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Title
Effect of hypoxia on ventilatory control during exercise in children and adults.
Permalink
https://escholarship.org/uc/item/0168q5w7
Journal
Pediatric research, 25(3)
ISSN
0031-3998
Authors
Springer, C
Barstow, TJ
Cooper, DM
Publication Date
1989-03-01
DOI
10.1203/00006450-198903000-00016
License
https://creativecommons.org/licenses/by/4.0/ 4.0
Peer reviewed
eScholarship.org
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PEDIATRIC RESEARCH
Copyright O 1989 International Pediatric Research Foundation, Inc.
Vol. 25, No. 3, 1989
Printed in US. A.
Effect of Hypoxia on Ventilatory Control during
Exercise in Children and Adults
CHAIM SPRINGER, THOMAS J. BARSTOW, AND DAN M. COOPER
Division of Respiratory and Critical Care, Department of Pediatrics, Division of Respiratory and Critical Care
Physiology and Medicine, Department of Medicine, Harbor-UCLA Medical Center, Torrance, California 90509
ABSTRACT. Little is known about maturation of peripheral chemoreceptor tone (PCT) during growth. We recently
demonstrated that the increase in PCT was 49% greater
during hypoxic (15% 0 2 ) exercise in children compared to
adults. As the PCT is a major determinant of ventilatory
(VE) response at the onset of exercise (measured by the
time constant T ) , we hypothesized that hypoxia would affect
TVE (and TVC~,)to a greater extent in children. Nine
healthy children (6-10 y old) and nine healthy adults (1840 y old) performed multiple transitions from rest to constant work rate on the cycle ergometer. Studies were done
breathing,21% 0 2 and 15% 0 2 . Hypoxic breathing quickened the VE responses in all of the adults and children, but
the magnitude of the hypoxic effect did not differ between
the two groups (in children, TVEwas 50.9 9.9 s during
21% O2 breathing and 32.6 f 6.9 s during hypoxia; in
adults, TVE was 69.4 f 17.6 S, which fell to 50.9 f 18.4 s
during hypoxia). The hypothesized greater ventilatory response to hypoxia in children compared to adults during
exercise was not observed. During 21% 0 2 breathing, the
data demonstrated that children stored relatively less C 0 2
(by 49%) than did adults in the transition between rest and
exercise, possibly explaining the faster ventilatory kinetics.
We speculate that there must be additional respiratory
control differences between adults and children such that
for a given increase in PCT-induced by hypoxia, the VE
response at the onset of exercise is less in children than in
adults. (Pediatr Res 25:285-290, 1989)
+
Abbreviations
VE, minute ventilation
vco,, CO2 output
VO,, 0 2 uptake
AT, anaerobic threshold
PCT, peripheral chemoreceptor tone
Much is known about the peripheral chemoreceptors (carotid
bodies) as the important mediators of the hypoxic drive to
ventilation in both babies and adults (1-3). But little is known
about their function and possible maturation during the growth
process of normal children. Recently, we examined the PCT in
a group of children and adults by measuring the fall in VE during
a hyperoxic switch [i.e. the sudden imposition of 80% oxygen
that is known to eliminate carotid body input to ventilation (4,
Received June 6, 1988; accepted November 3, 1988.
Correspondence Dan M. Cooper, M.D., A-17 Annex, Harbor-UCLA Medical
Center, 1000 West Carson Street, Torrance, CA 90509.
CS is supported by a fellowship from the Joseph Drown Foundation. This work
was supported by NIH Grant HL11907 and a grant from the California Lung
Association.
5)] during steady-state exercise (6). The PCT was then defined
as the maximum percentage of reduction in ventilation seen
during the hyperoxic switch. PCT was similar in children and
adults during air-breathing exercise (27.9 5 10.7% 1 SD reduction in children and 23.3 + 6.3% in adults, not statistically
significant), but during 15% 0 2 breathing, the peripheral chemoreceptor contribution to ventilation was much greater in the
children (57.6 a 3.6% in children and 38.9 a 5.5% in adults, p
< 0.000 I). We concluded that peripheral chemoreceptor function
matures during growth and is characterized by decreasing sensitivity to hypoxia.
