This study investigated the influence of cardiorespiratory responses, blood lactate concentration and muscle oxygenation during incremental exercise tests in normoxia and hypoxia. Seven healthy subjects performed an incremental cycle ergometer exercise test breathing in random order either room air or a 15% O2 gas mixture. Ventilation and pulmonary gas exchange were measured and computed breath-bybreath. Arterial oxygen saturation (SaO2) was estimated continuously via pulse oxymeter. Forearm venous blood for measurement of blood lactate was collected every minute. Continuous-wave near infrared spectroscopy measured peripheral tissue saturation (SO2NIRS) in the vastus lateralis muscle. Significant reduction in oxygen uptake (p<0.01), power output (p<0.01) and SaO2 (p<0.001) was found in peak incremental exercise during hypoxia compared with normoxia. For the same power output in the twoconditions, hypoxia significantly decreased SaO2 (ANOVA: p<0.001) and blood lactate concentration (ANOVA: p<0.05) and increased minute ventilation (ANOVA: p<0.01). In the hypoxic condition, oxygen uptake and SO2NIRS were not found when exercising at the same power output compared with normoxia. This study would suggest that mild hypoxia may be avoided through ventilatory compensation at the alveolar level, and oxygen consumption in alveolar and peripheral tissue oxygenation can be maintained while exercising for the same power output

