A stable rat model of high altitude pulmonary edema established by hypobaric hypoxia combined diurnal temperature fluctuation and exercise

Abstract

Hypobaric hypoxia (HH) is regarded as the main cause of high-altitude pulmonary edema (HAPE), however, the effect of diurnal temperature fluctuation and exercise has been overlooked. The aim of current study was to elucidate the role of diurnal temperature fluctuation and exercise in the development of HAPE and establish a reliable experimental rat model. Male SPF Wistar rats were assigned to control group (1400 m, 25 °C) and five model groups: Model Ⅰ group (6000 m, 25 °C), Model Ⅱ group (6000 m, 2 °C), Model Ⅲ group (6000 m, 12 °C/2 °C light/dark cycle), Model IV group (6000 m, 2 °C, and exercise) and Model V group (6000 m, 12 °C/2 °C light/dark cycle, and exercise). After exposure for 72 h, the blood and lung tissues were collected for further research. The rats in Model I group did not show signs of HAPE. Compared with Model I group, the rats in Model II and Model III groups were suffered from more damage, evidence by enhanced oxidative stress and inflammatory reaction, but still did not show signs of HAPE. Model IV and Model V could induce HAPE, display the obvious pathological changes and edema, more serious oxidative stress and inflammatory reaction in lung tissues, suggesting that the key role of exercise in the development of HAPE. The rats in the Model V group showed the best performance in terms of modeling indicators, indicating that diurnal temperature fluctuation could further aggravate the degree of lung edema. In summary, HH combined with diurnal temperature fluctuation and exercise is a stable and reliable modeling method for HAPE, which can be used for subsequent research on the prevention and treatment of HAPE.

Keywords: Cold stress; Diurnal temperature fluctuation; Exercise; Experimental animal model; High altitude pulmonary edema.