Our studies on carotid body tone were made during steadystate exercise. But the ability of the organism to maintain homeostasis is better assessed by focusing on the transition between
rest and exercise when sudden and large increases in cellular CO2
output and 0 2 consumption occur. The carotid bodies are known
to play an important role in the ventilatory response that occurs
in the transition from rest to exercise (1, 3, 7). The responses are
slow in carotid body resected patients (3) and, as noted above,
in healthy subjects who breathe high concentrations of 0 2 . Conversely, breathing hypoxic gas mixtures stimulates the carotid
bodies and quickens the ventilatory responses to exercise (1). We
wondered whether an increase in peripheral chemoreceptor tone
induced by breathing hypoxic air would have the same effect on
ventilatory responses to exercise in the child as in the adult.
To examine the linkage of peripheral chemoreceptor tone and
the ventilatory response, we measured the gas exchange responses
to the sudden onset of exercise in a group of children and adults
using cycle ergometry and breath by breath data acquisition. The
ventilatory response to the transition between rest and exercise
has been characterized in both adults and children to consist,of
three phases (7, 8), where phase 1 is the rapid increase in VE,
Vco, and Vo, in the first 15-20 s of exercise; phase 2 is the
exponential increase, and phase 3 is the final steady-state response. The phase 2 response is apparently most influenced by
the carotid bodies (3) with phase 1 reflecting a sudden increase
in cardiac output (9). In both the adults and children, the
responses were measured under air-breathing conditions and
compared to hypoxic gas breathing, which stimulated the peripheral chemoreceptors.
MATERIALS AND METHODS
Population. Nine healthy children (five boys and four girls,
aged 6-10 y, mean age 8.2 1.4 y) and nine healthy adults (five
males and four females, aged 18-40 y, mean age 28.2 a 6.9 y)
comprised the study population (Table I). All were volunteers,
had no chronic diseases, and did not smoke or use medications.
The study was approved by the Human Subjects Committee of
Harbor-UCLA Medical Center. Informed consent was obtained
from each subject and guardian when appropriate.
Protocol. I) Progressive exercise tests: Each subject performed
a ramp-type progressive exercise test on a cycle ergometer (10)
*
286
SPRINGER ET AL.
Table 1. Subjects data
Children
Adults
WR*
No.
1
2
3
4
5
6
7
8
9
Sex
Age (y)
Wt (kg)
Ht (cm)
(w)
F
9.1
6.0
7.5
8.1
7.2
9.2
10.0
6.9
10.0
26.4
20.0
27.0
28.1
22.7
23.2
38.6
28.1
49.0
126
113
127
145
127
132
150
124
151
15
15
20
14
15
15
22
14
30
1
2
3
4
5
6
7
8
9
8.2
1.4
29.2
9.1
133
13
18
5
Mean
SD
M
M
F
M
F
F
M
M
Mean
SD
* WR, work rate.
No.
Sex
Age (y)
Wt (kg)
Ht (cm)
WR
(W)
F
18.0
26.3
25.0
26.2
40.0
34.2
34.3
21.4
28.5
63.2
70.1
58.6
64.3
65.2
66.5
50.3
62.2
75.3
166
180
161
168
170
173
160
168
175
29
40
30
40
45
80
35
60
55
28.2
6.9
64.0
7.0
169
6
46
16
M
F
F
M
M
M
M
M
breathing 15% O?.'l'liis test Wi1S L I S C to
~ cstimatc tlic A'I' during
15% O? brcalhi~lg.2 ) Constant work rate cxcrcisc tcsts: liacli
sul?jcct pcrli)r~iicdlive rest to constant work late cxcrcisc tcsts,
[luring air-brcntliing nncl during 15% 0 2 brcatliing. The sul?jcct
was signaled to begin cxcrcisc by a gsccn light that was activated
at cntl cxpil-ation. 'l'lic crgomctcr wliccl was motorized and
mainti~incd a ri~tcof 60 rpm until tlic sliu-t of cxcrcisc to
minimize tlic energy expenditure nccdcd to ovcrcomc tlic Ily(It1 !-I1 I X I 1tCISI - whccl inertia. 'l'hc work 1 x 1i~scd
