DTIC ADA545957: Effect of Repeated Normobaric Hypoxia Exposures during Sleep on Acute Mountain Sickness, Exercise Performance, and Sleep during Exposure to Terrestrial Altitude

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2011 Am J Physiol Regul Integr Comp Physiol
4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER
Effect of Repeated Normobaric Hypoxia Exposures During Sleep on Acute
Mountain Sickness, Exercise Performance, and Sleep During Exposure to
5b. GRANT NUMBER
Terrestrial Altitude
5c. PROGRAM ELEMENT NUMBER
6. AUTHOR(S) 5d. PROJECT NUMBER
C.S. Fulco, S.R. Muza, B.A. Beidleman, R. Demes, J.E. Staab, J.E. Jones, A.
Cymerman
5e. TASK NUMBER
5f. WORK UNIT NUMBER
7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION
REPORT NUMBER
Thermal and Mountain Medicine Division
M10-25
U.S. Army Research Institute of Environmental Medicine
Natick, MA 01760-5007
9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S)
Same as #7 above
11. SPONSOR/MONITOR'S REPORT
NUMBER(S)
12. DISTRIBUTION/AVAILABILITY STATEMENT
Approved for public release; distribution unlimited.
13. SUPPLEMENTARY NOTES
14. ABSTRACT
There is an expectation that repeated daily exposures to normobaric hypoxia (NH) will induce ventilatory acclimatization (VEacc)
and be effective for lessening acute mountain sickness (AMS) and the exercise performance decrement during subsequent hypobaric
hypoxia (HH) exposure. However, this notion has not been tested objectively. Healthy, unacclimatized sea level (SL) residents
slept for 7.5 hrs each night for 7 consecutive nights in hypoxia rooms under either NH (n=14, 24±5 yr; mean±SD) or “sham” (n=9,
25±6 yr) conditions. The ambient %O2 for the NH group was progressively reduced by 0.3%O2 (150 meters equivalent) each night
from 16.2%O2 (2200 m eq) on the 1st night to 14.4%O2 (3100 m eq) on the 7th night, while that for the ventilatory and
exercise-matched sham group remained at 20.9%O2. Beginning 25 hrs post-sham or NH treatment all ascended and lived for 5 days
at HH (4300 m). Partial pressure of end-tidal CO2 (PetCO2), oxygen saturation (SaO2), AMS, and heart rate (HR) were measured
repeatedly during daytime rest, sleep or exercise (11.3 km treadmill time trial (TT)). From pre-to post-treatment at SL, resting
PetCO2 decreased (p<0.01) for the NH group (39±3 to 35±3 mmHg) but not for the sham group (39±2 to 38±3 mmHg). Throughout
15. SUBJECT TERMS
HH, only sleep SaO2 was higher (80±1% vs 76±1%, P<0.05) and only AMS upon awakening was lower (0.34±0.12 vs 0.83±0.14,
PV<e0n.t0il2a)t oirny t hacec NliHm agtrizoautpio cno, mApMarSe,d p thoy tshiec aslh paemrf ogrrmouapn;c neo, hoythpeorb bareitcw heyepno-gxrioa,u apr rteersita, ls olexeypg, eonr seaxteurrcaitsieo nd,i fSfaeOre2nces were observed at
HH. These results indicate that the VEacc induced by NH sleep was primarily expressed during HH sleep. Under HH conditions,
the higher sleep SaO2 may have contributed to a lessening of AMS upon awakening but had no impact on AMS or exercise
1p6e.r fSoErCmUaRnIcTeY f CorL AthSeS rIFeImCAaiTnIOdeNr OofF :e ach day. 17. LIMITATION OF 18. NUMBER 19a. NAME OF RESPONSIBLE PERSON
a. REPORT b. ABSTRACT c. THIS PAGE ABSTRACT OF Charles S. Fulco
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Unclassified Unclassified Unclassified 9 19b. TELEPHONE NUMBER (Include area code)
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AmJPhysiolRegulIntegrCompPhysiol300:R428–R436,2011.
FirstpublishedDecember1,2010;doi:10.1152/ajpregu.00633.2010.
Effect of repeated normobaric hypoxia exposures during sleep on acute
mountain sickness, exercise performance, and sleep during exposure
to terrestrial altitude
Charles S. Fulco, Stephen R. Muza, Beth A. Beidleman, Robby Demes, Janet E. Staab, Juli E. Jones,
and Allen Cymerman
ThermalandMountainMedicineDivision,USArmyResearchInstituteofEnvironmentalMedicine,Natick,Massachusetts
Submitted20September2010;acceptedinfinalform25November2010
FulcoCS,MuzaSR,BeidlemanBA,DemesR,StaabJE,Jones mountainsickness(AMS)andimprovedexerciseperformance
JE,CymermanA.Effectofrepeatednormobarichypoxiaexposures during HH residence (1, 11, 12, 14). Some studies show that
during sleep on acute mountain sickness, exercise performance, and VEacccanalsobeinducedby1–4hofHHexposurerepeated
sleepduringexposuretoterrestrialaltitude.AmJPhysiolRegulIntegr
dailyataltitudesof4,300–4,500minasfewas7daysandthat
Comp Physiol 300: R428–R436, 2011. First published December 1,
thismethodofHHexposureisasbeneficialascontinuousHH
2010;doi:10.1152/ajpregu.00633.2010.—Thereisanexpectationthat
residence for reducing AMS and improving exercise perfor-
repeated daily exposures to normobaric hypoxia (NH) will induce
mance (2, 4, 18). D
ventilatoryacclimatizationandlessenacutemountainsickness(AMS) o
andtheexerciseperformancedecrementduringsubsequenthypobaric A comparable degree of VEacc can similarly be induced as w
n
hypoxia (HH) exposure. However, this notion has not been tested aresultofrepeateddailynormobarichypoxia(NH)exposures lo
objectively.Healthy,unacclimatizedsea-level(SL)residentssleptfor (maintained P and (cid:3)20.9% O ) using many different combi- ad
B 2 e
7.5heachnightfor7consecutivenightsinhypoxiaroomsunderNH nations of hypoxia duration, severity, and frequency (22). d
[n(cid:1)14,24(cid:2)5(SD)yr]or“sham”(n(cid:1)9,25(cid:2)6yr)conditions. Whathasnotbeenestablished,however,iswhetherNHexpo- fro
Tbyhe0.a3m%bi[e1n5t0pmerceeqnutivOa2lefnotr(tehqeuNivH)]geraocuhpnwigahstpfrroomgre1s6s.i2v%ely(2re,2d0u0cemd sure is any more effective than no treatment for mitigating am
undesirableoutcomessuchasAMSortheinitiallargeimpair- jp
equiv)onnight1to14.4%(3,100mequiv)onnight7,whilethatfor mentinexerciseperformanceduringsubsequentHHresidence re
tBheegvinennitnilgatoatry2-5anhdaeftxeerrcshisaem-moartcNhHedtsrheaamtmgenrot,uapllresmubajiencetdsaats2ce0n.9d%ed. (22). The only controlled, experimental studies reporting that gu.p
AMS,exerciseperformance,andotherphysiologicaloutcomes h
r(aeSnsadtO,l2is)v,leeAedpMf,oSor,r5aendxdaehyrcesiasarettrH(a1tH1e.w3(4-ek,r3me0m0tremeaa)sd.umrEeindldlr-tetiipmdeaealtetPrdCilaOyl2)d.,uOFrri2onmgsadtuparryaett-iimotnoe wtreearetmaefnfetcpteridorfatvoorHaHblyrerseildaetinvceeto(2–no4,tr1e8a)tmoernNt HutiltirzeeadtmHenHt ysiolo
g
pthoestNtrHeat(mfreonmta3t9S(cid:2)L,3retsoti3n5g(cid:2)end3-tmidmalHPgC)O,2budtecnroetafsoerdt(hPe(cid:3)sha0m.01(f)rofomr ppruibolristhoedNrHecreenstildye(n5c,e27(1),7n,o22d)a.taUenxtiisltetwdotoodtehteerrmstiundeiedsirwecetrlye y.org
3w9as(cid:2)hi2ghtoer3(88(cid:2)0 (cid:2)31mmvsH. g7)6, (cid:2)gro1u%p.,TPhr(cid:3)oug0h.0o5u)taHnHd,oonnlylyAsMleeSpuSpaoOn2 wtrehaettmheerntNdHurintrgeastumbesneqtuwenotuHldHbreesimdeonrece.beneficial than no on J
awakeningwaslower(0.34(cid:2)0.12vs.0.83(cid:2)0.14,P(cid:3)0.02)inthe In one of these studies, our group (5) showed that, after un
