central command contributes to increased blood flow in... (1)
TRANSCRIPT
-
7/27/2019 Central Command Contributes to Increased Blood Flow in... (1)
1/15
Centralcommandcontributestoincreasedbloodflowinthenoncontractingmuscleatthestartofone-leggeddynamicexerciseinhumansKeiIshii,NanLiang,AnnaOue,AiHirasawa,KoheiSato,TomokoSadamotoandKanjiMatsukawaJApplPhysiol112:1961-1974,2012.Firstpublished12April2012;doi:10.1152/japplphysiol.00075.2012Youmightfindthisadditionalinfouseful...Thisarticlecites52articles,38ofwhichyoucanaccessforfreeat:
http://jap.physiology.org/content/112/12/1961.full#ref-list-1Updatedinformationandservicesincludinghighresolutionfigures,canbefoundat:
http://jap.physiology.org/content/112/12/1961.fullAdditionalmaterialandinformationaboutJournalofAppliedPhysiologycanbefoundat:
http://www.the-aps.org/publications/japplThisinformationiscurrentasofAugust21,2013.
JournalofAppliedPhysiologypublishesoriginalpapersthatdealwithdiverseareaofresearchinappliedphysiology,especiallythosepapersemphasizingadaptiveandintegrativemechanisms.Itispublished24timesayear(twicemonthly)bytheAmericanPhysiologicalSociety,9650RockvillePike,BethesdaMD20814-3991.Copyright2012theAmericanPhysiologicalSociety.ESSN:1522-1601.Visitourwebsiteathttp://www.the-aps.org/.
-
7/27/2019 Central Command Contributes to Increased Blood Flow in... (1)
2/15
8750-7587/12Copyright 2012theAmericanPhysiologicalSociety
JApplPhysiol112:19611974,2012.FirstpublishedApril12,2012;doi:10.1152/japplphysiol.00075.2012.
Centralcommandcontributestoincreasedbloodflowinthenoncontractingmuscleatthestartofone-leggeddynamicexerciseinhumans
KeiIshii,1NanLiang,1AnnaOue,2AiHirasawa,2KoheiSato,2TomokoSadamoto,2andKanjiMatsukawa11DepartmentofPhysiology,GraduateSchoolofHealthSciences,HiroshimaUniversity,Hiroshima,Japan;and 2ResearchInstituteofPhysicalFitness,JapanWomensCollegeofPhysicalEducation,Tokyo,JapanSubmitted17January2012;acceptedinfinalform10April2012
Ishii K, Liang N, Oue A, Hirasawa A, Sato K, Sadamoto T,MatsukawaK.Centralcommandcontributestoincreasedbloodflowinthenoncontractingmuscleatthestartofone-leggeddynamicexerciseinhumans.JApplPhysiol112:19611974,2012.FirstpublishedApril12,2012;doi:10.1152/japplphysiol.00075.2012.Whetherneurogenicva-sodilatation contributes to exercise hyperemia is still controversial.Bloodflowtononcontractingmuscle,however,ischieflyregulatedbya neural mechanism. Although vasodilatation in the nonexercisinglimb was shown at the onset of exercise, it was unclear whethercentral command or muscle mechanoreflex is responsible for thevasodilatation. To clarify this, using voluntary one-legged cyclingwith the right leg in humans, we measured the relative changes inconcentrations of oxygenated-hemoglobin (Oxy-Hb) of the noncon-tractingvastuslateralis(VL)musclewithnear-infraredspectroscopyas an index of tissueblood flow and femoralblood flow to thenonexercising leg. Oxy-Hb in the noncontracting VL and femoralblood flow increased (P 0.05) at the startperiod of voluntaryone-legged cycling without accompanying a rise in arterialbloodpressure.Incontrast,noincreasesinOxy-Hbandfemoralbloodflowwere detected at the startperiod ofpassive one-legged cycling,suggestingthatmusclemechanoreflexcannotexplaintheinitialva-sodilatationofthenoncontractingmuscleduringvoluntaryone-leggedcycling.Motorimageryofthevoluntaryone-leggedcyclingincreasedOxy-HbofnotonlytherightbutalsotheleftVL.Furthermore,anincreaseinOxy-HbofthecontractingVL,whichwasobservedatthestartperiodofvoluntaryone-leggedcycling,hadthesametimecourseand magnitude as the increase in Oxy-Hb of the noncontractingmuscle. Thus it is concluded that the centrally induced vasodilatorsignal is equally transmitted to thebilateral VL muscles, not onlyduringimageryofexercisebutalsoatthestartperiodofvoluntaryexerciseinhumans.vasodilatation;musclemechanoreflex;near-infraredspectroscopy;ul-trasoundDopplerflowmetryWHETHERNEUROGENIC VASODILATATION contributes to exercisehyperemia is still controversial. Our laboratory recently re-portedthatasympatheticcholinergicmechanismiscapableofevoking exercise hyperemia at the onset of voluntary staticexerciseinconsciouscats(31).Skeletalmusclevasodilatation via the sympathetic cholinergic system hasbeen observedduringthedefensereactionorclassicalconditioning task(2,3,19). Other literature, however, indicates that the sympatheticcholinergicmechanismisnotessentialfortherapidvasodila-tation in active skeletal muscle at thebeginning of exercise,becausesurgicalsympathectomy andganglionicormuscarinicblockade had little influence on increasedblood flow to the
Addressforreprintrequestsandothercorrespondence:K.Matsukawa,Dept.ofPhysiology,GraduateSchoolofHealthSciences,HiroshimaUniv.,1-2-3Kasumi, Minami-ku, Hiroshima 734-8551, Japan (e-mail: [email protected]).
exercisinglimbafterabriefforearmcontraction(9,14)andattheonsetofintermittenthandgripexerciseinhumans(48)andduringtreadmillexerciseindogs(10).Thediscrepancyabouta role of sympathetic vasodilatation at the onset of exercisemaybe attributed to the fact that neurogenic vasodilatationoccurs during a more voluntary type of exercise with greatervolitional effort and is maskedby other vasodilator mecha-nisms,suchasmetabolicorflow-mediatedvasodilatation.
In contrast to contracting muscle, a neural mechanism viathesympatheticnervoussystemappearstoregulatebloodflowof noncontracting muscle,because muscle contraction is ab-sent,andnometabolitesarereleasedinthemuscle.Ingeneral,ithasbeenthoughtthatanincreaseinsympatheticadrenergicvasoconstrictoroutflowrestrictsbloodflowinnoncontractingmusclesduringthelaterphaseofexercise(morethan 2minaftertheexerciseonset)(7,27,33,42).However,otherstudiesdemonstrated transient increases inblood flow and vascularconductance of the nonexercising limb at the initialphase ofstaticordynamicexercise(until 12minfromtheexerciseonset) (5, 18, 23, 50). The initial vasodilator response de-pendedonarelativeforceofcontractionratherthanonamassof the muscles involved (17, 53). These results suggest thatbloodflowinnoncontractingskeletalmusclemayincreaseatthe start of exercise, and the vasodilatation is evokedby aneurogenicmechanisminassociationwithvolitionaleffort.
