BOOKCHAPTER

CARDIACELECTROPHYSIOLOGYANDTHE
ELECTROCARDIOGRAM
W.JonathanLederer
MedicalPhysiology,CHAPTER21,504528

Differentcardiaccellsservedifferentandveryspecializedfunctions,butallareelectricallyactive.
Theheart'selectricalsignalnormallyoriginatesinagroupofcellshighintherightatriumthat
depolarizespontaneouslyitthenspreadsthroughouttheheartfromcelltocell(Fig.211(f1)).As
thisactionpotentialpropagatesthroughtheheartsometimescarriedbycellsthatform
specializedconductingpathwaysandsometimesbytheverycellsthatgeneratetheforceof
contractionitassumesdifferentappearanceswithinthedifferentcardiaccells(Fig.212(f2)).By
thespeedoftheupstroke,wecancharacterizeactionpotentialsaseitherslow(SAandAVnodes)
orfast(atrialmyocytes,Purkinjefibers,andventricularmyocytes).

Figure211
Conductionpathwaysthroughtheheart.Asectionthroughthelongaxisoftheheartisshown.
Figure212
Cardiacactionpotentials.Thedistinctiveshapesofactionpotentialsatfivesitesalongthespreadofexcitation
areshown.

Becausetheexcitationofcardiacmyocytestriggerscontractionaprocesscalledexcitation
contractioncoupling(seeChapter9)thepropagationofactionpotentialsmustbecarefullytimed
tosynchronizeventricularcontractionandtherebyoptimizetheejectionofblood.Thischapter
focusesonthemembranecurrentsresponsibleforthegenerationandtransmissionofaction
potentialsinhearttissue.Wealsoexaminehowtorecordtheheart'selectricalflowbyplacement
ofelectrodesonthesurfaceofthebody,creatingoneofthesimplestandyetoneofthemostuseful
diagnostictoolsavailabletothecliniciantheelectrocardiogram.

ELECTROPHYSIOLOGYOFCARDIACCELLS
Thecardiacactionpotentialstartsinspecializedmusclecellsofthesinoatrial
nodeandthenpropagatesinanorderlyfashionthroughouttheheart
Thecardiacactionpotentialoriginatesinagroupofcellscalledthesinoatrial(SA)node(Fig.
211(f1)),locatedintherightatrium.Thesecellsdepolarizespontaneouslyandfireoffaction
potentialsataregular,intrinsicratethatisusuallybetween60and100timesperminuteforan
individualatrest.Bothparasympatheticandsympatheticneuralinputcanmodulatethisintrinsic
pacemakeractivity,orautomaticity(seeChapter16).
Becausecardiaccellsareelectricallycoupledthroughgapjunctions(Fig.213A(f3)),theaction
potentialpropagatesfromcelltocellinthesamewaythatanactionpotentialinnerveconducts
alongasingle,longaxon.AspontaneousactionpotentialoriginatingintheSAnodewillconduct
fromcelltocellthroughouttherightatrialmuscleandspreadtotheleftatrium.Theexistenceof
discreteconductingpathwaysintheatriaisstilldisputed.Aboutonetenthofasecondafterits
origination,thesignalarrivesattheatrioventricular(AV)node(Fig.211(f1)).Theimpulse
doesnotspreaddirectlyfromtheatriatotheventriclesbecauseofthepresenceofafibrous
atrioventricularring.Instead,theonlyavailablepathwayisfortheimpulsetotravelfromthe
AVnodetotheHisPurkinjefibersystem,anetworkofspecializedconductingcellsthat
carriesthesignaltothemuscleofbothventricles.
Figure213
Conductionintheheart.A,Anactionpotentialconductingfromlefttorightcausesintracellularcurrenttoflow
fromfullydepolarizedcellsontheleft,throughgapjunctions,andintocellA.DepolarizationofcellAcauses
currenttoflowfromcellAtocellB(IAB).PartofIABdischargesthecapacitanceofcellB(depolarizingcell

B),andpartflowsdownstreamtocellC.B,SubthresholddepolarizationofcellAdecayswithdistance.C,The
speedofconductionincreaseswithgreaterdepolarizationofcellA(blueversusredcurves)orwithamore
negativethreshold.

Thecardiacactionpotentialconductsfromcelltocellthroughgapjunctions
Theelectricalinfluenceofonecardiaccellonanotherdependsonthevoltagedifferencebetween
thecellsandontheresistanceofthegapjunctionconnectionbetweenthem.Agapjunction(see
Chapter8)isanelectricalsynapse(Fig.213A(f3))thatpermitselectricalcurrenttoflow
betweenneighboringcells.AccordingtoOhm'slaw,thecurrentflowingbetweencellAandthe
adjacentcellB(IAB)isproportionaltothevoltagedifferencebetweenthetwocells(VAB)but
inverselyproportionaltotheelectricalresistancebetweenthem(RAB):

VA VB VAB
IAB = =
R AB R AB

WhenRABisverysmall(i.e.,whenthecellsaretightlycoupled),thegapjunctionsareminimal
barrierstotheflowofdepolarizingcurrent.

Imaginethatseveralinterconnectedcellsareinitiallyallattheirnormalrestingpotentials(Fig.21
3B(f3)).AnactionpotentialpropagatingfromtheleftofcellAnowinjectsdepolarizingcurrent
intocellA.Asaresult,thecelldepolarizestoVA,whichisnowsomewhatpositivecomparedwith
VB.Thus,asmalldepolarizingcurrent(i.e.,positivecharges)willalsomovefromcellAtocellB
anddepolarizecellB.Inturn,currentflowingfromcellBwillthendepolarizecellC.Bythis
process,thecellsclosesttothecurrentsourceundergothegreatestdepolarization.

Imaginethattheinjectedcurrent,comingfromtheactiveregionofthehearttotheleft,
depolarizescellAjusttoitsthreshold(Fig.213C,redcurve(f3))butthatcellAhasnotyetfiredan
actionpotential.Atthisinstant,thecurrentpassingfromcellAtocellBcannotbringcellBtoits
threshold.Ofcourse,cellAwilleventuallyfireanactionpotentialand,intheprocess,depolarize
enoughtoinjectenoughcurrentintocellBtoraisecellBtoitsthreshold.Thus,theaction
potentialpropagatesdownthechainofcells,butrelativelyslowly.Ontheotherhand,iftheactive
regiontotheleftinjectsmorecurrentintocellA(Fig.213C,bluecurve(f3))producingalarger
depolarizationincellAthecurrentpassingfromcellAtocellBwillbegreaterandsufficientto
depolarizecellBbeyonditsvoltagethresholdforaregenerativeactionpotential.However,atthis
instant,thecurrentpassingfromcellBtocellCisstillnotsufficienttotriggeranactionpotential
incellC.ThatwillhavetowaituntiltheactiveregionmovesclosertocellC,butthewaitisnotas
longasinthefirstexample(redcurve).Thus,theactionpotentialpropagatesmorerapidlyinthis
secondexample(bluecurve).
Inprinciple,wecouldmaketheactionpotentialpropagatemorerapidlydownthechainofcellsin
twoways.First,wecouldallowmoreionchannelstoopenintheactiveregionoftheheart,sothat
depolarizingcurrentislarger(bluecurveinFig.213C(f3)).Second,wecouldlowerthethreshold
fortheregenerativeactionpotential(morenegativethresholdinFig.213C(f3)),sothateventhe
smallcurrentrepresentedbytheredcurveisnowsufficienttotriggercellB.

Justasinanerveaxonconductinganactionpotential,theintracellularandextracellularcurrents
inheartmusclemustbeequalandopposite.Intheactiveregionoftheheart(totheleftofcellAin
Fig.213B(f3)),cellshavereachedthresholdandtheiractionpotentialsprovidethesourceof
currentthatdepolarizescellsthatareapproachingthreshold(e.g.,cellsAandB).AscellAitselfis
depolarizingtoandbeyondthreshold,itsNa+andCa2+channelsareopening,enablingthese
cations(i.e.,positivecharge)toenter.ThepositivechargethatenterscellAnotonlydepolarizes
cellAbutalsoproducesaflowofpositivechargetocellBintracellularcurrent.Thisflowof
positivechargedischargesthemembranecapacitanceofcellB,therebydepolarizingcellBand
releasingextracellularpositivechargesthathadbeenassociatedwiththemembrane.The
movementofthisextracellularpositivechargefromaroundcellBtowardtheextracellularregion
aroundcellAconstitutestheextracellularcurrent.Theflowofintracellularcurrentfromcell
AtocellBandtheflowofextracellularcurrentfromaroundcellBtoaroundcellAareequaland
opposite.Itistheflowofthisextracellularcurrentintheheartthatgivesrisetoaninstantaneous
electricalvector,whichchangeswithtime.Eachpointonanelectrocardiogram(ECG)isthe
sumofthemanysuchelectricalvectors,generatedbythemanycellsoftheheart.

Cardiacactionpotentialshaveasmanyasfivedistinctivephases
Theinitiationtime,shape,anddurationoftheactionpotentialaredistinctivefordifferentpartsof
theheart,reflectingtheirdifferentfunctions(Fig.212(f2)).Thesedistinctionsarisebecausethe
myocytesineachregionofthehearthaveacharacteristicsetofchannelsandanatomy.
Underlyingcardiacactionpotentialsarefourmajortimedependentandvoltagegatedmembrane
currents(Table211(cetable1)):

1.TheNa+current(INa)isresponsiblefortherapiddepolarizingphaseoftheaction
potentialinatrialandventricularmuscleandinPurkinjefibers.