NexHerctihsaenditfhfeeresnhcaemswgreoreupo;bsneorvoetdheartHbeHtw.Teehne-sgerroeuspultrsesint,discleaetep,thoart induction of VEacc with 21 h of NH treatment (PO2 (cid:1) 90 e 15
the ventilatory acclimatization induced by NH sleep was primarily mmHg for 2 h/day and 110 mmHg for 1 h/day) over 7 , 2
expressed during HH sleep. Under HH conditions, the higher sleep consecutive days, the impairment of time-trial (TT) exercise 01
1
Sa mayhavecontributedtoalesseningofAMSuponawakeningbut performance assessed within a few hours after rapid ascent to
O2
hadnoimpactonAMSorexerciseperformancefortheremainderof HH (446 mmHg) was not attenuated. The other study (27),
eachday. which used 14–18 h of NH treatment (12–16% O for 70–90
2
min/day,3days/wk,for4wk),alongwithanovernightstayat
ventilatoryacclimatization;physicalperformance;hypobarichypoxia;
3,611 m, reported no differences in arterial blood gases or
arterialoxygensaturation
AMS compared with no NH treatment during subsequent HH
residenceat4,559m.Oneinterpretationsuggestedforthelack
ALTITUDE ACCLIMATIZATION RESULTS from numerous interrelated ofeffectivenesswasalossofVEaccpriortoHHresidence(5)
physiological adjustments that compensate for hypoxemia, thatresultedfrombeingatsealevel(SL)withoutNHtreatment
with augmented ventilation being one of the most important formuchlongerthanthe(cid:1)24husedduringprevioussuccess-
and consistently reported (17, 18, 22, 28). Ventilatory accli- fulHHtreatmentstudies(2,4).However,thisinterpretationis
matization (VEacc) can be characterized by the progressive inconsistent with the results of at least one study (17) that
decreaseintheend-tidalPCO2(PETCO)thatleadstoanincrease reportedthatVEaccremainedevidentwhenassessedunderNH
2
in arterial O2 saturation (SaO) during the first several days of ambient conditions 1 mo after the NH treatment ended. An
2
moderate-tohigh-altituderesidence[hypobarichypoxia(HH), alternative interpretation for the lack of effectiveness could
reduced barometric pressure (PB) and 20.9% O2] (7, 28). The then be that NH treatment does not provide any additional
enhanced oxygenation is closely linked with reduced acute ventilatory, AMS symptom, or exercise performance benefit
during subsequent HH residence.
The main purpose of the current study was to assess the
Addressforreprintrequestsandothercorrespondence:C.S.Fulco,Thermal
effectiveness of NH treatment per se by minimizing the time
andMountainMedicineDivision,USARIEM,KansasSt.,Natick,MA01760
(e-mail:[email protected]). between the end of NH treatment and the beginning of HH
R428 http://www.ajpregu.org
NORMOBARICHYPOXIAPRETREATMENTANDALTITUDEEXPOSURE R429
Fig. 1. Experimental design. Resting measures [i.e.,
ventilation, arterial O saturation (Sa ), heart rate
2 O2
(HR), venous blood] and exercise determinations of
peakO2uptake(V˙O2peak)andenduranceperformance
(steadystateat45%ofV˙O2peakanda7-miletimetrial)
wereobtainedduringthe(cid:5)2-wksea-level(SL)base-
line phase. Also during the baseline phase, resting
measures were obtained on all volunteers during an
acute (cid:3)1-h exposure to normobaric hypoxia [NH
(12.2%O,4,300mequivalent)].Afterbeingassigned
2
to the NH (solid line) or the “sham” control sleep
(dotted line) treatment group, volunteers slept for 7
consecutivenightsinoneoftwoadjacentandidentical
2.4(cid:6)3.0(cid:6)2.3mrooms;volunteerswereblindtothe
treatmenttheyreceived.Before(at(cid:5)2200)andafter
(at(cid:5)0530)eachnightofsleep,acutemountainsick-
ness (AMS) was assessed, and Sa and HR were
O2
obtained.Motion,Sa ,andHRwereobtainedcontin-
O2
uously during sleep. Within 2 h ofawakening after
night7,posttreatmentrestingmeasureswereobtained
atSL.Allvolunteerswerethenflownwithinseveral
hourstoColoradoSprings,CO[2,100m,barometric
pressure(P )(cid:5)600mmHg],wheretheyresideduntil D
B
(cid:5)0600thenextmorning.At(cid:5)0700,allarrivedbycar ow
atthesummitofPikesPeak(4,300m). n
lo
a
d
e
d
raeirspidlaennecetr.aWveelainndclaundoedverinnigthhetsstohpoortveenreadtatimmeodienrtaetrevaalltibtuodthe ExperimentalDesignOverview from
Eachvolunteerparticipatedinthreedistinctphasesattwodifferenttest
of 2,100 m to provide a more realistic scenario that would a
likelybeusedbyindividualsforworkorrecreationalactivities. fbaacsieliltiineesoSvLerasasteostsamlpeenrtiopdhoasfe3–at4UwSkAinRtIhEeMfo,lNloawtiicnkg,oMrdAer((2Fwigk.1,)5:01m)a, jpre
ThesubsequentHHresidencewasalsolengthenedto5daysto PB(cid:5)756(cid:2)2mmHg),2)a7-nightsleep-treatmentphaseinNatick, gu
determine whether prior NH treatment would alter the rate of MA,and3)a5-dayHHphaseatthesummitofPikesPeak,Colorado .p
h
acclimatization. Springs,CO(4,300m,P (cid:5)459mmHg).Duringtestinginallphases, y
B s
Our approach was to subject individuals to moderate levels thetemperaturewasmaintainedat21(cid:2)3°C. io
of NH during sleep, so that the daily “dose” would be as long After SL baseline testing was completed but before the sleep- log
as practically possible without interfering with daytime activ- treatment phase began, “squads” of two to four volunteers were y.o
ities and also not so severe as to disrupt sleep. This approach randomlyassignedtoaNHsleep-treatmentgroup(n(cid:1)14)orasham rg
sleep-treatmentcontrolgroup(n(cid:1)9).Assignmentofeachvolunteer o
also minimized the NH stimulus “down time” between con- n
secutive treatment exposures (22). To that end, treatment to each squad was based on their availability to travel to Colorado Ju
Springs on predetermined dates. All volunteers were blind to their n
involvedsleepingfor7.5heachnightfor7consecutivenights e
ignreassrivoeolmyiunncdreearsianmgbailetnittudNeHsrcaonngdinitgiofnrosmth2a,t2s0i0mtuola3t,e1d00prmo-. usblneetdewepre-terSneLagtmraoneundptsNaesHsxiigs(nt1emdehfnotorufangetixel,ptohwseeueirgenhdtt,oofh9eth3igehmst,tmuPdHEyTg.CNOao2mddbuiiferfinentrgePnrcOee2ss)t 15, 20
The total NH treatment duration was therefore 52.5 h, which conditions,andpeakandTTexerciseperformance(Table1).1 1
1
was nearly twice as long as the minimal total HH treatment During the sleep-treatment phase, a squad reported each night at
duration previously determined to be beneficial during subse- 2200 to a large room containing two identical 2.4 m wide (cid:6) 3.0 m
quent HH residence (5) and approximately three times longer
than the two recent NH treatment-to-HH residence studies
describedabove(5,27).WehypothesizedthatVEaccinduced 1At2daysafterthesleep-treatmentphasebegan,avolunteerinthesham
group broke a toe (unrelated to the study) and could not participate in the
byNHtreatmentwouldbeevident,AMSsusceptibilitywould
remaining exercise tests but did participate in all other assessments and
be reduced, and TT exercise performance would be improved
activities.Onlyhisrestingandsleepdatawereincludedinthefinalanalyses.
