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Introduction. Acute exposure to high altitude induces inflammation. However, the relationship between inflammation and high altitude related illness such as high altitude pulmonary edema (HAPE) and acute mountain sickness (AMS) is poorly understood. We tested if soluble urokinase-type plasminogen activator receptor (suPAR) plasma concentration, a prognostic factor for cardiovascular disease and marker for low grade activation of leukocytes, will predict susceptibility to HAPE and AMS. Methods. 41 healthy mountaineers were examined at sea level (SL, 446 m) and 24 h after rapid ascent to 4559 m (HA). 24/41 subjects had a history of HAPE and were thus considered HAPE-susceptible (HAPE-s). Out of the latter, 10/24 HAPE-s subjects were randomly chosen to suppress the inflammatory cascade with dexamethasone 8 mg bid 24 h prior to ascent. Results. Acute hypoxic exposure led to an acute inflammatory reaction represented by an increase in suPAR (1.9 ± 0.4 at SL versus 2.3 ± 0.5 at HA, p < 0.01), CRP (0.7 ± 0.5 at SL versus 3.6 ± 4.6 at HA, p < 0.01), and IL-6 (0.8 ± 0.4 at SL versus 3.3 ± 4.9 at HA, p < 0.01) in all subjects except those receiving dexamethasone. The ascent associated decrease in PaO2 correlated with the increase in IL-6 (r = 0.46, p < 0.001), but not suPAR (r = 0.27, p = 0.08); the increase in IL-6 was not correlated with suPAR (r = 0.16, p = 0.24). Baseline suPAR plasma concentration was higher in the HAPE-s group (2.0 ± 0.4 versus 1.8 ± 0.4, p = 0.04); no difference was found for CRP and IL-6 and for subjects developing AMS. Conclusion. High altitude exposure leads to an increase in suPAR plasma concentration, with the missing correlation between suPAR and IL-6 suggesting a cytokine independent, leukocyte mediated mechanism of low grade inflammation. The correlation between IL-6 and PaO2 suggests a direct effect of hypoxia, which is not the case for suPAR. However, suPAR plasma concentration measured before hypoxic exposure may predict HAPE susceptibility.

We have previously demonstrated that prophylactic intake of dexamethasone improves maximal oxygen uptake (Vo(2)max) in high altitude pulmonary edema (HAPE) susceptible subjects 4 to 6 h after a 2-day climb to 4559 m. However, since with this ascent protocol HAPE usually develops after the first night at 4559 m or later, we hypothesized that a continued dexamethasone prophylaxis would result in an even more pronounced improvement of Vo(2)max after an additional night at high altitude. Vo(2)max of 24 HAPE susceptibles was evaluated on a bicycle ergometer at an altitude of 490 m and at 24 h after rapid ascent to 4559 m. Subjects were divided into two groups: The control group (n=14) performed both tests without dexamethasone, whereas the dexamethasone group (n=10) received dexamethasone 8 mg twice a day (b.i.d), starting 24 h prior to ascent. At 4559 m, Vo(2)max was 61% ± 6% of the baseline value in the control group and 70% ± 9% in the dexamethasone group (p=0.025). Similarly, O(2) pulse (Vo(2)/heart rate) was 68% ± 7% and 77% ± 11% of baseline, respectively (p=0.043). Arterial O(2) saturation at maximal exercise did not differ between groups, whereas at rest it was 83% ± 10% in the control group and 91% ± 4% in the dexamethasone group (p=0.009). Dexamethasone prophylaxis increased Vo(2)max of HAPE-susceptible individuals after the first night at 4559 m without affecting arterial O(2) saturation at maximal exercise. This might be explained by a sustained effect of dexamethasone on maximal cardiac output and pulmonary O(2) diffusion, both resulting in enhanced convectional O(2) transport to the locomotor muscles., (© Mary Ann Liebert, Inc.)