2.TheCa2+current(ICa)isresponsiblefortherapiddepolarizingphaseoftheaction
potentialintheSAnodeandAVnodeitalsotriggerscontractioninallcardiomyocytes.

3.TheK+current(IK)isresponsiblefortherepolarizingphaseoftheactionpotential
inallcardiomyocytes.

4.Thepacemakercurrent(If)isresponsible,inpart,forpacemakeractivityinSAnodal
cells,AVnodalcells,andPurkinjefibers.

Table211
MajorCardiacMembraneCurrentsThatAreTimeDependentandVoltageGated
Current Name ChannelProtein Human ReversalPotential Inhibitors
Gene ofCurrent(mV)
Symbol

INa Na+current Nav1.5(voltagegated SCN +60 TTX

Na+channel)
Local
anesthetics

ICa Ca2+ Cav1.2(LtypeCa2+ CACNA +120 Nifedipine

current channel)
Verapamil

IK Repolarizing HERG+miRP1* KCNH2+ 100 Ba2+

IKR (cetablefn1) KCNE2
Cs+
Repolarizing KvLQT1+minK* KCNQ1+
IKS (cetablefn1) KCNE1 TEA

Kv4.3(voltagegatedK KCND3
Ito
+
channel) KCNJ
Gprotein
activated GIRK*(cetablefn1) KCNJ

ATP KirSUR*(cetablefn1)+
sensitive =KATP*(cetablefn1)

If(Na+ Pacemaker HCN HCN 35 Cs+

current
+K+)

TTX,tetrodotoxinTEA,tetraethylammoniumHERG,humanetheragogorelatedgene(relatedtoKvfamily
ofK+channelgenes)GIRK,GproteinactivatedinwardlyrectifyingK+channelHCN,hyperpolarization
activated,cyclicnucleotidegated.

*Theseareheteromultimericchannels.

Besidesthesefourcurrents,channelscarrynumerousothercurrentsinheartmuscle.Inaddition,
twoelectrogenictransporterscarrycurrentacrossplasmamembranes:theNaCaexchanger

(NCX1)andtheNaKpump(seeChapter5).

Traditionally,thechangesinmembranepotential(Vm)duringthecardiacactionpotentialare
dividedintoseparatephases,asillustratedinFigure214A(f4)forcardiacactionpotentialsfrom
theSAnodeandinFigure214B(f4)forthosefromventricularmuscle.
Figure214
Phasesofcardiacactionpotentials.Therecordsinthisfigureareidealized.IK,INa,ICa,andIfare

currentsthroughK+,Na+,Ca2+,andnonselectivecationchannels,respectively.

Phase0istheupstrokeoftheactionpotential.IftheupstrokeisdueonlytoICa(Fig.214A(f4)),
itwillbeslow.IftheupstrokeisduetobothICaandINa(Fig.214B(f4)),itwillbefast.

Phase1istherapidrepolarizationcomponentoftheactionpotential(whenitexists).Thisphase
isduetoalmosttotalinactivationofINaorICaandmayalsodependontheactivationofaminorK
+
currentnotlistedpreviously,calledIto(fortransientoutwardcurrent).

Phase2istheplateauphaseoftheactionpotential,whichisprominentinventricularmuscle.It
dependsonthecontinuedentryofCa2+orNa+ionsthroughtheirmajorchannelsandonaminor

membranecurrentduetotheNaCaexchangerNCX1.

Phase3istherepolarizationcomponentoftheactionpotential.ItdependsonIK(Table211
(cetable1)).

Phase4constitutestheelectricaldiastolicphaseoftheactionpotential.Vmduringphase4is
termedthediastolicpotentialthemostnegativeVmduringphase4isthemaximum
diastolicpotential.InSAandAVnodalcells,changesinIK,ICa,andIfproducepacemaker
activityduringphase4.PurkinjefibersalsoexhibitpacemakeractivitybutuseonlyIf.Atrialand
ventricularmusclehavenotimedependentcurrentsduringphase4.

TheNa+currentisthelargestcurrentintheheart
TheNa+current(INaTable211(cetable1))isthelargestcurrentinheartmuscle,whichmay

haveasmanyas200Na+channelspersquaremicronofmembrane.Thesechannelsareabundant
inventricularandatrialmuscle,inPurkinjefibers,andinspecializedconductionpathwaysofthe
atria.ThiscurrentisnotpresentinSAorAVnodalcells.
ThechannelthatunderliesINaisaclassicvoltagegatedNa+channel,withbothand1subunits
(seeChapter7).Theuniquecardiacsubunit(Nav1.5)hasseveralphosphorylationsitesthat

makeitsensitivetostimulationbycAMPdependentproteinkinase(seeChapter3).

Atthenegativerestingpotentialsoftheventricularmusclecells,theNa+channelsareclosed.
However,thesechannelsrapidlyactivate(in0.1to0.2ms)inresponsetolocaldepolarization
producedbyconductedactionpotentialsandproduceamassiveinwardcurrentthatunderlies
mostoftherapidupstrokeofthecardiacactionpotential(phase0inFig.214B(f4)).IfVm
remainsatapositivelevel,thesechannelsclosegradually,inaprocessknownasinactivation.
Thisprocess,whichisslowerthanactivationbutstillfairlyrapid(halftime,1ms),ispartly
responsiblefortherapidrepolarizationoftheactionpotential(phase1).Atthepotentials
maintainedduringtheplateauofthecardiacactionpotentialslightlypositiveto0mVduring
phase2averysmallbutimportantcomponentofthiscurrentremains.ThesustainedlevelofINa
helpsprolongphase2.

IncardiactissuesotherthantheSAandAVnodes,theregenerativespreadoftheconductedaction
potentialdependsinlargepartonthemagnitudeofINa(Fig.213C(f3)).Thedepolarization

producedbytheNa+currentnotonlyactivatesINainneighboringcellsbutalsoactivatesother
membranecurrentsinthesamecell,includingICaandIK.Localanestheticantiarrhythmic
drugs,suchaslidocaine,workbypartiallyblockingINa.

TheCa2+currentintheheartpassesprimarilythroughLtypeCa2+channels
TheCa2+current(ICaTable211(cetable1))ispresentinallcardiacmyocytes.TheLtypeCa2+

channel(Cav1,seeChapter7)isthedominantoneintheheart.TtypeCa2+channels,with
differentbiophysicalandpharmacologicalproperties,arealsopresentbutinsmalleramounts.

IntheSAnode,theroleofICa,likethatoftheothertimeandvoltagedependentmembrane
currents,istocontributetopacemakeractivity.InboththeSAandAVnodes,ICaistheinward
currentsourcethatisresponsiblefortheupstrokes(phase0)oftheSAandAVnodalaction
potentials.BecausethenodalcellslackthelargerINa,theirupstrokesareslowerthanthosein
atrialandventricularmuscle(compareAandBofFig.214(f4)).Therefore,thesmallerICa
dischargesthemembranecapacitanceofneighboringcellsintheSAandAVnodeslessrapidly,so
thatthespeedoftheconductedactionpotentialismuchslowerthanthatofanyothercardiac
tissue.ThisfeatureintheAVnodeleadstoanelectricaldelaybetweenatrialcontractionand
ventricularcontractionthatpermitsmoretimefortheatriatoemptybloodintotheventricles.

Althoughitissmaller,ICasumswithINaduringtheupstrokeoftheactionpotentialsofthe
ventricularandatrialmuscleandthePurkinjefibers.Inthisway,itincreasesthevelocityofthe
conductedactionpotentialinthesetissues.LikeINa,ICaproducesvirtuallynocurrentatvery

negativepotentialsbecausethechannelsareclosed.AtmorepositivevaluesofVm,theCa2+
channelsrapidlyactivate(in1ms)and,byacompletelyseparateandtimedependentprocess,
inactivate(halftime,10to20ms).AsmallICaremainsduringthephase2oftheactionpotential,

helpingtoprolongtheplateau.Inatrialandventricularmusclecells,theCa2+enteringthroughL
typeCa2+channelsactivatesthereleaseofCa2+fromthesarcoplasmicreticulum(SR)by
calciuminducedCa2+release(seeChapter9).BlockersofLtypeCa2+channels

therapeuticagentssuchasverapamil,diltiazem,andnifedipineactbyinhibitingICa.

TherepolarizingK+currentturnsonslowly
Cardiacactionpotentialslasttwoordersofmagnitudelongerthanactionpotentialsinskeletal
musclebecausetherepolarizingK+currentturnsonveryslowlyandinthecaseofatrial
myocytes,Purkinjefibers,andventricularmyocyteswithaconsiderabledelay.The
repolarizingK+current(IKTable211(cetable1))isfoundinallcardiacmyocytesandis
responsibleforrepolarizingthemembraneattheendoftheactionpotential(phase3inFig.214A,
B(f4)).TwocurrentsunderlieIKarelativelyrapidcomponent(IK )carriedbyheteromeric
R

HERG/miRP1channelsandarelativelyslowcomponent(IKS)carriedbyheteromeric
KvLQT1/minKchannels(seeChapter7fortheboxaboutheartdefects).TheIKmembranecurrent
isverysmallatnegativepotentials.Withdepolarization,itslowlyactivates(20to100ms)but
doesnotinactivate.InSAandAVnodalcells,itcontributestopacemakeractivitybydeactivating

atthediastolicvoltage.

