Impact of venous return on pulmonary oxygen uptake kinetics during dynamic exercise: in silico time series analyses from muscles to lungs

The aim of the present study was to investigate whether a single-compartment (SCM) and a multi-compartment (MCM) venous return model will produce significantly different time-delaying and distortive effects on pulmonary oxygen uptake (V̇o2pulm) responses with equal cardiac outputs (Q̇) and muscle oxygen uptake (V̇o2musc) inputs. For each model, 64 data sets were simulated with alternating Q̇ and V̇o2musc kinetics—time constants (τ) ranging from 10 to 80 s—as responses to pseudorandom binary sequence work rate (WR) changes. Kinetic analyses were performed by using cross-correlation functions (CCFs) between WR with V̇o2pulm and V̇o2musc. Higher maxima of the CCF courses indicate faster system responses—equal to smaller τ values of the variables of interest (e.g., τV̇o2musc). The models demonstrated a highly significant relationship for the resulting V̇o2pulm responses ( r = 0.976, P < 0.001, n = 64). Both models showed significant differences between V̇o2pulm and V̇o2musc kinetics for τV̇o2musc ranging from 10 to 30 s ( P < 0.05 each). In addition, a significant difference in V̇o2pulm kinetics ( P < 0.05) between the models was observed for very fast V̇o2musc kinetics (τ = 10 s). The combinations of fast Q̇ dynamics and slow V̇o2musc kinetics yield distinct deviations in the resultant V̇o2pulm responses compared with V̇o2musc kinetics. Therefore, the venous return models should be used with care and caution if the aim is to infer V̇o2musc by means of V̇o2pulm kinetics. Finally, the resultant V̇o2pulm responses seem to be complex and most likely unpredictable if no cardiodynamic measurements are available in vivo. NEW & NOTEWORTHY A single-compartment and a multi-compartment venous return model were tested to see whether they result in different pulmonary oxygen uptake (V̇o2pulm) kinetics from equal cardiac output and muscle oxygen uptake (V̇o2musc) kinetics. To infer V̇o2musc kinetics by means of V̇o2pulm kinetics, both models should only be used for V̇o2musc time constants ranging from 40 to 80 s. The resultant V̇o2pulm responses seem to be complex and most likely unpredictable if no cardiodynamic measurements are available.

Skeletal muscle blood flow and oxygen uptake at rest and during exercise in humans: a pet study with nitric oxide and cyclooxygenase inhibition

The aim of the present study was to determine the effect of nitric oxide and prostanoids on microcirculation and oxygen uptake, specifically in the active skeletal muscle by use of positron emission tomography (PET). Healthy males performed three 5-min bouts of light knee-extensor exercise. Skeletal muscle blood flow and oxygen uptake were measured at rest and during the exercise using PET with H2O15 and 15O2 during: 1) control conditions; 2) nitric oxide synthase (NOS) inhibition by arterial infusion of NG-monomethyl-l-arginine (l-NMMA), and 3) combined NOS and cyclooxygenase (COX) inhibition by arterial infusion of l-NMMA and indomethacin. At rest, inhibition of NOS alone and in combination with indomethacin reduced ( P < 0.05) muscle blood flow. NOS inhibition increased ( P < 0.05) limb oxygen extraction fraction (OEF) more than the reduction in muscle blood flow, resulting in an ∼20% increase ( P < 0.05) in resting muscle oxygen consumption. During exercise, muscle blood flow and oxygen uptake were not altered with NOS inhibition, whereas muscle OEF was increased ( P < 0.05). NOS and COX inhibition reduced ( P < 0.05) blood flow in working quadriceps femoris muscle by 13%, whereas muscle OEF and oxygen uptake were enhanced by 51 and 30%, respectively. In conclusion, by specifically measuring blood flow and oxygen uptake by the use of PET instead of whole limb measurements, the present study shows for the first time in humans that inhibition of NO formation enhances resting muscle oxygen uptake and that combined inhibition of NOS and COX during exercise increases muscle oxygen uptake.

Low blood flow at onset of moderate-intensity exercise does not limit muscle oxygen uptake

The effect of low blood flow at onset of moderate-intensity exercise on the rate of rise in muscle oxygen uptake was examined. Seven male subjects performed a 3.5-min one-legged knee-extensor exercise bout (24 ± 1 W, mean ± SD) without (Con) and with (double blockade; DB) arterial infusion of inhibitors of nitric oxide synthase ( NG-monomethyl-l-arginine) and cyclooxygenase (indomethacin) to inhibit the synthesis of nitric oxide and prostanoids, respectively. Leg blood flow and leg oxygen delivery throughout exercise was 25–50% lower ( P < 0.05) in DB compared with Con. Leg oxygen extraction (arteriovenous O2 difference) was higher ( P < 0.05) in DB than in Con (5 s: 127 ± 3 vs. 56 ± 4 ml/l), and leg oxygen uptake was not different between Con and DB during exercise. The difference between leg oxygen delivery and leg oxygen uptake was smaller ( P < 0.05) during exercise in DB than in Con (5 s: 59 ± 12 vs. 262 ± 39 ml/min). The present data demonstrate that muscle blood flow and oxygen delivery can be markedly reduced without affecting muscle oxygen uptake in the initial phase of moderate-intensity exercise, suggesting that blood flow does not limit muscle oxygen uptake at the onset of exercise. Additionally, prostanoids and/or nitric oxide appear to play important roles in elevating skeletal muscle blood flow in the initial phase of exercise.