compared with a no-treatment control (“sham”) group during
thefirst5daysofresidenceataterrestrialelevationof4,300m.
Table 1. Volunteer characteristics
METHODS
NHTreatment ShamTreatment
(n(cid:1)14) (n(cid:1)9)
Volunteers
Age,yr 24(cid:2)5 25(cid:2)6
Twenty-threeunacclimatizedSLresidents(20menand3women) Weight,kg 76(cid:2)15 75(cid:2)16
volunteeredtoparticipate.Nonewasbornataltitudes(cid:4)2,100m,and Height,cm 173(cid:2)10 174(cid:2)9
allhadbeenlivingatlowaltitudes((cid:3)1,000m)for(cid:2)3mopriortothe Sex 12/2 8/1
startofthestudy.Allprovidedverbalandwrittenconsentsafterbeing End-tidalPco2,mmHg
fully informed of the nature of the study and its possible risks and Sealevel 39(cid:2)3 39(cid:2)2
benefits. The study was approved by the Institutional Review Normobarichypoxia 36(cid:2)2 36(cid:2)2
PeakO uptake,ml(cid:1)kg(cid:7)1(cid:1)min(cid:7)1 46(cid:2)8 48(cid:2)6
Boards of the US Army Research Institute of Environmental 2
Sea-leveltime-trialperformance,min 75(cid:2)13 73(cid:2)8
Medicine(USARIEM)andtheHumanResearchProtectionOffice,
US Army Medical Research and Materiel Command. Valuesaremeans(cid:2)SD.
AJP-RegulIntegrCompPhysiol•VOL300•FEBRUARY2011•www.ajpregu.org
R430 NORMOBARICHYPOXIAPRETREATMENTANDALTITUDEEXPOSURE
long(cid:6)2.3mhighclearvinyl-sided,portablehypoxiarooms(Colo- theEnvironmentalSymptomsQuestionnaire(ESQ)(6).TheESQwas
rado Altitude Training, Boulder, CO). One room was always main- administeredusingapersonaldigitalassistant(modeliPAQ,Hewlett-
tained at SL conditions (sham: P (cid:5)756, O (cid:1) 20.9%), while the Packard). A weighted average of scores from 11 symptoms (e.g.,
B 2
ambient O concentration of the other room was progressively re- headache,lightheadedness,dizziness),designated“AMS-C,”wascal-
2
ducedby(cid:5)0.30%O [orincreasedby150mequivalents(equiv)]on culated.AMS-Cscores(cid:2)0.7indicatedthepresenceofAMS.Foreach
2
consecutive nights from (cid:5)16.2% O (2,200 m equiv) on night 1 to dayatHH,theAMS-Cscoreobtainedat0700andthepeakAMS-C
2
(cid:5)14.4%O (3,100meq)onnight7.CO scrubberunitsmaintained scoreobtainedafter0700wereusedintheanalyses.Prevalencewas
2 2
a low concentration of CO (0.04–0.10%) within each room on all definedasthepercentageofindividualsineachgroupwhoweresick
2
nights. The environmental conditions for the hypoxia rooms were (i.e.,AMS-Cscore(cid:2)0.7)at0700andafter0700.
stabilized before the volunteers reported each night. All volunteers AtthecompletionofeachAMSassessment,Sa wasmeasuredfor
O2
remainedintheirroomuntil0530eachmorning.Thusallvolunteers 1 min by finger pulse oximetry (Voyager Pulse Oximeter, Dolphin
remainedintheirrespectiveenvironmentalconditionforatotalof7.5 Medical,Hawthorne,CA).ThemeanSa wasthereforematchedin
O2
heachnight. realtimetoeachAMSassessment.
Betweenthetwoadjacenthypoxiaroomswasastaffmember,who PeakO2uptake.OnepeakO2uptake(V˙O2peak)testwasconducted
each night monitored and controlled the ambient conditions of the duringtheUSARIEMbaselinephaseatSL.Anincremental,progres-
hypoxia rooms. The tubing, wires, vents, fans, and sensors were siveexercisebouttovolitionalexhaustiononamotor-driventreadmill
presentedandvisuallyorientedsuchthatthevolunteerswereunaware (model 9.15HR, Smooth Fitness, King of Prussia, PA) was used to
ofO2leveldifferenceswithintherooms. assess V˙O2peak. Measurements of O2 uptake (V˙O2) for each of the
In the morning after night 7 of sleep, resting measurements were 2-min stages were obtained using a metabolic cart (True Max 2400,
obtained at SL outside the hypoxia rooms. The volunteers were ParvoMedics,Sandy,UT).Volunteerswalkedforatotalof10min(5
blindedtoalldatadisplays.Thenthevolunteersweredriventoalocal stages) starting at 3 METS (4.8 m/h and 0% grade) and ending at 8
D
airport and flown to Colorado Springs, CO (2,100 m, P (cid:5)600 METS(6.4m/hand7%grade).Thetreadmillspeedandgradewere o
B w
mmHg)tostayovernightinanapartmentunderstaffsupervision.The thenchangedsothatthevolunteerswouldrunat9.7m/hand0%(10 n
staff in Colorado Springs was blinded to the volunteers’ sleep treat- METS), respectively. Then, for every 2-min stage thereafter, the lo
a
mentuntiltheentirestudywascompleted.From0600to0700onthe speed and/or grade were changed, such that each successive power d
e
next morning, the volunteers were driven from the apartment to the output increased by (cid:5)1 MET (or 3.5 ml·min(cid:7)1·kg(cid:7)1). The test d
summitofPikesPeakforthe5-dayHHphase. continued until V˙O2 failed to increase or the volunteer could not fro
m
continue.
