EVIDENCE AGAINST AN INCREASE IN CAPILLARY-PERMEABILITY IN SUBJECTS EXPOSED TO HIGH-ALTITUDE

A potential pathogenetic cofactor for the development of acute mountai n sickness and high-altitude pulmonary edema is an increase in capilla ry permeability, which could occur as a result of an inflammatory reac tion and/or free radical-mediated injury to the lung. We measured the systemic albumin escape by intravenously injecting 5 mu Ci of I-125-la beled albumin and the plasma concentrations of cytokines, F-2-isoprost anes (products of lipid peroxidation), and acute-phase proteins in 24 subjects exposed to 4,559 m. Ten subjects developed acute mountain sic kness, 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 in significant 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, alpha(-)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 t he subjects with high-altitude pulmonary edema, whereas tumor necrosis factor-alpha and F-2-isoprostanes did not change at all. This suggest s that the inflammatory reaction was rather a consequence than a causa tive factor of high-altitude pulmonary edema. In summary, these data a rgue against a dominant role for increased systemic capillary permeabi lity in the development of acute mountain sickness and high-altitude p ulmonary edema.