Thesis (Ph. D.)--Ohio State University, 2005. / Title from first page of PDF file. Includes bibliographical references (p. 126-136).

No description available.

Emphysema is a condition of the lung characterized by abnormal, permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by a destruction of their walls. The primary pathogenesis of emphysema is poorly understood. One of the major issues of COPD is that no diagnostic tests are sensitive enough to detect early disease. Standard pulmonary function tests (PFTs) do not explain the underlying pathophysiology of airflow limitation, nor do they provide information on how COPD may be affecting pulmonary blood flow. Functional imaging, specifically ventilation and perfusion (V/Q) Single Photon Emission Computed Tomography (SPECT), is a sensitive tool that can provide information on pulmonary function in different lung regions. When V/Q images are co-registered to CT, regional analysis can be coupled to structural information. The objective of this study was to examine how emphysematous change identified and localized by CT density based thresholds affects lung function as measured by V/Q SPECT in a mouse model of the disease. A dose response study was conducted where Female BALB/c mice were exposed intranasally to 0.0, 0.5, 2.5 and 5.0 units (U) of porcine pancreatic elastase (PPE). V/Q SPECT/CT scanning was performed 45 days post exposure, followed by measurement of lung compliance using the Flexivent® rodent ventilator 46 days post exposure. Whole lung slice analysis software was used to quantify airspace enlargement and alveolar capillary density from histological sections of the lung. CT pulmonary angiography (CTPA) was also performed on controls and mice exposed to 5 U PPE to examine vascular density. In this mouse model of emphysema, V/Q SPECT was useful in quantitatively examining how ventilation and perfusion is affected in mild and severe emphysema while providing evidence of low log(V/Q) ratio in otherwise normal lung densities. This could be caused by airflow obstruction as a result of widespread narrowing or loss of small conducting airways. Low log(V/Q) ratio is caused by mild emphysema indicating airflow obstruction or dysfunctional hypoxic vasoconstriction in underventilated regions of the lung. The majority of severely emphysematous regions of the lung have matched but equally reduced log(V/Q), although low log(V/Q) is also present. Pulmonary hypertension in response to chronic hypoxia may explain our finding of reduced perfusion activity and vascular density in emphysematous lung, but further research is required to investigate the presence of this pathology. V/Q SPECT was also shown to be superior in the detection of emphysema compared to CT and Flexivent measured lung compliance providing evidence towards shifting the current assessment and monitoring paradigms. Due to the widespread availability of this imaging technique, it could be used to screen asymptomatic smokers for early disease and identify and locate pathology so therapies targeting the appropriate disease pathway can be prescribed. This will inevitably improve patient care. / Thesis / Master of Science (MSc)

Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Thesis (doctoral)--Rijksuniversiteit te Utrecht, 1992. / Thesis statement, summary, afterword, and vita in Dutch. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 162-176).

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 5 uppsatser.

