Expiratory muscle loading increases intercostal muscle

blood flow during leg exercise in healthy humans

Dimitris Athanasopoulos, Zafeiris Louvaris, Evgenia Cherouveim, Vasilis
Andrianopoulos, Charis Roussos, Spyros Zakynthinos and Ioannis Vogiatzis

J Appl Physiol 109:388-395, 2010. First published 27 May 2010; doi:10.1152/japplphysiol.01290.2009

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Jordan A. Guenette, William R. Henderson, Paolo B. Dominelli, Jordan S. Querido, Penelope M.
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J Appl Physiol 109: 388395, 2010.

First published May 27, 2010; doi:10.1152/japplphysiol.01290.2009.

Expiratory muscle loading increases intercostal muscle blood flow during leg
exercise in healthy humans
Dimitris Athanasopoulos,1,2 Zafeiris Louvaris,1,2 Evgenia Cherouveim,2 Vasilis Andrianopoulos,1
Charis Roussos,1 Spyros Zakynthinos,1 and Ioannis Vogiatzis1,2
1

Department of Critical Care Medicine and Pulmonary Services, Evangelismos Hospital, M. Simou, and G. P. Livanos
Laboratories, and 2Department of Physical Education and Sport Sciences, National and Kapodistrian University of Athens,
Athens, Greece
Submitted 17 November 2009; accepted in final form 25 May 2010

expiratory flow limitation; quadriceps muscle blood flow; near-infrared spectrometry

EXPIRATORY FLOW LIMITATION (EFL) is present in a significant
proportion of patients with chronic obstructive pulmonary
disease (COPD) during resting breathing, resulting in dynamic
hyperinflation (20, 35). During exercise, EFL occurs in the
majority of COPD patients (31), and it is associated with
impaired exercise performance due to dynamic hyperinflation
(5, 20, 31).
When EFL is imposed via a Starling resistor in healthy
subjects during exercise, tolerance is limited by severe dyspnea
sensations, abdominal pressure increases excessively during
E) decreases, resulting in
expiration, and minute ventilation (V

Address for reprint requests and other correspondence: I. Vogiatzis, Thorax

Foundation, 3 Ploutarhou st. 10675, Athens, Greece (e-mail: gianvog@phed.
uoa.gr).
388

retention of CO2 (4, 6, 29). The increased work of breathing

and the metabolic requirement of the respiratory muscles
during exercise with EFL have been alleged to aggravate the
competition for blood flow between the locomotor and the
respiratory muscles. Under such circumstances, competition
for blood flow could be further exacerbated by a reduction in
cardiac output (CO) that has been previously documented
when expiratory flow is limited during exercise in healthy
subjects (6, 7).
On the other hand, experiments showed that increasing the
workload of the respiratory muscles had no effect on CO, but
it caused vasoconstriction in locomotor muscles, thereby compromising locomotor muscle perfusion (27, 28) in a similar
manner, as it was originally shown when arm exercise was
added to leg exercise, causing attenuation of blood flow in the
legs (41). However, in the former experiments (27, 28), only
limb and not respiratory muscle blood flow measurements were
performed, and as such it is uncertain whether at a given CO
respiratory muscle blood flow actually increases at the expense
of blood flow to the locomotor muscles.
Measuring blood flow to the respiratory muscles is difficult
owing to their anatomical arrangement, their extensive vascular network, and the large variation in muscular recruitment
with varying degrees of ventilation. However, there are recent
studies (25, 43, 50) succeeding in measuring changes in blood
flow over the left seventh intercostal space, either during
hyperpnea, or during submaximal and maximal exercise with
the use of near-infrared spectroscopy (NIRS) and the lightabsorbing tracer indocyanine green (ICG) dye. Blood flow
measurements over the left seventh intercostal space primarily
reflect the activity of the internal and external intercostal
muscles (25).
Accordingly, the purpose of the present study was to investigate whether an increase in total demand for respiratory
muscle blood flow induced by the induction of EFL would
actually increase blood flow to the intercostal muscles and at
the same time would decrease blood flow to the quadriceps
muscles. To accomplish our goal, we performed simultaneous
measurements of CO, as well as intercostal and vastus lateralis
muscle blood flow during exercise, with and without EFL,
while keeping leg muscle work constant. It was reasoned that,
if intercostal muscle blood flow during exercise with EFL was
greater than that recorded during exercise without EFL, while
vastus lateralis muscle blood flow was reduced, this would be
consistent with the notion (27, 28) that the increase of the load
placed on the respiratory muscles during exercise causes an
increase in blood flow to these muscles at the expense of blood
flow to the locomotor muscles.

