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Relating pulmonary oxygen uptake to muscle oxygen consumption at exercise onset: in vivo and in silico studies

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Abstract

Assessment of the rate of muscle oxygen consumption, UO2m, in vivo during exercise involving a large muscle mass is critical for investigating mechanisms regulating energy metabolism at exercise onset. While UO2m is technically difficult to obtain under these circumstances, pulmonary oxygen uptake, VO2p, can be readily measured and used as a proxy to UO2m. However, the quantitative relationship between VO2p and UO2m during the nonsteady phase of exercise in humans, needs to be established. A computational model of oxygen transport and utilization—based on dynamic mass balances in blood and tissue cells—was applied to quantify the dynamic relationship between model-simulated UO2m and measured VO2p during moderate (M), heavy (H), and very heavy (V) intensity exercise. In seven human subjects, VO2p and muscle oxygen saturation, StO2m, were measured with indirect calorimetry and near infrared spectroscopy (NIRS), respectively. The dynamic responses of VO2p and StO2m at each intensity were in agreement with previously published data. The response time of muscle oxygen consumption, \(\tau_{{\rm UO}_{{2{\rm m}}}},\) estimated by direct comparison between model results and measurements of StO2m was significantly faster (P < 0.001) than that of pulmonary oxygen uptake, \(\tau_{{\rm VO}_{{2{\rm p}}}},\) (M: 13 ± 4 vs. 65 ± 7 s; H: 13 ± 4 vs. 100 ± 24 s; V: 15 ± 5 vs. 82 ± 31 s). Thus, by taking into account the dynamics of oxygen stores in blood and tissue and determining muscle oxygen consumption from muscle oxygenation measurements, this study demonstrates a significant temporal dissociation between UO2m and VO2p at exercise onset.

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Abbreviations

A :

Response of VO2p, VO2m, and UO2m at the onset of exercise (l O2 min−1)

A ss :

Response of VO2p, VO2m, and UO2m at steady state condition (l O2 min−1)

C Hb :

Concentration of Hb in the whole body (g l−1)

C rbc,Hb :

Concentration of Hb in the red blood cell (mM)

C mc,Mb :

Concentration of Mb in myocyte (mM)

\(C_{x}^{{\rm B}}\) :

Bound oxygen concentration in artery, capillary, and tissue (mM)

\(C_{x}^{{\rm F}}\) :

Free oxygen concentration in artery, capillary, and tissue (mM)

\(C_{x}^{{\rm T}}\) :

Total oxygen concentration in artery, capillary, and tissue (mM)

H body :

Body height (m)

Hct:

Hematocrit (fraction of red blood cells in blood) (–)

HR:

Heart rate (beat min−1)

K Hb :

Hill constant at which Hb is 50% saturated by O2 (mM−n)

K Mb :

Hill constant at which Mb is 50% saturated by O2 (mM−1)

M body :

Body mass (kg)

MWHb :

Molecular weight of hemoglobin (g mol−1)

n :

Hill coefficient (–)

OD:

Oxygen deficit (l O2)

PScap :

Permeability surface area product (l min−1)

Q m :

Muscle blood flow (l min−1)

Q p :

Cardiac output (l min−1)

S cap,Hb :

Oxygen hemoglobin saturation in blood capillary (–)

S tis,Mb :

Oxygen myoglobin saturation in muscle tissue (–)

StO2m :

Muscle oxygen saturation (–)

SV:

Stroke volume (ml beat−1)

t :

Time (min)

t ex :

Time at the end of exercise (min)

t 0 :

Time at the onset of the exercise (min)

UO2m :

Muscle oxygen utilization (l O2 min−1)

V cap, V mus, V tis :

Anatomical volume of capillary, muscle, and tissue (l)

\(V_{{{\rm cap},{\rm O}_{2}}},\,V_{{{\rm tis},{\rm O}_{2}}}\) :

Effective volume of O2 in capillary and tissue (l)

VCO2p :

Pulmonary carbon dioxide output (l CO2 min−1)

V I, V E :

Flow rate inspired and exhaled air (l min−1)

VO2m :

Muscle oxygen uptake (l O2 min−1)

VO2p :

Pulmonary oxygen uptake (l O2 min−1)

VO2p,peak :

Maximum pulmonary oxygen uptake (l O2 min−1)

WR:

Work rate (W)

W mc :

Myocyte volume fraction (–)

ΔQ m :

Amplitude of response of muscle blood flow (l min−1)

Δ UO2m, Δ VO2p :

Amplitude of response of UO2m and VO2p (l O2 min−1)

ΔWR:

Exercise incremental work rate (W)

η:

Mechanical efficiency (–)

τA :

Mean response time (s)

τHR :

Time constant of heart rate (s)

τPCr :

Time constant of the Phosphocreatine kinetics (s)

\(\tau_{{Q_{{\rm m}}}}\) :

Time constant of the muscle blood flow rate (s)

\(\tau_{{{\rm UO}_{2{\rm m}} }}\) :

Time constant of the muscle oxygen utilization (s)

\(\tau_{{{\rm VO}_{2{\rm m}} }}\) :

Mean response time of the muscle oxygen uptake (s)

\(\tau_{{{\rm VO}_{2{\rm p}} }}\) :

Mean response time of the pulmonary oxygen uptake (s)

B:

Bound oxygen concentration

F:

Free oxygen concentration

H:

Heavy condition

j:

Exercise intensity

M:

Moderate condition

R:

Resting condition

T:

Total oxygen concentration

V:

Very heavy condition

W:

Warm-up condition

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Acknowledgments

We thank the reviewers for providing thoughtful and constructive criticisms. We are grateful to Dean E. Myers for his expert technical assistance in the use of the near infrared spectroscopy device. This research was supported by the grant GM-66309-01 from the National Institute for General Medical Science (NIGMS) of the National Institute of Health (NIH) for establishing the Center for Modeling Integrated Metabolic Systems (MIMS) at Case Western Reserve University, and by a grant (NCC3-988) from NASA.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, 44106-6011, USA

    N. Lai, G. M. Saidel & M. E. Cabrera

  2. Department of Pediatrics, Case Western Reserve University, Cleveland, OH, 44106-6011, USA

    R. K. Dash, M. M. Nasca & M. E. Cabrera

  3. Center for Modeling Integrated Metabolic Systems, Case Western Reserve University, Cleveland, OH, 44106-6011, USA

    N. Lai, R. K. Dash, G. M. Saidel & M. E. Cabrera

  4. Pediatric Cardiology, Rainbow Babies and Children’s Hospital, MS 6011, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH, 44106-6011, USA

    M. E. Cabrera

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  1. N. Lai
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Lai, N., Dash, R.K., Nasca, M.M. et al. Relating pulmonary oxygen uptake to muscle oxygen consumption at exercise onset: in vivo and in silico studies. Eur J Appl Physiol 97, 380–394 (2006). https://doi.org/10.1007/s00421-006-0176-y

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