INTRODUÇÃO E OBJETIVOS: A Circulação extracorpórea (CEC) é associada a ativação leucocitária, resposta inflamatória e disfunção pulmonar. Objetivou-se avaliar os efeitos da filtragem leucocitária sobre a resposta inflamatória e a função pulmonar em indivíduos submetidos à revascularização do miocárdio (RM) com CEC. MÉTODO: Após aprovação pelo Comitê de Ética Institucional e obtenção do consentimento informado dos indivíduos, foi realizado estudo prospectivo randomizado, para comparar indivíduos adultos submetidos à RM com CEC, utilizando-se filtragem leucocitária (n=09) ou filtro standard (n=11) durante a CEC. Tomografia computadorizada (CT) de tórax, espirometria, análise da oxigenação e hemograma foram realizados antes da cirurgia. A anestesia foi induzida por via venosa com etomidato (0,3 mg.kg-1), sufentanil (0,3 ug.kg-1), pancurônio (0,08 mg.kg-1) e mantida com isoflurano (0,5 - 1,0 CAM) e sufentanil (0,5 ug.kg-1.h-1). A ventilação mecânica utilizou volume corrente de 8 mL.kg-1, com FiO2 de 0,6 e PEEP de 5 cm H2O, exceto durante a CEC. No grupo Filtragem, durante a CEC, foi inserido um filtro de leucócitos na linha arterial do circuito (LG-6, Pall Biomedical Products) e, no grupo Controle, foi utilizado o filtro Standard. Contagem leucocitária foi realizada após a indução, aos 5, 25 e 50 min de CEC, ao final da cirurgia, com 12 e 24 h PO. Dados hemodinâmicos, PaO2/FiO2, fração de Shunt, interleucinas, elastase e mieloperoxidase foram colhidos antes e após a CEC, no final da cirurgia, com 6,12 e 24 h PO. Trinta minutos depois da indução, e trinta após a CEC, três amostras sequenciais de ar exalado foram colhidas para análise de óxido nítrico (NO), por quimiluminescência. Espirometria e CT de tórax foram realizadas no primeiro dia pós-operatório. Os dados foram analisados por meio de ANOVA de duplo fator para medidas repetidas. RESULTADOS: O tempo de CEC foi similar entre os grupos controle e filtragem (86,78 ± 19,58 versus 104,64 ± 27,76 min, p=0,161). O grupo Filtragem mostrou menor contagem leucocitária que o grupo Controle até 50 min de CEC (3384 ± 2025 versus 6478 ± 3582 U.mm-3 U.mm-3, p=0,036), menor fração de shunt até 6 h PO (10 ± 2% versus 16 ± 5%, p=0,040) e menores níveis de IL-10 até o final da cirurgia (1571 ± 1137 pg.mL-1 versus 3108 ± 1694 pg.mL-1, p=0,031). Não houve diferença estatisticamente significativa entre os grupos em relação ao restante dos parâmetros avaliados (p > 0,05). CONCLUSÕES: A filtragem leucocitária durante a CEC, quando comparada à utilização de filtro convencional, promove diminuição da contagem de neutrófilos até 50 minutos de CEC, menor liberação de IL-10 até o final da cirurgia e menor alteração da fração de shunt intrapulmonar até 6 h PO, protegendo os pulmões apenas temporariamente contra a injúria aguda relacionada / BACKGROUND AND OBJECTIVE: The Cardiopulmonary bypass (CPB) is related to leukocyte activation, inflammatory response and lung dysfunction. The aim of this study was to evaluate the effects of CPB-leukocyte filtration on the inflammatory response and lung function after coronary artery bypass grafting (CABG). METHODS: After approval by the institutional ethics committee and informed consent, a prospective randomized study was performed to compare CABG-patients undergoing CPB-leukocyte filtration (n=9) or standard CPB (n=11). Espirometry, chest computed tomography (CT), oxygenation analysis and leukocyte count were performed before surgery. Anesthesia induction was performed intravenously with etomidate (0,3 mg.kg-1), sufentanil (0,3 ug.kg-1), pancuronium bromide (0,08 mg.kg-1) e sustained with isoflurano (0,5 - 1,0 CAM) and sufentanil (0,5 ug.kg-1.h-1). The tidal volume used during mechanical ventilation was 8 mL.kg-1, the FiO2 0.6 and PEEP 5 cm H2O, except during CPB. In Filtered group, during CPB, was inserted a leukocyte filter in the arterial line of CPB circuit (LG-6, Pall Biomedical Products) and, in Control group, the Standard arterial line filter was utilized. Hemodynamic data, PaO2/FiO2, shunt fraction, interleukins, elastase and myeloperoxidase were evaluated before and after CPB, at the end of surgery, and 6, 12 and 24 h PO. Thirty minutes after induction, and Thirty after CPB, three sequential exhaled air samples were collected to perform analysis of nitric oxide (NO), by chemiluminescence technique. Espirometry and chest CT were performed on first PO. Data were analyzed using two-factor ANOVA for repeated measurements. RESULTS: Length of CPB was similar in the filtered and control groups (86.78 ± 19.58 versus 104.64 ± 27.76 min, p = 0.161). The filtered group showed lower neutrophil counts than the control group up to 50 minutes of CPB (3384 ± 2025 versus 6478 ± 3582 U/mm-3, p = 0.036), lower shunt fraction up to 6 hours after surgery (10 ± 2% versus 16 ± 5%, p = 0.040), and lower levels of IL-10 at the end of surgery (1571 ± 1137 pg.ml-1 versus 3108 ± 1694 pg.ml-1, p = 0.031). There were no significant differences between the groups with respect to rest of the parameters evaluated (p >u0,05). CONCLUSIONS: The leukocyte filtration during CPB, when compared to the use of conventional filter, promotes lower neutrophil counts up to 50 minutes of CPB, lower levels of IL-10 at the end of surgery and lower shunt fraction up to 6 hours after surgery, protecting the lungs only temporarily against the acute injury related Trial registration: Clinicaltrials.gov identifier: NCT01469676