InadditiontoIK,severalotherK+currentsarepresentincardiactissue.

EarlyOutwardK+Current(AtypeCurrent)
Atrialandventricularmusclecellshavesomeearlytransientoutwardcurrent(Ito).Thiscurrent
isactivatedbydepolarizationbutrapidlyinactivates.Itcontributestophase1repolarizationandis
analogoustotheAtypecurrents(seeChapter7)seeninnerves.AKv4.3channelmediatestheA
typecurrentinheartandcertainothercells.

GProteinActivatedK+Current
Acetylcholineactivatesmuscarinicreceptorsand,throughthesubunitsofaGprotein,activates
anoutwardK+currentmediatedbyGIRKK+channels(seeChapter7).Thiscurrentisprominent
inSAandAVnodalcells,whereitdecreasespacemakerratebycellhyperpolarizationwhenitis
activated.ItalsoslowstheconductionoftheactionpotentialthroughtheAVnode.

KATPCurrent

ATPsensitiveK+channels(KATPseeChapter7),activatedbylowintracellular[ATP],arepresent
inabundanceandmayplayaroleinelectricalregulationofcontractilebehavior.Thesechannels
areheteromultimersofKirandSUR.
TheIfcurrentismediatedbyanonselectivecationchannel
Thepacemakercurrent(If)isfoundinSAandAVnodalcellsandinPurkinjefibers(Fig.214A,
bluecurve(f4)).ThechannelunderlyingthiscurrentisanonspecificcationchannelcalledHCN
(forhyperpolarizationactivated,cyclicnucleotidegated),whichisrelatedtothecyclic
nucleotidegatedchannels(seeChapter6).BecausetheHCNchannelsconductbothK+andNa+,
thereversalpotentialofIfisaround20mV,betweentheNernstpotentialsforK+(about90

mV)andNa+(about+50mV).TheHCNchannelshavetheunusualproperty(hencethesubscript
f,forfunnycurrent)thattheydonotconductatpositivepotentialsbutareactivatedby
hyperpolarizationattheendofphase3.Theactivationisslow(100ms),andthecurrentdoesnot
inactivate.Thus,Ifproducesaninward,depolarizingcurrentasitslowlyactivatesattheendof
phase3.TheIfcurrentisnottheonlycurrentthatcontributestopacemakeractivityinSAand
AVnodalcells,ICaandIKalsocontributesignificantlytothephase4depolarization.

Differentcardiactissuesuniquelycombineioniccurrentstoproduce
distinctiveactionpotentials

Theshapeoftheactionpotentialdiffersamongdifferentcardiaccellsbecauseoftheunique
combinationofvariouscurrentsboththevoltagegated/timedependentcurrentsdiscussedin
theprecedingfoursectionsandthebackgroundcurrentspresentineachcelltype.InChapter6,
weintroducedEquation612,whichdescribesVmintermsoftheconductancesforthedifferent
ions(GNa,GK,GCa,GCl)relativetothetotalmembraneconductance(Gm)andthe
equilibriumpotentials(ENa,EK,ECa,ECl):

GK GNa GCa GCl

Vm = EK + ENa + ECa + ECl
Gm Gm Gm Gm

Therefore,astherelativecontributionofaparticularmembranecurrentbecomesdominant,Vm
approachestheequilibriumpotentialforthatmembranecurrent(Table212(cetable2)).Howfast
Vmchangesduringtheactionpotentialdependsonthemagnitudeofeachofthecurrents(see
Equation612).Notonlydoeseachcurrentindependentlyaffecttheshapeoftheactionpotential,
butthevoltageandtimedependentcurrentsinteractwithoneanotherbecausetheyaffectand
areaffectedbyVm.Otherimportantinfluencesontheshapeofthecardiacactionpotentialare
themembranecapacitanceofeachcellandthegeometryoftheconductionpathway(e.g.,AV
node,bundleofHis,ventricularmuscle)astheactionpotentialpropagatesfromcelltocellinthis
functionalsyncytiumthroughgapjunctions.Therefore,itiseasytounderstand,ataconceptual
level,howaparticularcell'suniquecomplementofionchannels,thepropertiesofthesechannels
ataparticularinstantintime,theintracellularionconcentrations,andthecell'sgeometrycanall
contributetotheshapeofanactionpotential.

Table212
EquilibriumPotentials

Ion IntracellularConcentration ExtracellularConcentration EquilibriumPotential

 (mM) (mM) (mV)

Na+ 10 145 +72

K+ 120 4.5 88

Cl 35 116 32

H+ pH=7.1 pH=7.4 19

Ca 0.0001 1.0 +123

2+

Thesinoatrialnodeistheprimarypacemakeroftheheart
TheConceptofPacemakerActivity
Thenormalhearthasthreeintrinsicpacemakingtissues:theSAnode,theAVnode,andthe
Purkinjefibers.Thetermpacemakeractivityreferstothespontaneoustimedependent
depolarizationofthecellmembranethatleadstoanactionpotentialinanotherwisequiescent
cell.Anycardiaccellwithpacemakeractivitycaninitiatetheheartbeat.Thepacemakerwiththe
highestfrequencywillbetheonetotriggeranactionpotentialthatwillpropagatethroughoutthe
heart.Inotherwords,thefastestpacemakersetstheheartrateandoverridesallslower
pacemakers.Thus,cardiacpacemakershaveahierarchyamongthemselves,basedontheir
intrinsicfrequency.Twofundamentalprinciplesunderliepacemakeractivity.Thefirstisthat
inwardordepolarizingmembranecurrentsinteractwithoutwardorhyperpolarizingmembrane
currentstoestablishregularcyclesofspontaneousdepolarizationandrepolarization.Thesecond
isthatinaparticularcell,thesecurrentsinteractduringphase4withinanarrowrangeofdiastolic
potentials:between70and50mVinSAandAVnodalcells,andbetween90and65mVin
Purkinjefibers.

SinoatrialNode
TheSAnodeisfoundintherightatriumandistheprimarysiteoforiginoftheelectricalsignalin
themammalianheart(Table213(cetable3)).Itisthesmallestelectricalregionoftheheartand
constitutesthefastestnormalpacemaker,withanintrinsicrateof60beatsperminuteorfaster
inanindividualatrest.SAcellsarestableoscillatorswhosecurrentsarealwaysvaryingwithtime.
Theinteractionsamongthreetimedependentandvoltagegatedmembranecurrents(ICa,IK,
andIf)controltheintrinsicrhythmicityoftheSAnode.Thesumofadecreasingoutward
current(IKgreencurveinFig.214A(f4))andtwoincreasinginwardcurrents(ICaandIfred
andbluecurvesinFig.214A(f4))producestheslowpacemakerdepolarization(phase4)
associatedwiththeSAnode.Themaximumdiastolicpotential(i.e.,themostnegativeVm)ofthe

SAnodalcells,whichoccursduringphase4oftheactionpotential,isbetween60and70mV.
AsVmrisestowardthethresholdofabout55mV,ICabecomesincreasinglyactivatedand
eventuallybecomesregenerative,producingtheupstrokeoftheactionpotential.This

depolarizationrapidlyturnsoff(i.e.,deactivates)If,andthewholeprocessbeginsagain.
Table213
ElectricalPropertiesofDifferentCardiacTissues

Tissue Function PrincipalTimeDependent Adrenergic Cholinergic

Name andVoltageDependent Effect* Effect
Currents (cetablefn2) (cetablefn3)

SAnode Primary ICa,IK,If Conduction Pacemaker

pacemaker velocity rate

Pacemaker Conduction
rate velocity

Atrial Expelbloodfrom INa,ICa,IK Strengthof Littleeffect

muscle atria contraction

AVnode Secondary ICa,IK,If Conduction Pacemaker

pacemaker velocity rate

Pacemaker Conduction
rate velocity

Purkinje Rapidconduction INa,ICa,IK,If Pacemaker Pacemaker

fibers ofactionpotential rate rate

Tertiary
pacemaker

Ventricular Expelbloodfrom INa,ICa,IK Contractility Littleeffect

muscle ventricles

*Forexample,epinephrine.

Forexample,acetylcholine.

Thesemembranecurrentsareunderthecontroloflocalandcirculatingagents(e.g.,acetylcholine,
epinephrine,andnorepinephrine)andarealsotargetsfortherapeuticagentsdesignedto
modulatetheheart'srhythm(e.g.,Ca2+channelblockersandadrenergicblockers).

AtrioventricularNode
TheAVnode,locatedjustabovetheatrioventricularring,isthesecondarysiteoforiginofthe
electricalsignalinthemammalianheart.Normally,theAVnodemaybeexcitedbyanimpulse
reachingitbywayofthespecializedatrialconductionpathways(seelater).LikethatoftheSA
node,theintrinsicrhythmicityoftheAVnodedependsontheinteractionofthreetimedependent
andvoltagegatedcurrents:IK,ICa,andIf.Electrically,theSAandAVnodessharemany
propertiestheyhavesimilaractionpotentials,pacemakermechanisms,anddrugsensitivitiesand
asimilarlyslowconductionofactionpotentials.BecausetheintrinsicpacemakerrateoftheAV
nodeisslower(40beats/min)thanthatoftheSAnode,itdoesnotsettheheartrateits
pacemakeractivityisconsideredsecondary.However,iftheSAnodeshouldfail,theAVnodecan
assumecontroloftheheartanddriveitsuccessfully.