SleepMonitoring a
jp
TreadmillEnduranceAssessments re
Relative activity during sleep for 2 nights during the SL baseline g
u
phase,7nightsduringthetreatmentphase,and4nightsduringtheHH Endurance was determined using a treadmill (model 9.15HR, .p
exposurephasewasquantitatedforeachvolunteerbyasmallmotion Smooth Fitness) twice during the USARIEM baseline SL phase and hy
detector worn on one wrist, as previously described (16). Briefly, threetimesduringHHresidence(days1,2,and5).Thefirstassess- sio
sleep/awakedurationandnumberofawakeningsweredeterminedby mentatSLwasusedforpracticetofamiliarizethevolunteerstothe lo
g
motionanalysis(MotionLoggerwithAction4software,version1.13, procedures. All treadmill endurance assessments included 5 min of y
Awmrisbtu,lvatoolruyntMeeorsnitaolsriongw,oArerdsalesym,aNllYp).ulDseuroinxgimseleteerp,(monodtehle3o1th0e0r, wsteaalkdiyn-gstaatte4.e8xmer/chisaendat0%a pgorawdeerfoorutwpuartme-quupalfotlolow45ed(cid:2)by52%0mofinSoLf o.org
Nonin,Plymouth,MN)thathadanadhesivefingersensorforrecord- V˙O2peak.Duringsteady-stateexercise,thespeedwasmaintainedat5.6 n J
i(n(cid:4)g6o%f dSraoOp2,fhroemartbraasteeli(nHeRfo),ra(cid:2)nd8sth).eTnoumavboeirdopfodsseisbalteurvaatriioanbielivteynitns mvo/lhunatnedert,hethgerasadmeewasspereadiseadndasgarapdperowpreiraeteu(siefdnefcoersasallrys)t.eaFdoyr-estaacthe une
devicesensitivity,volunteerswereassignedthesamemotiondetector assessmentsatSLandduringHHresidence.Duringthelast5–10min 15
andoximeterthroughoutthestudy. ofeach20-minsteady-stateexercisesession,V˙O2wasmeasuredusing , 2
Ventilatory measures. Resting ventilation was determined at SL, ametaboliccart(TrueMax2400,ParvoMedics).Thevolunteerswere 01
after 1 h during NH conditions equivalent to 4,300 m (PO2 (cid:1) 93 thenallowed5mintostretch,usethebathroom,etc. 1
mmHg),atSLinthemorningafterthelastnightofsleeptreatment, Thevolunteersthencompleted11.3kmasfastaspossible(tread-
andondays1,2,3,and5duringHHresidence.Allrestingventilation millTT).Whilethegraderemainedat3%,thevolunteerscouldalter
tests,aswellaspulseoximetry,weredonewiththevolunteersawake, thespeedtowalkorrunatanytimeforanydurationduringtheTT.
fasting,andrestedfor(cid:2)30min.Duringtheseprocedures,thevolun- Volunteers were continuously informed of the distance, but not the
teerswereinaseatedpositionwhileconnectedtoabreathingcircuit time, elapsed. This type of TT performance test has high test-retest
byarubbermouthpieceandnoseclipandtoafingerpulseoximeter reproducibility and low coefficient of variance and has been used
unit (model 8600, Nonin) for recording of resting SaO2 and HR. All similarlyataltitude(11,15).Between-groupchangesinTTduration
procedureswereperformedusingabreath-by-breathgasanalyzerand were the primary means to assess whether NH treatment minimized
metabolic measurement system (Vmax 229, Sensormedics, Yorba thedecrementinexerciseperformanceduringHHresidence.
Linda, CA). The mean PETCO2 obtained over the last 10–15 min of
eachoftherestingventilationtestsessionswastheprimaryvariable OtherMeasuresAssociatedWithExerciseTests
usedtoassessVEacc.
During all exercise tests, HR was monitored continuously with a
AcuteMountainSickness HR watch (Polar Electro, Woodbury, NY), Sa was monitored via
O2
noninvasive finger pulse oximetry (model 8600, Nonin), and ratings
AMS was assessed 1) twice during SL baseline (morning and of perceived exertion [RPE, 6–20 on the Borg scale (8)] were
afternoon),eacheveningat2200justbeforethevolunteersenteredthe determinedattheendofeveryworkload(duringV˙O2peak)orevery5
hypoxiaroomsandtheneachmorningat0530hbeforetheyleftthe min(duringtheendurancetests).
hypoxia room; 2) at 2,100 m just prior to ascending Pikes Peak
(0530);and3)whilelivingatPikesPeak,fourtimeseachondays1–4 VenousBloodSamples
[0700(i.e.,(cid:3)1hafterawakening),1400,1700,and2000]andtwice
onday5(0700and1400).TheprevalenceandseverityofAMSwere WhilethevolunteerswereseatedjustpriortoexerciseatSLandon
determined from information gathered using a shortened version of the mornings ((cid:5)0800 to 0900) of days 1, 2, and 5 during HH
AJP-RegulIntegrCompPhysiol•VOL300•FEBRUARY2011•www.ajpregu.org
NORMOBARICHYPOXIAPRETREATMENTANDALTITUDEEXPOSURE R431
performance was greatly improved by HH treatment. With the as-
sumption that NH treatment would similarly reduce PETCO2 at 4,300
m, a minimum of eight volunteers in each group were required for
detectionofastatisticallysignificantbetween-groupdifference((cid:8)(cid:3)
0.05, (cid:9) (cid:3)0.20). Daily differences between groups for AMS preva-
lence during HH residence were analyzed using (cid:10)2 test for indepen-
dent groups. Values are means (cid:2) SD. P (cid:1) 0.05 was considered
statisticallysignificantforallanalyses.
RESULTS
Before Hypobaric Exposure
Sleep monitoring during treatment. Each night during sleep
treatment,Sa waslower(P(cid:3)0.01)fortheNHgroupthanfor
O
2
the sham group, with the nightly difference between groups
becoming progressively larger from night 1 to night 7 as the
ambient O concentrations for the NH group progressively
2
decreased (Fig. 2). HR did not differ between groups for any
Fig.2.Sa duringNHandshamtreatment.Fortheshamgroup,Sa remained
at(cid:5)96%Of2ortheentire7daysoftreatment.Sa fortheNHgrouOp2 beganat night and was maintained at 64 (cid:2) 7 beats/min over the 7
(cid:5)92%andprogressivelyfelloverthe7nightstoO(cid:5)2 88%(aP(cid:3)0.01).Foreach nights. For each of the 7 nights, both groups experienced D
ogfrotuhpe.7nights,SaO2fortheNHgroupwaslower(*P(cid:3)0.01)thanforthesham ipdeerncetinctaalgreaotefsboeifngawaaslkeeenpinwghsil(e1th(cid:2)ey1wpeerer snuigphint)ea(9n4d(cid:2)sim5%ila)r, ownlo
with no change among nights. Also for all nights, the sham ad
e
residence,2-mlrestingvenousbloodsamplesweretakenfromanarm groupdidnotexperienceanydesaturationevents.Fornights1 d
veinfordeterminationofHbconcentrationandhematocrit(Hct)using and2,thenumberofdesaturationevents((cid:3)3perhour)forthe fro
ani-STATportableclinicalanalyzer(AbbottPointofCare,Princeton, NH group did not differ from their SL baseline or from the m
NJ).AtSLandinthemorningsonday2(i.e.,(cid:5)25hafterarrival)and sham group. However, beginning on night 3 (4 (cid:2) 4 desatura- ajp
day 5 in HH, additional 13-ml resting venous blood samples were tionevents/h)andcontinuingthroughnight7(33(cid:2)33desatu- re
obtainedforanalysisoferythropoietin(EPO;QuantikineIVDELISA, g
ration events/h), the number of desaturation events progres- u
R(H&PLDC;SByisot-eRmasd,)M, ainndnecaoprotilsiso,lManNd)a,ledpoisnteeprohnriene(eannzdymneoriempimneupnhoianse- sivelyincreasedfortheNHgroup(P(cid:3)0.01)andalsodiffered .phy
say;ALPCODiagnostics,Salem,NH). (P (cid:3) 0.01) from the sham group. Lastly, not one volunteer in sio
either group reported AMS on any night during the entire lo
StatisticalAnalyses sleep-treatment period. gy
.o
Datawereanalyzedusingcommercialsoftware(Statistica,version Inthemorningafternight7ofshamorNHtreatment,each rg
7.1,Statsoft,Tulsa,OK).Twofactor(group(cid:6)time)ANOVAswith volunteer was asked privately if they thought they slept under o
n