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Athanasopoulos D, Louvaris Z, Cherouveim E, Andrianopoulos V, Roussos C, Zakynthinos S, Vogiatzis I. Expiratory muscle

loading increases intercostal muscle blood flow during leg exercise in
healthy humans. J Appl Physiol 109: 388 395, 2010. First published
May 27, 2010; doi:10.1152/japplphysiol.01290.2009.We investigated whether expiratory muscle loading induced by the application of
expiratory flow limitation (EFL) during exercise in healthy subjects
causes a reduction in quadriceps muscle blood flow in favor of the
blood flow to the intercostal muscles. We hypothesized that, during
exercise with EFL quadriceps muscle blood flow would be reduced,
whereas intercostal muscle blood flow would be increased compared
with exercise without EFL. We initially performed an incremental
exercise test on eight healthy male subjects with a Starling resistor in
the expiratory line limiting expiratory flow to 1 l/s to determine
peak EFL exercise workload. On a different day, two constant-load
exercise trials were performed in a balanced ordering sequence,
during which subjects exercised with or without EFL at peak EFL
exercise workload for 6 min. Intercostal (probe over the 7th intercostal
space) and vastus lateralis muscle blood flow index (BFI) was calculated by near-infrared spectroscopy using indocyanine green, whereas
cardiac output (CO) was measured by an impedance cardiography
technique. At exercise termination, CO and stroke volume were not
significantly different during exercise, with or without EFL (CO: 16.5
vs. 15.2 l/min, stroke volume: 104 vs. 107 ml/beat). Quadriceps
muscle BFI during exercise with EFL (5.4 nM/s) was significantly
(P 0.043) lower compared with exercise without EFL (7.6 nM/s),
whereas intercostal muscle BFI during exercise with EFL (3.5 nM/s)
was significantly (P 0.021) greater compared with that recorded
during control exercise (0.4 nM/s). In conclusion, increased respiratory muscle loading during exercise in healthy humans causes an
increase in blood flow to the intercostal muscles and a concomitant
decrease in quadriceps muscle blood flow.

INTERCOSTAL MUSCLE BLOOD FLOW ELEVATION DURING EXERCISE

METHODS

Table 1. Pulmonary function and peak exercise data

with EFL
Age, yr
Height, cm
Weight, kg
FEV1, liter
FVC, liter
WRpeak, W
O2peak, l/min
V
HRpeak, beats/min
Epeak, l/min
V
VTpeak, l/min
fpeak, breaths/min
SpO2peak, %
Borg dyspnea scores
Borg leg effort scores

27 12
176 3
77 3
4.1 0.4
4.3 0.2
120 8
1.71 0.06
142 5
46.2 10.3
1.68 0.40
29 3
89 2
81
61

Values are means SE for 8 subjects. Exercise data depict the results of the
incremental exercise test to the limit of tolerance by the application of a
Starling resistor in the expiratory line, causing expiratory flow limitation
(EFL). FEV1, force expiratory volume in 1 s; FVC, force vital capacity;
O2peak, peak oxygen uptake; HRpeak, peak heart rate;
WRpeak, peak work rate; V
Epeak, peak minute ventilation; VTpeak, peak tidal volume, fpeak, peak breathV
ing frequency, SpO2peak (%), percentage of arterial pressure oxygen saturation
measured by pulse oximetry.
J Appl Physiol VOL