INTRODUÇÃO E OBJETIVOS: A Circulação extracorpórea (CEC) é associada a ativação leucocitária, resposta inflamatória e disfunção pulmonar. Objetivou-se avaliar os efeitos da filtragem leucocitária sobre a resposta inflamatória e a função pulmonar em indivíduos submetidos à revascularização do miocárdio (RM) com CEC. MÉTODO: Após aprovação pelo Comitê de Ética Institucional e obtenção do consentimento informado dos indivíduos, foi realizado estudo prospectivo randomizado, para comparar indivíduos adultos submetidos à RM com CEC, utilizando-se filtragem leucocitária (n=09) ou filtro standard (n=11) durante a CEC. Tomografia computadorizada (CT) de tórax, espirometria, análise da oxigenação e hemograma foram realizados antes da cirurgia. A anestesia foi induzida por via venosa com etomidato (0,3 mg.kg-1), sufentanil (0,3 ug.kg-1), pancurônio (0,08 mg.kg-1) e mantida com isoflurano (0,5 - 1,0 CAM) e sufentanil (0,5 ug.kg-1.h-1). A ventilação mecânica utilizou volume corrente de 8 mL.kg-1, com FiO2 de 0,6 e PEEP de 5 cm H2O, exceto durante a CEC. No grupo Filtragem, durante a CEC, foi inserido um filtro de leucócitos na linha arterial do circuito (LG-6, Pall Biomedical Products) e, no grupo Controle, foi utilizado o filtro Standard. Contagem leucocitária foi realizada após a indução, aos 5, 25 e 50 min de CEC, ao final da cirurgia, com 12 e 24 h PO. Dados hemodinâmicos, PaO2/FiO2, fração de Shunt, interleucinas, elastase e mieloperoxidase foram colhidos antes e após a CEC, no final da cirurgia, com 6,12 e 24 h PO. Trinta minutos depois da indução, e trinta após a CEC, três amostras sequenciais de ar exalado foram colhidas para análise de óxido nítrico (NO), por quimiluminescência. Espirometria e CT de tórax foram realizadas no primeiro dia pós-operatório. Os dados foram analisados por meio de ANOVA de duplo fator para medidas repetidas. RESULTADOS: O tempo de CEC foi similar entre os grupos controle e filtragem (86,78 ± 19,58 versus 104,64 ± 27,76 min, p=0,161). O grupo Filtragem mostrou menor contagem leucocitária que o grupo Controle até 50 min de CEC (3384 ± 2025 versus 6478 ± 3582 U.mm-3 U.mm-3, p=0,036), menor fração de shunt até 6 h PO (10 ± 2% versus 16 ± 5%, p=0,040) e menores níveis de IL-10 até o final da cirurgia (1571 ± 1137 pg.mL-1 versus 3108 ± 1694 pg.mL-1, p=0,031). Não houve diferença estatisticamente significativa entre os grupos em relação ao restante dos parâmetros avaliados (p > 0,05). CONCLUSÕES: A filtragem leucocitária durante a CEC, quando comparada à utilização de filtro convencional, promove diminuição da contagem de neutrófilos até 50 minutos de CEC, menor liberação de IL-10 até o final da cirurgia e menor alteração da fração de shunt intrapulmonar até 6 h PO, protegendo os pulmões apenas temporariamente contra a injúria aguda relacionada / BACKGROUND AND OBJECTIVE: The Cardiopulmonary bypass (CPB) is related to leukocyte activation, inflammatory response and lung dysfunction. The aim of this study was to evaluate the effects of CPB-leukocyte filtration on the inflammatory response and lung function after coronary artery bypass grafting (CABG). METHODS: After approval by the institutional ethics committee and informed consent, a prospective randomized study was performed to compare CABG-patients undergoing CPB-leukocyte filtration (n=9) or standard CPB (n=11). Espirometry, chest computed tomography (CT), oxygenation analysis and leukocyte count were performed before surgery. Anesthesia induction was performed intravenously with etomidate (0,3 mg.kg-1), sufentanil (0,3 ug.kg-1), pancuronium bromide (0,08 mg.kg-1) e sustained with isoflurano (0,5 - 1,0 CAM) and sufentanil (0,5 ug.kg-1.h-1). The tidal volume used during mechanical ventilation was 8 mL.kg-1, the FiO2 0.6 and PEEP 5 cm H2O, except during CPB. In Filtered group, during CPB, was inserted a leukocyte filter in the arterial line of CPB circuit (LG-6, Pall Biomedical Products) and, in Control group, the Standard arterial line filter was utilized. Hemodynamic data, PaO2/FiO2, shunt fraction, interleukins, elastase and myeloperoxidase were evaluated before and after CPB, at the end of surgery, and 6, 12 and 24 h PO. Thirty minutes after induction, and Thirty after CPB, three sequential exhaled air samples were collected to perform analysis of nitric oxide (NO), by chemiluminescence technique. Espirometry and chest CT were performed on first PO. Data were analyzed using two-factor ANOVA for repeated measurements. RESULTS: Length of CPB was similar in the filtered and control groups (86.78 ± 19.58 versus 104.64 ± 27.76 min, p = 0.161). The filtered group showed lower neutrophil counts than the control group up to 50 minutes of CPB (3384 ± 2025 versus 6478 ± 3582 U/mm-3, p = 0.036), lower shunt fraction up to 6 hours after surgery (10 ± 2% versus 16 ± 5%, p = 0.040), and lower levels of IL-10 at the end of surgery (1571 ± 1137 pg.ml-1 versus 3108 ± 1694 pg.ml-1, p = 0.031). There were no significant differences between the groups with respect to rest of the parameters evaluated (p >u0,05). CONCLUSIONS: The leukocyte filtration during CPB, when compared to the use of conventional filter, promotes lower neutrophil counts up to 50 minutes of CPB, lower levels of IL-10 at the end of surgery and lower shunt fraction up to 6 hours after surgery, protecting the lungs only temporarily against the acute injury related Trial registration: Clinicaltrials.gov identifier: NCT01469676