A total of 108 adult male Sprague–Dawley rats (Envigo, Casatenovo, Italy) with an initial weight of 211 ± 28 g (mean ± SD) were used in the study. Animals were housed at 25°C ± 2°C and maintained on a 12-h light–dark cycle, with ad libitum access to water and food (even during cold and hypoxia exposures). After 1 week of quarantine, rats were randomly divided into four groups: (1) control (CTRL), maintained in normoxia at 25°C; (2) intermittent cold exposed (COLD); (3) IHH exposed (HYPO); and (4) rats simultaneously submitted to intermittent cold and hypobaric hypoxia (COHY). Animals from these different groups were submitted to the assigned intervention procedure for 9 or 21 days.

All procedures were performed in accordance with European Union guidelines for the care and management of laboratory animals and were under license from the Catalan authorities (reference no. 1899), as approved by the University of Barcelona’s Ethical Committee for Animal Experimentation.

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