain business growth. Regarding the medical service and cooperation model for renal calculus patients, we discover that it is the equipment suppliers that are responsible for CRM rather than hospitals establishment. The retention number and returning frequency is the key to the revenues of the equipment suppliers, which means the relationship between hospitals and suppliers are unbroken. Our research indicates that the business model of extracorporeal shock wave lithotripsy machine can apply the concept of CRM. The medical equipment business and medical organization develop the model of the patient service with the base; CRM, the core value: customers and the hospital vision. We construct the ¡§four wins¡¨ model for the hospital, the patient, the Health Insurance Bureau and the business with the decision-making strategy, customer service and IT application.

Given that pandemic swine flu outbreak led to substantial admission in intensive care unit, extracorporeal membrane oxygenation has been increasingly applied to those who suffered from H1N1 infection induced acute respiratory distress syndrome. This review is going to evaluate the effectiveness of using ECMO based on five related observational studies. The result, discussion and policy implication in Hong Kong are discussed. Since the ECMO system has been technological improved in recent years, there are less complications when applying ECMO. In view of evidence of reviewed studies, application of ECMO in Hong Kong can be considered as cost effective. And since only a few hospitals in Hong Kong can offer ECMO application, retrieval teams are needed to ensure safety transfer between hospitals. / published_or_final_version / Public Health / Master / Master of Public Health