Orientador: José Reinaldo Cerqueira Braz / Banca: Luiz Antonio Vane / Banca: Jorge João Abrão / Banca: Luiz Marcelo Sá Malbonisson / Banca: Rosa Inês Costa Pereira / Resumo: As variáveis hemodinâmicas e de oxigenação sistêmica não refletem com precisão a hipoperfusão esplâncnica durante o choque hipovolêmico, dificultando o tratamento adequado. A expansão volêmica após a reposição fluídica é fundamental para promover a oxigenação sistêmica e regional após o choque hemorrágico. Em contraste com as soluções convencionais de reposição volêmica, a menor expansão plasmática proporcionada pela administração de hidroxietilamido em solução hipertônica de cloreto de sódio, durante o choque hemorrágico, poderia determinar uma menor oferta de oxigênio sistêmico, com prejuízo à oxigenação gástrica. O estudo teve como objetivo comparar a expansão volêmica e os efeitos imediatos na oxigenação sistêmica e da mucosa gástrica após a administração de hidroxietilamido a 6% (peso molecular de 130 kDa, grau de substituição de 0,4) em solução hipertônica de cloreto de sódio a 7,5% (HHEA), Ringer lactato (RL) e hidroxietilamido a 6% (130/0,4) em cloreto de sódio a 0,9% (HEA), em cães submetidos à choque hemorrágico. Trinta cães, sem raça definida, sob anestesia e esplenectomizados, foram submetidos a sangramento (30 ml/kg) visando manter a pressão arterial média de 40 a 50 mm Hg durante 45 9 Introdução e Literatura minutos, sendo feita a reposição volêmica após este período com RL (n=10), na razão de 3:1 para o sangue removido; HEA (n=10), na razão de 1:1 para o sangue removido; e HHEA (n=10), 4 ml/kg. A expansão do volume intravascular (através da diluição do azul de Evans e da hemoglobina), e os atributos hemodinâmicos, e de oxigenação sistêmica e gástrica (através da tonometria gástrica), foram determinados no momento basal, após 45 minutos de hemorragia, e aos 5, 45 e 90 minutos após a reposição volêmica. A solução de HHEA aumentou o volume sanguíneo, devido à alta eficiência na... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Hemodynamic and global oxygen transport variables have failed to reflect splanchnic hypoperfusion, resulting in a failure to recognize inadequately treated hemorrhagic shock. Volemic expansion after fluid resuscitation is essential to improve global and regional oxygen in hemorrhagic shock. We hypothesized that, in contrast with conventional plasma expanders, the smaller volemic expansion from hypertonic hydroxyethyl starch solution administration in hemorrhagic shock may determine lesser systemic oxygen delivery and gastric oxygenation. We used hemorrhaged dogs to compare the early intravascular volume expansion and systemic and gastric oxygenation effects of 7.5% NaCl 6% hydroxyethyl starch 130/0.4 (HHES), lactated Ringer's (LR), and 0.9% NaCl 6% hydroxyethyl starch (HES) solutions. Thirty mongrel dogs anesthetized and submitted to splenectomy, were bled (30mL/kg) to hold mean arterial pressure at 40-50 mm Hg over 45 minutes and were randomly resuscitated in three groups: LR (n=10) at 3:1 ratio to shed blood; HES (n=10) at 1:1 to shed blood; and HHES (n=10), 4mL/kg. Intravascular volume expansion (Evans blue and hemoglobin dilution), hemodynamic, systemic oxygenation and gastric intramucosal- arterial PCO2 gradient (PCO2 gap) variables were measured at baseline, after 45 min of hemorrhage, and 5, 45, and 90 min after fluid resuscitation. HHES increased blood volume, due to the 11 Introdução e Literatura high volume expansion efficiency, but intravascular volume expansion with this solution was the smallest of the solutions. All three solutions induced a similar hemodynamic performance but HHES showed lower mixed venous oxygen saturation and higher systemic oxygenation extraction and PCO2 gap than LR and HES. In conclusion, the smaller volume state from HHES after resuscitation provides worse systemic and gastric oxygenation recovery compared to LR and HES in dogs submitted... (Complete abstract click electronic access below) / Doutor

