Prabhakaran P, Tripathi KK. Autonomic modulations during 5 hours at 4574 m (15,000 ft) breathing 40% oxygen. Aviat Space Environ Med 2011; 82:863–70. Introduction: This study was done to evaluate the effects of exposure to hyperoxic hypobaria on the autonomic reactivity and hence G tolerance of high-performance aircraft aircrews. Methods: Heart rate variability (HRV) indices and traditional measures of autonomic functions were measured during normobaric baseline, hourly at hyperoxic hypobaria for 5 h, and during normobaric recovery in 15 subjects at an equivalent altitude of 4574 m breathing 40% oxygen. Results: Supine and resting-sitting R-R interval, E:I ratio, and time domain indices of HRV increased significantly, with no change in Valsalva ratio. Power in both low- (LF) and high-frequency (HF) bands of HRV spectra increased significantly, which persisted even after normalization with mean R-R² (LF 1177 ± 801 at baseline to 1837 ± 1032 at 5 h and HF 944 ± 683 at baseline to 1545 ± 1095 at 5 h). Pressor response to handgrip was attenuated, as evident from a significant interaction between the effects of handgrip and hypobaria. Discussion: Increases in R-R interval, E:I ratio, and all the time domain indices of HRV and HF power suggest an increase in parasympathetic influences. Increase in LF power is explained by the ability of the parasympathetic system to modulate the HRV spectrum in regions lower than respiratory frequency. Attenuation of pressor response to isometric handgrip contraction could have resulted from an increase in the transmural pressure gradient across the carotid sinuses due to hypobaria, which can adversely affect the anti-G straining maneuver.