Pik Lenin High Altitude Research Expedition 2009

Cell-derived Microparticles, Oxidative Stress

expedition, hypoxia, blood coagulation disorders, cell-derived microparticles, oxidative stress, N-Acetylcystein, vitamins

Exposure to hypobaric hypoxia demands maximum effort of the body and can lead to high altitude illnesses. Recently, there is rising interest on coagulation activation during trekking and mountaineering in higher regions and on development of oxidative stress due to hypoxia. 30 volunteers have been examined during an high altitude research expedition to the 7134m high mount Pik Lenin in Kyrgyzstan to investigate mechanisms of coagulation activation and effects of antioxidant supplements on oxidative stress.

Reactions to acute exposure to high altitude and the process of acclimatization has been of scientific interest since many years. High altitude illnesses are specified by three different entities: acute mountain sickness (AMS), high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). Prevalence of AMS is known to be between 10 to 20% for altitudes between 4000 and 5000m, increasing significantly in higher altitude. The prevalence depends on the ascent rate, individual susceptibility and physical exhaustion. Although mechanisms leading to high altitude illnesses are not yet completely clear some progress has been made. It is well accepted that excessive pulmonary hypertension may lead to HAPE. Furthermore, there is rising evidence about endothelial dysfunction being involved in disease progression. Some cellular and molecular mechanisms of acute (hypobaric) hypoxia, possibly leading to endothelial dysfunction, have been studied in a few experimental and field settings. Paradoxical increase in systemic oxidative stress is seen under hypoxic conditions, such as high altitude stay. Reactive oxygen species (ROS) could be demonstrated in many endothelial disorders and capillary leakage syndromes such as septicaemia, myocardial infarct and stroke. Furthermore, coagulation activation might result from endothelial dysfunction but also amplify endothelial interruption. Still, most of our knowledge concerning effects of hypoxia in general but also concerning oxidative stress is from in vitro studies (e.g. cancer cells). In the context of a high altitude expedition human subjects can safely be submitted to prolonged hypoxia to explore generation of ROS and extent of procoagulatory state. Objective The purpose of our study is to confirm excessive oxidative stress found in our previous study in 2005 and to investigate whether oxidative stress during high altitude exposure can be modified by dietary supplementations of specific antioxidants. Moreover, we like to study mechanisms of coagulation activation by assessing extent of thrombocytic and endothelial microparticles. Methods After approval of the study by the regional ethics committee, written informed consent has been obtained from 30 healthy volunteers (low land residents with mountaineering experience, age 18-65 years). After baseline testing, double-blind randomization into 2 groups of 15 persons took place. One group received oral medication with vitamin E, vitamin C, vitamin A and acetylcystein daily, while the other group was provided with an identical appearing placebo preparation. Substitution started 2 month before the expedition. After examination at ground 0 in Zurich (409m) all members underwent testing in Base Camp (3550m), twice in advanced Base Camp (4550m), in Camp 1 (5430m), and in Camp 2 (6265m). Beside blood sampling, clinical examinations were performed. Metabolomics, a mass-spectrometry based analysis, for measurement of oxidative stress, will be performed. In a subgroup microparticles will be detected by annexin V based ELISA and by flow cytometry using specific antibodies.

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