Intermittent hypoxia preconditioning can attenuate acute hypoxic injury after a sustained normobaric hypoxic exposure: A randomized clinical trial

Abstract

Abstract Background Intermittent hypoxia (IH) is emerging as a cost‐effective nonpharmacological method for vital organ protection. We aimed to assess the effects of a short‐term moderate intermittent hypoxia preconditioning protocol (four cycles of 13% hypoxia lasting for 10 min with 5‐min normoxia intervals) on acute hypoxic injury induced by sustained hypoxic exposure (oxygen concentration of 11.8% for 6 h). Methods One hundred healthy volunteers were recruited and randomized to the IH group and the control group to receive IH or sham‐IH preconditioning for 5 days, respectively, and then were sent to a hypoxic chamber for simulated acute high‐altitude exposure (4500 m). Results The overall incidence of acute mountain sickness was 27% (27/100), with 14% (7/50) in the IH group and 40% (20/50) in the control group ( p = 0.003). After 6‐h simulated high‐altitude exposure, the mean Lake Louise Score was lower in the IH group as compared to controls (1.30 ± 1.27 vs. 2.04 ± 1.89, p = 0.024). Mean peripheral oxygen saturations (SpO 2 ) and intracranial pressure (ICP) measures after acute hypoxic exposure exhibited significant differences, with the IH group showing significantly greater SpO 2 values (85.47 ± 5.14 vs. 83.10 ± 5.15%, p = 0.026) and lower ICP levels than the control group (115.59 ± 32.15 vs. 130.36 ± 33.83 mmH 2 O, p = 0.028). IH preconditioning also showed greater effects on serum protein gene product 9.5 (3.89 vs. 29.16 pg/mL; p = 0.048) and C‐reactive protein (−0.28 vs. 0.41 mg/L; p = 0.023). Conclusion The short‐term moderate IH improved the tolerance to hypoxia and exerted protection against acute hypoxic injury induced by exposure to sustained normobaric hypoxia, which provided a novel method and randomized controlled trial evidence to develop treatments for hypoxia‐related disease.

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