Remote ischemic preconditioning delays the onset of acute mountain sickness in normobaric hypoxia

Abstract

Acute mountain sickness (AMS) is a neurological disorder occurring when ascending too fast, too high. Remote ischemic preconditioning (RIPC) is a noninvasive intervention protecting remote organs from subsequent hypoxic damage. We hypothesized that RIPC protects against AMS and that this effect is related to reduced oxidative stress. Fourteen subjects were exposed to 18 hours of normoxia (21% oxygen) and 18 h of normobaric hypoxia (12% oxygen, equivalent to 4500 m) on different days in a blinded, randomized order. RIPC consisted of four cycles of lower limb ischemia (5 min) and 5 min of reperfusion, and was performed immediately before the study room was entered. A control group was exposed to hypoxia (12% oxygen, n = 14) without RIPC. AMS was evaluated by the Lake Louise score (LLS) and the AMS-C score of the Environmental Symptom Questionnaire. Plasma concentrations of ascorbate radicals, oxidized sulfhydryl (SH) groups, and electron paramagnetic resonance (EPR) signal intensity were measured as biomarkers of oxidative stress. RIPC reduced AMS scores (LLS: 1.9 ± 0.4 vs. 3.2 ± 0.5; AMS-C score: 0.4 ± 0.1 vs. 0.8 ± 0.2), ascorbate radicals (27 ± 7 vs. 65 ± 18 nmol/L), oxidized SH groups (3.9 ± 1.4 vs. 14.3 ± 4.6 μmol/L), and EPR signal intensity (0.6 ± 0.2 vs. 1.5 ± 0.4 × 10(6)) after 5 h in hypoxia (all P < 0.05). After 18 hours in hypoxia there was no difference in AMS and oxidative stress between RIPC and control. AMS and plasma markers of oxidative stress did not correlate. This study demonstrates that RIPC transiently reduces symptoms of AMS and that this effect is not associated with reduced plasma levels of reactive oxygen species.

Keywords: AMS; high altitude; oxidative stress; prevention; reactive oxygen species.

Figure 1

Study protocol. RIPC was performed by four 5-min cycles of lower limb ischemia interspaced with 5 min of reperfusion. Due to the nature of the intervention blinding subjects with respect to RIPC was not possible. Therefore, the data obtained in hypoxia (study day B) were compared with control data obtained in a previous study from 14 subjects that were exposed to hypoxia (FiO₂ = 0.12) without RIPC (historic control).(Schommer et al. 2012) AMS scores were assessed with the Lake Louise score and the AMS-C score of the Environmental Symptom Questionnaire. Venous blood samples were drawn from a catheter inserted into a cubital vein for the analyses of reactive oxygen species (ROS), and capillary blood samples were taken from the hyperemic ear lobe for blood gas measurements.

Figure 2

(A) Severity of AMS as evaluated by the Lake Louise score, and by the AMS-C score of the Environmental Symptom Questionnaire (B). A Lake Louise score of ≥5 points and an AMS-C score of ≥0.7 points represents AMS. H-RIPC: group exposed to hypoxia undergoing RIPC. H-Control: group exposed to hypoxia without RIPC. *P < 0.05 vs. H-Control.