~ k)r llic constant cxcrcisc tcsts
1 IMI.
was 75% ol'tlic hyl,oxic A'I' ('l.al>lc I). 'l'liis work ratc was chosen
to ensure tliat the tcsts pcrfor~iicdduring botli air breathing and
lny poxic gas breathing would be below tlic sul?jcct's AT. As
chilcircn and adults have widely dill'crcnt cxcrcisc capabilities,
1;ig. I . C'liangcs in tisstlc ( ' 0 2 stores will1 cxercis~.Stored ( ' 0 2 was
the work ratc chosen was ~ior~ii:~lizcd
in each sub.jcct to a sl>ccilic, calculatctl using the equation shown. AV(.~,,is the incrcasc in v(,(),, lioln
pliysiologic:~lly based, work intensity. Ry choosing work riungcs rest to stci~tly-statecxcrcisc. ant1 TV(.(>,, and 7 v 0 ? :lrc the time constants
below the AT, possible conli)unding cll'ccts of li~cticacidosis on li)r v<.o,,:111<1 vo,.
ventilation were avoided in both the adults and children. Stcadyst:~tccxcrcisc continued li)r 10 niin, li)llowcd l?y n,pcric!d of rest
15-20 s nlicr the start of cxcrcisc) wcrc analyzed by lilting the
long cnougli (approxi~iiatclyI0 min) to allow V1:, Vo?, V(,()?,and data to a lirst order cxponcntial modcl ( 14, 15). 'l'hc l i ~ n c
licarl sale to return to tlic ~~rccxcrcisc
Icvcls. The pcriplicl'al constant (7) o f t h e r c s p o ~ ~W
s c~ I Sdetermined l j o ~ i the
i equation:
clncmorcccptor contribution to the ventilatory drive during
~ ( t =) v ( ~ ~( )1 . c-l('-" i))lrl)
steady-state cxcrcisc, both under ail--hrcatliing and liypoxic gasbrcolliing conditions !i tlic same sul>jccts has bccn reported by w1ic1-c~ ( t is) tlic incrcasc in vl;, v(,~)?,
or vO,above tlic previous
measuring the lhll in VI. cluri~igtlic imposition of80'%, 0, k)r I0 control valucs at luny given time (1);. V(ss) is tlic dill'crcncc
breaths, performed nflcr 6 min ofcxcrcisc (6).
bctwccn.rcst and steady-stale cxcrcisc V; 7 is the t i ~ n cto rcacli
M(~rr.sr/ro~r?c~ir/
(!/' vor~/i/(r/io/r, ~ I . Y~.X.(~/I(III~~O.
(11rc1 / r ( ~ r r / - u r / ( ~ . 63% of V(ss); and T I , is tlic time delay.
Ventilation and gas exchange wcrc mcasurcd breath by bl-catli. A.s.sca.srno7/ o~/'/i.s.sricL'O2 .slorc:s. T o assess the change in tissuc
This allows a precise asscssmcnt of tlic kinetic rcsponscs of tlic COz storcs (using gas cxcliiungc data) during the transition from
ventilatory system. 'l'lic si~b.jcctsbrcatlicd through a moutlipiccc rest to cxcrcisc, one must cstimatc the dill'crcncc bctwcct~COz
connected to a turbine flowmctcr and a low resistance ?-way produced at tlic ~nusclcand C 0 7 mcasurcd at the mouth. The
valve for conlini~ousrncasurcmc~itof inspired and cxl,ircd vol. dill'crcncc bctwccn thcsc valucs represent storcd tissuc CO2 (1 6).
