Spencer MD, Murias JM, Grey TM, Paterson DH. Regulation of VO 2 kinetics by O2 delivery: insights from acute hypoxia and heavy-intensity priming exercise in young men. J Appl Physiol 112: 1023-1032, 2012. First published December 22, 2011 doi:10.1152/japplphysiol.01215.2011.-This study examined the separate and combined effects of acute hypoxia (Hypo) and heavy-intensity "priming" exercise (Hvy) on pulmonary O 2 uptake (V O2p) kinetics during moderate-intensity exercise (Mod). Breath-by-breath V O2p and near-infrared spectroscopy-derived muscle deoxygenation {deoxyhemoglobin concentration [HHb]} were monitored continuously in 10 men (23 Ϯ 4 yr) during repetitions of a Mod 1-Hvy-Mod 2 protocol, where each of the 6-min (Mod or Hvy) leg-cycling bouts was separated by 6 min at 20 W. Subjects were exposed to Hypo [fraction of inspired O 2 (FIO 2 ) ϭ 15%, Mod 2 ϩ Hypo] or "sham" (FI O 2 ϭ 20.9%, Mod 2-N) 2 min following Hvy in half of these repetitions; Mod was also performed in Hypo without Hvy (Mod 1 ϩ Hypo). On-transient V O2p and [HHb] responses were modeled as a monoexponential. Data were scaled to a relative percentage of the response (0 -100%), the signals were time-aligned, and the individual [HHb]-to-V O2 ratio was calculated. Compared with control (Mod 1), V O2p and the O2 deficit (26 Ϯ 7 s and 638 Ϯ 144 ml, respectively) were reduced (P Ͻ 0.05) in Mod 2-N (20 Ϯ 5 s and 529 Ϯ 196 ml) and increased (P Ͻ 0.05) in Mod 1 ϩ Hypo (34 Ϯ 14 s and 783 Ϯ 184 ml); in Mod 2 ϩ Hypo, V O2p was increased (30 Ϯ 8 s, P Ͻ 0.05), yet O 2 deficit was unaffected (643 Ϯ 193 ml, P Ͼ 0.05). The modest "overshoot" in the [HHb]-to-V O2 ratio (reflecting an O 2 delivery-to-utilization mismatch) in Mod 1 (1.06 Ϯ 0.04) was abolished in Mod 2-N (1.00 Ϯ 0.05), persisted in Mod 2 ϩ Hypo (1.09 Ϯ 0.07), and tended to increase in Mod 1 ϩ Hypo (1.10 Ϯ 0.09, P ϭ 0.13). The present data do not support an "O 2 delivery-independent" speeding of V O2p following Hvy (or Hvy ϩ Hypo); rather, this study suggests that local muscle O2 delivery likely governs the rate of adjustment of V O2 at V O2p greater than ϳ20 s. oxygen extraction; oxygen distribution; muscle blood flow; nearinfrared spectroscopy THE FUNDAMENTAL ADJUSTMENT of pulmonary O 2 uptake (V O 2p ) kinetics displays an exponential profile during the on-transient to moderate-intensity exercise (Mod). Whether the rate of this adjustment, given by the V O 2p time constant (V O 2p ), is limited by factors related to local muscle O 2 availability, intracellular factors related to metabolic substrate provision and enzyme activation, or a combination of both remains a topic of debate. Poole et al. (30) proposed that there is a "point" beyond which O 2 uptake (V O 2 ) kinetics are O 2 -dependent, such that the provision of O 2 becomes limiting and, thus, V O 2 is lengthened. While this proposal has received much attention within the literature, it has yet to be demonstrated that provision of "additional" O 2 resolves any potential O 2 delivery limitation.In contrast to this possibility, Grassi et...