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)

Orientador: Renato Guiseppe Terzi / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T22:34:54Z (GMT). No. of bitstreams: 1 Ferreira_JulianaHeloisaTerra_M.pdf: 2639255 bytes, checksum: fcee62586088020b3a17254a5a9df91f (MD5) Previous issue date: 2006 / Resumo: A literatura aborda de forma muito ampla os mecanismos responsáveis pela gênese da hipoxemia no tromboembolismo pulmonar (TEP). O objetivo deste estudo foi analisar quais os mecanismos que contribuíram para a hipoxemia em um modelo de TEP agudo experimental. A embolização com coágulos autólogos foi realizada em sete porcos com peso de 24,00±0,6 kg, anestesiados e mecanicamente ventilados na modalidade controlada, com fração de oxigênio no ar inspirado (FiO2) de 0,21. A análise do intercâmbio gasoso foi realizada pela correlação entre a gasometria arterial e a capnografia volumétrica. Foi observada uma significativa redução das pressões parciais de oxigênio tanto no sangue arterial quanto no ar alveolar calculada pela equação do ar alveolar. A ventilação alveolar efetiva apresentou significativa redução, evidenciando a consistente queda do volume de gás alveolar que efetivamente participou das trocas gasosas (VAef). A relação entre a ventilação alveolar que efetivamente participou das trocas gasosas e o débito cardíaco (V¿Aef/Q¿), também apresentou uma redução significativa após a embolização. Embora a pressão parcial de dióxido de carbono (CO2) no sangue arterial aumente significativamente, a pressão parcial de CO2 no final da expiração (PetCO2) apresentou significativa redução, retornando ao basal aos quarenta minutos após a embolia. Conseqüentemente, a diferença artério-alveolar de pressão parcial de dióxido de carbono (P(a-et)CO2) aumentou significativamente. Houve um aumento de espaço morto alveolar e fisiológico. Concluímos, com base nos dados obtidos que a grave hipoxemia arterial observada pode ser explicada por redução da pressão alveolar de oxigênio, além da redução da ventilação alveolar efetiva e da razão V¿Aef/Q¿. Também demonstramos que a razão V¿Aef/Q¿ aumentou progressivamente depois da embolização, um fato atribuído, ou por lise dos trombos, ou por redistribuição da ventilação alveolar induzida por broncoconstrição hipocápnica / Abstract: The literature broadly approaches the mechanisms responsible for the genesis of the hypoxemia in pulmonary embolism (PE). The aim of this study is to analyze the ventilation/perfusion ratio, which contributed to the hypoxemia in PE by analyzing blood gases and volumetric capnography in a model of experimental acute PE. Pulmonary embolization with autologous blood clots was carried out in seven pigs weighing 24.00±0.6Kg, anesthetized and mechanically ventilated. A significant reduction in the oxygen partial pressures was observed in both, the arterial blood and alveolar air. The effective alveolar ventilation exhibited a significant reduction consistent with the fall in the alveolar gas volume that effectively participated in gas exchange. The relation between the alveolar ventilation that effectively participated in gas exchange and cardiac output (V¿Aeff/Q¿ ratio) also presented a significant reduction after embolization. The carbon dioxide partial pressure increased significantly in the arterial blood (PaCO2), but decreased significantly in the exhaled air at the end of the respiratory cycle (PetCO2). PetCO2 returned to baseline values forty minutes after embolism. The arterial to alveolar carbon dioxide gradient (P(a-et)CO2), increased significantly, as well as the calculated alveolar and physiological dead spaces. We conclude, based on our data, that the severe arterial hypoxemia observed in this experimental model may be attributed to the reduction of the effective alveolar ventilation ratio (V¿Aeff/Q¿). We were also able to demonstrate that V¿Aeff/Q¿ progressively improves after embolization, a fact attributed to the lysis of thromby or by alveolar ventilation redistribution induced by hypocapnic bronchoconstriction / Mestrado / Pesquisa Experimental / Mestre em Cirurgia

The mismatching of alveolar ventilation and perfusion (VA/Q) is the major determinant of impaired gas exchange. The gold standard for analyzing VA/Q distribution is the multiple inert gas elimination technique (MIGET), conventionally based on gas chromatography (GC), and, although simple in principle, a technically demanding procedure limiting its use. A new technique based on micropore membrane inlet mass spectrometry (MMIMS) combined MIGET with mass spectrometry, simplifying the sample handling process, and potentially providing VA/Q distributions for a general clinical approach. The kinetics of volatile anesthetics are well known in patients with healthy lungs. The uptake and distribution of inhaled anesthetics have usually been modeled by physiologic models. However, these models have limitations, and they do not consider ventilation/perfusion matching. Respiratory diseases account for a large part of morbidity and mortality and are associated with pulmonary VA/Q mismatch that may affect uptake and elimination of volatile anesthetics. The objectives of the studies were firstly to investigate assessment of VA/Q mismatch by MMIMS and secondly to investigate the effects of asthma-like VA/Q mismatch on the kinetics of volatile anesthetics in an experimental porcine model. Anesthetized and mechanically ventilated piglets were studied. In study I, a direct comparison of MIGET by MMIMS with the conventional MIGET by GC in three animal models that covered a wide range of VA/Q distributions was preformed. The two methods agreed well, and parameters derived from both methods showed good agreement with externally measured references. In studies II–IV, a stable method of inducing and maintaining asthma-like VA/Q mismatch with methacholine (MCh) administration was established, and the effect of VA/Q mismatch on the pharmacokinetics of desflurane and isoflurane was investigated. The present model of bronchoconstriction demonstrates a delay in volatile anesthetic uptake and elimination, related to the heterogeneity of MCh-inhalation induced ventilation. The difference in solubility of volatile anesthetics has a significant influence on their uptake and elimination under VA/Q mismatch. The higher blood soluble isoflurane is affected to a lesser degree than the fairly insoluble desflurane.

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.