Implication de l’oxygénation cérébrale dans les limitations à l’exercice musculaire des personnes non-entraînées et sportifs d’endurance. L’objectif général de ce travail était de déterminer si l’oxygénation cérébrale était un facteur de la limitation à l’exercice de type aérobie. Dans un premier temps, nous nous sommes attachés à étudier le rôle de l’oxygénation cérébrale mesurée par la Spectroscopie dans le proche Infra-Rouge (NIRS) dans la limitation de l’exercice progressif maximal en rampe. Nous avons montré l’existence d’un seuil de déclin de l’oxygénation cérébrale associé au point de compensation respiratoire (RCP). L’amélioration de la performance avec une supplémentation d’O2 était liée au décalage de ce seuil à de plus hautes intensités d’exercice chez des sujets actifs (étude 1). Dans un second temps, nous avons montré que ce seuil de déclin de l’oxygénation, retrouvé aussi chez des sportifs entraînés en endurance apparaîssait à de plus hautes intensités d’exercice que chez des sujets non-entraînés (étude 2). Enfin, nous avons déterminé l’impact de l’hypoxémie artérielle induite par l’exercice (HIE) des sportifs d’endurance sur l’oxygénation cérébrale au cours d’un exercice maximal en rampe et d’un exercice de temps limite à charge constante. Nous avons ainsi montré que l’oxygénation cérébrale était augmentée avec la HIE suggérant un effet compensatoire à l’hypoxémie artérielle au cours de l’exercice progressif maximal en rampe. Ceci, n’existait pas au cours de l’exercice de temps limite ne supportant pas l’implication de l’oxygénation cérébrale dans ce type d’exercice (étude 3). Ces travaux ont donc mis en évidence l’implication de l’oxygénation cérébrale dans la limitation de l’exercice maximal en rampe chez des sujets actifs et des sportifs entraînés en endurance présentant ou pas une HIE. Toutefois, elle ne semble pas être un facteur majeur de limitation de l’exercice de temps limite. / Involvement of cerebral oxygenation in muscular exercice limitation in untrained and trained endurance men. A decrease in oxygen availability in the brain could be a physiological mechanism limiting aerobic fitness. We first studied the role of cerebral oxygenation measured by Near Infra-Red Spectroscopy (NIRS ) in maximal cycle ramp exercise limitation. We showed a cerebral oxygenation threshold decline associated with respiratory compensation point (RCP). This threshold appeared for higher exercise intensities -related to performance improvement with hyperoxia in untrained endurance men (study 1). Secondly , we showed that the cerebral oxygenation threshold in athletes occurred for higher sub-maximal exercise intensities than untrained (study 2). Finally , we determined the involvement of exercise-induced arterial hypoxemia (EIH) in endurance athletes on cerebral oxygenation during maximal cycle ramp exercice and exercice time to exhaustion. We showed that cerebral oxygenation was improved by EIH suggesting a compensatory effect of EIH during the maximal cycle ramp. This did not occur during exercise time to exhaustion, and does not support the involvment of cerebral oxygenation in this type of exercise (study 3). This work has therefore highlighted the involvement of cerebral oxygenation in maximal cycle ramp exercice limitation in untrained and trained endurance men with or without EIH. However, it was unlikely been the major factor limiting the exercise time to exhaustion.

Relative changes are detectable in the blood of end-stage renal disease (ESRD) patients during hemodialysis (HD) treatment using optical spectroscopy. However, the potential impacts of several confounding factors that could affect the detection of these changes have not been evaluated. The objectives of this thesis were to: 1) investigate how the variations and/or changes in acid-base and oxygen parameters during HD treatment can affect the optical signature of whole blood of ESRD patients, 2) to investigate the effect of heparin on the optical properties of whole blood and its impact on our method. Blood samples were drawn from 23 ESRD patients at 5 time points during a 4 hour HD treatment and sent for blood gas and blood spectroscopy analyses. No significant correlations were found between the changes in the blood transmittance spectra and acid-base and oxygen parameters. This indicates that the perturbations in these parameters due to HD procedures do not confound the detection of changes in the blood transmittance spectra of ESRD patients during HD treatment. Additionally, the effect of heparin in modifying the optical properties of whole blood does not confound the detection of changes in the blood of ESRD patients due to HD treatment using whole blood-based optical spectroscopy. ANOVA revealed significant (P<0.05) measurable changes in the blood transmittance spectra of ESRD patients during HD treatment. Significant spectral differences (P<0.05) were found between ESRD patients. The lack of uniform spectral characteristics across patients is

