Respiratory Physiology & Neurobiology 185 (2013) 287–295
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Respiratory Physiology & Neurobiology
j our nal ho me p age: www.elsevier.com/locate/resphysiol
Oxygen uptake kinetics at work onset: Role of cardiac output and of
phosphocreatine breakdown
M.P. Francescato
∗
, V. Cettolo, P.E. di Prampero
Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy
a r t i c l e i n f o
Article history:
Accepted 27 September 2012
Keywords:
Exercise
Oxygen deficit
Oxygen stores
Venous blood volume
a b s t r a c t
The hypothesis that variability in individual’s cardiac output response affects the kinetics of pulmonary
O
2
uptake (
˙
V
O
2
) was tested by investigating the time constants of cardiac output (
˙
Q ) adjustment (
Q
), of
PCr splitting (
PCr
), and of phase II pulmonary O
2
uptake (
V
O
2
) in eight volunteers.
˙
V
O
2
,
˙
Q , and gastrocne-
mius [PCr] (by
31
P-MRS) were measured at rest and during low intensity two-legged exercise. Steady state
˙
V
O
2
and
˙
Q increased (
˙
V
s
O
2
= 182 ± 58 mL min
-1
;
˙
Q = 1.3 ± 0.4 L min
-1
), whereas [PCr] decreased sig-
nificantly (21 ± 8%).
V
O
2
,
PCr
and
Q
were significantly different from each other (38.3 ± 4.0, 23.9 ± 2.5,
11.6 ± 4.6 s, respectively; p < 0.001).
PCr
assumed to be equal to the time constant of
˙
V
O
2
at the muscle
level (
mV
O
2
), was not related to
Q
, whereas
V
O
2
and
Q
were significantly related (p < 0.05) as were
V
O
2
and
PCr
(p < 0.05). Venous blood O
2
stores changes, as determined from arterio-to-mixed-venous O
2
content, were essentially equal to those estimated as (
V
O
2
–
PCr
)
•
˙
V
s
O
2
. This suggests that cardiac output
responses affect O
2
stores utilization and hence
V
O
2
: thus
V
O
2
is not necessarily a good estimate of
mV
O
2
.
© 2012 Elsevier B.V. All rights reserved.
1. Introduction
At the onset of a sudden constant-load exercise the pulmonary
oxygen uptake (p
˙
V
O
2
), after a short delay (usually called phase I),
approaches a new steady state with an exponential time course
(phase II, e.g. Rossiter, 2011; Whipp et al., 1982). The time con-
stant of this “fundamental” or phase II component (
V
O
2
; Rossiter,
2011; Rossiter et al., 2002) has been widely investigated to deter-
mine the interplay between high-energy phosphates and oxidative
metabolism contribution to the overall energy turnover at the mus-
cle level. However, between the actual O
2
sink (the muscle) and the
measuring site (the lung) there are at least two main buffers, i.e., the
cardiovascular system and the amount of O
2
bound to the venous
blood.
Computer simulations were carried out by Barstow and co-
workers (Barstow et al., 1990; Barstow and Mole, 1987) to assess
the effects of cardiovascular adjustments on pulmonary O
2
uptake,
assuming predetermined time courses of muscle O
2
uptake (m
˙
V
O
2
)
and cardiac output changes at work onset. Simulation results led
∗
Corresponding author at: Department of Medical and Biological Sciences,
University of Udine, P.le Kolbe 4, 33100 Udine, Italy. Tel.: +39 0432 494336;
fax: +39 0432 494301.
E-mail addresses: maria.francescato@uniud.it (M.P. Francescato),
valentina.cettolo@uniud.it (V. Cettolo), pietro.prampero@uniud.it
(P.E. di Prampero).
the authors to state that “. . .2) the contribution of changes in
venous O
2
stores to p
˙
V
O
2
kinetics and the O
2
deficit occur almost
entirely in phase I, 3) under a wide variety of manipulations, the
kinetics of p
˙
V
O
2
in phase II are within a couple of seconds of that
assigned to m
˙
V
O
2
(i.e., there is not an obligatorily slowing of
˙
V
O
2
kinetics at the lungs relative to those at the muscles);. . .” (Barstow
et al., 1990). The latter conclusion was confirmed by invasive mea-
surements of muscular O
2
consumption (Grassi et al., 1996; Koga
et al., 2005) and non-invasive measurements (McCreary et al.,
1996; Rossiter et al., 1999), assuming that the PCr splitting kinet-
ics (
PCr
) is the mirror image of the muscular O
2
uptake kinetics
(
mV
O
2
) (Mahler, 1985), leading to the common view that actually
V
O
2
closely reflects
mV
O
2
. Nevertheless, using a different approach
(i.e., calculating the rate of change of the venous blood O
2
stores
throughout the entire rest-to-work transient starting from actual
measurements of breath-by-breath alveolar O
2
uptake and cardiac
output) Inman et al. (1987) obtained a significantly faster kinetics
for m
˙
V
O
2
as compared to p
˙
V
O
2
and showed that the change in the
venous blood O
2
stores are not limited to phase I, but occur during
the entire transient.
To the authors’ knowledge, since the publications of Barstow
et al. (1990), Barstow and Mole (1987) and Inman et al. (1987),
the influence of the cardiac output adjustment on the coupling of
muscle and lung
˙
V
O
2
kinetics has been recently assessed only in
silico (Bowen et al., 2011), but was never investigated experimen-
tally in vivo. We hypothesize that, at exercise onset, whereas the
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http://dx.doi.org/10.1016/j.resp.2012.09.015