(HR) was determined using the R-R interval from a 12-lead online
electrocardiogram (Marquette Max; Marquette Hellige), whereas percentage of arterial oxygen saturation (%SaO2) was determined using a
pulse oximeter (Nonin 8600, Nonin Medical). The modified Borg
scale, using a 10-point scale (9), was used to rate the magnitude of
dyspnea and leg discomfort at the end of the incremental exercise test.
Constant-load exercise tests. During these tests, recording of pulmonary gas exchange and ventilatory variables was performed as mentioned
above. After 3 min of baseline measurements, followed by 3 min of
unloaded pedaling, the work rate was set and maintained at WRpeak EFL
(i.e., the work rate achieved during the preliminary incremental test with
EFL; Table 1) for 6 min in both constant-load exercise tests. CO was
continuously monitored by an impedance cardiography device, while
flow was measured with a hot wire pneumotachograph (Vmax 229;
Sensor Medics) near the mouthpiece, and tidal volume changes were
obtained by integrating the flow signal. The magnitude of dyspnea and
leg discomfort was assessed every minute.
Subject preparation to measure blood flow. Subjects were prepared
with a venous catheter for measurement of intercostal and quadriceps
muscle blood flow. Using local anesthesia (2% lidocaine) and sterile
technique, a catheter was introduced percutaneously into the right
antecubital forearm vein, oriented in the proximal direction. The
catheter was used to inject ICG, while it was kept patent throughout
the experiment by periodic flushing with saline.
Intercostal and quadriceps muscle BFI by NIRS. To calculate intercostal and quadriceps muscle BFI, two sets of NIRS optodes were placed,
one on the skin over the left seventh intercostal space, and the other over
the left vastus lateralis muscle 10 12 cm above the knee, both secured
using double-sided adhesive tape. NIRS signals were collected continuously during exercise.
The BFI has been calculated based on the indication that, for any
time interval less than the time to reach peak tissue accumulation of
tracer, the tissue receives the same fraction of the ICG bolus as
quantified in arterial blood. BFI was obtained by dividing the muscle
ICG concentration difference from 10 to 90% of peak height by the
rise time (26, 33). A recent study demonstrated a good agreement
between the NIRS ICG determined BFI and the NIRS ICG blood flow
calculated by the Fick principle for both intercostal and vastus
lateralis muscle groups (26, 33).
The NIRS optode separation distance was 4 cm, corresponding to
a penetration depth of 2 cm. The left intercostal space was used to
avoid potential blood flow contributions from the liver on the right
side of the body. Optodes were connected to a NIRO 200 spectrophotometer (Hamamatsu Photonics KK, Hamamatsu, Japan), which
was used to measure known volumes of ICG (range: 0.8 1.2 ml at 5
mg/ml) concentration injected into the right antecubital forearm vein,
followed by a rapid 10-ml flush of isotonic saline. Tissue microcirculatory ICG was detected transcutaneously by measuring light attenuation with NIRS at 775-, 813-, and 850-nm wavelengths and analyzed using an algorithm incorporating the Modified Beer-Lambert
Law (21, 32, 46).
Intercostal and quadriceps muscle oxygenation by NIRS. Muscle
oxygenation was assessed by the same NIRO 200 spectrophotometer
as used for the measurement of muscle BFI. High ICG tissue concentrations during the passage of the dye bolus through the muscle may
interfere with Hb results. Therefore, to avoid any interference between
ICG and Hb wavelengths, tissue oxygenation data were averaged over
10 s immediately before ICG injection. The variables assessed by
NIRS were the concentration changes of oxygenated, deoxygenated,
and total Hb. A commonly derived parameter from NIRS studies in
humans is the ratio of oxygenated Hb to total Hb, an index of changes
in tissue O2 saturation relative to rest (14, 17). Among the NIRS
variables, several laboratories have adopted the deoxy-Hb signal
(deoxy-Hb) as the preferred indicator of changes in muscle microvascular oxygenation during exercise (24). The deoxy-Hb response to
exercise is then considered a proxy of O2 extraction in the microcirculation, reflecting the balance between O2 delivery and utilization.