PurkinjeFibers
TheHisPurkinjefibersystemoriginatesattheAVnodewiththebundleofHisandsplitstoform
theleftandrightbundlebranches(Fig.211(f1)).Therightbundleconductstheelectricalsignal
totherightventricle,andtheleftbundleconductsthesignaltotheleftventricle.Theanatomyof
theleftbundleisvariable,butthisbundlefrequentlydividesintotwomainbranchestheleft
anterosuperiorfascicle(orhemibundle)andtheleftposteroinferiorfascicle.

Purkinjefibercellshavetheslowestintrinsicpacemakerrate(20beats/minorless).Thus,
PurkinjefibercellsbecomefunctionalpacemakersonlyiftheSAandAVpacemakersfailandare
consideredtertiarypacemakers.Ontheotherhand,thebundleofHisandthePurkinjefibersare
aneffectiveconductionsystemwithintheventriclesbecausetheyconductactionpotentialsmore
quicklythananyothertissuewithintheheart(Table214(cetable4)).

Table214
ConductionVelocityinDifferentCardiacTissues

Tissue ConductionVelocity(m/s)

SAnode 0.05

Atrialpathways 1

AVnode 0.05

BundleofHis 1

Purkinjesystem 4

Ventricularmuscle 1

TheactionpotentialofthePurkinjefibersdependsonfourtimeandvoltagedependent
membranecurrents:INa(notpresentintheSAandAVnodalcells),ICa,IK,andIf.The

maximumdiastolicpotentialis80mV.FromthatnegativeVm,thesecellsproduceaveryslow
pacemakerdepolarization(phase4)thatdependsonIf.Becauseoftheirlowrateofpacemaker
depolarizationandthereforetheuncertaintyofreachingthethresholdfortriggeringofanaction
potential,Purkinjefibercellsareunreliableaspacemakers.Normally,theactionpotentialpassing
throughtheAVnodeactivatesthePurkinjefibercells,resultinginarapidupstroke(phase0),
mediatedbyINaandICa.BecauseINaislarge,Purkinjefibersconductactionpotentialsrapidly.
Atrialandventricularmyocytesfireactionpotentialsbutdonothave
pacemakeractivity
Therestingpotentialofatrialandventricularmyocytesissubstantiallymorenegative(about80
mV)thanthemaximumdiastolicpotentialofSAandAVnodepacemakercells(Fig.211(f1)).

AtrialMuscle
Withineachatrium,theactionpotentialspreadsamongcardiacmyocytesbyadirectcelltocell
pathway.Theatrialactionpotentialdependsonthreeprimarytimeandvoltagedependent
membranecurrents:INa,IK,andICa.Thereisnonormalspontaneous(i.e.,pacemaker)activity
inatrialmuscle.Ithasbeenproposedthatatrialmusclehasfourspecialconductingbundles(Fig.
211(f1)).One,Bachman'sbundle(anteriorinteratrialmyocardialband),isinteratrialand
conductsthecardiacactionpotentialfromtheSAnodetotheleftatrium.Threeotherinternodal
pathwaystheanterior,middle,andposteriorinternodalpathwaysappeartoconducttheaction
potentialfromtheSAnodetotheAVnode.Therefore,thefirststepinpropagationofthecardiac
actionpotentialisthedepolarizationoftheatria,followingageneralaxisfromrighttoleftand
downward(Fig.215,step1(f5)).
Figure215
Sequenceofdepolarizationincardiactissue.

IftheconductionpaththroughtheAVnodeisblocked,theventricleswillnotbeactivated
electricallyandwillnotcontract.ThespontaneousactivitythatcanariseinthePurkinjefibercells
mayprovidethenecessaryelectricalsignaltoactivatetheventricles,butthisactivationoccurs
normallyonlyataverylowrate,andPurkinjefiberpacemakeractivityisfairlyunreliable.

VentricularMuscle
AftertheactionpotentialreachestheAVnode,ittravelstotheHisPurkinjefibernetworkandout
intotheventricularmuscle.Theonlynormalelectricalaccessbetweenatrialmuscleandthe
ventriclesistheAVnode.Becauseofthissingleelectricalconnectionbetweentheatriaandthe
ventricles,thereisawelldefinedandorderlysequenceofelectricalactivitythroughtherapidly
conductingHisPurkinjenetworktotheventricles.Withintheventricularmuscle,theaction
potentialconductsfromcelltocell.Steps2to6inFigure215(f5)summarizethesequenceof
eventsinventricularactivation,whichiscompletedin100ms:

Step2:Theseptumdepolarizesfromlefttoright.

Step3:Theanteroseptalregiondepolarizes

Step4:Themyocardiumalwaysdepolarizesfromtheendocardium(thecellsliningthe
ventricles)towardtheepicardium(cellsontheoutersurfaceoftheheart).Theleftventricle
depolarizesattheapexwhilethePurkinjefibersarestillintheprocessofconductingthe
actionpotentialtowardthebaseoftheleftventricle

Step5:Depolarizationspreadsfromtheapextowardthebase,carriedbythePurkinjefibers.
Thisspreadtothebasebeginsevenasthesignalintheapexisstillspreadingfromthe
endocardiumtotheepicardium.Thelastregiontodepolarizeistheposterobasalregionof
theleftventricle

Step6:Theventriclesarefullydepolarized.
 Ventricularmusclehasthreemajortimeandvoltagegatedmembranecurrents:INa,ICa,
andIK(Fig.214B(f4)).VentricularmusclehasnoIf,andhealthyventricularmusclecellsshow

nopacemakeractivity.Startingfromarestingpotentialof80mV,therapidupstrokeofthe
ventricularactionpotentialresultsfromtheactivationofINabyanexternalstimulus(e.g.,an
impulseconductedtothemusclebyaPurkinjefiberorbyaneighboringventricularmusclecell).
TheCa2+currentisofparticularimportancetoventricularmusclebecauseitprovidestheCa2+
influxthatactivatesthereleaseofCa2+fromtheSR.Therapidrepolarization(phase1),the
plateau(phase2),andtherepolarization(phase3)allappeartobegovernedbymechanisms
similartothosefoundinthePurkinjefibers.However,theplateauphaseisprolongedin
ventricularmusclebecausetheinwardandoutwardcurrentsareratherstableduringthattime
(green,orange,andredcurvesinFig.214B(f4)).

Onceaventricularmusclecellisactivatedelectrically,itisrefractorytoadditionalactivation.This
effectiverefractoryperiodarisesbecausetheinwardcurrents(INaandICa)thatare
responsibleforactivationarelargelyinactivatedbythemembranedepolarization(Fig.214B(f4)).
Theeffectiverefractoryperiodisthesameastheabsoluterefractoryperiodinnerveandskeletal
muscle.Duringtheeffectiverefractoryperiod,anadditionalelectricalstimulushasnoeffecton
theactionpotential.Attheendoftheplateau,thecellbeginstorepolarizeasIKincreasesin
magnitude.AsICaandINabegintorecoverfrominactivation,therelativerefractoryperiod
begins.Duringthisperiod,anadditionalelectricalstimuluscanproduceanactionpotential,buta
smalleronethanusual.Refractorinessprovidestheheartwithameasureofelectricalsafety
becauseitpreventsextraneouspacemakers(whichmayarisepathologically)fromtriggering
ectopicbeats.Anextrasystoliccontractionwouldmaketheheartalessefficientpump.
Refractorinessalsopreventstetanus(seeChapter9),afeatureobservedinskeletalmuscle.
Tetanusoftheheartwouldmeanperpetualsystoleandnofurthercontractions.

Acetylcholineandcatecholaminesmodulatepacemakeractivity,conduction
velocity,andcontractility
Inprinciple,theSAnodecanslowthefiringrateofitspacemaker(i.e.,negativechronotropic
effect)bythreemechanisms.First,thesteepnessofthedepolarizationduringphase4can
decrease,therebylengtheningthetimenecessaryforVmtoreachthreshold(Fig.216A,bluecurve
(f6)).Inthisway,diastoleislongerandtheheartratefalls.Second,themaximumdiastolic
potentialcanbecomemorenegative(Fig.216B,greencurve(f6)).Inthiscase,beginningatalower
value,Vmrequiresalongertimetoreachthethreshold,assumingnochangeinthesteepnessof
thephase4depolarization.Third,thethresholdfortheactionpotentialcanbecomemorepositive
(Fig.216C,purplecurve(f6)).Assumingnochangeineitherthemaximumdiastolicpotential(i.e.,
startingpoint)orthesteepnessofthephase4depolarization,Vmrequiresalongertimetoreacha
morepositivethreshold.Obviously,acombinationofthesethreemechanismswouldhavean
enhancedeffect.Conversely,theSAnodecellscanuseeachofthesethreemechanismsinthe
oppositesensetoincreasetheirfiringrate(positivechronotropiceffect).
Figure216
Modulationofpacemakeractivity.