Firstofall,itisconceivablethatcentralcommandisrespon-sibleforvasodilatationinthenoncontractingmuscleatthestartof voluntary exercise,because mental stress (6, 16, 41), im-mobilealertingandfightingbehavior(2,3,19),andelectricalor chemical stimulation of neurons in some regions of thehypothalamus and midbrain in animalpreparation elicit anincrease in skeletal muscleblood flow (1, 4, 12, 25, 26, 30,3436, 39). Sanders et al. (44) observed that the voluntaryisometrichandgripexercisewithonearminducedadecreaseinvascular resistance of the other arm, which wasblockedbyatropinebut notbypropranolol. This finding suggests thatcentrally induced activation of the sympathetic cholinergicsystemplays a role in increasingblood flow to the noncon-tractingmuscleinhumans.Next,exercisepressorreflexfromthe contracting muscle may cause vasodilatation in the con-tralateral limb. Inparticular, muscle mechanoreflex willbeaddedasapossiblecandidateresponsiblefortheinitialvaso-dilatation,becausethepassiveknee-extensionexerciseslightlyincreased femoralblood flow of the nonexercising limb (52).Ontheotherhand,posthandgripischemiacausedvasoconstric-tion of the calf vascularbed, instead of vasodilatation (46),suggestingthatmusclemetaboreflexisunlikelytoplayaroleintheneurogenicvasodilatationinthenoncontractingmuscle.
http://www.jappl.org 1961
-
7/27/2019 Central Command Contributes to Increased Blood Flow in... (1)
3/15
1962 CentralCommandandMuscleBloodFlow IshiiKetal.Toclarifywhichofthetwomechanisms(centralcommand
andmusclemechanoreflex)playsamoreimportantroleintheinitialneurogenicvasodilatation ofthenoncontracting muscle,wecomparedtherelativechangesinconcentration ofoxygen-ated-hemoglobin (Oxy-Hb) in the noncontracting vastus late-ralis (VL) muscle with near-infrared spectroscopy (NIRS) asanestimateofmuscletissuebloodflowandfemoralbloodflowto the nonexercising leg with Doppler ultrasoundbetweenvoluntary andpassive one-legged ergometer exercise. As aresult, Oxy-Hb in the noncontracting VL muscle and fem-oral blood flow increased at the start of the voluntarycyclingbut not thepassive cycling, suggesting that centralcommand is the sole candidate for the initial neurogenicvasodilatation innoncontractingmuscle.Tofurthertestthehypothesis, we examined the responses of Oxy-Hb in thenoncontracting muscle during imagery of the voluntaryone-legged exercise. The descending vasomotor outflowbycentral command wouldbe transmitted, not only to the non-exercising limbbut also to the exercising limb during one-legged exercise, because a recent study demonstrated thatmany medullary vasomotor neurons were dually infectedbyrecombinants ofpseudorabies virus injected into thebilateralhindlimbs of rats (32). To test the second hypothesis, wecomparedtheresponsesofOxy-HbinthebilateralVLmusclesnot only during the voluntary one-legged exercisebut alsoduringmotorimageryoftheexercise.Apartofthisstudyhasbeenpublishedinpreliminaryform(28).METHODSSubjects
Twelve healthy volunteers (eight males and four females; age,24 1yrs;height,170 2cm;bodywt,58 2kg)participatedinthepresent study.None of the subjects suffered from any knowncardiovascular
and
neuromuscular
diseases
or
took
any
medications.
Theexperimentalproceduresandprotocolswereperformedinaccor-dancewiththeDeclarationofHelsinkiandapprovedbytheInstitu-tionalEthicalCommittee.Thesubjectsgavetheirinformed,writtenconsentpriortotheexperiments.Allexperimentswereperformedinathermoneutralandsoundproofenvironment,andallwereconductedatHiroshimaUniversity. One-LeggedCyclingExercise
The subjects lay down in the supineposition on a comfortablerecliningseatofaspeciallydesignedcycleergometer(StrengthErgo240 BK-ERG-003, Mitsubishi Electric Engineering, Tokyo, Japan)andperformedvoluntaryone-leggedexercisewiththerightleg.Theergometerenabledpassiveone-leggedcycling,drivenwithamotor.The right foot wasput on a specially designed shoe, affixed at thepedal.Thepositionsofthecrank,pedal,andseatwereadjustedsoastoallowthesubjectstoremaininacomfortableandcertainposture.Thesubjectswereinstructedtoperformone-leggedisotoniccyclingwiththerightlegaloneandtokeeptheleftlegrelaxedthroughouttheexperiments.Torqueagainstthewheelshaftandpedaldisplacementof the ergometer were measured continuously. We confirmed thatelectrical activity of the left VL muscle was absent during theone-leggedexercise(Fig.1).
Todeterminethemaximalintensityofvoluntaryone-leggedexer-cise,thesubjectsconductedanincrementalone-leggedexercisetestonaseparatedaypriortothemainexperiments.One-leggedcyclingwiththerightlegwasperformedfor1minat50rpm,startingatanintensityof8Nmformalesand3Nmforfemalesandincreasingtheworkloadby4Nmformalesandby3Nmforfemales.Theinterval
betweenboutswassetat35min.Theincrementalboutwascontin-ueduntilthesubjectscouldnolongerperformthecyclingormaintaintherequiredrevolutionspeed.Themaximalexercisethatthesubjectscompletedwasdefinedasthemaximalvoluntaryeffort.MeasurementsofMuscleandSkinTissueBloodFlow
The relative concentrations of Oxy-Hb and deoxygenated-hemo-globin(Deoxy-Hb)intheleftVLmuscleweremeasuredwithNIRS,while skinblood flow over the muscle was recorded with LaserDopplerFlowmetry.ThebasicprincipleofNIRSisthatnear-infraredlight, emitted from three laserphotodiodes with different wave-lengths,penetratesskeletalmuscletissueandthatsomeofthelightisabsorbedby Hb, myoglobin (Mb), and cytochromes, and others,scatteredbythetissue,arepickedupwithphotodetectors(8,21,37).Seiyama et al. (47) reported that the total contribution of Mb andcytochromestothesignalsofNIRSis 10%inisolatedratskeletalmuscle,indicatingthattheHbinbloodvesselsofmuscletissuechieflyaffectsthesignalsofNIRS.ThemuscleoxygenationsignalsofNIRSaredependentonabalanceofoxygensupplyanduseinthetissue.Aslong as oxygen use is constant and at the minimum (e.g., noncon-tracting muscle), the signal of Deoxy-Hb willbe constant, and thesignalofOxy-Hbmayreflectmuscletissuebloodflow.Wemonitoredthe Oxy-Hb as an estimate of tissueblood flow in noncontractingskeletalmuscle.Apairofphotoemissionandphotodetectionprobeswasplaced two-thirds from the greater trochanter to the top of thepatellaandattached4cmapartontheskinovertheleftVLmusclesothatnear-infraredlightintersectedthemusclebundles.Thereflectednear-infrared light (wavelengths: 775 nm, 810 nm, and 850 nm),throughmuscletissue,wassampledatarateof6Hzandconvertedtooptical densities with a near-infrared spectrometer (NIRO-200,HamamatsuPhotonics,Hamamatsu,Japan).