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Subjects. Eight healthy male subjects (whose physical characteristics are given in Table 1) participated in the study, which was
approved by the authors University Hospital Ethics Committee.
Before participation in the study, all subjects were informed of any
risks and discomforts associated with the experiments and gave
written, signed, informed consent.
Experimental design. Experiments were conducted in two visits. In
visit 1, subjects underwent an incremental exercise test to the limit of
tolerance by the application of a Starling resistor in the expiratory line
[peak EFL exercise workload (WRpeak EFL)]. In visit 2, subjects
underwent, in a balanced ordering sequence, two 6-min constant-load
exercise tests at work rates corresponding to WRpeak EFL, with or
without (control) the application of a Starling resistor. In more detail,
consecutive patients were alternatively exercised first without flow
limitation and then with flow limitation (protocol 1), or followed the
opposite sequence, i.e., first exercised with flow limitation and then
exercised without flow limitation (protocol 2). Therefore, ultimately
four subjects followed protocol 1 and four subjects followed protocol
2. Between tests, there was a 3-h resting period. EFL was imposed by
placing a Starling resistor in the expiratory line, limiting expiratory
flow to 1 l/s. Blood flow was measured by NIRS through the
assessment of the blood flow index (BFI) that was calculated from the
rate of tissue ICG accumulation over time according to the Sapirstein
principle (40) (see below for more details). BFI over the seventh
intercostal space and over the vastus lateralis muscle was measured
only during the final minute of each constant-load exercise test.
Incremental exercise test. In visit 1, the incremental exercise tests
were performed on an electromagnetically braked cycle ergometer
(Ergoline 800; Sensor Medics, Anaheim, CA) to establish the individual subjects peak workload when EFL was imposed (to record
WRpeak EFL) by the application of a Starling resistor. After 3 min of
baseline measurements, followed by 3 min of unloaded pedaling, the
work rate was increased every min by 20 W to the limit of tolerance
(the point at which the work rate could not be tolerated due to severe
sensation of dyspnea; see Table 1), with the subjects maintaining a
pedaling frequency of 50 60 rpm. The following pulmonary gas
exchange and ventilatory variables were recorded breath by breath
(Vmax 229; Sensor Medics): oxygen uptake, carbon dioxide elimina E, tidal volume, breathing frequency, duty cycle (inspiratory to
tion, V
total cycle duration ratio), and respiratory exchange ratio. Heart rate

389

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INTERCOSTAL MUSCLE BLOOD FLOW ELEVATION DURING EXERCISE

RESULTS

Hemodynamic responses. CO during quiet breathing, unloaded cycling, and exercise, with and without EFL, is shown
in Fig. 1A. During both constant-load exercise tests, CO
increased linearly up to the third minute of exercise and leveled
off thereafter. During exercise with expiratory muscle loading,
CO tended to be greater compared with control (P 0.088)
(Fig. 1A). In addition, flow limitation was associated with
slower (P 0.032) on-exercise CO kinetics compared with
control exercise (mean time constant 93 9 compared with
68 4 s). Furthermore, HR was significantly greater (P
0.022) during flow-limited exercise compared with control.
Ventilatory responses and sensations of dyspnea and leg
E, %SaO , end-tidal carbon dioxide, and sensadiscomfort. V
2
tions of dyspnea and leg discomfort during rest, unloaded
cycling (UNL), and exercise, with and without EFL, are shown
E increased linearly up to
in Fig. 1. During control exercise, V
the second minute of exercise and leveled off thereafter (Fig.
E increased up to the
1D), while, during exercise with EFL, V
E was
first minute of exercise and then exhibited a plateau. V
J Appl Physiol VOL

significantly lower (P 0.022) during flow-limited exercise.

