The Effects of Acute Hypoxia on Tissue Oxygenation and Circulating Alarmins in Healthy Adults

The binding of high-mobility group box-1 (HMGB-1) to the membrane receptor for advanced glycation end-products (mRAGE) is a key early mediator of non-infectious inflammation and its triggers include ischaemia/hypoxia. The effects of acute hypoxia on soluble RAGE (sRAGE) are unknown. Fourteen healthy adults (50% women; 26.6±3.8 years) were assessed at baseline normoxia (T0), followed by four time-points (T90, 95, 100 and 180 minutes) over three hours of continuous normobaric hypoxia (NH, 4450m equivalent) and again 60 minutes after return to normoxia (T240). A 5-minute exercise step-test was performed during NH at T90. Plasma concentrations of HMGB-1, sRAGE VCAM-1, ICAM-1, VEGF IL-8 and IL-13 were measured using venous blood. Arterial and tissue oxygen saturations were measured using pulse oximetry (SpO2) and near-infrared spectroscopy (StO2) respectively. NH led to a significant reduction in SpO2, StO2, sRAGE and VEGF, which was compounded by exercise, before increasing to baseline values with normoxic restoration (T240). NH-Exercise led to a paired increase in HMGB-1. sRAGE inversely correlated with HMGB-1 (r=-0.32; p=0.006), heart rate (r=-0.43; p=0.004) but was not linked to SpO2 or StO2. In conclusion short-term NH leads to a fall in sRAGE and VEGF concentrations with a transient rise post NH-exercise in HMGB-1.

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