Exercise At Simulated Altitude Increases Gastrointestinal Barrier Damage And Promotes Leukocyte Activation

Abstract

PURPOSE: This study tested whether altitude-associated ischemic stress damages the gastrointestinal barrier, activates leukocytes, and promotes inflammation. METHODS: Subjects (N = 5) completed two 60 min bouts of matched-workload treadmill exercise (65% VO2max). One under control conditions (Normoxia, FIO2 = 20.9%) and the other at ~4000 m of simulated altitude (Hypoxia, FIO2 = 13.5%). Pulse oximetry was used to measure peripheral oxygen saturation (SpO2) and near-infrared spectroscopy was used to measure absolute tissue saturation (StO2) at 5 min intervals throughout exercise. Fatty acid-binding protein (I-FABP), markers of leukocyte activation (CD14, ICAM-1, IL-8, MCP-1, MPO), and cytokines (TNFα, IL-1β, IL-6, IL-10, IL-12) were measured in plasma samples that were collected Pre, Post, 1hr-Post, and 4hr-Post exercise. Data were analyzed with 2-Way (Condition x Time) RM ANOVAs with significance set at p ≤ 0.05. Post hocs (Newman-Keuls) were run where appropriate. RESULTS: Significant reductions in SpO2 and StO2 were shown during exercise at simulated altitude [(SpO2: Hypoxia = 79 ± 1% vs Normoxia = 94 ± 0.5%, p = 0.03) (StO2: Hypoxia = 61 ± 2 vs Normoxia = 69 ± 2, p < 0.01)]. A significant interaction effect was shown for I-FABP (p = 0.05), with post hoc analysis indicating I-FABP increased more from Pre to Post in Hypoxia (112%) than in Normoxia (30%). IL-8 increased more from Pre to Post (60%) and 1hr-Post (83%) in Hypoxia than in Normoxia (33% & 57%, respectively). Significant main effects were also shown for IL-6, ICAM-1, CD14, and MCP-1. All were higher in Hypoxia (p ≤ 0.05). MPO increased at Post in Normoxia (121%, p = 0.05) but did not increase until 1hr-Post in Hypoxia (129%, p = 0.02). CONCLUSIONS: Preliminary data suggest exercise at altitude may increase gastrointestinal barrier damage and leukocyte activation, as indicated by higher levels of I-FABP, IL-8, and MCP-1. Increased CD14 and ICAM-1 suggest TLR4-mediated inflammatory signaling may also be elevated, but the delayed increase in MPO following exercise at altitude warrants further investigation.