E during exercise with EFL resulted in a signifiThe lower V
cantly higher (P 0.001) end-tidal carbon dioxide (Fig. 1E)
and significantly lower (P 0.005) %SaO2 (Fig. 1B). Duty
cycle was significantly shorter (P 0.001) during exercise
with EFL. Sensations of dyspnea (Fig. 1C) and leg discomfort
(Fig. 1F) during exercise with EFL were significantly greater
(P 0.003 and 0.045, respectively) compared with control
exercise.
BFI responses. Figure 2 displays changes from baseline (i.e.,
quiet breathing) to the end of exercise in absolute values for
both intercostal and quadriceps muscle blood flow indexes,
with and without EFL for each subject. The increase from
baseline in intercostal muscle BFI during exercise with EFL
was significantly greater (P 0.021) compared with that
during control exercise, whereas the increase from baseline in
quadriceps muscles BFI during exercise with EFL was significantly lower (P 0.043) compared with that during control
exercise.
Intercostal and quadriceps muscle oxygenation by NIRS.
Figure 3 displays changes from baseline (i.e., quiet breathing)
for intercostal and quadriceps muscle oxygen saturation and
deoxygenated hemoglobin during unloaded cycling and exercise, with and without EFL. During control exercise, intercostal muscle oxygen saturation (Fig. 3A) and deoxygenated
hemoglobin (Fig. 3B) remained unchanged compared with
baseline, whereas, during exercise with EFL, intercostal muscle oxygen saturation (Fig. 3A) significantly decreased and
intercostal muscle deoxygenated hemoglobin (Fig. 3B) significantly increased. Hence, intercostal muscle oxygen saturation
and deoxygenated hemoglobin were significantly different
(P 0.037 and 0.017, respectively) between the two constantload exercise tests (Fig. 3, A and B).
During control exercise, quadriceps muscle oxygen saturation (Fig. 3C) and deoxygenated hemoglobin (Fig. 3D) remained unchanged compared with baseline throughout the test.
In contrast, during exercise with EFL, quadriceps muscle
oxygen saturation (Fig. 3C) significantly decreased from baseline, while quadriceps deoxygenated hemoglobin (Fig. 3D)
exhibited a tendency to increase (P 0.074). Quadriceps
muscle oxygen saturation and deoxygenated hemoglobin were
significantly different (P 0.017 and 0.038, respectively)
between the two constant-load exercise tests (Fig. 3, C and D).
DISCUSSION

The present study investigated whether, during exercise, an

increase in respiratory muscle loading induced by EFL decreases blood flow to the quadriceps muscles, while at the same
time it increases blood flow to the intercostal muscles. Simultaneous measurements of intercostal and vastus lateralis muscle blood flow indexes using NIRS and the light-absorbing
tracer ICG dye were performed during exercise, with and
without EFL, while keeping leg muscle work constant. The
novel finding of the present study is that, during exercise with
EFL, directly measured intercostal muscle blood flow was
greater and quadriceps muscle blood flow was lower compared
with exercise without EFL. Therefore, it is suggested that EFL
most likely causes redistribution of blood flow from the locomotor to the respiratory muscles.

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To reduce the potential influence of low arterial O2 saturation from

