HIGHCARE , medical research on Himalaya-Everest

Having accumulated four years’ experience of high altitude research at Monte Rosa (Hut Regina Margherita, 4559 m a.s.l.), Istituto Auxologico Italiano (Ospedale S. Luca, Milano, Osp. S. Giuseppe, Piancavallo, Verbania) and University of Milano-Bicocca (Dept. of Clinical Medicine and Prevention) organize an expedition aimed to assess the physiological changes induced by the exposure to more marked and more prolonged hypobaric hypoxia and to determine how these changes may be influenced by angiotensin AT1 receptor blockade and by other non-pharmacological interventions.
A number of other Institutions have been invited to participate in the project, either directly or through their cultural support and contribution.
The expedition will take place in the Himalaya region around Mount Everest, on the Chinese/Tibetan side if possible, otherwise on the Nepal side. Most of data collection will be made at Mt. Everest Base Camp (5300 m a.s.l.) and at Mt. Everest Advanced Base Camp (6400 m a.s.l), while a subgroup of alpinists will attempt to collect data also during the ascent to Mt. Everest summit (8848 m a.s.l.).
Most of the physiological changes occurring at high altitude are due to decreased atmospheric pressure leading to hypoxia and hypoxemia. The study of the high altitude exposure is important because it allows a better understanding of the mechanisms of adaptation to high altitude and of acute mountain sickness (AMS) but also because this condition may serve as a model to explore the pathophysiology and to test therapeutic interventions of diseases associated with tissue hypoxia, such as chronic heart failure, chronic obstructive pulmonary disease, arterial hypertension related to sleep apnoea syndrome and/or severe obesity.
This involves the assessment of pharmacological and non-pharmacological treatment strategies not only for AMS related symptoms, but also and more importantly for chronic pathological conditions accompanied by hypoxemia. This makes high altitude medical research interesting also in the perspective of better understanding and treating such conditions.
Renin-angiotensin-aldosterone system (RAAS) is involved in the pathogenesis a number of cardiovascular pathological conditions, including hypertension and heart failure, and drugs interfering with RAAS, including AT1 angiotensin receptor blockers, are beneficial in these conditions.
High altitude induces important changes in RAAS although the exact character of these changes is poorly understood. Moreover, so far no information on the effects of AT1 inhibition in this setting is available.
Telmisartan is one of AT1 antagonists, characterized by a prolonged effect which allows 24h coverage with a single daily dose. It has also been suggested to exert metabolic effects through PPAR-gamma agonism. This feature may be relevant at high altitude since insulin sensitivity is reduced in this condition.
Based on our previous research in the Alps, two non-pharmacologic interventions aimed at counteracting high altitude hypoxia have been shown to have immediate efficacy in terms of improvement in oxygen exchange: controlled slow breathing and continuous positive airway pressure (CPAP) application. However, the mechanisms underlying this improvement are still not adequately understood.

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