To clarify the contribution of skinblood flow to the signals ofNIRS,skinbloodflowwasmonitoredwithaLaserDopplerinstru-ment(ALF21,Advance,Tokyo,Japan).ADopplerflowprobewasplacedontheleftVLmusclesurfaceadjacenttotheNIRSprobes.TheDopplerflowsignalwastimeaveragedwithatimeconstantof0.1s.MeasurementofFemoralBloodFlow
Bloodflowoftheleftfemoralarterywasmeasuredwithahigh-resolution ultrasound Doppler instrument (Vivid e, GE Healthcare,Tokyo,Japan).A10-MHzlinearprobewasplacedbelowtheinguinalligamentand 23cmabovethebifurcationintotheprofundusandsuperficialbranches (49). Blood flow velocity measurements wereperformedwiththeinsonationangle 60andwerecorrectedfortheinsonationangle.Carewastakentoensurethattheprobepositionandtheinsonationanglewereappropriateandstableandthatthesamplevolume waspositioned in the center of the vessel and adjusted tocover the width of the vessel diameter. Ultrasound B-mode imageswereusedtomeasuresystolicanddiastolicinternaldiameterofthefemoralartery.ApulsedDopplermodewasusedtomeasurefemoralbloodflowvelocity.Themeaninternaldiameterwascalculated basedon
the
following
equation:
mean
internal
diameter
[(systolic
inter-
nal diameter 1/3)] [(diastolic internal diameter 2/3)], asreportedby Sato et al. (45). The time-averaged meanblood flowvelocityover5swasdefinedasmeanbloodflowvelocity.Femoralbloodvolumeflowwascalculatedbymultiplyingthecross-sectionalarea [ (mean internal diameter/2)2]by the meanblood flowvelocity.CardiovascularandElectromyogramRecordings
Apairofelectrodes(Magnerode,TE-18,FukudaDenshi,Tokyo,Japan)andagroundelectrodewereattachedonthechestformeasur-ingECG.TheECGsignalandrespiratorymovementweremonitoredwith a telemetry system (DynaScope DS-3140, Fukuda Denshi).Arterialbloodpressure (AP) was measured noninvasively and con-
JApplPhysiol doi:10.1152/japplphysiol.00075.2012 www.jappl.org
-
7/27/2019 Central Command Contributes to Increased Blood Flow in... (1)
4/15
CentralCommandandMuscleBloodFlowIshiiKetal. 1963
Fig. 1.A: representative recordings of motorperformanceandthecardiovascularandelectro-myogram (EMG) responses in transition fromresttovoluntary1-leggedcyclingwithaninten-sityof33%ofthemaximaleffortinasubject.Theexerciseonsetwasdefinedastheonsetofpedaldisplacement(asindicatedbyanarrow).Concentrationofoxygenated-hemoglobin (Oxy-Hb)inthenoncontractingvastuslateralis(VL)muscleandheartrate(HR)increasedatthestartof voluntary 1-legged cycling with no distinctchangesindeoxygenated-Hb(Deoxy-Hb),skinblood flow, and arterialbloodpressure (AP).B:theaverageintegratedEMGactivityofthecontracting () and noncontracting () VLmuscleduringvoluntary1-leggedcycling(n 7subjects).Vertical,dashedlinesindicatethestartandendof1-leggedcycling.NotethatnoEMGactivitywasobservedinthenoncontractingVLmuscleduringvoluntary1-leggedcycling.
JApplPhysiol doi:10.1152/japplphysiol.00075.2012 www.jappl.org
-
7/27/2019 Central Command Contributes to Increased Blood Flow in... (1)
5/15
-
7/27/2019 Central Command Contributes to Increased Blood Flow in... (1)
6/15
CentralCommandandMuscleBloodFlowIshiiKetal. 1965Table1. Thehemodynamicresponsesduringvoluntaryandpassive1-leggedcycling
Voluntary1-leggedcycling Passive1-leggedcyclingBefore During Before During
HR(beats/min) 63 2.9 100 2.4*, 61 2.8 69 3.6*SV(ml) 96 6.2 103 7.5* 99 4.3 102 4.4*CO(l/min) 6.0 0.4 10.3 0.7*, 6.0 0.2 6.9 0.2*MAP(mmHg) 97 5.1 108 4.8*, 94 2.4 95 2.6TPR(mmHgminl 1) 16.8 1.7 11.0 1.1*, 15.8 0.5 14.0 0.6*
Baselinehemodynamicvalueswerenotsignificantly different(P 0.05)betweenvoluntaryandpassive1-leggedcyclingin7subjects.HR,heartrate;SV,strokevolume;CO,cardiacoutput;MAP,meanarterialbloodpressure;TPR,totalperipheralresistance.TheaverageresponsesinHR,CO,MAP,andTPRduringpassivecyclingweresmaller(P 0.05)ascomparedwiththoseduringvoluntarycycling.*Significantdifference(P 0.05)fromthebaselinebeforetheexercise;significantdifference(P 0.05)betweenvoluntaryandpassivecycling.Valuesaremeans SE.
duringthevoluntarycyclingaresummarizedinFig.2.HRandCObegantoincreasesignificantly(P 0.05)at02sfromtheonsetofvoluntarycyclingandcontinuedtoincreaseby393beats/min and 4.5 0.5 l/min until the end of exercise,whereasSVremainednearthebaseline.TPRbegantodecrease(P 0.05)at3saftertheonsetofexercise,andthereductionreachedaplateauof6.3 1.0mmHgminl 1at15saftertheexercise onset, which was maintained until the end of theexercise. MAP increased (P 0.05) at the exercise onset,returned to thebaseline at the startperiod, and subsequently,increasedby15 3mmHgduringthelaterperiodofvoluntaryone-leggedcycling(Fig.2andTable1).TheOxy-HbandDeoxy-HbResponsestoVoluntaryOne-LeggedCycling
Assoonasvoluntaryone-leggedcyclingstarted,Oxy-Hbofthenoncontracting VLmusclewasincreasedabruptlywithoutchangingDeoxy-Hbofthenoncontracting VLandskinbloodflow,
as
shown
in
Fig.
1A.
Thus
the
initial
increase
in
Oxy-Hb
reflectedanincreaseinmuscletissuebloodflowbutnotskintissuebloodflow.ThetimecoursesoftheaveragechangesinOxy-Hb and Deoxy-Hb of the noncontracting VL muscleduringvoluntaryone-leggedcyclingaresummarizedinFig.3.Oxy-Hbbegantoincrease(P 0.05)at78sfromtheonsetofvoluntaryone-leggedcyclingandremainedincreaseduntilthe end of the exercise, whereas Deoxy-Hb was unchanged(P 0.05)throughouttheexercise.TheCardiovascularResponsesandNIRSSignalsDuringPassiveOne-LeggedCycling
There were no obvious changes in the cardiovascular vari-ables at the start ofpassive one-legged cycling, although aslightriseinMAPappearedat310sfromthecyclingonset(Fig. 2). In addition,both Oxy-Hb and Deoxy-Hb failed tochange(P 0.05)atthestartperiodofpassivecycling(Fig.3). The changes in HR, CO, TPR, and Oxy-Hb at the startperiodofpassiveone-leggedcyclingwerebluntedanddelayed(P 0.05byatwo-wayANOVA)comparedwiththoseduringthe voluntary one-legged cycling. After that, HR and COincreasedslightly,andTPRdecreasedduringthelaterperiod(1260saftertheonset)ofpassiveone-leggedcycling(Fig.2).Simultaneously, Oxy-Hb increased, and Deoxy-Hb decreasedduringthelaterperiod(3660sfromtheonset)ofthepassivecycling(Fig.3).