Kawaguchi, Kotaro

Onari, Kiyoshi

Sekikawa, Kiyokazu

Tabira, Kazuyuki

Tabusadani, Mitsuru

Hiroshima University Institutional Repository

It is well accepted that hypoxia, reduces the partialpressure of arterial oxygen and has an influence onventilatory, circulatory and metabolic processes duringexercise; measuring the gas exchange has been used tostudy cardiorespiratory response under hypoxicconditions. Recently, muscle metabolism andoxygenation, as well as arterial oxygenation andcardiorespiratory action, are seen as being limited inhealthy subjects under hypoxic conditions, and also underconditions of pulmonary patient induced hypoxemia. Toassess muscle metabolism, muscle biopsy during restingand phosphorus magnetic resonance spectroscopy duringexercise are often used and to assess muscleIntroduction oxygenation; using arterial and venous blood sampling.However, this requires invasive techniques, which limitsits application to physiological and clinical measurements.Recently, measurements using near infrared spectroscopy(NIRS) have made it possible to noninvasively measure invivo changes in tissue of both oxygenated anddeoxygenated hemoglobin and myoglobin. Althoughseveral incremental exercise experiments in hypoxicconditions have been reported5-7, 9, 10, 13, 15-17） , fewinvestigations have been done in respect to therelationship between cardiorespiratory responses andoxygenation in exercising muscle during mild hypoxia.The purpose of this study was to determine therelationships among gas exchange responses, bloodlactate concentrations, and NIRS responses duringInfluence of mild hypoxia on cardiorespiratory responsesand muscle oxygenation during incremental exerciseKiyokazu Sekikawa１）, Mitsuru Tabusadani１）, Kazuyuki Tabira２）,Kotaro Kawaguchi３）and Kiyoshi Onari３）Key words：1. near-infrared spectroscopy 2. hypoxia3. incremental exercise・低酸素吸入が呼吸循環応答及び活動筋酸素動態に及ぼす影響・氏名：関川　清１），髻谷　満１），田平一行２），川口浩太郎３），大成浄志３）・所属：１）広島大学大学院医学系研究科保健学専攻　２）吉島病院　３）広島大学医学部保健学科理学療法学専攻・英文所属：１）Health Sciences, Graduate School of Medical Sciences, Hiroshima University２）Yoshijima Hospital ３）Division of Physical Therapy, Institute of Health Scinces, Faculty of Medicine, Hiroshima University・広島大学保健学ジャーナル　Vol. 2(1)：85～89，200285This study investigated the influence of cardiorespiratory responses, blood lactate concentration andmuscle oxygenation during incremental exercise tests in normoxia and hypoxia. Seven healthy subjectsperformed an incremental cycle ergometer exercise test breathing in random order either room air or a15％ O2 gas mixture. Ventilation and pulmonary gas exchange were measured and computed breath-by-breath. Arterial oxygen saturation (SaO2) was estimated continuously via pulse oxymeter. Forearm venousblood for measurement of blood lactate was collected every minute. Continuous-wave near infraredspectroscopy measured peripheral tissue saturation (SO2NIRS) in the vastus lateralis muscle. Significantreduction in oxygen uptake (p<0.01), power output (p<0.01) and SaO2 (p<0.001) was found in peakincremental exercise during hypoxia compared with normoxia. For the same power output in the twoconditions, hypoxia significantly decreased SaO2 (ANOVA: p<0.001) and blood lactate concentration(ANOVA: p<0.05) and increased minute ventilation (ANOVA: p<0.01). In the hypoxic condition, oxygenuptake and SO2NIRS were not found when exercising at the same power output compared with normoxia.This study would suggest that mild hypoxia may be avoided through ventilatory compensation at thealveolar level, and oxygen consumption in alveolar and peripheral tissue oxygenation can be maintainedwhile exercising for the same power output.原 著incremental exercise under normoxic and acute mildhypoxic conditions.Subjects Seven healthy men, but not currently involved inactive physical training, were recruited for this study.Age, height and weight were 23.4 (SD 1.6) yr, 170.4 (SD4.2) cm and 63.9 (SD 7.4) kg respectively. Each subjectgave informed consent after understanding the nature,purpose, and risks in this study.Exercise protocolAll subjects performed two incremental exercisetests on an electrically braked ergometer (232c-XL,Combi, Co., Ltd) during random ordered breathing ofroom air or hypoxic gas mixture (15％O2, N2 balance).While breathing the hypoxic mixture, subjects breathedthrough a facemask with a J-valve from a reserve bag.Subjects