Acetylcholine
Thevagusnerve,whichisparasympathetic(seeChapter14),releasesacetylcholineontotheSA
andAVnodesandslowstheintrinsicpacemakeractivitybyallthreemechanismsdiscussedinthe
precedingparagraph.First,acetylcholinedecreasesIfintheSAnode(Table211(cetable1)),
reducingthesteepnessofthephase4depolarization(Fig.216A(f6)).Second,acetylcholineopens
GIRKchannels,increasingrelativeK+conductanceandmakingthemaximumdiastolicpotential
ofSAnodalcellsmorenegative(Fig.216B(f6)).Third,acetylcholinereducesICaintheSAnode,
therebyreducingthesteepnessofthephase4depolarization(Fig.216A(f6))andalsomovingthe
thresholdtomorepositivevalues(Fig.216C(f6)).Allthreeeffectscooperatetolengthenthetime
fortheSAnodetodepolarizetothresholdtheneteffectistolowertheheartrate.

TheeffectsofacetylcholineoncurrentsintheAVnodearesimilartothoseintheSAnode.
However,becausethepacemakernormallydoesnotresideintheAVnode,thephysiologicaleffect
ofacetylcholineontheAVnodeistoslowconductionvelocity.Themechanismisaninhibition
ofICathatalsomakesthethresholdmorepositiveforAVnodalcells.Becauseitismoredifficult
foronecelltodepolarizeitsneighborstothreshold,conductionvelocityfalls.

Catecholamines
Sympatheticinnervationtotheheartisplentiful,releasingmostlynorepinephrine.Inaddition,the
adrenalmedullareleasesepinephrineintothecirculation.Catecholamines,whichactthrough1
adrenergicreceptors,produceanincreaseinheartratebytwomechanisms.First,catecholamines
increaseIfinthenodalcells,therebyincreasingthesteepnessofthephase4depolarization(i.e.,
oppositetotheeffectinFig.216A(f6)).Second,catecholaminesincreaseICainallmyocardial
cells.TheincreaseinICaintheSAandAVnodalcellssteepensthephase4depolarization(i.e.,
oppositetotheeffectinFig.216A(f6))andalsomakesthethresholdmorenegative(i.e.,opposite
totheeffectinFig.216C(f6)).Notethatcatecholaminesdonotappeartochangethemaximum
diastolicpotential.Theydo,however,produceshorteractionpotentialsasaresultoftheactions
theyhaveonseveralspecificcurrents.

Inatrialandventricularmuscle,catecholaminescauseanincreaseinthestrengthofcontraction(
positiveinotropiceffect)forfourreasons.First,theincreasedICa(i.e.,Ca2+influx)leadstoa

greaterlocalincreasein[Ca2+]iandalsoagreaterCa2+inducedCa2+releasefromtheSR.

Second,thecatecholaminesincreasethesensitivityoftheSRCa2+releasechanneltocytoplasmic
Ca2+(seeChapter9).Third,catecholaminesalsoenhanceCa2+pumpingintotheSRby
stimulationoftheSERCACa2+pump(seeChapter5),therebyincreasingCa2+storesforlater
release.Fourth,theincreasedICapresentsmoreCa2+toSERCA,sothatSRCa2+storesincrease

overtime.ThefourmechanismsmakemoreCa2+availabletotroponinC,enablingamore
forcefulcontraction.

THEELECTROCARDIOGRAM
Anelectrocardiogramgenerallyincludesfivewaves
Theelectrocardiogram(ECG)isthestandardclinicaltoolusedtomeasuretheelectricalactivityof
theheart.Itisarecordingofthesmallextracellularsignalsproducedbythemovementofaction
potentialsthroughcardiacmyocytes.Toobtainastandard12leadECG,oneplacestwo
electrodesontheupperextremities,twoonthelowerextremities,andsixonstandardlocations
acrossthechest.Invariouscombinations,theelectrodesontheextremitiesgeneratethesixlimb
leads(threestandardandthreeaugmented),andthechestelectrodesproducethesixprecordial
leads.Inalead,oneelectrodeistreatedasthepositivesideofavoltmeterandoneormore
electrodesasthenegativeside.Therefore,aleadrecordsthefluctuationinvoltagedifference
betweenpositiveandnegativeelectrodes.Bythevariationofwhichelectrodesarepositiveand
whicharenegative,astandard12leadECGisrecorded.Eachleadlooksattheheartfromaunique
angleandplane,thatis,fromwhatisessentiallyitsownuniquepointofview.
 Thefluctuationsinextracellularvoltagerecordedbyeachleadvaryfromfractionsofa
millivolttoseveralmillivolts.Thesefluctuationsarecalledwavesandarenamedwiththeletters
ofthealphabet(Fig.217(f7)).ThePwavereflectsdepolarizationoftherightandleftatrial
muscle.TheQRScomplexrepresentsdepolarizationofventricularmuscle.TheTwaverepresents
repolarizationofbothventricles.Finally,therarelyseenUwavemayreflectrepolarizationofthe
papillarymuscle.Theshapeandmagnitudeofthesewavesaredifferentineachleadbecauseeach
leadviewstheelectricalactivityoftheheartfromauniquepositioninspace.Forhisdiscoveryof
themechanismoftheelectrocardiogram,WillemEinthovenwasawardedthe1924NobelPrizein
PhysiologyorMedicine.

Figure217
ComponentsoftheECGrecording.

Ifapatienthasanatrialtachycardia,suchasatrialflutteroratrialfibrillation,
electricalimpulsesfromtheAVnodeandabovemaypummeltheventriclesanddrivethem
ataveryhighrate.Theventricularratemaybecomesohighthattheeffectivenessoftheir
pumpingishindered.Becauseallimpulsesactivatingtheventriclesmustpassthroughthe
AVnode,useofacetylcholinetoslowimpulseconductionthroughtheAVnodecanslowthe
ventricularrate.Thus,socalledvagalmaneuvers,whichincreaseparasympatheticactivity,
canalsodecreaseventricularrate.OneexampleisthereleasefromaValsalvamaneuver.
DuringaValsalvamaneuver,onemakesaforcedexpiratoryeffortagainstaclosedairway
(e.g.,gruntingwhileliftingaheavyobject),raisingintrathoracicpressure.Subsequently,
openingoftheairwayallowsintrathoracicpressuretofall,sothatthenowincreased
transmuralpressurestretchestheaorta,stimulatingtheaorticbaroreceptorsandtriggering
areflexactivationofthevagusnerve(seeChapter23).Alternatively,massageofthe
bifurcationofthecarotidarteryintheneckdirectlystretchesthewallofthecarotidsinus,
therebystimulatingthebaroreceptors.Therefore,byeithermaneuver,thebaroreceptor
outputsignalsbrainstemcenterstostimulatethevagusnerve,therebyslowingtheheart.
 Digitaliscompounds(seeChapter5)mayalsobeusedtotreatsupraventriculartachycardias
becausethesedrugsmayincreasevagaltoneanddecreasesympathetictone,therebyslowing
theconductionofatrialimpulsesthroughtheAVnode.Patientswithcongestiveheartfailure
mayhavealowbaselinevagaltoneandahighbaselinesympathetictone.Inthesepatients,
digitalislikedrugsincreasemyocardialcontractility(seeChapter22)andcardiacoutput,

causingareflexincreaseinvagaltone.

VagalManeuvers

BecausetheECGmachineuseselectrodesattachedtotheskintomeasurethesumofthe
heart'selectricalactivity,itrequiresspecialamplifiers.TheECGmachinealsohaselectricalfilters
thatreducetheelectricalnoise.Movinglimbs,breathing,coughing,shivering,andfaultycontact
betweentheskinandanelectrodeproduceartifactsontherecordedECG.

Becausethemovementofcharge(i.e.,thespreadingwaveofelectricalactivityintheheart)has
bothathreedimensionaldirectionandamagnitude,thesignalmeasuredonanECGisa
vector.Thesystemthatcliniciansusetomeasuretheheart'sthreedimensional,timedependent
electricalvectorissimpletounderstandandeasytoimplement,butitcanbechallengingto
interpret.

Apairofelectrocardiogramelectrodesdefinesalead
Torecordthecomplicatedtimedependentelectricalvectoroftheheart,thephysicianorECG
technicianconstructsasystemofleadsintwoplanesthatareperpendiculartoeachother.One
plane,thefrontalplane,isdefinedbythesixlimbleads(Fig.218A(f8)).Aperpendicular
transverseplaneisdefinedbythesixprecordialleads(Fig.218B(f8)).Eachleadisanaxis
inoneofthetwoplanes,ontowhichtheheartprojectsitselectricalactivity.TheECGrecording
fromasingleleadshowshowthatleadviewsthetimedependentchangesinvoltageoftheheart.
Figure218
TheECGleads.

OlderECGmachinesrecordeddatafromthe12leadsoneatatime,sequentially.Thus,relatively
rareeventscapturedbytherecordinginoneleadmightnotbereflectedinanyoftheothers,which
wereobtainedatdifferenttimes.ModernECGmachinesobtainleadssynchronouslyingroupsof3
or12.Becausetherealelectricalvectoroftheheartconsistsofjustonetimedependentvector
signal,youmightthinkthatathreeleadrecordingwouldsufficetolocalizethevectorsignalin
space.Inprinciple,thisistrue:onlytwoleadsinoneplaneandoneleadinanotherplaneare
neededtofullydefinetheoriginalelectricalvectoroftheheartatallmoments.However,recording
fromall12leadsisextremelyusefulbecauseasignalofinterestmaybeeasiertoseeinonelead
thaninanother.Forexample,anacutemyocardialinfarctioninvolvingtheinferior
(diaphragmatic)portionoftheheartmightbeeasilyvisualizedinleadsII,III,andaVFbutgo
completelyundetected(orproducesocalledreciprocalchanges)intheotherleads.