repeatedmeasuresononefactor(time)wereperformedondependent SL or NH conditions for the 7 nights. Of the nine volunteers J
u
variables(e.g.,PETCO2,SaO2)thatrelateddirectlyorindirectlytothe who slept under sham conditions, four were correct and five ne
mainhypothesis.Inallcases,whensignificantmaineffectsorinter- “had no idea.” Of the 14 volunteers who slept under NH 1
astcutidoinesswoferseimfoiluanrde,xNpeewrimmeannt-aKlepurloscpeodsutrheoscutseisntgwuansaacpcplilmieadt.izReedceSnLt cidoenad.”itions, 4 were correct, 3 were incorrect, and 7 “had no 5, 20
volunteers were consulted to determine appropriate sample sizes for 1
Ventilatory measures before and immediately after sleep 1
the major hypothesis related to changes in PETCO2, AMS symptom- treatment.Table2showsrestingventilatoryassessmentsfor
atology, and exercise performance (3, 12, 23). It was assumed that
both groups measured during the SL baseline phase, during
sham treatment would have no effect on PETCO2 and that the magni- the acute NH exposure to 4,300 m equiv ((cid:5)1 h), and in the
ttuodtehaotficnhdauncgeedsbiynHPEHTCtOre2aitnmdeunctedofbaysNimHiltarreactomheonrttwofosuilxdvboelusinmteielarsr morningatSLwithin2hafterawakeningfromnight7ofthe
o(2f).3I.n6th(cid:2)ats2t.u1dymamtH4,g3,00AmM(S2,w3)a,sPnETeCarOl2ywealsimreidnuatceedd,bayndaneaxveerrcaigsee sdliefefepr-etnrecaetsmbeenttwseeessniognr.oPurpisorintoasnleyepoftrtehaetmmeenat,suthreesreawt eSrLenoor
Table 2. Resting ventilatory measures before and after sleep treatment
SLBaseline AcuteNH PostTreat,SL
Sham NH Sham NH Sham NH
Ventilation,l/minbtps 8.9(cid:2)2 8.5(cid:2)1 9.8(cid:2)1 10.0(cid:2)2* 8.8(cid:2)1† 8.7(cid:2)2†
O uptake,ml/min 311(cid:2)73 296(cid:2)35 377(cid:2)78* 392(cid:2)74* 291(cid:2)61† 281(cid:2)53†
2
CO output,ml/min 234(cid:2)59 242(cid:2)32 251(cid:2)60 266(cid:2)51* 243(cid:2)58 228(cid:2)42†
2
End-tidalPo,mmHg 101(cid:2)5 103(cid:2)6 49(cid:2)4* 49(cid:2)3* 104(cid:2)4† 106(cid:2)4†
2
End-tidalPco,mmHg 39.1(cid:2)1.9 39.1(cid:2)3.0 36.1(cid:2)1.7* 36.2(cid:2)2.3* 38.3(cid:2)3.0 34.9(cid:2)2.6*†‡
2
ArterialO saturation,% 97(cid:2)1 97(cid:2)1 81(cid:2)3* 81(cid:2)5* 97(cid:2)1† 97(cid:2)1†
2
HR,beats/min 62(cid:2)9 64(cid:2)9 72(cid:2)12 72(cid:2)7* 64(cid:2)9 70(cid:2)10
Valuesaremeans(cid:2)SD.Acute,(cid:3)1hofexposureto4,300mequivalent;PostTreat,SL,(cid:3)2hafterawakeningafternight7ofsleeptreatment,measuredat
sealevel(SL);Sham,shamcontrolgroup;NH,normobarichypoxiagroup.*P(cid:3)0.05vs.within-groupSLbaseline.†P(cid:3)0.05vs.acuteNH.‡P(cid:3)0.01vs.
PostTreat,SLsham.
AJP-RegulIntegrCompPhysiol•VOL300•FEBRUARY2011•www.ajpregu.org
R432 NORMOBARICHYPOXIAPRETREATMENTANDALTITUDEEXPOSURE
during the (cid:3)1-h exposure to NH. Moreover, in general, all
values were similarly changed for both groups from SL base-
linetoacuteNH(P(cid:3)0.05).AtthepostsleeptreatmentatSL,
all values were nearly identical to their corresponding values
measured during SL baseline, except for a PETCO for the NH
group(P(cid:3)0.01).PETCO fortheNHgroupalsowa2slowerthan
their acute NH PETCO (2P (cid:3) 0.05) and than the sham group
during the posttreatme2nt measurement (P (cid:3) 0.01). The lower
within- and between-group PETCO for the NH group indicates
2
that VEacc was successfully induced by the nightly NH treat-
ments.
Traveldays.Thevolunteerswereawakenedat(cid:5)0530onthe
day of travel to Colorado. After the resting ventilatory assess-
ments, volunteers showered, ate breakfast, and were driven to
Logan Airport (Boston, MA). Depending on availability,
flights departed between 0900 and 1400 (median 1200) and
arrived in Colorado between 1130 and 1630 (median 1430).
Fig.3.VentilatoryacclimatizationaftertreatmentatSLandPikesPeak.There
Thevolunteerswerethendriventoalocalapartment(2,100m
altitude), where they stayed until (cid:5)0600 the next morning, werenobetween-groupdifferencesinrestingend-tidalPCO2(PETCO2)forany
ofthetestdaysonthesummitofPikesPeak,eventhoughtherewasalarge D
when they were driven in (cid:5)1 h to the Pikes Peak Laboratory difference(cid:5)25hearlier,justaftertreatmentatSL(#P(cid:3)0.01).Onmorning o
w
avavtnoodAll4uu,n3nnth0ttee0ieneeirrrtmessr.aswvrtraeeilpvrepaoelfedxa(cid:5)optuo2Pts5ieokdfehstthooePc(cid:5)ehcay2ukp1r.roehxWdioaibftrheomitonwomedteshenirisantteiNhneHatetHirtcivmkac,leo,MnttdAhhiee-, 1Pf(gsa*irEmlPooTlufiCsl(cid:3)pOaihmr2yb0dipve.l0ioaaidn1lrbulg)anyertoilhfcotoarwfodnhmee(cid:5)yfcropl3Hirotn3hxtHehaimane1fumN(ftrHhotHHherHgeirgbr,1ro)rfwo,terhuoisPtppmhgEe(TrcPPoHCtEuiOH(cid:1)vTp2eC2shO0p(ta2.oa0odPf8sHatd)tl(cid:3).HrleieOcn3ar0gnte.moa0Hmrs1eeHHn)od,tr2Hew,fv5oPfiatrolEfhuroTberCPotshOEethe2Ti(t*CchsgPOoehrn2rao(cid:3)tmufgionprrousg0uer.et0dpoao1.uct)phoa. nloaded from
tions ((cid:5)2,100 m) that included (cid:5)5 h of air travel and (cid:5)16 a
jp
h of living in the apartment in Colorado Springs. Just prior re
to departure from the apartment, resting Sa for both However, there were no other clear distinctions between g
O u
groups was similar ((cid:5)95 (cid:2) 3%), resting HR was2 lower for groupsforalltheothervariablesmeasuredorcalculatedduring .p
h
the NH group than for the sham group (66 (cid:2) 10 vs. 77 sleep (i.e., HR, number of desaturation events, or duration of y
s
beats/min, P (cid:3) 0.05), and not one volunteer in either group wakefulness). io
lo
reported AMS at 2,100 m. From night 1 to night 4 of sleep during HH residence, for g
both groups combined, there were declines (P (cid:3) 0.05) in HR y.o
(from 80 (cid:2) 10 to 74 (cid:2) 7 beats/min), number of desaturation rg
Exposure to High Altitude (HH) events (from 333 (cid:2) 381 to 201 (cid:2) 233 per hour), and number on
Restingventilation.Thebetween-groupdifferenceinresting of nightly awakenings (from 17 (cid:2) 9 to 11(cid:2) 5) and increases Ju
PabElTeCOd2uaritnSgLHpHostrterseiadtemnecnet((FPig(cid:3). 30)..01R)eswtiansgnPoElToCnOgerfodretbeoctth- (tiPm(cid:3)e a0s.l0e5e)pin(fsrolemep7S6aO(cid:2)2(1fr8omto7864(cid:2)(cid:2)51t4o%8)1.(cid:2) 4%)andpercent ne 15
groupsdeclinedfromday1today2(from(cid:5)33to321mmHg, Daytime AMS. On day 1, (cid:5)80% of the volunteers in each , 2
P(cid:3)0.01)beforelevelingoffat(cid:5)30mmHgondays3and5. group reported AMS. On day 2, AMS prevalence fell to 29% 01
1
There also were no differences between groups during HH for the NH group but only to 67% for the sham group (P (cid:3)
residence on any day for resting ventilation (V˙E), V˙O2, CO2 0.01). For each of the remaining 3 days, AMS prevalence for
output, end-tidal PO2, and HR. SaO measured concomitantly both groups became similar. The mean AMS-C score was
with resting V˙E increased (P (cid:3) 0.021) from acute NH (81 (cid:2) highestforbothgroupsduringday1butthenfellrapidlytoor
4%) and days 1 and 2 during HH residence (82 (cid:2) 4%) to day below the AMS-C score of 0.70 for each of the remaining 4
5duringHHresidence(85(cid:2)5%),buttherewasnodifference days for both groups (P (cid:3) 0.01). There were no significant
between groups on any of the days. differences between groups for any of the days for AMS-C
DaytimerestingSa .TheSa datathatwereindependently scores during the HH exposure.