'l'lic apparatus dead space was 140 m 1, Ibr the children and 170 Wc assumed tliat CO? production at the ~iiusclcfollowcd the
were measured by sanic time course as ~iiusclc0 2 cxtsaclio~ili.0111 the blood, thus
1111,li)r the adults. C'02 and O? co~icc~itrations
:I mass spcctromctcr that san?l,lcd continuously li-om the moi~lli- any dill'crcncc bctwccn Vo, kinctics ~ u i dV(.()?kinctics at the
piccc at I ml/s. Vl (DTPS), Vo, (STPD), V,.O,(STPD), end tidal nloi~tliwas attributed to a change in tissuc CO? stol-cs (17).
prcssurc for O2 (PI.I.,,,)and fol'C07 (PI..,.,,,)were computed on- 1:inally. we made the assumption tliat any cliangcs ill cxcrcisc
line, hrc:~tIn by brcntli. as I > I . C V ~ O L I S I ~ ~icscribcd(I I ) . I lcarl rntc respiratory cluoticnt occurrcd im ~iicdiatclyafter the onset of
was mcasurcd beat by beat by a standard lead I I ( ' ( i using three cxcrcisc (i.c~.as a square wave). In Ihct, the pattern of rcspiratol-y
clcctrotics placed o n the clicst. Tlic data from each lest wcrc cluoticnt cliiungc has bccn shown to have little cll'cct on the
storcd o n digital tape for li~rtlicranalysis.
calculi~tionof0':'(
stores li)r rest to exercise transitions (I 6). The
/)tilt/ tr~rrr!lisi.s. '1.11~ A'I' was mcasurcd noninvasivcly li-om the
cstiniatcd changes in storcd t i s s ~ ~C'cO:! were tlii~scalculated as
gas cxcli:~ngc data c~htaincdduring the progressive cxcrcisc. AT li)llows (scc Fig. I ):
was clclincd as tlic VO?at which tlic ventilatory ccluivalcnt for O?
aco, (storcs) = ( T V ( . ~-) )7 ~ 0 ) .) A V , ~ ~ ,
(VI./VO,,)
and PI ,I.,,,, ~ I ~ C I . C ~ \withoi~t
SL'
a n incrcasc in the ventilatory
wlicrc T V ( , ~ ) and
,
T V ( , , wcrc calculated li-o~nan cxponcntial lit to
c c ~ i ~ i v i ~ lfix
c ~ C'O?
i t (Vl/v(,o!) i11ici I>IY~,,.,,!
(10, 12, 13).
'l'lic rcsults of each rest to cxcrcisc transition for each subject the gas cxchangc data. starling at tlic onset of cxcrcisc, and where
wcrc timc,aligncd, and averaged to obtain a scco~idby second AV,~,),,is tlic dill'crcncc bctwccn rest and steady-state cxcrcisc
response. V I and V<.(,,phase 2 kinctics (beginning i~pproximatcly V(.(,,.'1'0 compare cliangcs in tissi~cCOz storcs bctwccn cliildrcn
-
287
HYPOXIA AND VENTILATORY CONTROL DURING EXERCISE
and adults, we normalized the increase in
in the two groups to body wt:
vco2during exercise
ACO,(stores) .kg-' = (7VCO2
- 7 ~ 0 2.) aVCo2.
kg-]
Thus, for the same increase in vco2.kg-' in both children and
adults, the increase in tissue.C02 stores can be estimated simply
by the difference between rVCO2and 7Vo2.
Statistical analysis. Unpaired t tests were used to compare the
results between the same variables in children and adults. Paired
t tests were used to compare the results of different conditions in
the same group. Differences were considered significant at p <
0.05. Values are expressed as mean + 1 SD.
Phase I responses. Phase 1 response of vEto exercise (the VE
at 20 s expressed as the percentage of change from rest to steadystate exercise) decreased significantly during hypoxia in both the
children and the adults (Fig. 3). In children, the mean phase 1
V, decreased from 36.2 k 6.6% during air breathing to 25.5 +
2.6% during hypoxic gas breathing, p < 0.0005. In adults, the
mean phase 1 VE decreased from 42.2 f 10.7% to 32.3 + 8.0,
respectively, p < 0.0005. The absolute value of the phase I
changes paralle!ed those of the relative changes. In children, the
mean phase 1 VE decreased from 3.1 1 . min-' in room air to 2.4
RESULTS
Hypoxic gas breathing resulted in a significant decrease in
steady-state exercise PETo2both in children (air breathing: 110 f
3 mm Hg, 15% 0 2 breathing: 70 f 3 mm Hg p < 0.0001) and
in adults (106 4 mm Hg and 67 + 3 mm Hg, respectively, p
< 0.000 1). Exercise Pmo2 was significantly higher in the adults
compared to the children both during air breathing (adults: 44
f 4 mm Hg; children 41 + 1 mm Hg, p < 0.05) [similar to our
previous study (13)] and also during hypoxic gas breathing
(adults: 42 + 3 mm Hg; children: 39 + 2 mm Hg, p < 0.05).