pulse oximetry (SpO2) values on deoxy-Hb response, the following
correction was applied: [deoxy-Hb] corr [deoxy-Hb] {(1 SpO2)
[deoxy-Hb]} (where brackets denote concentration) (10).
CO. An impedance cardiography device (Physioflow PF05L1,
Manatec Biomedical, Macheren, France) was used to determine HR,
stroke volume (SV), and CO at rest and during exercise. The Physioflow device uses changes in transthoracic impedance in response to
an administered electrical current during cardiac ejection to calculate
SV. The device emits a high-frequency (75 kHz) and low-amperage
(3.8 mA peak to peak) alternating electrical current via skin electrodes
(13). The Physioflow device has been previously validated against the
direct Fick method (8, 12, 13, 34, 36).
CO data were interpolated in 5 s for kinetic analysis (SigmaPlot
10.0, Systat Software, San Jose, CA). Since we used data from a
single transition, we opt to fit CO data from 60 s of baseline pedaling
to 360 s after the onset of exercise (10, 16). The model used for fitting
the kinetics response of CO was the following monoexponential
equation: [Y]t [Y]b Ap[1 e(t TDp)/p], where [Y] is the
variable under analysis; the subscripts b and p are baseline unloaded
cycling and primary component, respectively; A is amplitude, TD is
the time delay, is time constant of the exponential response of
interest, and t is time. In the analysis, the TDp was taken as zero,
because there is no time delay in CO (10, 16).
Statistical analysis. All data are reported as means SE, unless
otherwise stated. SE was used rather than SD, because our interest is
in mean differences between the two constant-load exercise tests
rather than in differences between subjects. Two-way ANOVA with
repeated measures was used to identify statistically significant differences across different time points during exercise between the two
constant-load exercise tests for CO, HR, SV, as well as intercostal and
quadriceps muscle tissue O2 saturation, deoxygenated Hb (deoxy-Hb),
and all pulmonary gas exchange variables. One-way ANOVA with
repeated measures was used to identify statistically significant differences across the mean values within each constant-load exercise test
for all of the aforementioned variables. When one- or two-way
ANOVA detected statistical significance, pairwise differences were
identified using Tukeys honestly significant difference post hoc
procedure. Comparisons for the blood flow indexes for quadriceps and
intercostal muscles (calculated only during the final minute of exercise) between control and EFL constant-load trials were made by
paired t-tests. The level of significance for all of the above analyses
was set at P 0.05.

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Fig. 1. Effect of flow limitation on breathing pattern. Cardiac output (A), percentage of oxygen saturation (B), sensations of dyspnea (C), minute ventilation (D),
end-tidal carbon dioxide (E), and sensations of leg discomfort (F) are shown during quiet breathing (QB), unloaded cycling (UNL), and exercise with expiratory
flow limitation (EFL;
) and without EFL (control; ). Values are means SE for 8 subjects. Significant differences between the two conditions, and
*compared with 6th min of exercise: P 0.05.

EFL as a model of expiratory muscle loading. The experimental model used in this study has been shown to induce intolerable
dyspnea sensations, CO2 retention, impaired exercise performance, excessive expiratory muscle recruitment, reduced duty
cycle, and decreased SaO2 (6) in healthy subjects. In addition,
previous studies by Aliverti and colleagues (4, 6, 29) have shown
that the major effect of EFL is that it slows expiratory flow and
increases inspiratory flow. Thus EFL imposes a load that decreases the shortening velocity of expiratory muscles and at the
same time increases the shortening velocity of inspiratory musJ Appl Physiol VOL

cles. The result is that the power output of the rib cage muscles,
the diaphragm, and the expiratory abdominal muscles is increased
up to fourfold during flow-limited compared with control exercise, thereby indicating an increase in central drive to all respiratory muscles (4, 29). In the present study, we did not assess the
power of the respiratory muscles, albeit we reported that flow
limitation, as in previous studies (4, 6, 29), led to hypoxemia (Fig.
E (Fig.
1B), hypercapnia (Fig. 1E), decreased duty cycle, and V
1D), whereas all subjects experienced intolerable dyspnea sensations (Fig. 1C).

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INTERCOSTAL MUSCLE BLOOD FLOW ELEVATION DURING EXERCISE

Fig. 2. Intercostal and quadriceps muscle blood

flow index. Individual changes are shown from
baseline (i.e., QB) to the end of exercise in the
blood flow index of the intercostal (A) and quadriceps (B) muscles with EFL and without EFL
(control).
, Mean values for 8 subjects. Significant differences between the two conditions,
P 0.05.

