Subacute Hypoxic Exposure Increases Lung Transvascular Protein Escape in Rats

Abstract

Pulmonary edema occasionally develops following rapid ascent to high altitude. Despite wide recognition of the clinical features and natural history of this condition, its pathophysiology remains poorly understood. Considerable debate exists concerning the relative roles of increases in hydrostatic pressure and vascular permeability in leading to the development of edema at altitude. Although pulmonary artery pressures are significantly elevated in this condition, several features suggest that increases in vascular permeability may play a role in high-altitude pulmonary edema. First, findings from autopsy studies 1 Arias-Stella J Kruger H Pathology of high altitude pulmonary edema. Arch Pathol. 1963; 70: 43-53 Google Scholar and analysis of bronchoalveolar lavage 2 Schoene RB Swenson ER Pizzo C Maunder RJ Roach RC Hackett PH et al. High altitude pulmonary edema: Comparison with other forms of lung injury. Am Rev Respir Dis. 1986; 133: A269 PubMed Google Scholar demonstrate significant elevations of protein content, suggesting a breakdown in the normal vascular barrier to protein flux. In addition, pulmonary capillary wedge and left atrial pressures are consistently normal in this condition, suggesting by exclusion that a permeability defect is responsible for the development of the edema. 3 Hultgren JN High altitude pulmonary edema. in: Staub NC Lung water and solute exchange. Marcel Dekker, New York1978: 437-469 Abstract Full Text Full Text PDF Google Scholar However, direct attempts to measure hypoxia-induced increases in vascular permeability have produced conflicting results that may reflect differences in experimental design, animal species, or in the methods used to measure vascular permeability, which may not have been sensitive enough to detect mild degrees of lung injury. The purpose of this study was to determine whether abrupt exposure to simulated altitude in a hypobaric facility led to increases in pulmonary vascular permeability in rats using a technique capable of differentiating changes in surface area recruitment from changes in vascular barrier function. 4 Dauber I Pluss WT Van Grondelle A Trow RS Weil JV Specificity and sensitivity of noninvasive measurement of pulmonary vascular protein leak. J Appl Physiol. 1985; 59: 564-574 PubMed Google Scholar