Hypoxia gradually augments metabolic and thermoperceptual responsiveness to repeated whole-body cold stress in humans.

We examined whether hypoxia would modulate thermoeffector responses during repeated cold stress encountered in a single day. Eleven men completed two ∼10 h sessions, while breathing, in normobaria, either normoxia or hypoxia ( P O 2 : 12 kPa). During each session, subjects underwent sequentially three 120 min immersions to the chest in 20°C water (CWI), interspersed by 120 min rewarming. In normoxia, the final drop in rectal temperature (Trec ) was greater in the third (∼1.2°C) than in the first and second (∼0.9°C) CWIs (P < 0.05). The first hypoxic CWI augmented the Trec fall (∼1.2°C; P = 0.002), but the drop in Trec did not vary between the three hypoxic CWIs (P = 0.99). In normoxia, the metabolic heat production ( M ̇ ) was greater during the first half of the third CWI than during the corresponding part of the first CWI (P = 0.02); yet the difference was blunted during the second half of the CWIs (P = 0.89). In hypoxia, by contrast, the increase in M ̇ was augmented by ∼25% throughout the third CWI (P < 0.01). Regardless of the breathing condition, the cold-induced elevation in mean arterial pressure was blunted in the second and third CWI (P < 0.05). Hypoxia aggravated the sensation of coldness (P = 0.05) and thermal discomfort (P = 0.04) during the second half of the third CWI. The present findings therefore demonstrate that prolonged hypoxia mediates, in a gradual manner, metabolic and thermoperceptual sensitization to repeated cold stress.