Purpose Endurance athletes often compete and train at altitude where exercise capacity is reduced. Investigating acclimation strategies is therefore critical. Ischemic preconditioning (IPC) can improve endurance performance at sea level through improved O2 delivery and utilization, which could also prove beneficial at altitude. However, data are scarce, and there is no study at altitudes commonly visited by endurance athletes. Methods In a randomized, crossover study, we investigated performance and physiological responses in 13 male endurance cyclists during four 5-km cycling time trials (TT), preceded by either IPC (3 × 5 min ischemia/5-min reperfusion cycles at 220 mm Hg) or SHAM (20 mm Hg) administered to both thighs, at simulated low (FIO2 0.180, ~1200 m) and moderate (FIO2 0.154, ~2400 m) altitudes. Time to completion, power output, cardiac output (Q?), arterial O2 saturation (SpO2), quadriceps tissue saturation index (TSI) and RPE were recorded throughout the TT. Differences between IPC and SHAM were analyzed at every altitude using Cohen effect size (ES) and compared with the smallest worthwhile change. Results At low altitude, IPC possibly improved time to complete the TT (-5.2 s, -1.1%; Cohen ES ± 90% confidence limits -0.22, -0.44; 0.01), power output (2.7%; ES 0.21, 0.08; 0.51), and Q? (5.0%; ES 0.27, 0.00; 0.54), but did not alter SpO2, muscle TSI, and RPE. At moderate altitude, IPC likely enhanced completion time (-7.3 s; -1.5%; ES -0.38, -0.55; -0.20), and power output in the second half of the TT (4.6%; ES 0.28, -0.15; 0.72), increased SpO2 (1.0%; ES 0.38, -0.05; 0.81), and decreased TSI (-6.5%; ES -0.27, -0.73; 0.20) and RPE (-5.4%, ES -0.27, -0.48; -0.06). Conclusions Ischemic preconditioning may provide an immediate and effective strategy to defend SpO2 and enhance high-intensity endurance performance at moderate altitude.
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