The long term goal is to define the factors which control lung microvascular pressure (Pmv), which is the most important determinant of lung water and solute exchange. The issue is crucial to the further understanding of the basic pathophysiology of pulmonary edema. To determine the regulation of Pmv, mechanisms of segment specific vasoconstriction will be investigated by the lung micropuncture technique. A major advance will be the establishment of the open-thorax, anesthetized rabbit preparation for intact lung micropuncture. During brief periods of arrested ventilation, lung microvessels viewed directly through a microscope, will be micropunctured for pressure measurement by the servo-null technique. Specific hypotheses to be tested are that pulmonary vasoconstrictors such as 5-Hydroxytryptamine, histamine, norepinephrine and hypoxia, cause postcapillary vasoconstriction. The significance is that postcapillary vasoconstriction may increase Pmv, hence promote pulmonary edema. Therefore the mechanisms of postcapillary vasoconstriction must be determined in lungs of living animals. An additional experiment will be to test the hypothesis that the oxygen radical causes segmental vasoconstriction in lung. For this, intact lungs will be micropunctured to determine segmental Pmv in rabbits prior exposed to long term hyperoxia. In a separate series involving micropuncture of the isolated blood perfused rat lung, segmental Pmv will be determined to test hypotheses concerning segmental vasoconstriction attributable to calcium loading or to calcium channel potentiation. An important new experiment will be to micropuncture the intact lung of infant rabbit in which hypotheses concerning distribution of Pmv and sites of hypoxic vasoconstriction will be tested. The results of these investigations will elucidate fundamental mechanisms in the regional control of Pmv. Consequently, they will significantly improve understanding of the basic pathophysiology of pulmonary edema in adults and infants.
| Bhattacharya, S; Fu, C; Bhattacharya, J et al. (1995) Soluble ligands of the alpha v beta 3 integrin mediate enhanced tyrosine phosphorylation of multiple proteins in adherent bovine pulmonary artery endothelial cells. J Biol Chem 270:16781-7 |
