Effects of hypobaric hypoxia on vascular endothelial growth factor and the acute phase response in subjects who are susceptible to high-altitude pulmonary oedema.

In order to investigate whether vascular endothelial growth factor (VEGF) and inflammatory pathways are activated during acute hypobaric hypoxia in subjects who are susceptible to high-altitude pulmonary oedema (HAPE-S), seven HAPE-S and five control subjects were exposed to simulated altitude corresponding to 4000 m in a hypobaric chamber for 1 day. Peripheral venous blood was taken at 450 m (Zürich level) and at 4000 m, and levels of erythropoietin (EPO), VEGF, interleukin-6 (IL-6) and the acute-phase proteins complement C3 (C3), alpha1-antitrypsin (alpha1AT), transferrin (Tf) and C-reactive protein (CRP) were measured. Peripheral arterial oxygen saturation (SaO2) was recorded. Chest radiography was performed before and immediately after the experiment. EPO increased during altitude exposure, correlating with SaO2, in both groups (r = -0.86, P < 0.001). Venous serum VEGF did not show any elevation despite a marked decrease in SaO2 in the HAPE-S subjects [mean (SD) HAPE-S: 69.6 (9.1)%; controls: 78.7 (5.2)%]. C3 and alpha1AT levels increased in HAPE-S during hypobaric hypoxia [from 0.94 (0.11) g/l to 1.07 (0.13) g/l, and from 1.16 (0.08) g/l to 1.49 (0.27) g/l, respectively; P < 0.05], but remained within the clinical reference ranges. No significant elevations of IL-6, Tf or CRP were observed in either group. The post-exposure chest radiography revealed no signs of oedema. We conclude that VEGF is not up-regulated in HAPE-S and thus does not seem to increase critically pulmonary vascular permeability during the 1st day at high altitude. Furthermore, our data provide evidence against a clinically relevant inflammation in the initial phase of exposure to hypoxia in HAPE-S, although C3 and alpha1AT are mildly induced.