TheResponsesinFemoralBloodFlowDuringVoluntaryandPassiveOne-LeggedCycling
Whentheexerciseintensityofvoluntaryone-leggedcyclingwasreducedto18 1%ofthemaximaleffort,theresponsesofMAPandTPR(Fig.4)tendedtobesmallercomparedwiththose during voluntary one-legged cycling with the higherintensity (as shown in Fig. 2). Femoralblood flow velocityincreasedby60%(P 0.05,from14.9 1.7to23.8 2.4cm/s) during voluntary cycling at 1545 s from the exerciseonset,whereasmeaninternaldiameterofthefemoralarterydidnot change from thebaseline of 0.81 0.06 cm. Thus inproportiontofemoralbloodflowvelocity,femoralbloodflowincreasedby50%(P 0.05,from495 115to744 138ml/min) at 1545 s from the exercise onset. A significantincreaseof48%infemoralvascularconductance(from4.81.1 to 7.1 1.2 mlmin 1mmHg 1) was also detected. Thevasodilator response was observed consistently in each indi-vidualduringvoluntaryone-leggedcycling(Fig.5A).Further-more, there was a good temporal coincidencebetween theincreasesinfemoralvascularconductance(Figs.4and5)andOxy-Hb(Fig.3),althoughtheexerciseintensitywaslowerinDopplerultrasoundflowmetry.
Incontrasttovoluntaryone-leggedcycling,femoralinternaldiameter,blood flow velocity,blood flow, and vascular con-ductancewereunchanged(P 0.05)fromthebaselineduringpassive one-legged cycling (Fig. 4). Accordingly, there weresignificant differences (P 0.05by a two-way ANOVA) intheresponsesoffemoralbloodflowandvascularconductance,as well as TPR,betweenpassive and voluntary one-leggedexercise (Fig. 4). However, an increase in femoral vascularconductancewasobservedinthreeofthesubjectsatthelaterperiod(2560s)ofpassivecycling(Fig.5B).Thevasodilatorresponse corresponded with the delayed increase in Oxy-Hbduringpassive cycling (Fig. 3). In the remaining subjects,femoral vascular conductance did not change throughout thepassivecycling.TheInfluenceofMotorImageryontheOxy-HbandFemoralBloodFlowResponses
To identify any influence of central command on musclebloodflow,wemeasuredhemodynamicsandtheresponsesinfemoralbloodflowandtheNIRSsignalsduringmotorimageryofvoluntaryone-leggedcycling,asshowninFig.6.Cycling-imageryinducedanincreaseinOxy-HboftheleftVLmusclewithoutchangingDeoxy-Hb(Fig.6A).HRincreasedslightly,
JApplPhysiol doi:10.1152/japplphysiol.00075.2012 www.jappl.org
-
7/27/2019 Central Command Contributes to Increased Blood Flow in... (1)
7/15
1966 CentralCommandandMuscleBloodFlow IshiiKetal.imagery, HR significantly (P 0.05)but slightly increased,whereasSV,CO,MAP,andTPRremainedunchanged(Table2). Motor imagery of voluntary one-legged cycling also in-creased(P 0.05)notonlyOxy-HbofthecontralateralleftVLbutalsoOxy-HboftheipsilateralrightVL(Fig.7A).ItwasofinterestthattheincreaseofOxy-Hbduringcycling-imagery wasequalbetweentheleftandrightVL(3.1 0.6%vs.3.10.3%,respectively). Corresponding totheincreaseinOxy-HboftheleftVL,femoralbloodflowvelocity,volumeflow,andvascular conductance increased (P 0.05) during cycling-imagery with no changes in mean internal diameter of thefemoral artery (Fig. 7B and Table 2). In contrast, Oxy-Hb ofthebilateralVLmusclesfailedtochangeduringcircle-imagery (Fig. 7A), although the VAS score rating the vividness ofimagerywasnotdifferent(P 0.05)betweenthetwoimageryconditions (Fig. 7C). Furthermore, circle-imagery elicited no
Fig.2.Thetimecoursesofthecardiovascularresponsesduringvoluntary()andpassive()1-leggedcyclingin7subjects.Eachvaluewascalculatedsequentially every 1 s. Vertical, dashed lines indicate the start and end of1-leggedcycling,whereasavertical,dottedlineisplacedat15sfromtheexerciseonset.HRandcardiacoutput(CO)increased,andtotalperipheralresistance(TPR)decreasedatthestartofvoluntary1-leggedcycling,andthechangesweresustaineduntilthecessationoftheexercise.Incontrast,HRandCOincreasedslightly,andTPRdecreasedslightly,onlyduringthelaterperiod( 1260s)ofpassive1-leggedcycling.SV,strokevolume;MAP,meanAP.*Significant difference from thebaseline (P 0.05) in the data duringvoluntary 1-legged cycling; significant difference from thebaseline (P0.05)inthedataduringpassive1-leggedcycling.butAPdidnotchangeduringcycling-imagery.Femoralbloodflow velocity increased without a change in mean internaldiameterofthefemoralartery.Thuscentralcommandinvolvedin cycling-imagery was able to cause tachycardia and hyper-emiainskeletalmuscle.Incontrast,whenthesubjectimaginedacirclewithnorelationtoexercise,nodistinctchangesinanyvariableswereobserved(Fig.6B).
Theabsolutevaluesofthehemodynamics andfemoralbloodflow during cycling- and circle-imagery are summarized inTable2.TherelativechangesinOxy-HboftherightandleftVLmusclesandthefemoralbloodflowresponsearecomparedbetweenthetwoimageryconditionsinFig.7.Duringcycling-
Fig.3.ThetimecoursesoftherelativechangesinOxy-HbandDeoxy-HbofthenoncontractingVLmuscleduringvoluntary()andpassive()1-leggedcyclingin7subjects.TherelativepercentchangeinOxy-Hbwasdeterminedbyidentifyingthe0levelwithmuscleischemia.Eachvaluewascalculatedsequentially every 1 s. Vertical, dashed lines indicate the start and end of1-leggedcycling,whereasavertical,dottedlineisplacedat15sfromtheexerciseonset.Oxy-Hbbegantoincrease(P 0.05)at78sfromtheonsetof voluntary 1-legged cycling, whereas Deoxy-Hb unchanged (P 0.05)throughouttheexercise.Incontrast,Oxy-HbandDeoxy-Hbfailedtochange(P 0.05)atthestartofpassive1-leggedcycling.*Significantdifferencefromthebaseline (P 0.05) in the data during voluntary 1-legged cycling;significantdifferencefromthebaseline(P 0.05)inthedataduringpassive1-leggedcycling.
