{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T19:32:40Z","timestamp":1773430360565,"version":"3.50.1"},"reference-count":33,"publisher":"European Respiratory Society (ERS)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2009,8,26]]},"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:p>Hypoxia and exertion are considered as the two main factors in the development of high-altitude pulmonary oedema (HAPE), however its pathophysiology remains unclear. Therefore, we established a model in which 32 Sprague\u2013Dawley rats were randomly assigned to normoxic rest, hypoxic rest, normoxic exercise and hypoxic exercise.<\/jats:p><jats:p>An altitude of 4,700\u2005m was simulated using hypobaric hypoxia, while exercise consisted 48\u2005h walk with 15\u201320\u2005min breaks every 4\u2005h. Arterial blood gas, bronchoalveolar lavage (BAL), lung wet-to-dry weight (W\/D) ratio and histological measurements were conducted on each animal.<\/jats:p><jats:p>In rats exercising in hypoxia, BAL protein and lung W\/D ratio were significantly increased but no changes in BAL leukotriene B<jats:sub>4<\/jats:sub>and immunoglobulin M were observed. In the same group, lung histology showed typical haemorrhagic lung oedema and disruption of both alveolar epithelium and capillary endothelium while hypoxia or exertion alone only induced slight endothelium and epithelium swelling\/disruption.<\/jats:p><jats:p>Our study established a direct link between histological and physiological evidence of HAPE-like symptoms and we demonstrated that hypoxia and exertion can synergistically induce HAPE-like symptoms in Sprague\u2013Dawley rats without inducing lung inflammation. 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