Key pointsr This study assessed the respective contributions of haematological and skeletal muscle adaptations to any observed improvement in peak oxygen uptake (V O 2 peak ) induced by endurance training (ET).rV O 2 peak , peak cardiac output (Q peak ), blood volumes and skeletal muscle biopsies were assessed prior (pre) to and after (post) 6 weeks of ET. Following the post-ET assessment, red blood cell volume (RBCV) reverted to the pre-ET level following phlebotomy andV O 2 peak andQ peak were determined again.r We speculated that the contribution of skeletal muscle adaptations to an ET-induced increase inV O 2 peak could be identified when offsetting the ET-induced increase in RBCV.rV O 2 peak ,Q peak , blood volumes, skeletal muscle mitochondrial volume density and capillarization were increased after ET. Following RBCV normalization,V O 2 peak andQ peak reverted to pre-ET levels.r These results demonstrate the predominant contribution of haematological adaptations to any increase inV O 2 peak induced by ET.Abstract It remains unclear whether improvements in peak oxygen uptake (V O 2 peak ) following endurance training (ET) are primarily determined by central and/or peripheral adaptations. Herein, we tested the hypothesis that the improvement inV O 2 peak following 6 weeks of ET is mainly determined by haematological rather than skeletal muscle adaptations. Sixteen untrained healthy male volunteers (age = 25 ± 4 years,V O 2 peak = 3.5 ± 0.5 l min −1 ) underwent supervised ET (6 weeks, 3-4 sessions per week).V O 2 peak , peak cardiac output (Q peak ), haemoglobin mass (Hb mass ) and blood volumes were assessed prior to and following ET. Skeletal muscle biopsies were analysed for mitochondrial volume density (Mito VD ), capillarity, fibre types and respiratory capacity (OXPHOS). After the post-ET assessment, red blood cell volume (RBCV) was re-established at the pre-ET level by phlebotomy andV O 2 peak andQ peak were measured again. We speculated that the contribution of skeletal muscle adaptations to the ET-induced increase inV O 2 peak would be revealed when controlling for haematological adaptations.V O 2 peak andQ peak were increased (P < 0.05) following ET (9 ± 8 and 7 ± 6%, respectively) and decreased (P < 0.05) after phlebotomy (−7 ± 7 and −10 ± 7%). RBCV, plasma volume and Hb mass all increased (P < 0.05) after ET (8 ± 4, 4 ± 6 and 6 ± 5%). As for skeletal muscle adaptations, capillary-to-fibre ratio and total Mito VD increased (P < 0.05) following ET (18 ± 16 and 43 ± 30%), but OXPHOS remained unaltered. Through stepwise multiple regression analysis,Q peak , RBCV and Hb mass were found to be independent predictors ofV O 2 peak . In conclusion, the improvement inV O 2 peak following 6 weeks of ET is primarily attributed to increases inQ peak and oxygen-carrying capacity of blood in untrained healthy young subjects.

High altitude (HA) exposure facilitates a rapid contraction of plasma volume (PV) and a slower occurring expansion of hemoglobin mass (Hbmass). The kinetics of the Hbmass expansion has never been examined by multiple repeated measurements, and this was our primary study aim. The second aim was to investigate the mechanisms mediating the PV contraction. Nine healthy, normally trained sea-level (SL) residents (8 males, 1 female) sojourned for 28 days at 3,454 m. Hbmass was measured and PV was estimated by carbon monoxide rebreathing at SL, on every 4th day at HA, and 1 and 2 wk upon return to SL. Four weeks at HA increased Hbmass by 5.26% (range 2.5-11.1%; P < 0.001). The individual Hbmass increases commenced with up to 12 days of delay and reached a maximal rate of 4.04 ± 1.02 g/day after 14.9 ± 5.2 days. The probability for Hbmass to plateau increased steeply after 20-24 days. Upon return to SL Hbmass decayed by -2.46 ± 2.3 g/day, reaching values similar to baseline after 2 wk. PV, aldosterone concentration, and renin activity were reduced at HA (P < 0.001) while the total circulating protein mass remained unaffected. In summary, the Hbmass response to HA exposure followed a sigmoidal pattern with a delayed onset and a plateau after ∼3 wk. The decay rate of Hbmass upon descent to SL did not indicate major changes in the rate of erythrolysis. Moreover, our data support that PV contraction at HA is regulated by the renin-angiotensin-aldosterone axis and not by changes in oncotic pressure.

Mito increased with 55 ± 9% (P < 0.001), whereas the number of mitochondrial profiles per area of skeletal muscle remained unchanged following training. Citrate synthase activity (CS) increased (44 ± 12%, P < 0.001); however, there were no functional changes in oxidative phosphorylation capacity (OXPHOS, CI+II ) or cytochrome c oxidase (COX) activity. Correlations were found between Mito and CS (P = 0.01; r = 0.58), OXPHOS, CI+CIIP (P = 0.01; R = 0.58) and COX (P = 0.02; R = 0.52) before training; after training, a correlation was found between Mito and CS activity only (P = 0.04; R = 0.49). Intrinsic respiratory capacities decreased (P < 0.05) with training when respiration was normalized to Mito This was not the case when normalized to CS activity although the percentage change was comparable CONCLUSIONS: Mito was increased by inducing mitochondrial enlargement rather than de novo biogenesis. CS activity may be appropriate to track training-induced changes in Mito