JApplPhysiol doi:10.1152/japplphysiol.00075.2012 www.jappl.org
-
7/27/2019 Central Command Contributes to Increased Blood Flow in... (1)
8/15
CentralCommandandMuscleBloodFlowIshiiKetal. 1967
Fig.4.Thetimecoursesofthehemodynamicandfemoralblood flow responses in the nonexercising limb duringvoluntary()andpassive()1-leggedcyclingin6sub-jects.MAPandTPRwerecalculatedsequentiallyevery1s,whereasthefemoralbloodflowdatawerecalculatedse-quentiallyevery5s.Vertical,dashedlinesindicatethestartandendof1-leggedcycling,whereasavertical,dottedlineisplacedat15sfromtheexerciseonset.Thesignificantincreasesinfemoralbloodflowvelocity,bloodflow,andvascularconductancewereobservedat1545sofvolun-tary 1-legged cyclingbut notpassive 1-legged cycling.*Significantdifferencefromthebaseline(P 0.05)inthedataduringvoluntary1-leggedcycling;significantdiffer-encefromthebaseline(P 0.05)inthedataduringpassive1-leggedcycling.
significantincreases(P 0.05)infemoralbloodflowvelocity,volumeflow,vascularconductance,andmeaninternaldiame-ter. Also, none of the hemodynamic variables changed (P0.05)fromthebaselineduringcircle-imagery (Table2).TheResponsesinOxy-HboftheContractingvs.NoncontractingMuscleDuringVoluntaryOne-LeggedCycling
Figure8showsatypicalexampleoftherawNIRSsignalsofthe right (contracting) and left (noncontracting) VL musclesduring voluntary one-legged cycling without conducting a
moving average. Although theNIRS signals of the right VLmusclecontainedartifactsduetolimbmovement,Oxy-Hbinthebilateral VL muscles seemed to increase at the start ofvoluntary cycling without changing Deoxy-Hb. Inparticular,the initial increase in Oxy-Hb of the right (contracting) VLmusclewasfollowedbyasubsequentdecreaseinOxy-HbandanincreaseinDeoxy-Hb.
The time courses of the changes in moving-averagedOxy-HbandDeoxy-HbofbothcontractingandnoncontractingVLmusclesduringvoluntaryone-leggedcyclingaresumma-
JApplPhysiol doi:10.1152/japplphysiol.00075.2012 www.jappl.org
-
7/27/2019 Central Command Contributes to Increased Blood Flow in... (1)
9/15
(mlmin
-1mmHg-1
)
(mlmin
-1mmHg-1
)
1968 CentralCommandandMuscleBloodFlow IshiiKetal.ing muscle at the start of voluntary one-legged exercise inhumans.Themajornewfindingsofthepresentstudyarethat1) Oxy-Hb in the noncontracting VL muscle increased at thestartperiodofvoluntaryone-leggedcyclingwithnochangesinDeoxy-Hb and skinblood flow, and the initial increase inOxy-Hbwasprobablyduetoincreasedbloodflowinnoncon-tracting muscle;2) Oxy-Hb in the noncontracting VL wasunchangedatthestartperiodofpassivecyclingandthereafterincreased;3)theincreasesinfemoralbloodflowandvascularconductance in the nonexercising limb were observed at thestartperiod of voluntary one-legged cyclingbut notpassivecycling; 4) Oxy-Hb in thebilateral VL muscles did not alterduring circle-imagery but increased during motor imagery ofthe voluntary cycling without changing Deoxy-Hb; and5)Oxy-HbofthecontractingVLmuscleincreasedatthestartperiod of voluntary one-legged cycling with the same timecourseandmagnitudeastheOxy-Hbresponseofthenoncon-tractingVL.Takentogether,itislikelythatcentralcommandchieflycontributestotheinitialvasodilatation innoncontract-ingmuscleduringvoluntaryexerciseandthattheneurogenicvasodilatation
may
occur
in
the
contracting
muscle
as
well.
EvaluationofMuscleBloodFlowwithNIRSandUltrasoundDopplerFlowmetry
Thepresent evaluation of muscle tissueblood flow withNIRS involves fundamental assumptions and limitations. Asmentionedbefore, the relative changes in theNIRS signalschiefly reflect the changes in near-infrared light,partly ab-sorbedbyOxy-andDeoxy-Hbinmuscletissues,becausethetotal contribution of Mb and cytochromes to the signals ofNIRSis 10%inisolatedratskeletalmuscle(47).Themuscle
Fig. 5. The time courses of the changes in femoral vascular conductanceresponsesduringvoluntary(A)andpassive(B)1-leggedcyclingin6subjects.Eachsolidlineindicatesthetimecoursedataoffemoralvascularconductancetakenfromeachsubject.Thevasodilatorresponsewasobservedconsistentlyineveryindividualduringvoluntary1-leggedcyclingbutnotpassive1-leggedcycling.rizedinFig.9.Asobservedinthenoncontracting VLmuscle,meanOxy-HbofthecontractingVLmuscleincreasedsignif-icantly (P 0.05), at 810 s after the onset of voluntarycycling,whereasmeanDeoxy-Hbinthecontracting VLmus-clebegantoincrease(P 0.05)at13saftertheexerciseonset.Atthestartperiodofexercise(012sfromtheexerciseonset),thetimecourseandmagnitudeoftheincreaseinmeanOxy-Hbwere not significantly differentbetween the contracting andnoncontracting VLmuscle(P 0.05byatwo-wayANOVA).As long as exercise was continued, decreased Oxy-Hb andincreasedDeoxy-HbweredetectedinthecontractingVL.ToevaluatetowhatextentlimbmovementaffectedtheNIRSdata,the effect ofpassive one-legged cycling on the meanNIRSsignalsoftherightVLwasexamined.ThemeanOxy-Hbdidnot change at the startperiod of thepassive cycling andthereafter,increasedwiththesametimecourseandmagnitudeas the Oxy-Hb observed in the noncontracting muscle (asshowninFig.3).DISCUSSION
ThisisthefirststudyusingNIRStosuggestwhethercentralcommandcontributestoincreasedbloodflowinnoncontract-
oxygenation signals ofNIRS are dependent on abalance ofoxygensupplyanduseinthetissue.Aslongasoxygenuseisat
the
minimum,
the
signal
of
Deoxy-Hb
will
be
constant,
and
the signal of Oxy-Hb may reflect muscle tissueblood flow.Indeed, the Oxy-Hb increased during one-legged cycling andduringimageryofthevoluntarycyclingwithoutaccompanyinganysignificantchangesintheDeoxy-Hb.AlthoughtheNIRSsignals are influencedby skinblood flow as well as muscleblood flow, no changes in skinblood flow were observedduringone-leggedcycling(Fig.1A).Accordingly,weassumedthattherelativepercentchangeinOxy-Hbcanbetakenasanindex of muscle tissueblood flow. The relative changes inOxy-Hboftheforearmandtricepssuraemusclesareknowntocorrelate linearly with the changes in limbbloodflow duringlower-bodynegativepressure(20)andduringisometricexer-ciseinhumans(38).SincetheNIRSsignalsisstronglyinflu-encedbyacontentofHb,achangeintissuebloodvolumeduetoperiodiclimbmovementcausedartifactsintheNIRSsignalsofthecontractingVLmuscle.Tocanceltheartifacts,themeanvalues of theNIRS signals were calculatedby conducting amovingaverageoverneighboring1,000points.TowhatextentlimbmovementaffectedthemeanNIRSdatawasevaluatedbyexamining the effect ofpassive one-legged cycling on theNIRSsignals.SincemeanOxy-Hbwasunchangedatthestartofpassivecyclingandsubsequently,increasedwiththesametimecourseandmagnitudeastheOxy-Hbinthenoncontract-ing muscle, the initial increase in mean Oxy-Hb of the con-tractingVLmuscleisunlikelytoresultfromanartifactduetolimbmovement.
