Oxygen administration, in concentrations of 60% or less, is being widely used in clinical medicine for the correction of arterial hypoxemia, as if it were innocuous. However, animals exposed to 60% O2 for seven days, developed microscopic lesions in the pulmonary capillary endothelium identified by light and electron microscopy. The physiological implications of these findings have not been documented. Our general objective is to correlate structural alterations with physiological changes in lungs of animals exposed to sublethal levels of O2. We will further establish whether these changes are permanent or reversible when the animals resume breathing air, and quantify whether the presence of acute and chronic lung injury exacerbates or delays the onset of severity of the oxygen induced damage. Conscious, unanesthetized, chronically instrumented sheep, will be exposed to 45 and 60% O2 at 1 ata for two weeks and then returned to air for an additional two weeks. Acute and chronic lung injury will be produced by the intratracheal instillation of bleomycin. The following variables will be measured periodically throughout the exposure: Minute ventilation and respiratory frequency, arterial and mixed venous oxygen and carbon dioxide tensions and pH, cardiac output, vascular and pleural pressures, functional residual capacity, the distribution of the pulmonary blood flow, the permeability of the alveolar epithelium and capillary endothelium to solute, and the pulmonary extravascular volumes of distribution of albumin and cyanocobalamin. These variables will be correlated with simultaneous histological, morphological and gravimetric measurements of lung tissue. Our results will establish whether exposure of the normal and injured lung to sublethal oxygen concentrations causes physiological damage (i.e. derangement of lung fluid balance, mechanics and hemodynamics) before or in the absence of overt clinical symptoms (i.e. impairment of gas exchange).
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