We have developed techniques to measure regional pulmonary blood flow (PBF), extravascular lung water (EVLW), and pulmonary vascular permeability to protein macromolecules, with positron emission tomography (PET) and appropriately labeled radionuclides. These methods will allow us to test the following hypothesis: The effect that regional PBF has on EVLW accumulation depends on the state of pulmonary vascular permeability at the time. If this is true, then pharmacologic maneuvers which decrease regional PBF while vascular permeability is abnormally elevated, should decrease the accumulation of regional EVLW. Thereafter, once vascular permeability has returned to normal (or near normal), increasing regional PBF may also affect the resolution of excess EVLW, depending on whether clearance of pulmonary edema occurs at least partially via the circulation or whether re- perfusion can lead to additional endothelial cell injury. Thus, the specific aims of the current application are: 1. To continue our validation of regional PBF and EVLW measurements with PET 2. To evaluate the quantitative importance of and temporal changes in vasoreactivity during experimental acute lung injury. 3. To evaluate the effects of changing regional PBF on EVLW accumulating and resolution during experimental acute lung injury. Our ability to make regional measurements of PBF, EVLW and vascular permeability, repetitively and non-invasively, allows us to test this hypothesis and to achieve our specific aims. Results from these studies could provide important new therapeutic approaches to illnesses such as the adult respiratory distress syndrome. In the absence of specific measures to treat this or similar syndromes, it is important to investigate means which could limit EVLW accumulation or hasten its resolution. Even if our hypothesis is not true, our studies will yield important new knowledge about the pathophysiologic interaction of PBF and vascular permeability on EVLW accumulation during acute lung injury.
Showing the most recent 10 out of 27 publications
