RT Journal Article SR Electronic T1 Stress failure plays a major role in the development of high-altitude pulmonary oedema in rats JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 584 OP 591 DO 10.1183/09031936.00001709 VO 35 IS 3 A1 C. Bai A1 J. She A1 A. Goolaerts A1 Y. Song A1 C. Shen A1 J. Shen A1 Q. Hong YR 2010 UL http://erj.ersjournals.com/content/35/3/584.abstract AB 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–Dawley rats were randomly assigned to normoxic rest, hypoxic rest, normoxic exercise and hypoxic exercise. An altitude of 4,700 m was simulated using hypobaric hypoxia, while exercise consisted 48 h walk with 15–20 min breaks every 4 h. Arterial blood gas, bronchoalveolar lavage (BAL), lung wet-to-dry weight (W/D) ratio and histological measurements were conducted on each animal. In rats exercising in hypoxia, BAL protein and lung W/D ratio were significantly increased but no changes in BAL leukotriene B4 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. 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–Dawley rats without inducing lung inflammation. We therefore propose that alveolar epithelium and capillary endothelium stress failure play a major role in the development of HAPE.