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Some limited data have been reported on the release of selected markers of angiogenesis, including VEGF in climbers exposed to high altitude with or without symptoms of acute mountain sickness (AMS). However, no study has explored the concomitant changes in VEGF, angiopoietin-2, and PGI2, as well as selected markers of inflammation and oxidation, concomitantly in relationship with good vs poor adaptation to high altitude.
We investigated the changes in selected markers of angiogenesis, prostaglandin, and some markers of subclinical inflammation and oxidative stress 24 hours prior to departure for the Bolivian Altiplano and within 24 hours of return to sea level. The objective of this expedition was to summit Mount Sajama, the highest peak in Bolivia, at an altitude of 6522 m. Participants were exposed to an altitude between 3600 and 6522 m for 19 days.
The study population consisted of 5 participants (4 males/1 female) aged 30 to 64 years living chronically at sea level. The diagnosis of AMS was performed using the Lake Louise
scoring systems at the highest point reached during the expedition.
From the 5 climbers, 2 participants developed moderately severe symptoms of AMS. One climber, aged 64 years, experienced mild headache, recurrent difficulty sleeping, profound fatigue, and dyspnea on minimal exertion at an altitude of 4800 m (Hackett score = 4; Lake Louise score = 6). This climber stopped his climb at 5300 m. One participant developed some fatigue and severe intractable headache at 5680 m and returned to base camp at 4800 m (Hackett score = 3; Lake Louise score = 4). Data are presented in the Table.
TableChanges in plasma markers prior to departure and within 24 hours upon return to sea level*
This exploratory study reports for the first time the plasma levels of multiple mediators of angiogenesis and selected markers of inflammation and oxidative stress concomitantly in 5 healthy volunteers prior to departure and within 24 hours of returning from 19 days on the Bolivian Altiplano. We report different plasma levels of VEGF and PGI2 in 2 climbers who experienced poor adaptation to high altitude. Here, we report a marked increase in VEGF and PGI2 within 24 hours of returning from an altitude of more than 4000 m for 19 days in the older climber who experienced some delay in the acclimatization process but who also exhibited some cardiopulmonary features of poor adaptation to high altitude. These observations contrast with the findings from the climber who experienced AMS mostly with central nervous system symptoms.
Vascular endothelial growth factor concentrations before the expedition were consistent with levels reported in previous investigations. The change in VEGF in response to high altitude has been a matter of controversy. Reports have shown no increase or a significant increase within 20 hours to 7 days upon exposure to an altitude of 3600 m or higher.
reported no evidence of an association between AMS and changes in VEGF at either 3650 or 5200 m. However, the clinical characteristics and the mode of presentation of AMS were incompletely reported in that specific study. In addition, none of these reports involved exposure to high altitude for more than a week. Here we also reported a concomitant increase in PGI2 level in the climber suffering from poor cardiopulmonary adaptation to high altitude, indicating a significant increase in cardiovascular stress.
There are some significant limitations to these observations. Vascular endothelial growth factor levels were not measured at different periods of the acclimatization process nor later during the expedition. In addition, VEGF soluble receptor-fms-related tyrosine kinase 1 was not measured. The participant with poor cardiopulmonary adaptation to high altitude was much older than the other climbers. Also, the small sample size did not allow for adjustment for the age effect, nor did it allow for further analyses about the relationship between clinical characteristics and biomarkers.
In conclusion, our study demonstrates that there were no significant changes in selected markers of angiogenesis, inflammation, and oxidative stress in climbers who did not experience mountain sickness, whereas in the 2 participants who experienced mountain sickness, the plasma concentrations of these biomarkers were perturbed. Vascular endothelial growth factor and PGI2 may be associated with poor cardiopulmonary maladaptation to high altitude. Whether these vascular biomarkers are truly related to altitude illness or inadequate acclimatization requires study in a larger population.
Tissot van Patot M.C.
Greater free plasma VEGF and lower soluble VEGF receptor-1 in acute mountain sickness.