The averaged, time-aligned, breath by breath VE responses
during air and hypoxic gas breathing in the children and the
adults are shown in Figure 2. The best fit exponential for the
responses are also shown for each group.
"
*
.>
0
P(0.0005
P(0 0005
b-:.
I
0.21
0.15
0 21
0.15
FI02
Fig. 3. Effect of hypoxia on VE, phase 1 in children and adults. VE is
expressed as the percentage of change from rest to steady-state exercise.
Hypoxia resulted in a significant decrease in VE in both the children and
the adults.
CHILDREN
-60
0
60
120
TIME
180
240
300
360
-60
0
60
120
TIME
(SEC)
180
240
300
360
240
300
360
ISEC)
ADULTS
n
m
-
-f ::
Z
Z
H
H
7%
A
Z
~2
H
Y
_I
H
52
+
u
+
+2
+
2
Z
W
W
n
m
0
0
-60
0
80
120
180
T I M E ISEC)
240
300
360
-60
0
60
120
180
T I M E ISECI
Fig. 2. Averaged time-aligned breath by breath vir,responses to exercise in children and adults during air-breathing (left) and hypoxic gasbreathing (right). Hypoxia led to faster VE responses in both the children and the adults.
288
SPRINGER ET AL.
1 .min-' during hypoxia ( p < 0.05) and in adults, the decrease decrease) terms. The mean A T V ~was 18.3 k 7.7 .s in children
(36%) and 18.5 + 8.1 s in adults (27%); mean A T V C ~was
,
10.5
was from 6.0 1.min-' to 4.6 1 . min-I ( p < 0.05).
Phase 2 kinetics, Children compared to adults had significantly k 6.5 s in children (24%) and 12.0 k 6.6 s in adults (20%).
The estimated increase in tissue C 0 2 stores/kg during sub-AT
shorter TVEand T V C O(Fig.
~
4) during air breathing. These results
are similar to our previous findings in a different group of healthy exercise for a given increase in Vco2 of 1 mL. min-' .kg-' was
subjects (8). In. response to, hypoxia, there was a significant significantly smaller in children as compared to adults [O. 18 a
reduction in TVE and in rVCo2 (Fig. 4) in .both groups; this 0.07 ml CO2. kg-' in children and 0.36 f. 0.13 ml C02. kg-' in
occurred in all subjects. In children, mean TVE decreased from adults, p < 0.05 (Table 2)].
Heart rate. Hypoxia significantly increased heart rate at rest
50.9 a 9.9 s to 32.6 k 6.9 s , p < 0.001, and mean TVCO,decreased
from 43,9 f 11.0 s to 33.4 6.8 s , p < 0.005. In the adults, and during exercise in the adults and children. In air-breathing
mean TVE decreased from 69.4 k 17.6 s to 50.9 f 18.4 s, p < exercise in adults, heart rate increased from a mean of 85 beats/
0.005, and mean 7Vco2 decreased from 59.6 k 16,2 s to 47.7 k min to 108 beats/min (mean increase, 28 k 12%), and in
15.2 s, p < 0.001. The mean decrease (A) in TVEand TVCO~ children, heart rate increased from 103 to 135 beats/min (mean
induced by hypoxia was not significantly different between chil- increase, 32 k 5%). With hypoxic gas breathing, heart rate
dren and adults both in absolute (s) or relative (percentage increased in adults from 89 to 114 beats/min (mean increase, 29
a 9%), and in children heart rate increased from 110 to 144
beats/min (mean increase, 32 a 9%). There were no significant
CHILDREN
differences among the percentage rest to exercise increases in
heart rate in children compared to adults.