Les laccases sont des enzymes de type oxydase, réalisant de manière efficace la réduction du dioxygène en eau. Des études réalisées au laboratoire ont permis de montrer que l’irradiation sous atmosphère inerte d’un système de type, EDTA/[Ru(bpy)3]2+/laccase, conduisait à la photoréduction de l’enzyme via la formation d'une espèce [Ru(bpy)3]2+*. La substitution de l’EDTA par un alcène de type p-styrène sulfonate conduit également à la photoréduction de l’enzyme. L'ouverture à l'air du système permet une consommation d’oxygène concomitante à la détection par RMN de produits d’oxydation tels que l’époxyde, le diol et le p-benzaldéhyde sulfonate. L’influence de la concentration des différents partenaires, de la source d’irradiation et du pH sur l’efficacité de cette réaction a été évaluée. D’autres alcènes tels que le styrène, le cyclohéxène ou le cyclooctène sont également substrats. Le marquage isotopique en présence soit d'H218O soit d'18O2 ainsi que l’utilisation de générateurs d’espèces réactives de l’oxygène, ont permis de proposer un mécanisme majoritaire où l’espèce RuIII, photoproduite avec l'assistance de la laccase, pourrait arracher un électron du substrat qui à son tour réagirait avec le dioxygène présent dans le milieu pour conduire aux produits observés. D’autres complexes photoactivables à base de ruthénium ou de manganèse ont également été employés. Afin d’aborder le contrôle de la réactivité, le greffage covalent d’un photosensibilisateur à base de ruthénium sur une lysine unique à proximité du site d'oxydation des substrats de l'enzyme a été effectué. / Laccases are oxidases that efficiently perform the reduction of dioxygen into water. Studies in the laboratory have allowed to show that irradiation under inert atmosphere of a EDTA/[Ru(bpy)3]2+/laccase system, lead to the photoreduction of the enzyme via the irradiation of [Ru(bpy)3]2+*. The substitution of EDTA by the alkene p-styrene sulfonate results similarly in a photoreduction of the enzyme. Opening the system to air allows a dioxygen consumption with a simultaneous detection of oxidation products such as the epoxide, diol and p-benzaldehyde sulfonate detected by NMR. The influence of the concentration of the partners, the irradiation source and pH on the efficiency of the reaction was evaluated. Other alkenes such as styrene, cyclohexene and cyclooctene are also substrates. Isotopic labeling experiments in the presence of either H218O or 18O2, as well as the use of reactive oxygen species generators, allowed us to propose a main mechanism where the laccase assisted RuIII photogenerated specie would withdraw an electron from the substrate which in turn would react with dioxygen to yield the products observed. Other ruthenium and manganese photosensitizers were also used. To address the control of the reactivity, a covalent grafting of a ruthenium photosensitizer, on a unique lysine nearby the substrate oxidation site of the laccase was done.

京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第22649号 / 社医博第109号 / 新制||社医||11(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 中山 健夫, 教授 川上 浩司, 教授 伊達 洋至 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM

Extracorporeal Membrane Oxygenation (ECMO) is a life-saving therapy usedfor support in critical heart and/or lung failure. Patient’s blood is pumped viaan artificial lung for oxygenation outside of the body. The circuit is composedof a blood pump, cannulae for drainage and reinfusion, a membrane lung,tubing and connectors. Its use is associated with thromboembolic complicationsand hemolytic damage. Detailed numerical studies of two blood pumps anda lighthouse tip drainage cannula were undertaken to characterize the flowstructures in different scenarios and their link to platelet activation. The pumpsimulations were modelled according to manufacturer’s proclaimed use but alsoin off-design conditions with flow rates used in adult and neonatal patients.Lagrangian Particle Tracking (LPT) was used to simulate the injection ofparticles similar in size to platelets to compute platelet activation state (PAS).The results indicated that low flow rates impacted PAS similarly to high flowrates due to increased residence time leading to prolonged exposure to shearstress despite the fact that shear per se was lower at low flow rate. Regardingthe cannula, the results showed that a flow pattern similar to a jet in crossflowdeveloped at the side holes. A parameter study was conducted to quantifydrainage characteristics in terms of flow rate distribution across the holes wheninput variables of flow rate, modelled fluid, and hematocrit were altered. Thefindings showed, across all the cases, that the most proximal hole row drainedthe largest fraction of fluid. The effects due to the non-Newtonian nature ofblood were confined to regions far from the cannula holes and the flow structuresshowed very limited dependence on the hematocrit. A scaling law was found tobridge the global drainage performance of fluid between water and blood. / <p>QC 210906</p>

