Methods to measure pulmonary blood flow (PBF) and extravascular lung water (EVLW) would be of value in both experimental and clinical investigation if they were quantitative, accurate, repeatable and non-invasive. Current techniques for the measurement of regional PBF and EVLW lack these desirable features. We propose that PET (positron emission tomography) can be used to make such measurements. Initial work by us has shown the feasibility of using PET for this purpose. Experiments proposed within this grant application will further validate our techniques. Subsequently, our methods will be used to investigate the relationship of gas exchange to PBF and EVLW during acute experimental respiratory failure. Our PET method for measuring regional PBF is an adaptation of the """"""""PET-autoradiographic"""""""" technique previously validated for use in studies of cerebral blood flow. Methods for further validating the results obtained by this model in PBF studies will include microsphere and angiographic techniques. For EVLW, as measured by PET, our method entails the subtraction of measurements of regional blood volume from those of an equilibrium distribution of 15O-labelled water. For these studies, gravimetric analyses will be used as the primary method of validation. Experiments are planned to resolve how changes in regional lung inflation and cardiac output affect our calculations of PBF and EVLW by PET. Further experiments are designed to investigate the sensitivity of our methods to changes in blood flow due to vascular obstruction, or hypoxic vasoconstriction, and to changes in EVLW due to experimental pulmonary edema. Finally, we will attempt to correlate patterns of PBF and EVLW to abnormalities in gas exchange due to acute experimental lung injury. We believe such studies will also form the appropriate ground work for application of these techniques to human studies of acute circulatory and respiratory failure. The repeatable, non-invasive, yet highly quantitative nature of PET should make it possible to test specific management strategies not easily evaluated with current techniques. In addition, these studies should be viewed as a first step toward the wider application of PET technology (e.g. metabolism, ventilation) to the study of pulmonary pathophysiology.
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