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 (V̇o_2pulm) responses with equal cardiac outputs (Q̇) and muscle oxygen uptake (V̇o_2musc) inputs. For each model, 64 data sets were simulated with alternating Q̇ and V̇o_2musc 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 V̇o_2pulm and V̇o_2musc. Higher maxima of the CCF courses indicate faster system responses-equal to smaller τ values of the variables of interest (e.g., τV̇o_2musc). The models demonstrated a highly significant relationship for the resulting V̇o_2pulm responses ( r = 0.976, P < 0.001, n = 64). Both models showed significant differences between V̇o_2pulm and V̇o_2musc kinetics for τV̇o_2musc ranging from 10 to 30 s ( P < 0.05 each). In addition, a significant difference in V̇o_2pulm kinetics ( P < 0.05) between the models was observed for very fast V̇o_2musc kinetics (τ = 10 s). The combinations of fast Q̇ dynamics and slow V̇o_2musc kinetics yield distinct deviations in the resultant V̇o_2pulm responses compared with V̇o_2musc kinetics. Therefore, the venous return models should be used with care and caution if the aim is to infer V̇o_2musc by means of V̇o_2pulm kinetics. Finally, the resultant V̇o_2pulm 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 (V̇o_2pulm) kinetics from equal cardiac output and muscle oxygen uptake (V̇o_2musc) kinetics. To infer V̇o_2musc kinetics by means of V̇o_2pulm kinetics, both models should only be used for V̇o_2musc time constants ranging from 40 to 80 s. The resultant V̇o_2pulm responses seem to be complex and most likely unpredictable if no cardiodynamic measurements are available.