performed ramp exercise at a work rate of20W/min, after breathing the gas mixture for 5 minsubsequent to 15min sitting at rest. The pedaling rate wasmaintained at 50 rpm. Workload was increased untilmaximal exercise effort occurred, which was determinedas being when: no longer able to keep the 50 rpmpedaling frequency because of breathlessness or legfatigue, or age predicted maximal HR calculated as 220less their age in years reached, or oxygen saturation lessthan 85％. Oxygen uptake (・VO2, standard temperature andpressure, dry (STPD), carbon dioxide production (・VCO2,STPD) and minute ventilation (・VE, body temperature andpressure, saturated with water vapor (BTPS)) weremonitored via a metabolic cart system (AE-280S, MinatoMedical Science Co., Ltd). The O2 and CO2 gas analyzerwere calibrated before and after each test, using standardgas. Heart rate (HR) was continuously measured byelectrocardiogram (DS-3140, Fukuda-Densi Co., Ltd.) andwas then entered into the metabolic cart system.Pulmonary exchange and HR were calculated as theaverage over 30 seconds for each minute during exercise.Oxygen saturation (SaO2) was estimated continuously viapulse oxymeter (MicroO2, Siemens, Co., Ltd.) and wasmeasured every minute. Forearm venous blood wassampled each minute of exercise by catheter formeasurement of blood lactate (Aqu-Sports, RocheDiagnostics Co., Ltd.). MethodsA near infrared spectrometer (BOM-L1TR, OmegaWave Inc,) was used to monitor tissue oxygenation. Thisinstrument uses three wavelengths (780, 810 and 830nm),and absorption characteristics generally depend on therelative oxy- hemoglobin (OxyHb), deoxy hemoglobin(DeoxyHb) levels in tissue based on a Modified Lambert-Beer's law. The absorption coefficient of hemoglobin ateach wavelength was based on data reported by Matcheret al.12） Tissue oxygen saturation (SO2NIRS) was calculatedfrom the ratio of OxyHb to TotalHbMb (= OxyHb +DeoxyHb) values. For measurement, the distancebetween the incident point and the detector was 30mm,with a resulting depth of penetration of about 15mm. ANIRS probe was placed over the right vastus lateralismuscle 10-12cm above the knee and was protected byadhesive tape with a rubber sheet. Tapes were wrappedaround the thigh to prevent displacement of the probeduring exercise. NIRS data were inputted to a Macintoshpersonal computer at a sampling frequency of 10 Hz viaan A/D transducer (Mac Lab 8s, AD Instrument Inc.).NIRS data were expressed by changes from the pre-exercise values (ΔOxyHb, ΔDeoxyHb, ΔTotalHb andΔSO2NIRS), which were determined as averages duringthe minute preceding the start of exercise using chartv3.6.8/s software.  Statistical analysisThe values were expressed as mean ± SE. The peakdata were compared by paired t-tests. A two-way repeatedmeasure ANOVA was used to evaluate the differencebetween the hypoxic and normoxic conditions frompaired exercise data. Statistical analysis was performedusing Stat View 5.0J software and the level of statisticalsignificance on all tests was set at p <0.05.ResultsReasons for stopping hypoxic exercise were: fivewere breathless and two had SaO2 less than 85％. Thepeak values for each condition are shown in Table 1.Hypoxia caused a reduction in maximal workperformance as indicated by the reduction in the peakwork rate from 228 ± 9.1 (range 180-240) to 178.6 ± 10.3(range 140-210) Watt (p<0.01). A significant reductionin・VO2, HR, ・VE and SaO2 was found in peak exerciseduring hypoxia as compared to normoxia (Table 1). Therewere significant differences in Δ OxyHb andΔSO2NIRS(p<0.05 respectively). For the same power outputs below 140Watts, SaO286(Fig. 1A) was significantly lower in hypoxia thannormoxia (ANOVA p<0.001). ・VE (Fig. 1C) increasedprogressively with exercise and hypoxic valuessignificantly exceeded those found in normoxia (ANOVAp<0.01). Blood lactate concentrations (Fig. 1D) increasedduring exercise in the two conditions; however, bloodlactate concentrations were significantly lower in hypoxiathan normoxia (ANOVA p<0.05). ・VO2 (Fig. 1B), ΔSO2NIRS (Fig. 2A), ΔTotal Hb (Fig.2B), ΔOxyHb (Fig.2C) and ΔDeoxy Hb (Fig.2D) were not found in exerciseduring hypoxia compared with normoxia for the samepower outputs.87広大保健学ジャーナル，Vol, 2�, 2002Fig.1. SaO2(A), ・VO2(B), ・VE(C) and Blood lactate(D) during exercise innormoxia(■) and hypoxia(●). Values are means ±SE.Fig.2. %change in