J Appl Physiol VOL

(26), we estimated that, compared with control exercise, mean

intercostal muscle blood flow during EFL exercise would
increase from 15 to 20 mlkg1100 g1, respectively (i.e.,
33% increase), whereas vastus lateralis mean muscle blood
flow would be reduced from 38 to 34 mlmin1100 g1,
respectively (i.e., 10% decrease). These values are in agreement with those recently reported by our group (50) in healthy
individuals during cycling at 120 W. Considering that, in
healthy trained individuals exhibiting similar anthropometric
characteristics to those of the subjects in the present study (13),
two-leg blood flow during exercise at 120 W requires 60 70%
of CO (13), then, in our control experiments, two-leg blood
flow is estimated to be in the range of 10 l/min as CO was 15
l/min. When EFL was imposed, quadriceps muscle blood flow
was reduced by 10%, and hence leg blood flow by 1.0 l/min.
This figure is in agreement with that (0.9 l/min) reported by
Harms et al. (27) when respiratory muscle load was imposed in
healthy subjects. Similarly, considering that respiratory muscle
blood flow requires 10 15% of CO during submaximal exercise (1), then it is estimated that respiratory muscle blood flow
in our experiments would be in the range of 2.0 l/min. Since
intercostal muscle blood flow increased by 33% by the application of EFL, this change would correspond to an increase of
0.75 l/min. As the mass of the intercostal muscles corresponds only to one-third of the total respiratory musculature
(37, 39), the estimated decrease in leg blood flow (by 1.0 l/min)
cannot be fully accounted for by the increase in blood flow to
the intercostal muscles (i.e., of 0.75 l/min is equivalent to 0.25
l/min). It is, therefore, likely that a significant proportion of
blood flow increase was distributed to other respiratory muscles, such as the diaphragm and especially the expiratory
abdominal muscles whose power has been shown to increase
by two- to fourfold during flow-limited exercise (4, 6, 29, 45).
Intercostal and quadriceps muscle oxygenation by NIRS.
Intercostal muscle oxygen saturation (Fig. 3A) and deoxygenated hemoglobin (Fig. 3B) [the latter a proxy of tissue fractional oxygen extraction (17, 2224)] did not change during
control exercise, thus suggesting that the oxygen demand of the
intercostal muscles was met by the available blood flow and
oxygen delivery. In contrast, intercostal muscle oxygen saturation declined and deoxygenated hemoglobin increased during

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Blood flow redistribution. High-intensity whole body exercise is known to induce expiratory muscle fatigue (45, 47).
During exercise with flow limitation, measurements of esophageal and gastric pressures have revealed that strong inspiratory and expiratory muscle recruitment takes place (3). Hence,
it is likely that persistent expiratory muscle recruitment taking
place during the flow-limited exercise trials in the present study
led to expiratory muscle fatigue. Fatigue of the respiratory
muscles would be expected to activate the so-called respiratory
muscle metaboreflex, thereby leading to locomotor muscle
vasoconstriction and to a decrease in limb blood flow (18, 19).
Interestingly, in the present study, we observed a reduction in
quadriceps muscle BFI compared with control exercise when
EFL was imposed (Fig. 2). This reduction in blood flow to the
locomotor muscles could potentially serve to increase blood
flow to the respiratory muscles (18, 19). In fact, we were also
able to demonstrate a significant increase in intercostal muscle
blood flow during exercise with EFL compared with control
(Fig. 2).
Blood flow measurements over the left seventh intercostal
space typically reflect the activity of the internal and external
intercostal muscles: the former being expiratory and the latter
inspiratory muscles (25). Hence, given that, during exercise
with EFL, all respiratory muscles typically increase their
power output up to fourfold (4, 29), the finding that blood flow
to the intercostal muscles increased during exercise with EFL
compared with control exercise (Fig. 2) could be attributed to
the increased load imposed on both internal and external
intercostal muscles. It is likely that, during exercise with EFL,
blood flow was preferentially devoted to the respiratory muscles as their metabolic demand was increased, while the demand of the locomotor muscles remained unchanged. This
finding is consistent with previous suggestions that, during
exercise, the increased load placed on the respiratory muscles
causes redistribution of blood flow from the locomotor to the
respiratory muscles (27, 28).
Was the decrease in leg matched by the increase in intercostal muscle blood flow? Based on a recently published study
showing good agreement between the NIRS ICG determined
BFI and the NIRS ICG blood flow calculated by the Fick
principle for both intercostal and vastus lateralis muscle groups