TheLimbLeads
Oneobtainsa12leadECGbyhavingthepatientrelaxinasupinepositionandconnectingfour
electrodestothelimbs(Fig.218A(f8)).Electrically,thetorsoandlimbsareviewedasan
equilateraltriangle(Einthoven'striangle)withonevertexonthegroinandtheothertwoonthe
shoulderjoints(Fig.219A(f9)).Becausethebodyisanelectricalvolumeconductor,an
electricalattachmenttoanarmiselectricallyequivalenttoaconnectionattheshoulderjoint,and
anattachmenttoeitherlegisequivalenttoaconnectionatthegroin.Byconvention,theleftleg
representsthegroin.Thefourthelectrode,connectedtotherightleg,isusedforelectrical
grounding.Thethreeinitiallimbleadsrepresentthedifferencebetweentwoofthelimb
electrodes:

I(positiveconnectiontoleftarm,negativeconnectiontorightarm).Thisleaddefinesan
axisinthefrontalplaneat0degrees(Fig.219A,B(f9)).

II(positivetoleftleg,negativetorightarm).Thisleaddefinesanaxisinthefrontalplaneat
60degrees.

III(positivetoleftleg,negativetoleftarm).Thisleaddefinesanaxisinthefrontalplaneat
120degrees.

Figure219
Axesofthelimbleads.A,Thefrontalplanelimbleadsbehaveasiftheyarelocatedattheshoulders(RA,
rightarmLA,leftarm)andgroin(LL,leftleg).LeadsI,II,andIIIareseparatedfromoneanotherby60
degrees.Theaugmentedleads,referencedtothecenteroftheheart,bisecteachofthe60degreeangles
formedbyleadsI,II,andIII.B,Translatingeachofthesixfrontalleadssothattheypassthroughacommon
pointdefinesapolarcoordinatesystem,providingviewsoftheheartat30degreeintervals.

Anelectronicreconstructionofthethreelimbconnectiondefinesanelectricalreferencepointin
themiddleoftheheart(Fig.219A(f9))thatconstitutesthenegativeconnectionforthe
augmentedunipolarlimbleadsandforthechestleads.Thethreeaugmentedunipolarlimbleads
compareonelimbelectrodetotheaverageoftheothertwo:

aVR(positiveconnectiontorightarm,negativeconnectioniselectronicallydefinedinthe
middleoftheheart).Theaxisdefinedbythislimbleadinthefrontalplaneis150degrees(
Fig.219B(f9)).Theastandsforaugmented,andtheVrepresentsunipolar.

aVL(positivetoleftarm,negativeismiddleoftheheart).Theaxisdefinedbythislimblead
inthefrontalplaneis30degrees

aVF(positivetoleftleg[foot],negativeismiddleoftheheart).Theaxisdefinedbythislimb
leadinthefrontalplaneis+90degrees.
Thus,thepositiveandnegativeendsofthesesixleadsdefineaxesevery30degreesinthefrontal
plane(Fig.219B(f9)).

ThePrecordialLeads
Theseleadslieinthetransverseplane,perpendiculartotheplaneofthefrontalleads.Thepositive
connectionisoneofsixdifferentlocationsonthechestwall(Fig.218B(f8)),andthenegative
connectioniselectronicallydefinedinthemiddleoftheheartbyaveragingofthethreelimb
electrodes.TheresultantleadsarenamedV1toV6,wheretheVstandsforunipolar:

V1:fourthintercostalspacetotherightofthesternum

V2:fourthintercostalspacetotheleftofthesternum

V4:fifthintercostalspaceatthemidclavicularline

V3:halfwaybetweenV2andV4

V6:fifthintercostalspaceatthemidaxillaryline

V5:halfwaybetweenV4andV6

Itisalsopossible,onrareoccasions,toobtainspecialleadsbyemployingthesamenegative
connectionusedfortheunipolarlimbandprecordialleadsandapositiveprobeconnection.
Specialleadsthatareusedincludeesophagealleadsandanintracardiaclead(e.g.,thatusedto
obtainarecordingfromtheHisbundle).

Asimpletwocellmodelcanexplainhowasimpleelectrocardiogramcanarise
WecanillustratehowtheECGarisesfromthepropagationofactionpotentialsthroughthe
functionalsyncytiumofmyocytesbyexaminingtheelectricalactivityintwoneighboringcardiac
cells,AandB,connectedbygapjunctions(Fig.2110A(f10)).Thedepolarizationandaction
potentialbeginfirstincellA(VAinFig.2110A,greenrecord(f10)).ThecurrentfromcellAthen
depolarizescellBthroughthegapjunctionsandabrieftimelatertriggersanactionpotentialin
cellB(VB).IfwesubtracttheVBrecordfromtheVArecord,weobtainarecordofthe

intracellularvoltagedifferenceVAVB(Fig.2110B(f10)).
Figure2110
TwocellmodeloftheECG.

WehavealreadyseenthataccordingtoOhm'slaw(Equation211(formula1)),theintracellular
currentfromcellAtocellB(IAB)isproportionalto(VAVB).Theextracellularcurrentflowing
fromtheregionofcellBtotheregionofcellAisequalbutoppositeindirectiontotheintracellular
currentflowingfromcellAtocellB.Imaginethatanextracellularvoltmeterhasitsnegative
electrodeplacedtotheleftofcellAanditspositiveelectrodetotherightofcellB(formingalead
withanaxisof0degrees).DuringtheupswingintheactionpotentialofcellA,whilecellBisstill
atrest,(VAVB)andIABarebothpositive,andthevoltmeterdetectsapositivedifferencein
voltage(Fig.2110C(f10))analogoustotheQRScomplexinarealECG.Later,duringthe
recoveryfromtheactionpotentialincellA,whilecellBisstilldepolarized,(VAVB)andIABare
bothnegative,andthevoltmeterwoulddetectanegativedifferenceinvoltage.Fromthe
extracellularvoltagedifferenceinFigure2110C(f10),wecanconcludethatwhenthewaveof
depolarizationmovestowardthepositivelead,thereisapositivedeflectionintheextracellular
voltagedifference.

Ifweplacethetwoelectrodesatthejunctionbetweenthetwocells,withthepositiveconnection
onthebottomandthenegativeconnectiononthetop,wecreatealeadwithanaxisof90degrees
tothedirectionofcurrentflow(Fig.2110D(f10)).Undertheseconditions,weobservenovoltage
differencebecausebothextracellularelectrodessensethesamevoltageateachinstantintime.
Thus,whenaleadisperpendiculartothewaveofdepolarization,themeasureddeflectiononthat
leadisisoelectric.
Ifweputourextracellularelectrodesinyetathirdconfigurationwiththepositiveelectrodeon
theleftandthenegativeelectrodeontherightweobserveanegativedeflectionduringthe
depolarizationofcellAbecausethewaveofdepolarizationismovingawayfromthepositive
electrode(Fig.2110E(f10)).

Thissimpletwocellmodeldemonstratesthatthewaveofdepolarizationbehaveslikeavector,
withbothmagnitudeanddirection.Twopracticalmethodstodeterminethedirection(oraxis)of
thevectorarepresentedinthebox,BasicInterpretationoftheElectrocardiogram.

TheQRSequivalentintheextracellularvoltagerecordofoursimplistictwocellanalysisisdueto
aspreadingwaveofdepolarization.TheTwaveequivalentisnegativecomparedwiththeQRS
equivalent,anditreflectsthewaveofrepolarization.IfcellAhasanactionpotentialthatismuch
longerthancellB(sothatpositivecurrentagainpropagatesfromAtoBaftertheactionpotential
inBiscompleted),thentheTwaveequivalentwillbeupright,asitisinmostECGs.Thus,on
average,theventricularmyocytesthatdepolarizelastarethefirsttorepolarize.Inotherwords,
theBcellshaveshorteractionpotentialsthantheAcells.

WhathappenedtothePwavethatweseeinarealECG?ThePwavereflectsthedepolarizationof
theatrialmyocytes.Inourmodel,wecouldrepresentthePwavebyintroducingasecondpairof
myocytes(i.e.,theatrialcells)andallowingthemtofiretheiractionpotentialsmuchearlierthan
thetwoventricularmyocytes.

CARDIACARRHYTHMIAS
Anychangeincardiacrhythmfromthenormalsinusrhythmisdefinedasanarrhythmia.
Althoughsomearrhythmiasarepathologicalandevenlifethreatening,othersarenormaland
appropriatelyadaptive,includingsinustachycardiaandsinusarrhythmia.

Sinustachycardiaisaheartratefasterthannormal,drivenbythesinusnode.Thisarrhythmia
isseeninfrightenedorstartledindividualsorduringnormalexercise.Rarely,sinustachycardia
canbepathological,forexample,inpatientswithacutehyperthyroidism(seeChapter49).

AnECGprovidesadirectmeasurementoftherate,rhythm,andtimedependentelectrical
vectoroftheheart.Italsoprovidesfundamentalinformationabouttheoriginand
conductionofthecardiacactionpotentialwithintheheart.Becausethedifferentpartsofthe
heartactivatesequentially,wecanattributethetimedependentchangesintheelectrical
vectorofthehearttodifferentregionsoftheheart.ThePwavereflectstheatrial
depolarization.TheQRScomplexcorrespondstoventriculardepolarization.TheTwave
reflectsventricularrepolarization.