O O
2 2
obtainedinconjunctionwiththeESQwereconsistentwiththe AMS just after awakening. Figure 5 shows that the preva-
Sa values collected as part of the resting ventilation assess- lenceofAMSuponawakeningwasmorethantwiceashighfor
O
men2t.Thatis,Sa increased(P(cid:3)0.01)forbothgroupsduring the sham group as for the NH group during mornings 1 and 2
O
HH residence from2 82 (cid:2) 4% on days 1 and 2 to 85 (cid:2) 5% on at HH (P (cid:3) 0.01). For mornings 3 and 4, the prevalence of
day 5, with no differences between groups on any of the days AMS fell sharply for the sham group but remained 8% and
during HH residence. 21% higher (P (cid:3) 0.01) than for the NH group. During HH
SleepmonitoringinHH.Incontrasttoalackofdifferencein residence,themeanoverallAMS-Cscoreuponawakeningwas
Sa between groups while awake during HH residence, the higherfortheshamgroupthanfortheNHgroup(0.83(cid:2)0.14
O
mea2nsleepSa washigherfortheNHgroupthanforthesham vs. 0.34 (cid:2) 0.12, P (cid:3) 0.02). Moreover, only the sham group’s
O
groupfortheen2tiresojourn(80 (cid:2)4vs.76 (cid:2)4%,P(cid:3)0.05), mean AMS-C score exceeded the AMS-C score of 0.70 while
with nightly between-group differences ranging from 2% to under HH conditions (mornings 1 and 2).
6%(Fig.4).TheNHgroupalsotendedtoawakenfewertimes Exercise assessments. Table 3 shows the responses of V˙E,
thantheshamgroup(12(cid:2)6vs.17(cid:2)7pernight,P(cid:1)0.06). V˙O2, HR, SaO, and RPE to the identical, individually deter-
2
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NORMOBARICHYPOXIAPRETREATMENTANDALTITUDEEXPOSURE R433
DISCUSSION
ThisstudytestedthehypothesisthatVEaccinducedbyNH
treatmentwouldbeevidentunderHHconditionsatanaltitude
of4,300mandwould,inturn,ameliorateAMSsymptomsand
benefit TT exercise performance. However, there was little
indication that VEacc induced by NH sleep treatment was
retained during wakefulness in HH, and there were no differ-
encesrelativetotheshamgroupforAMS(whenassessed(cid:4)1
h after awakening) or exercise performance outcomes during
the 5 days of residence at 4,300 m. In contrast, VEacc was
clearly and consistently expressed (via elevated Sa ) during
O
2
sleepinHHandmayhavecontributedtothereductioninAMS
and to the attenuated EPO response observed shortly after
awakening in HH.
Induction of VEacc has been reported previously during
repeated daily exposures to HH or NH treatment (17, 18, 20,
22). Acquisition and retention of VEacc resulting from the
Fig.4.SaO2duringsleepunderHHconditions.Duringsleepfortheentire4 repeated HH treatment appears to be an important response
nightsunderHHconditions,meanSa washigherfortheNHgroupthanfor
pthreogsrheasmsivgelryouipnc(r8e0ase(cid:2)df4rovms.n7i6gh(cid:2)t14Ot%o2,n*igPht(cid:3)4(0f.r0o5m).7F6or(cid:2)bo5t%h gtoro8u1ps(cid:2), S4a%O2, apsesrofocrimateadncweidtuhrirnegduscuebdseqAuMenStesxypmopsutormestoa4n,d30i0mmpr(o2v–ed4).TITn Dow
aP(cid:3)0.05). contrast,asignificantimprovementinSaO inducedover1wk nlo
of 3-h daily NH treatment exposures was2evident only when ad
e
measuredinNHconditions,butnotwhenassessedduringHH d
mined treadmill speed and grade at SL and during days 1, 2, residenceat4,300m,andtherewasalsonoimprovementinTT fro
performance (5). The lack of any retained ventilatory or TT m
and 5 of HH residence. Except for a higher RPE score for the a
sham group than for the NH group during day 1 of HH, all performance benefit during HH residence after NH treatment jp
wasconsideredtobeduetoalossofVEaccresultingfromthe re
responses between groups did not differ among the test days. g
For both groups, from SL to each day during HH, V˙E and HR nontreatmenttimeintervalsbeingtoolongortheNHtreatment u.p
werehigher,whileSa waslower(P(cid:3)0.05).Forbothgroups either not inducing sufficient VEacc or simply not being hy
f0r.o0m5),dawyh1iletoV˙dOa2yd5idduOnr2iontgcHhaHn,gVe˙EaanndddSidaOn2owtedreiffheirghbeertw(Pee(cid:3)n bbeansiesficoifalthdiusriinngforsmubastieoqnu,enthteHreHwraessiadnenecxep(e5c,ta2ti7o)n. Ofonr tthhee siology
groups. .o
TT exercise performance. TT performance, along with HR, rg
o
Sa , and RPE, at SL and during HH residence are shown in n
O2 J
Table 4. There were no differences between groups for any u
n
measure at SL or on any of the 3 test days during HH, except e
1
RPEwashigherfortheshamgrouponday1ofHH(P(cid:3)0.05). 5
HRandSa werereducedandTTperformancetimeincreased , 2
O 0
fromSLtoe2achdayduringHH(P(cid:3)0.05).Inbothgroups,TT 11
performance was significantly improved on day 5 of HH
compared with days 1 and 2 of HH (P (cid:3) 0.05).
