This thesis includes four research papers, based on four separate studies aiming to elucidate the importance of O2 extraction and blood volume (BV) for maximal O2 uptake (VO2max).
In study I, twelve untrained subjects (VO2max: 44 ml · kg-1 · min-1) completed ten weeks of supervised endurance training (three sessions per week). VO2max and maximal cardiac output (Qmax) were measured during upright and supine cycling before and after training, as well as immediately after the training-induced gain in BV was reversed by blood withdrawal. The supine position increases venous return to the heart and may thus counteract potential adverse effects of blood withdrawal. The BV increased by 4% (~2 dl) with training. After reversing BV to the pre-training level, VO2max and Qmax remained 11% and 9% higher than before training, respectively, regardless of exercise position. By using the Fick principle (VO2 = Q × a-v ̅O2diff), it was calculated that 30% and 70% of the increase in VO2max was attributed to increased O2 content difference between arterial and mixed venous blood (a-v ̅O2diff) and increased Qmax, respectively. These improvements coincided with increased protein content of mitochondrial enzymes, a small increase in the capillary-to-fibre ratio (m. vastus lateralis) and an increased left ventricular mass (echocardiography). Thus, VO2max may increase with endurance training independent of BV expansion, caused by combined central and peripheral adaptations.
In study II, thirteen subjects (VO2max: 63 ml · kg-1 · min-1) performed maximal exercise on a cycle ergometer in three experimental conditions: with normal BV and immediately after acute BV reductions of 150 ml and 450 ml, representing 2.5% and 7.6% of the total BV (6.0 l), respectively. After the 150 ml reduction, VO2max was preserved compared with the control test (non-significant reduction of 1%), likely caused by a rapid plasma volume (PV) restoration (calculated from changes in haematocrit and haemoglobin concentration). After the 450 ml BV reduction, VO2max was reduced by 7% despite partial PV restoration, increased maximal heart rate and increased leg O2 extraction as indicated by near-infrared spectroscopy. The reduction in VO2max was 2.5-fold larger after withdrawing 450 compared with 150 ml blood after normalising to the BV removed. Therefore, the body may cope with small but not moderate blood loss to preserve VO2max. These data may enhance our understanding regarding the impact of, e.g., acute BV manipulations, PV reduction following dehydration induced by prolonged exercise or hyperthermia, or daily oscillations of PV.
In study III, the muscle oxidative capacity in one leg was increased by six weeks of one-legged endurance training (3-4 sessions per week) in nine subjects (VO2max: 56 ml · kg-1 · min-1). The impact on leg O2 extraction fraction (arterial and femoral venous catheters) vs the untrained control leg was investigated during dynamic two-legged knee extension exercise with both legs performing the same power output. This exercise model involves a small muscle mass, does not tax Qmax and is thus not perfusion limited. Therefore, the muscle oxidative capacity may potentially be the principal limiting factor for O2 extraction and VO2 before training. At low to moderate exercise intensities, O2 extraction fraction was similar in both legs. At higher exercise intensities, which are associated with greater mitochondrial activation and lower time for haemoglobin-O2 off-loading, the O2 extraction fraction was increased in the trained leg. The between-leg difference in O2 extraction correlated with the between-leg difference in mitochondrial protein content (m. vastus lateralis). Therefore, our data suggest that endurance training improves O2 extraction in exercise models where the mitochondria do not possess an apparent excess oxidative capacity over O2 delivery, particularly when the exercise intensity is close to maximal.
In study IV, the relationships between pulmonary VO2max and systemic and leg O2 extraction fractions were investigated by statistically analysing data from 43 previously published catheterisation studies, comprising 377 subjects. It was observed that a-v ̅O2diff (mostly calculated by the Fick principle, and Qmax measured by the indicator-dilution method) increased curvilinearly and reached its maximum at ~4.5 l · min-1 in VO2max (moderately trained subjects), and was, if anything, slightly lower in those subjects with the highest VO2max (> 5 l · min-1). However, after accounting for the hypoxemia-induced lowering of arterial O2 content (CaO2) with increasing VO2max, the calculated systemic O2 extraction fraction (a-v ̅O2diff / CaO2) increased with VO2max up to ~4.5-5.0 l · min-1 and approached a plateau at ~90%. This pattern was strengthened by the direct measurements using arterial and femoral venous catheters, with leg O2 extraction fraction increasing progressively with VO2max until reaching ~90-95%. These analyses emphasise that a-v ̅O2diff and systemic O2 extraction fraction cannot be used interchangeably, and that the systemic and peripheral O2 extraction fractions improves with increasing VO2max and training status. By using the theoretical model of Piiper and Scheid, it appeared that the limiting factors to VO2max change with increasing VO2max: untrained, but healthy individuals display mixed perfusion-diffusion limitations, and this diffusion limitation reduces as VO2max increase.