ECGpaperhasagridofsmall1mmsquareboxesandlarger5mmsquareboxes.The
verticalaxisiscalibratedat0.1mV/mmthehorizontal(time)axis,at0.04s/mm(small
box)or0.2s/5mm(largebox).Thus,fivelargeboxescorrespondto1.0second(Fig.2111
(f11)).Table215(cetable5)summarizesthestepsforinterpretationofanECG.
 Figure2111
Anormal12leadECGrecording.Therecordingswereobtainedsynchronously,threeleadsata
time(I,II,andIIIsimultaneouslyaVR,aVL,andaVFsimultaneouslyV1,V2,andV3

simultaneouslyandV4,V5,andV6simultaneously).A1mV,200mscalibrationpulseisvisible
ontheleftofeachofthethreerows.Theleadsaremarkedonthetraces.(WethanktheDivisionof
Cardiology,UniversityofMarylandSchoolofMedicine,forobtainingthisECGrecordingfromthe
author.)

Table215
ApproachforReadinganECG

1. SearchforPwaves.

2. DeterminetherelationshipofPwavesandQRScomplexes.

3. Identifypacemaker.

4. Measuretheheartratesfromdifferentwaves(e.g.,PPinterval,RRinterval).

5. CharacterizeQRSshape(i.e.,narrowversuswide).
6. ExaminefeaturesofSTsegment.

7. EstimatethemeanQRSaxis(andtheaxesoftheotherwavesofinterest).

8. Examinethecardiacrhythm(e.g.,lookata20to30sECGrecordfromleadII).

Rate
Wecanmeasurerateintwoways.Thedirectmethodistomeasurethenumberofseconds
betweenwavesofthesametype,forexample,theRRinterval.Thequotientof60dividedby
theintervalinsecondsistheheartrateinbeatsperminute:

Rate (beats/ min) = (60s/ min) / (R Rinterval (s/beat))

Aquick,alternativemethodisquitepopular(Table216(cetable6)).Measurethenumberof
largeboxesthatformtheRRintervalandremembertheseries:300,150,100,75,60,50
whichcorrespondstoanintervalof1,2,3,4,5,or6largeboxes.Thus,

Rate = 300/ (numberoflargeboxes)

Table216
DeterminationofHeartRatefromtheECG

RRInterval(innumberoflargeboxesof0.2 Calculation HeartRate(beatsper

s) minute)

1 300/1 300

2 300/2 150

3 300/3 100

4 300/4 75

5 300/5 60

6 300/6 50

Forexample,if4largeboxesseparatetheRwaves,theheartrateis75beats/min.

Rhythm
Thedeterminationofrhythmismorecomplex.Onemustanswerthefollowingquestions:
Whereistheheart'spacemaker?Whatistheconductionpathfromthepacemakertothelast
cellintheventricles?Isthepacemakerfunctioningregularlyandatthecorrectspeed?The
normalpacemakeristheSAnodethesignalthenpropagatesthroughtheAVnodeand
activatestheventricles.Whentheheartfollowsthispathwayatanormalrateandinthis

sequence,therhythmiscalledanormalsinusrhythm.
Carefulexaminationoftheintervals,durations,andsegmentsintheECGtracingcanreveal
agreatdealabouttheconductedactionpotential(Fig.217(f7)).ThePwaveduration
indicateshowlongatrialdepolarizationtakes.ThePRintervalindicateshowlongittakes
theactionpotentialtoconductthroughtheAVnodebeforeactivatingtheventricles.The
QRSdurationrevealshowlongittakesforthewaveofdepolarizationtospread
throughouttheventricles.TheQTintervalindicateshowlongtheventriclesremain
depolarizedandisthusaroughmeasureofthedurationoftheoverallventricularaction
potential.TheQTsegmentgetsshorterastheheartrateincreases,reflectingtheshorter
actionpotentialsthatareobservedathighrates.Inaddition,manyotheralterationsinthese
wavesandthesegmentsseparatingthemreflectimportantphysiologicaland
pathophysiologicalchangesintheheart.

Vector(orAxis)ofaWaveintheFrontalPlane
Determinationofthevectorofcurrentflowthroughtheheartisnotjustanintellectual
exercisebutcanbeofgreatclinicalimportance.Thenormalaxisofventricular
depolarizationinthefrontalplaneliesbetween30and+90degrees.However,thisaxiscan
changeinanumberofpathologicalsituations,includinghypertrophyofoneorboth
ventricularwalls(acommonsequelaofsevereorprolongedhypertension)andconduction
blocksinoneorseveraloftheventricularconductingpathways.

Wecanusetwoapproachestomeasuretheaxisofawavewithinthefrontalplane(i.e.,with
useoflimbleads).Thefirstismoreaccurate,butthesecondisquickerandeasierandis
usuallysufficientforclinicalpurposes.

Thefirstapproachisageometricmethod.Itusesourknowledgeoftheaxesofthe
differentleadsandthemeasuredmagnitudeofthewaveprojectedontoatleasttwoleadsin
thefrontalplane.Itinvolvesfivesteps:

Step1:MeasuretheheightofthewaveontheECGrecordsintwoleads,usingany
arbitraryunit(e.g.,numberofboxes).Apositivedeflectionisonethatrisesabovethe
baseline,andanegativedeflectionisonethatfallsbelowthebaseline.Intheexample
inFigure2112A(f12),weareestimatingtheaxisoftheRwaveoftheQRScomplex.The
Rwaveis+2unitsinleadIIand1unitinleadaVR.
 Figure2112
EstimationoftheECGaxisinthefrontalplane.

Step2:Marktheheightofthemeasureddeflectionsonthecorrespondingleadlines
onacircleofaxes.Anyunitofmeasurewillsuffice,aslongasyouusethesameunitfor
bothmarkings.Startingatthecenterofthecircle,markapositivedeflectiontoward
thearrowheadandanegativedeflectiontowardthetailofthearrow.

Step3:Drawlines,perpendiculartotheleadaxes,througheachofyourtwomarks.

Step4:Connectthecenterofthecircleofaxes(tailofvector)totheintersectionof
thetwoperpendicularlines(headofvector).Inourexample,theintersectioniscloseto
theaVFaxis.

Step5:EstimatetheaxisofthevectorthatcorrespondstotheRwave,usingthe
anglescaleofthecircleofaxes.Inthiscase,thevectorisatabout95degrees,just
clockwisetotheaVFlead(i.e.,90degrees).

Thesecondapproachisaqualitativeinspectionmethod.Itexploitsthevarying
magnitudesofthewaveofinterestinrecordingsfromdifferentleads.Whenthewaveis
isoelectric(i.e.,nodeflection,orequalpositiveandnegativedeflections),thentheelectrical
vectorresponsibleforthatprojectionmustbeperpendiculartotheisoelectriclead,aswe
alreadysawforthetwocellmodelinFigure2110D(f10).Theinspectionapproachrequires
twosteps:

Step1:Identifyaleadinwhichthewaveofinterestisisoelectric(ornearly
isoelectric).IntheexampleinFigure2112B(f12),theQRScomplexisisoelectricinaVL
(30degrees).Thevectormustbeperpendicular(ornearlyperpendicular)tothat
lead(i.e.,aVL).Inourexample,thevectormustpoint90degreesfrom30degrees
andthereforeisateither+60degreesor120degrees.Becausetheleadsinthefrontal
planedefineaxesevery30degrees,everyleadhasanotherleadtowhichitis
perpendicular.

Step2:Identifyaleadinwhichthewaveislargelypositive.InFigure2112B
(f12),thiswouldbeleadII.Thevectormustlieroughlyinthesamedirectionasthe

orientationofthatlead.BecauseleadIIisat+60degrees,theaxisofthevectorofthe
QRSwavemustbeabout+60degreesandnot120degrees.
 Ifthewaveofinterestisnotisoelectricinanylead,thenfindtwoleadsontowhichthe
projectionsareofsimilarmagnitudeandsign.Thevectorhasanaxishalfwaybetweenthose
twoleads.

BasicInterpretationoftheElectrocardiogram

Sinusarrhythmiaisthenamegiventoanormalphenomenon:asubtlechangeinheartrate
thatoccurswitheachrespiratorycycle.Inspirationacceleratestheheartrate(seeChapter19)
expirationslowsit.Deepeningoftherespirationsexaggeratesthesecyclicchanges.Themagnitude
oftheeffectcanvarysignificantlyamongindividuals.Theheartrateisstillunderthecontrolof
theSAnode,butcyclicvariationsinsympatheticandparasympathetictonemodulatetheSA
node'spacemakerrate.Thelossofsinusarrhythmiacanbeasignofautonomicsystem
dysfunction,asmaybeseeninpatientswithdiabetes.

Althoughthelistofpathologicalarrhythmiasislong,twobasicproblemsareresponsiblefornearly
allarrhythmias:alteredconductionandalteredautomaticity.

Conductionabnormalitiesareamajorcauseofarrhythmias
Disturbancesofconductionmakeupthefirstmajorcategoryofcardiacarrhythmias.Conduction
disturbancescanhavemultiplecausesandcanoccuratanypointintheconductionpathway.
Conductiondisturbancescanbepartialorcomplete.Thetwomajorcausesofconduction
disturbancesaredepolarizationandabnormalanatomy.

Ifatissueisinjured(e.g.,bystretchoranoxia),analteredbalanceofioniccurrentscanleadtoa
depolarization.Thedepolarization,inturn,partiallyinactivatesINaandICa,slowingthe
spreadofcurrent(i.e.,slowingconduction).Asaresult,thetissuemaybecomelessexcitable
(partialconductionblock)orcompletelyinexcitable(completeconductionblock).