Blood measures. At SL, there were no differences between
groups in any of the preexercise resting blood values. In
addition, on any day during HH, there were no differences
between groups for Hb concentration or Hct. However, Hb
concentrationandHctwerehigheroneachdayduringHHthan
at SL (P (cid:3) 0.01).
EPOforbothgroupsincreased(P(cid:3)0.01)fromSLtoday2
ofHH.Onday2,EPOwaslower(P(cid:3)0.01)fortheNHgroup
thanfortheshamgroup.Thenfromday2today5duringHH,
EPO declined (P (cid:3) 0.01) for both groups and no longer
differed from the SL values. However, while under HH con-
ditions,EPOlevelsremainedlowerfortheNHgroupthanfor
the sham group (P (cid:3) 0.02).
There were no changes from SL to HH for epinephrine or
aldosterone,norwerethereanydifferencesbetweengroupson
any of the test days. Norepinephrine and cortisol increased Fig. 5. Symptoms of AMS upon awakening under HH conditions. A much
(P (cid:3) 0.01) from SL to day 5 during HH, but there were no ljaursgtearftperropaowratikoennionfgvothluronutegehrosuwteHreHs.icTkheinrethweasshaamnogvroeruapllthdaifnfethreenNceH(g*rPou(cid:3)p
differences between groups. 0.02)betweengroupsforAMSprevalenceandseverity(AMS-Cscore).
AJP-RegulIntegrCompPhysiol•VOL300•FEBRUARY2011•www.ajpregu.org
R434 NORMOBARICHYPOXIAPRETREATMENTANDALTITUDEEXPOSURE
Table 3. Responses during steady-state exercise at SL and HH
HH
SL Day1 Day2 Day5
Sham NH Sham NH Sham NH Sham NH
Restingventilation,l/minbtps 37(cid:2)9 37(cid:2)7 45(cid:2)9* 45(cid:2)11* 43(cid:2)9* 48(cid:2)7* 49(cid:2)9*† 51(cid:2)11*†
O uptake,ml/min 1,582(cid:2)351 1,573(cid:2)307 1,604(cid:2)321 1,595(cid:2)277 1,497(cid:2)324 1,652(cid:2)378 1,566(cid:2)372 1,588(cid:2)318
2
HR,beats/min 129(cid:2)18 124(cid:2)7 140(cid:2)15* 138(cid:2)7* 138(cid:2)15* 138(cid:2)11* 132(cid:2)12* 134(cid:2)15*
ArterialO saturation,% 97(cid:2)1 97(cid:2)1 74(cid:2)3* 75(cid:2)4* 73(cid:2)6* 75(cid:2)4* 76(cid:2)9*† 78(cid:2)4*†
2
RPE 8(cid:2)1 8(cid:2)1 11(cid:2)3‡ 9(cid:2)1 11(cid:2)3 10(cid:2)4 11(cid:2)3 10(cid:2)4
Valuesaremeans(cid:2)SD.HH,hypobarichypoxia;RPE,ratingofperceivedexertion.*P(cid:3)0.01vs.SL.†P(cid:3)0.05vs.HHday1.‡P(cid:3)0.05vs.HHday1
NH.
presentstudythat,byusingashortertimeintervalbetweenthe andstaffatPikesPeakwereblindtothetreatmentreceivedby
finalNHtreatmentandHHresidence,aswellasbyusingaNH each volunteer and to the results of all ventilatory, TT perfor-
treatment that was 2.5–3.8 times as long as previous NH mance, and hematological assessments until the entire study
treatment studies (5, 27) and over twice as long as a highly was completed.
successful HH treatment (4), VEacc would be retained, AMS Because of these experimental considerations, we are con-
would be reduced, and TT performance would be improved fident in stating that VEacc induced by NH sleep treatment is D
during subsequent HH residence. expressed primarily during sleep, but not wakefulness, during ow
We were therefore surprised in the present study that, after HHresidence.Overthe4nightsat4,300m,notonlywerethe nlo
sthuecrceeswsefurelinnodudciftfieornenocfeaslbaergtweeVeEnagcrcou(ip.es.,fo(cid:7)r4remstminHggorPsEtTeCaOdy2)-, tshleeerep wSaaOs2allesvoelas tseingdneifinccaynt(lPy (cid:1)hig0h.e0r6)fofrorthteheNHNHgrgoruopu,pbtuot aded
state exercise ventilatory measures, AMS symptoms (when awaken less than the sham group. Moreover, the higher sleep fro
assessed(cid:4)1hafterawakening),orTTperformancebeginning m
within a few hours after ascent to 4,300 m. The paucity of lSoawOe2roAbsMerSv-eCdsfcoorretshe((cid:1)N1Hhgarfoteurpawlikakeleynicnogn)tarinbduttehde rteoduthceeidr ajp
differences between groups during most of each day during restingbloodEPOlevels((cid:3)3hafterawakening)relativetothe reg
scwloeanekfpeo,fuuanltnd4ei,ns3sg0,0eaxmspewwreiamlsleliankstealltyhfenacocttloedrausrefdotoirfcfaeotrneltenraocselltaiabnlefSe,wapOo2treednautsiorainlnlsyg. sdhiraemctgrreoluatpiodnusrhinipgbHeHtwreeesnidehnigchee.rPrSeavOio2ulesvsetulsdiaensdreepiothretirngrea- u.phys
duced AMS (1, 3) or blood EPO levels (13, 19) or between io
1ivn)enTaoghuees,sbiwmloeioilgdahritvt,iaelhsueebisge,htwVt˙,eOer2enpsetgaiknr,oguapnSsdLdTuaTrnindpgeNrtfhHoermbPaaEsnTecCleOin2eduvpraealrutiieoosdn, orloeuswrpeoirnnSsteearOps2rpeeltecavitfiieolcsnit.aynWmdhaienytchrbeeerasroeedulartAefidMntdSoin(p9go)ssasoirbfelecaoppnphsayirssetineontlotsgwliecietaphl logy.org
prior to sleep treatment minimized the possibility that there o
wexoeurcldiseberensopno-ntsreesatmduernint-greHlaHtedredsiifdfeenrecnec.e2s)iSnavenwtialastomryonoir- dHiHffetrreenactmesenotrss(1ig0n,a2li5n)gthmatemchaaynibsemosfibnenreesfiptofnosrethtoepNlaHnnainngd n Ju
O n
taolwreadydsuerxinpgossehdamtoananddNrHecselieveipngtoseignnsuifirecatnhtaltythdeif2gferoreunptstwreearte- othfefuretusureltsacocflitmhiastisztautdioyn. strategiescannotbedeterminedfrom e 15
mentsforeachofthe7nights.Thesleepoximetersusedduring The daytime resting or exercise absolute values and re- , 20
the treatments were later used by the same volunteers during sponses from SL to the initial assessments during HH resi- 11
HH residence to eliminate possible differences in signal vari- dence, as well as for the observed rate of acclimatization over
ianbdileiptyenbdeetnwtleyenusdinevgicdeisff.eMrenotreborvaenrd,sSoafO2oxdiamtaetweresreamcoolnlegcttehde wthhee5ndjauysst aatw4a,3k0en0emd),,focratPeEcThCoOla2,mSinaOes2,,HaRnd,AflMuiSd(aonthdersttrheasns
multiple resting and exercise daytime assessments throughout hormones were similar for both groups. All the values, re-
each day to facilitate intrinsic data comparison and result sponses, and rates of change also were within an expected
validation. 3) Objective measures indicated that significant normal range relative to previous studies that used similar
VEacc was successfully induced by NH treatment and re- groups of unacclimatized SL residents who did not undergo
mained after the completion of treatment and on the day of treatmentbeforeorwhilelivingunderHHconditions(2,4,11,
travel. 4) To eliminate possible treatment bias, all volunteers 12,21,23,24,26,28).Collectively,theseresultsindicatethat
Table 4. Responses during time-trial performance assessments at SL and HH
HH
SL Day1 Day2 Day5
Sham NH Sham NH Sham NH Sham NH
HR,beats/min 172(cid:2)15 165(cid:2)11 148(cid:2)18* 152(cid:2)15* 153(cid:2)21* 151(cid:2)19* 149(cid:2)24* 153(cid:2)15*
ArterialO saturation,% 96(cid:2)1 97(cid:2)1 72(cid:2)6* 74(cid:2)4* 72(cid:2)6* 74(cid:2)7* 73(cid:2)6* 77(cid:2)4*
2
RPE 13(cid:2)2 13(cid:2)2 15(cid:2)3‡ 14(cid:2)4 15(cid:2)3 15(cid:2)4 15(cid:2)3 13(cid:2)4
Time,min 75(cid:2)13 73(cid:2)8 106(cid:2)21* 103(cid:2)19* 103(cid:2)21* 106(cid:2)22* 99(cid:2)18*† 95(cid:2)15*†
Valuesaremeans(cid:2)SD.Time,timetocomplete11.3-mtimetrial.*P(cid:3)0.01vs.SL.†P(cid:3)0.05vs.HHdays1and2.‡P(cid:3)0.05vs.HHday1NH.