JApplPhysiol doi:10.1152/japplphysiol.00075.2012 www.jappl.org
-
7/27/2019 Central Command Contributes to Increased Blood Flow in... (1)
10/15
CentralCommandandMuscleBloodFlowIshiiKetal. 1969
Fig.6.RepresentativedataofAP,HR,andOxy-andDeoxy-HboftheleftVLmuscleandbloodflowvelocityandmeaninternaldiameteroftheleftfemoralarteryduringcycling-andcircle-imageryinasubject.A:imageryofvoluntary1-leggedcycling.B:imageryofacircleunrelatedtoexercise.Cycling-imageryinducedanincreaseinOxy-HbwithoutchangingDeoxy-Hb.HRincreasedslightly,butAPwasunchangedduringcycling-imagery.Femoralbloodflowvelocityincreasedduringcycling-imagerywithoutachangeinmeaninternaldiameterofthefemoralartery.Incontrast,whenthesubjectimaginedacircleunrelatedtoexercise,nodistinctchangesinanyvariableswereobserved.
Also, there are some potential limitations with Dopplerflowmetry. First, since the exercise intensity of voluntaryone-legged cycling was reduced to minimize a movementartifact on the Doppler signal, it cannotbe denied that thebloodflowresponseofthefemoralarterymightbeunderesti-matedcomparedwiththeNIRSdata.Second,theNIRSsignalswere not measured simultaneously with femoralblood flowduring voluntary cycling, because an attempt to keep theultrasoundprobe at an appropriateposition usually causedartifacts for theNIRS signals. Third, it maybe difficult to
compare the blood flow responses obtained from DopplerultrasoundandNIRS,becausefemoralbloodflowcontainsnotonlybloodflowtotheentiremusculaturedownstreamfromthefemoral artery but also blood flow to cutaneous tissues,whereastheNIRSdataarefocusedonthevasculatureinvolvedinalocalizedregionoftheVLmuscleandskin.Nevertheless,itisconceivablethatachangeinfemoralbloodflowfollowsachange inblood flow to the quadriceps muscle,because skinbloodflowdidnotchangeduringone-leggedexercise,andthequadricepsmusclehasthegreatestmassinthelimb.
Table2. Theresponsesinhemodynamicsandfemoralbloodflowduringcycling-andcircle-imageryCycling-imagery Circle-imagery
Before During Before DuringHR(beats/min) 67 3.0 70 2.7* 69 2.2 69 2.8SV(ml) 85 7.4 84 7.5 82 5.9 83 6.9CO(l/min) 5.6 0.3 5.8 0.3 5.6 0.3 5.6 0.3MAP(mmHg) 95 2.9 99 3.3 96 2.1 99 3.2TPR(mmHgminl 1) 17.4 1.0 17.6 1.2 17.5 0.8 18.1 1.2Meaninternaldiameteroffemoralartery(cm) 0.84 0.02 0.85 0.02 0.83 0.02 0.85 0.03Femoralbloodflowvelocity(cm/s) 14.8 2.4 17.6 3.2* 14.1 1.3 14.3 1.2Femoralbloodflow(ml/min) 498 90 598 115* 464 59 496 63Femoralvascularconductance(mlmin 1mmHg 1) 5.1 1.0 6.1 1.3* 4.9 0.7 5.0 0.8
Thebaselinehemodynamicvalueswerenotsignificantlydifferent(P 0.05)betweencycling-andcircle-imageryin7subjects.Cycling-imageryincreasedHRandfemoralbloodflowvelocity,bloodflow,andvascularconductanceduringtheperiodof3045sfromtheonsetofcycling-imagery.Incontrast,anyvariablesdidnotchangesignificantly (P 0.05)duringcircle-imagery.*Significantdifference(P 0.05)fromthebaselinebeforetheimagery.Valuesaremeans SE.
JApplPhysiol doi:10.1152/japplphysiol.00075.2012 www.jappl.org
-
7/27/2019 Central Command Contributes to Increased Blood Flow in... (1)
11/15
1970 CentralCommandandMuscleBloodFlow
Fig. 7. The effects of cycling- and circle-imagery on the responses inOxy-HbofthebilateralVLmusclesandfemoralbloodflowandtheextentofvividnessofimagery.A:theaveragepercentchangesinOxy-Hboftheright(n 5subjects)andleft(n 7subjects)VLmuscle.B:theaveragechangesinmeaninternaldiameterofthefemoralartery,femoralbloodflowvelocity,femoralbloodflow,andfemoralvascularconductance(n7subjects).C:thevisualanalogscale(VAS)scoreratingthevividnessofimagery(n 7subjects).Cycling-imagery,butnotcircle-imagery,in-creased(P 0.05)Oxy-HbinthebilateralVLmusclestothesameextent,althoughtheVASscoreratingthevividnessofimagerywasnotdifferent(P 0.05)betweenthe2imageryprotocols.Femoralbloodflowvelocity,bloodflow,andvascularconductanceincreased(P 0.05)duringcycling-imagery,whereastheyfailedtochangeduringcircle-imagery.Thefemoralinternal diameter was unchanged during either imagery. *Significantdifferencefromthebaseline(P 0.05);significantdifference(P 0.05)betweencycling-andcircle-imageryprotocol.N.S.,notsignificant.
IshiiKetal.
VasodilatationinNoncontractingMuscleattheOnsetofVoluntaryExercise
In agreement withprevious studies (5, 18, 23, 50), COand femoral blood flow in the nonexercising leg wereincreased at the start of voluntary one-legged cycling. Theincrease in CO might contribute to increasedblood flow tothenonexercisinglimbwithoutachangeinarterialcontrac-tile state. Femoralblood flow, however, increased at thestart of one-legged exercise without any rise in MAP, andcalculatedvascularconductanceactuallyincreasedat1545s during voluntary one-legged exercise (Fig. 4), indicatingvasodilatation inthecontralateralleg.Furthermore,cycling-
imageryincreasedfemoralbloodflowwithoutchangingCO,suggesting that the hyperemic response is mediated withvasodilatation,presumably causedby a descending signalfrom higherbrain centers. Taken together, increasedbloodflowtothefemoralarteryisnotsimplyduetoanincreaseinsystemicperfusionpressure and/or CObut is associatedwith vasodilatation in the nonexercising limb. In addition,the internal diameter of the femoral artery was unchangedduring one-legged exercise, suggesting that vasodilatationoccurred in downstream resistance vessels.