SO2NIRS(A), Total Hb(B), Oxy Hb(C) and Deoxy Hb(D)during exercising inNormoxia(■) and hypoxia(●). Values are means ±SECardiorespiratory responsesReduced aerobic capacity has been found in acutehypoxia compared with normoxia, and a wide variabilityin reduction of ・VO2max decrements during hypoxicbreathing has been reported 7, 10, 15, 16）. In this study under15％O2 conditions, we found that peak・VO2 was reducedsignificantly compared with that under normoxicconditions. In breathing a gas mixture of 17％O2 5,13）,however, ・VO2max was not changed compared withnormoxia, findings that might be due to the difference inthe fraction of oxygen in the inspired gas.Several investigations have studied the influence ofacute hypoxia on cardiorespiratory dynamics and bloodlactate concentration for the same power output inincremental ergometer exercise protocols 6, 7）. Ibanez et al. 7）working with subjects under severe hypoxemia (10％O2),found a significant increase in ・VCO2, ・VE and bloodlactate concentration below 200 watt and a decrease in・VO2 between 150 and 200 watt. Hughson et al .6） found asignificant decrease in ・VO2 and an increase in lactateconcentration above 190 watt under 14％O2 air breathing.In our study under 15％O2 conditions, we found asignificant increase in ・VE and an insignificant change in・VO2 for the same workload below 140 watt. This wouldsuggest that hypoxemia during mild hypoxia may beavoided through respiratory compensation at the alveolarlevel, shown by the increase in ・VE, so minimizing theDiscussion reduction in saturation with a mild decrease in partialpressure of oxygen in arterial blood.Several investigations have reported that bloodlactate concentrations were higher, for the same absoluteexercise intensity, under acute hypoxia than innormoxia7,18）, and that increased ・VE was caused by thehighest blood lactate concentration during hypoxicexercise7）. However, no difference in blood lactateconcentrations for the same relative intensity was foundin 17％O2 breathing exercises5, 9）. Contrary to thesereports, we found a significant decrease in blood lactateaccumulation for the same power output. This suggeststhat the lowest blood lactate concentrations were causedby hypoxia-induced hyperventilation. Muscle oxygenation responsesRecently, measurements using NIRS have made itpossible to noninvasively measure in vivo changes in theoxygenated and deoxygenated hemoglobin and/ormyoglobin of tissue. Previously, few studies have foundany influence of hypoxia on muscle oxygenationmeasured by NIRS during incremental exercise, althoughseveral investigators have reported oxy- anddeoxygenation in vastus lateralis muscle duringergometer cycle exercise 1-4, 8, 17）. We found in the hypoxiccondition (15％O2) that peak workload, peak SaO2 andpeak ΔSO2NIRS were significantly lower compared withnormoxia (Table 1). The changes of total Hb represent those of bloodvolume, and SO2NIRS those of the averages of arterial,capillary, and venous hemoglobin oxygen saturation, aswell as the contributions from intracellular myoglobinoxygen saturation2, 14）. This would suggest that when thecondition is 15％O2, it contributes to the differentiation ofchanges in oxygen content and metabolic demand inexercising muscle during peak exercise. The time course of the NIRS change comparingnormoxia and hypoxia was evaluated by steady stateexercise. Costes F. et al.3） have reported that during 30-min steady state exercise, muscle oxygenation wassignificantly lower in hypoxia (inspired oxygenfraction=0.105) than in normoxia when PaO2 was shownto be 38torr at onset of exercise and 35torr at a maximumof 30min in hypoxic conditions. However, Macdonald et al. 11） showed that during 5-min steady state exercise,there were no significant changes in oxygen saturation inexercising muscle between normoxia and hypoxia (17％O2). The results of the present study indicated that ・VO288and ΔSO2NIRS did not significantly change in the twoconditions when exercising at the same power output.These findings suggested that hypoxemia during mildhypoxia (15％O2) may preserve oxygen consumption inalveolar and peripheral tissue oxygenation at the samepower output exercise. The muscle oxygen content depends on oxygendelivery, which is determined by the arterial oxygencontent and blood flow. NIRS techniques have been usedto assess changes in blood volume, and the