In der Neonatologie ist die Verabreichung von Erythrozytenkonzentrat (EK) eine der häufigsten therapeutischen Maßnahmen. Ursachen dafür sind die Frühgeborenen-anämie und die iatrogen durch diagnostische Blutentnahmen hervorgerufene sekundäre Anämie. Obwohl ca. 80% der Frühgeborenen während des postnatalen stationären Aufenthaltes EK erhalten, gibt es noch immer keine einheitlichen Richtlinien zur Bluttransfusion bei Frühgeborenen. In der vorliegenden Studie sollte der Effekt einer EK-Gabe mit Hilfe der Messung der cerebralen und peripheren Gewebsoxygenierung (crSO2 und prSO2) erfasst werden. Und es wurde der Annahme nachgegangen, dass in der Neonatologie Subgruppen existieren, welche unterschiedlich von einer EK-Transfusion profitieren. Im Rahmen dieser Promotionsarbeit wurden Frühgeborene der neonatologischen Abteilung der Universitätsklinik und Poliklinik für Kinder- und Jugendmedizin Leipzig prospektiv analysiert. Es konnte gezeigt werden, dass bei allen untersuchten Patienten sowohl die cerebrale als auch die periphere Gewebsoxygenierung unter EK-Transfusion ansteigen und auch nach einem Intervall von 24 Stunden noch auf diesem gesteigerten Niveau konstant bleiben. Zudem konnte nachgewiesen werden, dass Kinder mit niedrigen crSO2-Ausgangswerten vor Transfusion mehr Sauerstoffsättigungsabfälle unter 80% (SaO2<80%) aufweisen. Nach Transfusion ist bei diesen Patienten zusätzlich ein stärkerer Rückgang der Anzahl der SaO2<80% zu beobachten. Somit ist die Gewebsoxygenierung möglicherweise ein sinnvoller Parameter für die Indikation zur EK-Transfusion, welcher bei der Erarbeitung neuer Transfusionsricht-linien in der Neonatologie mit einbezogen werden sollte.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19603号 / 医博第4110号 / 新制||医||1014(附属図書館) / 32639 / 京都大学大学院医学研究科医学専攻 / (主査)教授 中山 健夫, 教授 富樫 かおり, 教授 松田 秀一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Extracorporeal membrane oxygenation (ECMO) is a method that allows extracorporeal life support in potentially reversible life-threatening conditions affecting the heart or lungs which are refractory to conventional treatment. Depending on the parameters of its setting, this method affects the haemodynamics of the cardiovascular system and the perfusion of the target organ. From the point of view of its character, the necessity for invasive application, and the function thereof in the conditions of the cardiovascular system, ECMO is regarded as a risky method accompanied by a number of complications. Among the critical complications are thromboembolic complications affecting the central nervous system (CNS) and haemorrhagic complications. The goal of this paper is to present and verify the prerequisites for the formation of periprocedural embolisms affecting the CNS and to evaluate the regional haemodynamics of the CNS. This is done by analysing the presence of embolisms and by analysing the parameters of blood flow rates in the right common carotid artery (arteria carotis communis-ACC) and the corresponding oxygenation of the brain tissue during various flow rate parameters generated by the ECMO support on induced heart failure in a biological porcine model. In the first section of the paper, 8...

ExtraCorporeal Membran Oxygenering (framgent ECMO) är en mycket användbar behandling i situationer där patientens tillstånd är kritiskt. ECMO kan potentiellt öka chanserna att överleva avsevärt för patienter som annars skulle avlida till följd av sina hjärt- eller lungproblem. Behandlingen är dock inte helt riskfri, utan komplikationer såsom tromboembolism och invärtes blödningar är vanliga. Dessa associeras båda med rapportens huvudsakliga ämne, nämligen blodplättsaktivering. Denna företeelse är en konsekvens av den icke fysiologiska miljö som slangsystemet utgör. Trombocyter (blodplättar) som utsätts för de höga skjuvspänningar och hastigheter i kombination med långa stillestånd i stagnationspunkter, löper ökad risk att aktiveras och därmed producera ansamlingar av koagulerat blod runtom i olika delar av systemet. I den här rapporten var kopplingarna, som utgör skarvar där olika delar av systemet kopplas samman, av intresse. Simuleringarna för att analysera kopplingarna i olika konfigurationer utfördes med hjälp av ANSYS Fluent på Parallelldatorcentrums (PDC) Beskow och Tegner. Det visade sig att flera kopplingar på rad ökade residenstiden för en individuell partikel mer än vad som vore väntat ifall resultaten från lika många enskilda koppling adderades. Från detta drogs slutsatsen att ett reducerat antal kopplingar är att föredra då det bidrar till att minska den totala blodplättsaktiveringen och därmed minska risken att patienten får komplikationer.