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NORMOBARICHYPOXIAPRETREATMENTANDALTITUDEEXPOSURE R435
there is little justification for using NH treatment prior to HH Perspectives and Significance
residence.
ThisstudyclearlyshowsthatNHtreatmentrelativetosham
RestingPETCO2istypicallyreportedtobelower(2,3,23,24) treatment provides little useful benefit during subsequent HH
when unacclimatized SL residents are rapidly exposed to HH
residence. It should be emphasized that the lack of effective-
(e.g., 4,300 m, PO2 (cid:5)93 mmHg). In the present study, it was ness of NH treatment was not likely related to an inadequate
bthaesreelfionreebnyot(cid:5)u3nemxmpeHctgedfotrhabtotPhETgCrOou2pfsellprsiiomritloarlaynyfroemxpeSriL- stimulus or response, since the magnitude of the ventilatory
acclimatization induced by NH treatment was comparable to
mental treatment in response to the lower ambient PO2 associ- that of previous similar studies using HH treatment. In addi-
ated with acute NH conditions (also (cid:5)93 mmHg). The (cid:5)6-
tion, the time interval between the end of NH and later HH
mmHg fall in PETCO for the sham group from SL baseline to residence in the present study was deliberately comparable to
2
day1duringHHresidencealsowasanticipatedonthebasisof
that of previous HH treatment-to-HH residence studies. Yet
previous resting ventilatory data collected from 37 men (24) only HH treatment reduced AMS and improved exercise per-
who were SL residents and similarly rapidly exposed to the formance during HH conditions. Interestingly, NH treatment
identical altitude of 4,300 m. We also anticipated that the does provide significant AMS and exercise benefits when the
reductioninPETCO duringinitialHHexposurewouldbegreater outcomemeasuresareassessedunderNHconditions.Themost
2
thanthatobservedduringacuteNHconditionsforthesamePO2of important conclusion resulting from the sum of all this infor-
(cid:5)93mmHgonthebasisofemergingevidencesuggestingventi- mation is that NH and HH treatments clearly cannot be used
latoryresponsedifferencesbetweenNHandHHexposuresatthe interchangeably and are not as effective as preacclimatization
sameambientPO2(10). strategies to reduce AMS and improve exercise performance Do
NHWghraotuwpadsidnontoetxrpeemcateindlwoawseoruthrafinndthinagtothfathtethsehPaEmTCgOro2oufptohne during subsequent HH residence. wnlo
anyofthe5daysduringHHresidence.Previouslyweshowed ACKNOWLEDGMENTS ad
e
rthedatucatio(cid:5)n4-ombmseHrvgedredinuctthioenpinresPeEnTtCOs2tu(di.ye).,ftohre SsaLmeresPiEdTeCnOts2 taleTnhtsisanlodnsgacarnifidciensvooflvmedansytuddeydiccoautelddinnodtivhiadvuealbs.eTenhesuacucthesosrfsutlhwanikthPoauutlthBe. d fro
Rock, who provided 24/7 on-site medical care, and COL Keith Hiatt, who m
undergoing 4-h daily HH treatments was retained 24 h later servedasmedicalmonitor.Theauthorsalsothankthefollowingindividualsfor a
lmdouwmrineHgrgfs)ou(rb2sm)e.qoIudneenartnaHtoeHt-haerlretistsiutdudedenycree(2asit4d4)e,,3nP0tEs0T(mCliOv(2i4na4lg6soamtwm1aH,s6g0(cid:5),0P4mOm2)(cid:1)mthH9agn3 tCFhoaervitrael,hloJar,r.dS,SSwGPoCJrkoRrgoatebetDrhtieaHzUo,SLllAienoRsn,IaESrGdMTDo.MrEalPlriikokteAts,.SPKGeraTyksSkLaorawabh,oEMrart.iocErRyll:i.oLSttGa,mVTminMic,eiMcnhtyaAreal. jpregu.p
L.Reese,SPCBodunrinG.Shobayo,IngridV.Sils,GuyTatum,andRichard h
for SL residents assessed at their respective baseline eleva- Viskochil.Mostofall,theauthorsthankallthevolunteers. ys
tions. When the SL and moderate-altitude residents were later io
aloswseesrseedacwhhdilaeylifvoinrgthaet 4fi,r3s0t05md,ayPsETfCoOr2trheemmaiondeedra(cid:5)te4-amltimtuHdge DISACpLprAoIvMedEfRorSpublicrelease;distributionisunlimited.Theviews,opinions, logy.o
residents than for the SL residents. The implication for the annodt/boerficnodnisntrgusecdonatsaiannedofinficthiailspDuebplaicrtamtioenntaoreftthhoeseAorfmtyhepaoustihtioorns,apnodlischyo,uoldr org
present study is that if NH treatment was to be as effective as n
HH treatment during HH residence, the induced (cid:5)4-mmHg dheucmisainonsuubnjelecstss,sthoediensviegsntaigteadtorbsyadohtheerreddtoocupmoleicniteastioofna.pFpolircathbelepFreodteecrtailoLnaowf Jun
bloewenersPimETiClaOr2lyofrtehtaeiNneHdgdruoruinpgthHanHthreessihdaemncge.roWuphyshtohuelrdehwavaes CinFfoRrm46e.dHcuomnsaennst.ubInjevcetsstpigaarttoicrispaatdehdeirnedthetoseAstrumdyiesRaefgteurlagtiivoinng70th-2ei5rfarnedeaUnSd e 15
noevidenceofinitialorretaineddifferenceforPETCO between AofrmvoyluMnteedeircsailnRreesseeaarrcchh.aAndnyMcaittaetriioenlsCoofmcmomanmdeRrceigaluolartgioanniz7a0t-i2o5nsoanntdhetraudsee , 20
2 1
the NH and sham treatment groups during HH residence names in this report do not constitute an official Department of the Army 1
remains to be determined. endorsementofapprovaloftheproductsorservicesoftheorganizations.
Collectively, in light of our results, experimental design
DISCLOSURES
considerations, and at least one study (17) that reported that
Noconflictsofinterest,financialorotherwise,aredeclaredbytheauthors.
VEacc induced by NH treatment remained evident for up to 1
mo(butonlywhenassessedunderNHconditions),alikelyand
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