balancebetween O2 delivery and O2 utilization. In the presentstudy, blood flow to individual muscles of the thigh wasnot measured, and needs to be studied further.In conclusion, the results of the present study wouldsuggest that the condition, breathing 15％O2, contributedto the differentiation of changes in oxygen content andmetabolic demand in exercising muscle at a peakexercise. We found that hypoxemia during mild hypoxiamay be avoided through ventilatory compensation at thealveolar level, and that oxygen consumption in alveolarand peripheral tissue oxygenation can be maintainedwhile exercising for the same power outputs.References1. Belardinelli, R., Georgiou, D. and  Barstow, T. J. : Nearinfrared spectroscopy and changes in skeletal muscleoxygenation during incremental exercise in chronic heartfailure: a comparison with healthy subjects. G. Ital. Cardiol.,25: 715-724, 1995.2. Boushel, R., Langberg, H. and Olesen, J. et al. : Monitoringtissue oxygen availability with near infrared spectroscopy(NIRS) in health and disease. Scand J. Med. Sci. Sports, 11:213-222, 2001.3. Costes, F., Barthelemy, JC. and Feasson, L. et al. :Comparison of muscle near-infrared spectroscopy andfemoral blood gases during steady-state exercise in humans.J. Appl. Physiol., 80: 1345-1350, 1996.4. Grassi, B., Quaresima, V. and Marconi, C. et al. : Bloodlactate accumulation and muscle deoxygenation duringincremental exercise. J. Appl. Physiol., 87 : 348-355, 1999.5. Hogan, MC., Cox, RH. and Welch,HG. : Lactateaccumulation during incremental exercise with variedinspired oxygen fractions. J. Appl. Physiol., 55: 1134-1140,1983.6. Hughson, RL., Green, HJ. and Sharratt, MT. : Gas exchange,blood lactate, and plasma catecholamines during incrementalexercise in hypoxia and normoxia. J. Appl. Physiol., 79: 1134-1141, 1995.7. Ibanez, J., Rama, R. and Riera, M. et al. : Severe hypoxiadecreases oxygen uptake relative to intensity duringsubmaximal graded exercise. Eur. J. Appl. Physiol., OccupPhysiol.,  67: 7-13, 1993.8. Kawaguchi, K., Tabusadani, M. and Sekikawa, K. et al. : Dothe kinetics of peripheral muscle oxygenation reflectsystemic oxygen intake? Eur. J. Appl. Physiol., 84: 158-161,2001.9. Knuttgen, HG. and Saltin, B. : Oxygen uptake, muscle high-energy phosphates, and lactate in exercise under acutehypoxic conditions in man. Acta Physiol. Scand., 87: 368-376,1973.10. Lawler, J., Powers, SK. and Thompson, D. : Linearrelationship between VO2max and VO2max decrementduring exposure to acute hypoxia. J. Appl. Physiol., 64: 1486-1492, 1988.11. MacDonald, MJ., Tarnopolsky, MA. and Green,HJ. et al. :Comparison of femoral blood gases and muscle near-infrared spectroscopy at exercise onset in humans. J. Appl.Physiol., 86: 687-693, 1999.12. Matcher, SJ., Elwell, CE. and Cooper, CE. et al. :Performance comparison of several published tissue near-infrared spectroscopy algorithms. Anal. Biochem., 227: 54-68, 1995.13. Mateika, JH. and Duffin, J. : The ventilation, lactate andelectromyographic thresholds during incremental exercisetests in normoxia, hypoxia and hyperoxia. Eur. J. Appl.Physiol. Occup. Physiol., 69: 110-118, 1994.14. McCully, KK. and Hamaoka, T. : Near-infrared spectroscopy: what can it tell us about oxygen saturation in skeletalmuscle? Exerc. Sport Sci. Rev., 28: 123-117, 2000.15. Murphy, PC., Cuervo, LA. and Hughson, RL. : study ofcardiorespiratory dynamics with step and ramp exercisetests in normoxia and hypoxia. Cardiovasc Res., 23: 825-832,1989.16. Paterson, DJ., Pinnington, JH. and Pearce, AR. et al. :Maximal exercise cardiorespiratory responses of men andwomen during acute exposure to hypoxia. Aviat SpaceEnviron Med., 58: 243-247, 1987.17. Wadazumi, T., Kimura, Y. and Oshima, Y. et al. : Differencesin breakpoint patterns in the muscle oxygenation curvemeasured by NIRS during ramp exercise. Ther Res., 17: 153-157, 1996.18. Wagner, JA., Miles, DS. and Horvath, SM. : Physiologicaladjustments of women to prolonged work during acutehypoxia. J. Appl. Physiol., 49: 367-373, 1980.89広大保健学ジャーナル，Vol, 2�, 2002

Influence of mild hypoxia on cardiorespiratory responses and muscle oxygenation during incremental exercise

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Influence of mild hypoxia on cardiorespiratory responses and muscle oxygenation during incremental exercise

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