+
Q-
DISCUSSION
p(0 001
0.21
0 15
Fig. 4. Effect of hypoxia on vEand vco2 responses to exercise in
children and adults. Children had significantly shorter time constants
both during air-breathing ( p < 0.05) and hypoxic gas-breathing (p <
0.05) studies. In both groups, hypoxia resulted in a significant decrease
in 7 i i E and 7 ~ ~ 0 , .
The results of the present investigation demonstrate that the
coupling of PCT assessed during steady-state exercise and ventilatory responses at the onset of exercise is different in children
than in adults. During normoxia, young children had significantly faster VE and Vco, responses to exercise than do teenagers
and adults [confirming the findings of our previous study in a
different group of normal subjects (8)], despite the fact that PCT
was the same in the two groups (Fig. 5). The VE and VCO,
responses to the onset of exercise became significantly faster in
both the children and the adults under hypoxic conditions (Fig.
4), but the magnitude of the change was the same in both groups.
This was surprising as the peripheral chemoreceptor contribution
to ventilatory drive during hypoxia was much greater in the
children (Fig. 5). In summary, the greater carotid body tone
during hypoxia in children compared to adults was not paralleled
by an increase of the same magnitude in the VE response at the
onset of exercise.
Cardiac output increases suddenly at the onset of exercise,
primarily by an increase in the stroke vol. When the change in
stroke vol is limited by increasing resting stroke vol (as occurs
when exercise is performed in the supine position), the accompanying ventilatory response is smaller as we11 (18). The apparent
dependence of the early ventilatory response on cardiac output
has been named cardiodynamic hyperpnea (9). This effect is
limited to phase 1, the first 20 s of exercise, and does not appear
to influence the subsequent phase 2 response. Interestingly, we
Table 2. T VCO, and T Vo2 during air breathing used for calculation of C 0 2 stores*
Children
7vq
Adults
6)
1
2
3
4
5
6
7
8
9
33.5
27.9
28.0
27.4
26.4
27.8
3 1 .O
19.0
26.8
42.8
38.0
41.2
37.0
40.4
40.8
50.0
25.4
31.0
9.3
10.1
13.2
9.6
14.0
13.0
19.0
6.4
4.2
0.40
0.40
0.38
0.32
0.39
0.40
0.44
0.26
0.65
Mean
27.5
3.9
38.5
11.0
7.0
4.4
0.40
0.1 1
No.
SD
A7
(s)
~vco,?
1.
min-I
7vc02
(s)
7vq
7vC02
A7
(4
avco2t
1.min-'
(s)
(4
1
2
3
4
5
6
7
8
9
31.8
33.9
24.0
27.1
39.1
14.8
43.7
23.7
31.3
49.5
53.7
55.2
42.1
60.5
27.7
80.1
47.9
45.6
17.7
19.8
31.2
15.0
21.4
12.9
36.4
24.2
14.3
0.46
0.57
0.5 1
0.54
0.75
0.84
0.68
0.79
0.75
Mean
29.9
8.7
51.4
14.2
21.4
8.0
0.65
0.14
No.
SD
* ~ V C and
O ~TVO,were calculated by fitting the gas-exchange data to a first order exponential function starting at the onset of exercise. A7 is the
difference between 7v02and 7vCO2.
1AVCO, is the rest to exercise increase in V C ~ ,
HYPOXIA AND VENTILATORY CONTROL DURING EXERCISE
PERIPHERAL CHEMORECEPTOR INPUT FOR
vE
(%)
Fig. 5. TVE as a function of peripheral chemoreceptor input for
ventilation in children (solid line) and adults (broken line) during airbreathing (solid circle) and hypoxic-gas-breathing (open circle) (error bars
indicate SEM). Peripheral chemoreceptor tone is shown on the x axis as
percentage of decrease in ventilation after the hyperoxic switch (6), and
TVE is shown on the y axis in s. While breathing air, children had
significantly shorter TVE than adults despite there being no significant
differences in the peripheral chemoreceptor tone. TVE became significantly shorter in both children and adults under hypoxic conditions;
however, was no difference in the magnitude of the change in the two
groups. The peripheral chemoreceptor contribution to VE was much
greater in children compared to adults.
found reduced phase 1 ventilatory responses as a result of hypoxia
in both the adults and children (Fig. 3). Acutely, reduction in
the Fio, is known to result in an increased cardiac output, heart
rate, and stroke vol(19), and, as noted, we observed increases in
heart rate at rest and during exercise in the adults and children.