INTERCOSTAL MUSCLE BLOOD FLOW ELEVATION DURING EXERCISE

393

exercise with EFL. This finding suggests that, despite the

increased blood flow (Fig. 2), the oxygen demand of the
intercostal muscles was not sufficiently met by the available
oxygen delivery, and the increased tissue fractional oxygen
extraction increased. Therefore, it seems likely that the increase in blood flow to the intercostal muscles during EFL
exercise was insufficient to offset the reduced SaO2 (Fig. 1B)
and to meet the increased oxygen demand, and, as such,
intercostal muscle oxygen saturation decreased, whereas deoxygenated hemoglobin increased (Fig. 3, A and B). Furthermore,
these findings infer a mismatch between oxygen delivery to,
and demand of, the intercostal muscles, thereby indicating that
limited respiratory muscle oxygen delivery may have contributed to the development of expiratory muscle fatigue. In
addition, during exercise with EFL quadriceps muscle, blood
flow was reduced compared with control exercise (Fig. 2). This
reduction is most likely responsible for the decline in quadriceps muscle oxygen saturation and the increase in deoxygenated hemoglobin during exercise with EFL compared with
control exercise (Fig. 3, C and D) and could, in part, justify the
J Appl Physiol VOL

greater degree of leg discomfort experienced by the subjects

(Fig. 1F).
There are studies reporting the effects of either the resistive
breathing or respiratory muscle unloading on leg muscle oxygenation during exercise (10, 16, 32). It has been documented
that respiratory muscle unloading, via a proportional-assist
ventilator, increased oxygen availability to the lower limbs
during constant-load exercise in patients with advanced COPD
(10). As these changes were not related to increased systemic
oxygen delivery, it was suggested that a fraction of CO was
redistributed from the respiratory to the locomotor muscles as
a consequence of proportional-assist, ventilator-induced reductions in respiratory muscle load and blood flow requirement. In
fact, the study by Borghi-Silva et al. (10) confirmed earlier
suggestions by Simon et al. (42) that, in some patients with
COPD, peripheral muscle blood flow and oxygen delivery to
the locomotor muscles are limited.
Hemodynamic responses. Although previous studies have
documented that expiratory loading during exercise significantly reduces CO (6, 30, 38, 44), CO during exercise with

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Fig. 3. Changes in intercostal and quadriceps muscle oxygenation. Changes are shown from baseline (QB) in percentage of oxygen saturation (StO2%; A and C)
and deoxygenated hemoglobin concentration (Deoxy Hb; B and D) [corrected for arterial arterial O2 saturation from pulse oximetry (11)] for the intercostal
muscles (A and B) and the quadriceps muscles (C and D) during UNL and exercise with EFL (
) and without EFL (control; ). Values are means SE for 8
subjects. Significant differences between the two conditions and *compared with QB: P 0.05.

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in blood flow to the intercostal muscles and a concomitant

decrease in quadriceps muscle blood flow.
GRANTS
This work was supported by the K. & V. Kostantakopoulos fellowship
through the Thorax Foundation.
DISCLOSURES
No conflicts of interest, financial or otherwise, are declared by the author(s).
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expiratory muscle loading in the present study tended to be

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Conclusion. Increased respiratory muscle loading induced
by EFL during exercise in healthy humans causes an increase

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