Indeed,agoodtemporalcoincidencebetweentheincreasesintheOxy-Hbandfemoralbloodflowsuggeststhattheinitial
JApplPhysiol doi:10.1152/japplphysiol.00075.2012 www.jappl.org
-
7/27/2019 Central Command Contributes to Increased Blood Flow in... (1)
12/15
CentralCommandandMuscleBloodFlowIshiiKetal. 1971increaseinredbloodcellvelocityperseinducedanincreaseinthe diameter of arterioles with a substantial time lag in thecremaster muscle of the anesthetized rat. Furthermore, whencomparing theNIRS data and femoralblood flow with thesame time frame, the increase in femoralblood flow did notprecede the rise in Oxy-Hb, indicating that the increase inupstreamfemoralbloodflowwasnotresponsiblefortheinitialvasodilatation in the noncontracting muscle. Taken together,neurogenicvasodilatation seemsthesolecandidateresponsiblefortheinitialhyperemiainthenoncontracting muscle.
Apossibilitythatahigherintensityandalongerdurationofone-leggedexercisemaymodifytheresponseinbloodflowto
Fig.8.Atypicalexampleoftherawnear-infraredspectroscopy(NIRS)signalsoftheright(contracting)andleft(noncontracting) VLmuscleduringvoluntary1-leggedcyclinginasubject.Vertical,dashedlinesindicatethestartandendof1-leggedcycling,whereasavertical,dottedlineisplacedat15sfromtheexerciseonset.TheNIRSsignalsoftherightVLmusclecontainedartifactsduetolimbmovement.*PeakincreasesinOxy-HbofthebilateralVLmusclesatthestartperiod(015s)ofvoluntary1-leggedcycling.vasodilatation in the noncontracting skeletal muscle contrib-utes to the increase in upstream femoralblood flow. SinceEMG of the noncontracting VL was absent during voluntaryone-legged cycling (Fig. 1), the increase in flow cannotbeattributedtometabolicvasodilatation duetoinadvertentmus-clecontraction.Thustheinitialhyperemiainthenoncontract-ingVLmusclemaybeexplainedbyflow-mediatedvasodila-tation via increasedperfusion and/or neurogenic vasodilata-tion.Anincreaseinbloodflowproducesshearstress-induced release of nitric oxide (NO) andprostacyclin from the endo-thelium, which in turn, causes flow-mediated vasodilatation (13). The contribution of flow-mediated vasodilatation to theinitial hyperemia in the noncontracting VL was unknown inthisstudy,becausewedidnotexaminetheeffectsofinhibitorsofendothelial NOand/orprostacyclin productionontheinitialhyperemia in the noncontracting muscle. However, it seemsthattheflow-mediatedvasodilatation hardlyexplainstherapidhyperemiaimmediatelyaftertheonsetofvoluntaryone-leggedcycling,because Koller and Kaley (29) demonstrated that an
Fig.9.Thetimecoursesoftherelativechangesinmoving-averagedOxy-Hband Deoxy-Hb of the contracting () and noncontracting () VL muscleduringvoluntary1-leggedcyclingin7subjects.Eachvaluewascalculatedsequentially every 1 s. Vertical, dashed lines indicate the start and end of1-leggedcycling,whereasavertical,dottedlineisplacedat15sfromtheexerciseonset.Atthestartofvoluntary1-leggedexercise,meanOxy-HbinthecontractingandnoncontractingVLmusclesincreasedwithalmostthesametimecourseandmagnitude;therewasnosignificantdifferenceintheOxy-Hbresponsebetweenthe2muscles(P 0.05,a2-wayANOVA).Subsequently,meanOxy-Hbdecreased,andmeanDeoxy-HbincreasedinthecontractingVL, as long as exercise was continued. *Significant difference from thebaseline (P 0.05) in the noncontracting VL data at the startperiod of1-leggedexercise;significantdifferencefromthebaseline(P 0.05)inthecontractingVLdataatthestartperiodoftheexercise.
JApplPhysiol doi:10.1152/japplphysiol.00075.2012 www.jappl.org
-
7/27/2019 Central Command Contributes to Increased Blood Flow in... (1)
13/15
1972 CentralCommandandMuscleBloodFlow IshiiKetal.the noncontracting muscle cannotbe neglected. Taylor et al.(50) reported that with the use of venous occlusionplethys-mography, vascular resistance of the noncontracting leg wasunchanged at the initialperiod (01.5 min) of one-legged cyclingatanintensityof3875%ofthepeakO2uptakeandonly increased during the laterperiod (23 min) of the exer-cise,dependingontheintensity.Yoshizawaetal.(53)reportedusingultrasoundDopplerflowmetryasanintensity-dependentincreaseinfemoralvascularconductanceofthenonexercisingleg at the start of one-legged knee extension exercise at1545% of the maximal voluntary contraction. The initialincrease in femoral vascular conductance was followedby adecrease in femoral vascular conductance at the end ( 24min) of 3045% exercise but not 15% (53). Taking thepreviousandpresentfindingsintoconsideration, itislikelythatintensity-dependentvasodilatation occursinthenonexercising limbatthestartofone-leggedexerciseandisprobablymedi-atedby either muscle mechanoreflex or central command,whereas vasoconstriction occurs in the nonexercising limbduring the laterperiod ( 2 min) of one-legged exercise, inparticular,
at
ahigher
intensity.
This
may
be
mediated
by
muscle metaboreflex,becauseposthandgrip ischemia causedvasoconstriction inthecalfvascularbed(46).NeurogenicMechanismResponsible fortheVasodilatation intheNoncontractingMuscle
Eithermusclemechanoreflexorcentralcommandisapos-sibleneurogenicmechanismresponsiblefortheinitialhyper-emia in the noncontracting muscle in this study, becausemusclemetaboreflexand -adrenergicvasodilatation, viacir-culating catecholamines from adrenal medulla, are not suffi-cientlyrapidtoinducetheinitialhyperemia.Inthisstudy,weusedpassive one-legged cycling to isolate an influence ofmuscle
mechanoreflex
on
muscle
blood
flow,
although
passive
exercise cannot fully develop muscular tension as voluntaryexerciseandcannotalwaysmimicthemechanicaleventduringthevoluntaryexercise.NoincreaseinOxy-Hbofthenoncon-tractingVLwasdetectedatthestartperiodofpassivecycling,andsubsequently,Oxy-Hbincreasedgraduallyinparallelwitha decrease in TPR. This result suggests that muscle mechan-oreflexdoesnotaccountfortheinitialhyperemicresponseinthe noncontracting VL,but it may induce delayed musclevasodilatation.