Similar to the studies done during supine exercise (18), the
magnitude of the stroke vol increase in the first 20 s of exercise
may have been reduced in our subjects during hypoxia, and this
could account for the reduced phase 1 ventilatory responses.
Moreover, the finding that the relative change in phase 1 ventilation due to hypoxia was the same in the children (hypoxic
phase 1 VE, 72 f,13% of the normoxic value) as in adults
(hypoxic phase 1 VE, 78 f 14%) is indirect evidence that the
cardiac output effects of hypoxia were similar in adults and
children.
It may be hypothesized that the circulation time (i.e. venous
vol/cardiac output) can influence the phase 2 gas exchange and
ventilatory kinetics at the onset of exercise. In fact, pulmonary
circulation time appears to be only slightly shorter in children
compared to adults. [Chalovpecky et al. (20) found pulmonary
circulation time to be 4 s in 6-y-old children and 6 s in 20-y-old
adults, using radiocirculographic methods.] If the circulation
time had a functional effect on gas exchange kinetics at the onset
of exercise, then we would have expected that both rVO2and
T V C Obecome
~
longer with increasing age or body size. But, as
demonstrated previously (21) and again in the present report,
the VO, kinetics in children could not be distinguished from
adults (Fig. 6). Therefore, it is unlikely that the different circulation times per se can explain the growth-related differences in
TVE and TVCO,we observed.
As noted, the relationship between peripheral chemoreceptor
tone and ventilatory responses at the onset of exercise was
different between children and adults both under room air- and
hypoxic-breathing conditions. This suggested to us the possibility
of a growth-related structural difference in the transport of C 0 2
from its production in the cells, to the respiratory centers and,
ultimately, to the atmosphere. One likely mechanism was the
relative size of COz stores in the body. Ward et al. (22) showed
that volitional hyperventilation before exercise, which depleted
COz stores, considerably slowed VE and VCO, kinetics in normal
subjects. ,Moreover, Poage et al. (23) have recently reported that
V E and Vco, kinetics at the onset of exercise in obese children
were significantly slower as compared to normal controls, which
Fig. 6. Group mean responses of VO, to exercise during air-breathing
in children and adults. Time 0 represents onset of exercise. VO, responses
were normalized in the two groups and presented as the fractional change
from rest (0)to steady-state exercise (1.0).There was no difference in the
response kinetics in the two groups.
may be due to the larger CO2 storage capacity in the obese
children.
We found in children that the relative increase in tissue CO2
stores during exercise was smaller by 49% compared to adults.
As less C 0 2 is stored at the onset of exercise, there may be a
more rapid arrival of metabolically produced C02 to the respiratory centers and lungs. This will result in a faster ventilatory
response to exercise consistent with our findings. The putative
difference in the relative C 0 2 storage capacity in children and
adults may be related to factors such as differences in body
composition, differences in Hb concentration (and thus vascular
COz stores) or, perhaps, to a more fundamental difference of the
tissue COz dissociation curve in children compared to adults.
In summary, we found that the coupling between peripheral
chemoreceptor tone and ventilatory responses at the onset of
exercise is not the same in children compared to adults. Under
normoxic conditions, differences in the relative size of C02
storage may explain the faster VE and Vco, kinetics with exercise
in children compared to adults, even though there was no signif-,
icant difference in PCT. But an explanation for our finding thai.
the increased PCT induced by hypoxia in children did not resuli.
in a proportional change in TVEand TVCO,is not readily apparent.
We speculate that other aspects of ventilatory control mature
during growth in children such that, as compared to adults, the
ventilatory response at the onset of exercise is smaller for a given
hypoxic stimulus.
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