Effect of hypoxia on ventilatory control during exercise in children and adults

UC Irvine UC Irvine Previously Published Works 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 Powered by the California Digital Library University of California 003 1-399818912503-0285$02.00/0 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. 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