Thus it is likely that central command contributes to in-creasedtissuebloodflowinthenoncontracting muscleatthestartofvoluntaryexercise.Thetwoconventional ideasaboutasympathetic mechanism responsible for centrally induced va-sodilatation aresympatheticwithdrawalandsympatheticcho-linergicvasodilatation. Callisteretal.(11)reportedthatmusclesympatheticnerveactivity(MSNA)toarestingarmisinhib-itedduringaperiodofpreparationandinitiationofergometerexercise,suggestingsympatheticwithdrawalpriortoandatthestartofvoluntaryexercise.However,theresponseofMSNAtotherestinglowerlegduringone-leggedcyclingiscontroversial [MSNAincreased(24),decreased(43),andunchanged(40)].Fisher et al. (22) reported that vascular conductance in theresting leg transiently increased at the onset of contralateral isometriccalfexercise,whereasMSNAtotherestinglowerlegwas unchanged, suggesting that the transient increase in vas-cular conductance at the onset of exercise is unrelated to
changesinMSNA.Therefore,itisunlikelythatadecreaseinMSNA causes the initial muscle vasodilatation. On the otherhand,Sandersetal.(44)reportedthattheinitialvasodilatationinthenonexercisinglimbwasblockedbyatropinebutnotbypropranolol,suggestingthatactivationofsympatheticcholin-ergic vasodilator fibers induced neurogenic vasodilatation.Takingtheresultsofthehumanstudyandourpreviousfindingofthecholinergicvasodilatationattheonsetofvoluntarystaticexercise in the cat (31) into consideration, it ispossible thatcentralcommandmayinducethecholinergicvasodilatationinthenoncontractingmuscleatthestartofvoluntaryexerciseinhumans. However, direct evidence for activation of sympa-theticcholinergicfibersremainstobestudied.BilateralMuscleVasodilatation byCentralCommand
MotorimageryofexerciseincreasesHRandrespiratoryrate(15),suggestingthatcentralcommandinvolvedinimageryofexercise can activate the cardiovascular and respiratory sys-temswithoutmuscularcontraction.Thusanincreaseinskeletalmuscleblood flow is expected, not only during voluntaryexercisebutalsoduringmotorimageryoftheexercise.Infact,cycling-imagery increased femoralblood flow and Oxy-HbwithnochangesinDeoxy-Hbandperfusionpressure(Figs.6and 7). This finding suggests a centrally induced musclevasodilatation.Sincetheinternaldiameterofthefemoralarterydidnotchangeduringthemotorimagery,thecentrallyinducedvasodilatation should occur inperipheral resistance vessels.The result is supportedby aprevious finding that electricalstimulation of the hypothalamic defense area evoked largeincreases in the internal diameter and cross-sectional area ofsmallarteriesinthehindlimbtricepssuraemuscleinanesthe-tizedcats(36).Incontrast,circle-imagerywithnorelationtoexerciseinducednosignificantchangesinfemoralbloodflowand
Oxy-Hb,
suggesting
that
imagery
per
se
did
not
induce
an
increase in muscleblood flow. Since the VAS score was notsignificantlydifferentbetweenthecycling-andcircle-imageryprotocol, the extent of vividness involved during imagerycould not explain the difference in the hyperemic responsebetween cycling- and circle-imagery. Consequently, the acti-vationofcentralneuronsrelatedtomotorimageryisimpor-tantforevokingneurogenicvasodilatationinmuscletissue.
Interestingly, cycling-imagery evoked similar increases inOxy-Hb of thebilateral VL muscles (Fig. 7A). This resultsuggests that central command induced simultaneous neuro-genic vasodilatation in thebilateral skeletal muscles to thesameextentduringimageryofexercise.Leeetal.(32)reportedthat many of the medullary neurons, especially in the rostralventrolateralmedullaandraphenuclei,wereduallyinfectedbyrecombinants ofpseudorabies virus injected into thebilateralhindlimbs of rats, suggesting that numerous sympatheticpre-motor neurons innervateboth left and right hindlimb. Sincevoluntary exercise shouldbe accompanied with central com-mand, centrally induced vasodilator signals willbe equallytransmittedtothebilateralVLmuscles,notonlyduringimag-eryofexercisebutalsoduringvoluntaryexercise.Ifso,centralcommandwouldinducebilateralvasodilatationinthecontract-ing and noncontracting muscle to the same extent duringvoluntaryone-leggedexercise.Indeed,atthestartofvoluntarycycling,theOxy-HbinthecontractingVLincreasedabruptlywith the same time course and magnitude as the Oxy-Hb of
JApplPhysiol doi:10.1152/japplphysiol.00075.2012 www.jappl.org
-
7/27/2019 Central Command Contributes to Increased Blood Flow in... (1)
14/15
-
7/27/2019 Central Command Contributes to Increased Blood Flow in... (1)
15/15
1974 CentralCommandandMuscleBloodFlow IshiiKetal.37. McCullyKK,HamaokaT.Near-infraredspectroscopy:whatcanittell
usaboutoxygensaturationinskeletalmuscle?ExercSportSciRev28:123127,2000.
38. MizunoM, TokizawaK,Muraoka I. Heterogeneous oxygenation innonexercisingtricepssuraemuscleduringcontralateralisometricexercise.EurJApplPhysiol97:181188,2006.
39. Nakamoto T,Matsukawa K, Liang N, Wakasugi R, Wilson LB,HoriuchiJ.Coactivationofrenalsympatheticneuronsandsomaticmotorneuronsbychemicalstimulationofthemidbrainventraltegmentalarea.JApplPhysiol110:13421353,2011.
40. Ray CA, Rea RF, Clary MP, Mark AL. Muscle sympathetic nerveresponsestodynamicone-leggedexercise:effectofbodyposture.AmJPhysiolHeartCircPhysiol264:H1H7,1993.
41. Roddie IC. Human responses to emotional stress. IrJ Med Sci 146:395417,1977.
42. RowellLB.HumanCardiovascularControl.NewYork:OxfordUniv.Press,1993.
43. SaitoM,ManoT.Exercisemodeaffectssympatheticnerveresponsive-ness.JpnJPhysiol41:143151,1991.
44. Sanders JS, Mark AL, Ferguson DW. Evidence for cholinergicallymediatedvasodilationatthebeginningofisometricexerciseinhumans.Circulation79:815824,1989.
45. SatoK,OgohS,HirasawaA,OueA,SadamotoT.Thedistributionofbloodflowinthecarotidandvertebralarteriesduringdynamicexerciseinhumans.JPhysiol589:28472856,2011.
46. SealsDR.Sympatheticneuraldischargeandvascularresistanceduringexerciseinhumans.JApplPhysiol66:24722478,1989.
47. SeiyamaA,HazekiO,TamuraM.Noninvasivequantitativeanalysisofbloodoxygenationinratskeletalmuscle.JBiochem103:419424,1988.
48. ShoemakerJK,HalliwillJR,HughsonRL,JoynerMJ.Contributionsofacetylcholineandnitricoxidetoforearmbloodflowatexerciseonsetandrecovery.AmJPhysiolHeartCircPhysiol273:H2388H2395,1997.
49. SugawaraJ,KomineH,HayashiK,YoshizawaM,OtsukiT,ShimojoN,MiyauchiT,YokoiT,MaedaS,TanakaH.Systemicalpha-adren-ergic and nitric oxide inhibition onbasal limbblood flow: effects ofendurancetraininginmiddle-agedandolderadults.AmJPhysiolHeartCircPhysiol293:H1466H1472,2007.
50. Taylor JA, JoynerMJ,ChasePB,SealsDR. Differential control offorearm and calf vascular resistance during one-leg exercise.JApplPhysiol67:17911800,1989.
51. Williamson JW,McColl R,MathewsD,Mitchell JH, Raven PB,MorganWP. Brain activationby central command during actual andimaginedhandgripunderhypnosis.JApplPhysiol92:13171324,2002.
52. WrayDW,DonatoAJ,UberoiA,MerloneJP,RichardsonRS.Onsetexercise hyperemia in humans:partitioning the contributors.J Physiol565:10531060,2005.
53. YoshizawaM,Shimizu-OkuyamaS,KagayaA.Transientincreaseinfemoralarterialbloodflowtothecontralateralnon-exercisinglimbduringone-leggedexercise.EurJApplPhysiol103:509514,2008.