Evidence against an increase in capillary permeability in subjects exposed to high altitude

Gian-Reto Kleger, Peter Bärtsch, Peter Vock, Bernhard Heilig, L. Jackson Roberts II, and Peter E. Ballmer Departments of Medicine and Radiology, University of Bern, Inselspital, CH-3010 Bern; Department of Medicine, Kantonsspital, CH-7000 Chur, Switzerland; Departments of Sports Medicine and Hematology, University of Heidelberg, D-69115 Heidelberg, Germany; and Departments of Pharmacology and Medicine, Vanderbilt University, Nashville, Tennessee 37232-6602 Received 10 November 1995; accepted in final form 25 June 1996. Kleger, Gian-Reto, Peter Bärtsch, Peter Vock, Bernhard Heilig, L. Jackson Roberts II, and Peter E. Ballmer. Evidence against an increase in capillary permeability in subjects exposed to high altitude. J. Appl. Physiol. 81(5): 1917-1923, 1996. A potential pathogenetic cofactor for the development of acute mountain sickness and high-altitude pulmonary edema is an increase in capillary permeability, which could occur as a result of an inflammatory reaction and/or free radical-mediated injury to the lung. We measured the systemic albumin escape by intravenously injecting 5 µCi of 125 I-labeled albumin and the plasma concentrations of cytokines, F 2 -isoprostanes (products of lipid peroxidation), and acute-phase proteins in 24 subjects exposed to 4,559 m. Ten subjects developed acute mountain sickness, and four subjects developed high-altitude pulmonary edema. The transcapillary escape rate of albumin was 6.9 ± 2.0%/h (SD) at low (550 m) and 6.3 ± 1.9%/h at high (4,559 m) altitude ( P = 0.23; n = 24). The subjects with high-altitude pulmonary edema had a modest but insignificant increase in the transcapillary escape rate of albumin (4.6 ± 1.9%/h at low vs. 5.7 ± 1.9%/h at high altitude; P = 0.42; n = 4). Plasma concentrations of fibrinogen, 1 -acid glycoprotein, C-reactive protein, and interleukin-6 were unchanged in the early phases and significantly increased by the end of the observation period in the subjects with high-altitude pulmonary edema, whereas tumor necrosis factor- and F 2 -isoprostanes did not change at all. This suggests that the inflammatory reaction was rather a consequence than a causative factor of high-altitude pulmonary edema. In summary, these data argue against a dominant role for increased systemic capillary permeability in the development of acute mountain sickness and high-altitude pulmonary edema. vascular permeability; high-altitude pulmonary edema; acute mountain sickness; free radicals; F 2 -isoprostanes 0161-75