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

In order to investigate whether vascular endothelial growth factor (VEGF) a nd inflammatory pathways are activated during acute hypobaric hypoxia in su bjects who are susceptible to high-altitude pulmonary oedema (HAPE-S), seve n HAPE-S and five control subjects were exposed to simulated altitude corre sponding to 4000 m in a hypobaric chamber for 1 day. Peripheral venous bloo d was taken at 450 m (Zurich level) and at 4000 m, and levels of erythropoi etin (EPO), VEGF, interleukin-6 (IL-6) and the acute-phase proteins complem ent C3 (C3), alpha(1)-antitrypsin (alpha(1)AT), transferrin (Tf) and C-reac tive protein (CRP) were measured. Peripheral arterial oxygen saturation (Sa O2) was recorded. Chest radiography was performed before and immediately af ter the experiment. EPO increased during altitude exposure, correlating wit h SaO2, in both groups (r = -0.86, P < 0.001). Venous serum VEGF did not sh ow 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 alpha(1)AT le vels 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 significa nt elevations of IL-6, Tf or CRP were observed in either group. The post-ex posure 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 criticall y pulmonary vascular permeability during the Ist day at high altitude. Furt hermore, our data provide evidence against a clinically relevant inflammati on in the initial phase of exposure to hypoxia in HAPE-S, although C3 and a lpha(1)AT are mildly induced.