Anothertypeofconductiondisturbanceisthepresenceofanaberrantconductionpathway,
reflectingabnormalanatomy.Onesuchexampleisanaccessoryconductionpathwaythat
rapidlytransmitstheactionpotentialfromtheatriatotheventricles,bypassingtheAVnode,
whichnormallyimposesaconductiondelay.PatientswiththecommonWolffParkinsonWhite
syndromehaveabypasspathwaycalledthebundleofKent.Theexistenceofasecondpathway
betweentheatriaandventriclespredisposesaffectedindividualstosupraventriculararrhythmias
(seeAccessoryConductionPathways).

Anacutemyocardialinfarction,orheartattack,beginswiththeocclusionofacoronary
artery.Theregionofmyocardiumsubservedbythatcoronaryarteryisdeprivedofoxygen
andwilldieunlessbloodflowresumesshortly.Duringtheinitialstages,themyocardialcells
areelectricallyactivebuttheirfunctionisimpaired,producingcharacteristicchangesinthe
ECG.Completebuttransientblockadeofbloodflowtothemyocardiumeventhoughit
doesnotleadtocelldeathmayleadtoapatternofECGchangessimilartothatseenduring
theacutephaseofmyocardialinfarction.Becausebloodflowisregional,theareasof
infarctionarealsoregional.Thus,thephysiciancanbestobservethechangesinelectrical
activitybyexaminingthespecificECGleadsthatprovidethebestviewoftheinvolvedregion
ofmyocardium.

Thefirstelectricalchangeassociatedwithanacutemyocardialinfarctionispeakingofthe
Twaves,followedsoonafterbyTwaveinversion.TheseTwavechangesarenot
specificforinfarctionandarereversibleifbloodflowisrestored.

Thenextchange,andonethatismorecharacteristicofanacutemyocardialinfarction,is
elevationoftheSTsegment.Thischangeoccursbecausethemyocytesclosesttothe
epicardiumbecomedepolarizedbythecellularanoxicinjury,buttheyarestillelectrically
coupled.Returningtothetwocellmodel(Fig.2113A(f13)),considerthecellontheleft(cell
A)tobenormalandthecellontheright(cellB)tobedamaged.Figure2113B(f13)showsthe
extracellularcurrent,whichisproportionaltothedifferencesintheactionpotentialsofthe
twocellsshowninFigure2113A(f13).BecausecellBhasamorepositiverestingpotential
thancellAbutthesameplateauduringtheactionpotential,thedifferenceinvoltage
betweencellAandcellBisdepressedeverywherebutattheSTsegmentmakingtheST
segmentappearelevated.ThisisalsotheECGchangethatoneviewswithanacute
myocardialinfarction.

Figure2113
Twocellmodelofamyocardialinfarction.A,ThedamagedcellB(bluerecord)hasalowerresting
potential,buttheplateauofitsactionpotentialisatthesamelevelasthenormalcellA(green
record).B,AftertherecordsinAaresubtracted,theapparentelevationofSTsegmentisthesame
asthedifferenceinrestingpotentialstheTPandPRregionsareactuallydepressed.

BriefperiodsofcoronaryarteryspasmcanalsoproduceSTelevation,presumablybythe
samemechanism.Rapidreperfusionofcoronaryarteriesafteracuteblockagemayleadto
rapidandcompleterecoveryofthemyocardialcells,asindicatedbytheevanescentnatureof
theECGchanges.

Ischemiawithoutcelldeathduetoafixeddegreeofocclusion(e.g.,thatcausedbya
thrombusoratherosclerosis)isoftenassociatedwithchangesintheECG,typicallyST
segmentandTwavechanges.However,thesechangesarequitevariable,presumably
broughtaboutbyalteredactionpotentialdurationintheaffectedregions.Patients
 experiencingexertionalchestpain(angina)duetodiminishedcoronarybloodflow
frequentlyhaveECGchangesduringtheanginalepisodethatincludeSTsegment
depressionandTwaveinversion.

Withirreversiblecelldeath,theECGtypicallyshowstheevolutionofdeepQwaves(a
largenegativedeflectionatthebeginningoftheQRScomplex).Qwavesdeveloponlyin
thoseleadsoverlyingorneartheregionoftheinfarction.TheQwavesindicateanareaof
myocardiumthathasbecomeelectricallysilent.Becauseactionpotentialscannotpropagate
intotheinfarctedarea,thenetvectoroftheremainingareasofventriculardepolarization
bydefaultpointsawayfromthisarea.TheresultisadeepnegativedeflectionontheECG
intheappropriateleads.Thus,aninferiorwallinfarctioninscribesdeepQwavesinleadsII,
III,andaVF.Aninfarctionaffectingthelarge,muscularanteriorwalloftheheartwill
inscribedeepQwavesinsomeoftheprecordialleads(V1throughV6).

NotallinfarctionscreatedeepQwavestheonlyvisiblechangesmaybeTwaveinversion
andSTsegmentdepression.Clinically,theseinfarctionsbehavelikeincompleteinfarctions,
andpatientsareatriskofasecond,completingevent.Therefore,thesepatientsare
investigatedandtreatedaggressivelytopreventfurtherinfarction.

MyocardialInfarction

Partial(orIncomplete)ConductionBlock
Threemajortypesofpartialconductionblockexist:slowedconduction,intermittentblock,and
unidirectionalblock.Wedeferthediscussionofunidirectionalblockuntilweconsiderreentry
phenomena.

Inslowedconduction,thetissueconductsalltheimpulses,butmoreslowlythannormal.
FirstdegreeAVblockreflectsaslowingofconductionthroughtheAVnode.OnanECG,first
degreeAVblockappearsasanunusuallylongPRinterval(compareAandBofFig.2114(f14)).
Figure2114
PathologicalECGs.InE,rightbundlebranchblockisvisibleintheV1orV2precordialleadsleftbundle

branchblockisvisibleintheV5orV6leads.

(DatafromChernoffHM:WorkbookinClinicalElectrocardiography.NewYork,Medcom,1972.)

Asecondexampleofpartialconductionblockisintermittentblock,inwhichthetissue
conductssomeimpulsesbutnotothers.IntheAVnode,intermittentblockleadstosecond
degreeAVblock,ofwhichtherearetwotypes.Bothreflectincomplete(i.e.,intermittent)
couplingoftheatriatotheventricles.InaMobitztypeIblock(orWenckebachblock),thePR
intervalgraduallylengthensfromonecycletothenextuntiltheAVnodefailscompletely,skipping
aventriculardepolarization(Fig.2114C(f14)).WithMobitztypeIblock,itismostcommontosee
everythirdorfourthatrialbeatfailtoconducttotheventricles.InaMobitztypeIIblock,the
PRintervalisconstantfrombeattobeat,buteverynthventriculardepolarizationismissing.In
Figure2114D(f14),thefirstcardiaccycleisnormal.However,thesecondPwaveisnotfollowedby
aQRSorT.Instead,theECGrecordisflatuntilthethirdPwavearrivesattheexpectedtime,
followedbyaQRSandaT.Thus,wesaythateverysecondQRSisdropped(2:1block).

Anotherformofintermittentconductionblock,calledratedependentblock,reflectsdisease
oftenseeninthelargebranchesoftheHisPurkinjefibersystem(i.e.,thebundlebranches).When
theheartrateexceedsacriticallevel,theventricularconductionsystemfails,presumablybecause
apartoftheconductingsystemlackssufficienttimetorepolarize.Withintermittentfailureofthe
HisPurkinjefibersystem,theimpulseislefttospreadslowlyandinefficientlythroughthe
ventriclesbyconductingfromonemyocytetothenext.Suchafailure,whetherintermittentor
continuous,isknownasabundlebranchblockandappearsontheECGasanintermittently
wideQRScomplex(Fig.2114E(f14)).Becausethisblockimpairsthecoordinatedspreadofthe
actionpotentialthroughouttheventricles,theresultingcontractionlosessomeefficiency.

CompleteConductionBlock
Incompleteblock,orthirddegreeAVblock,noimpulsesconductthroughtheaffectedarea,
ineitherdirection.Forexample,completeblockattheAVnodestopsanysupraventricular
electricalimpulsefromtriggeringaventricularcontraction.Thus,AVnodalblockelectrically
severstheatriaandventricles,eachofwhichbeatsundercontrolofitsownpacemakers.This
situationiscalledAVdissociation.Theonlyventricularpacemakersthatareavailableto
initiatecardiaccontractionarethePurkinjefibercells,whicharenotoriouslyunreliableandslow.
Thus,cardiacoutputmayfall,andbloodpressurealongwithit.AVdissociationcantherefore
constituteamedicalemergency,andplacementofanartificialventricularpacemakercanprove
lifesaving.OnanECG,completeblockappearsasregularlyspacedPwaves(i.e.,theSAnode
properlytriggerstheatria)andasirregularlyspacedQRSandTwavesthathavealowfrequency
andnofixedrelationshiptothePwaves(Fig.2114F(f14)).

Reentry
Anindependentfocusofpacemakeractivitycandevelopasaconsequenceofaconduction
disturbance.Thisclassofconductiondisturbanceiscalledreentry(orreentrantexcitationor
circusmovement).Itisoneofthemajorcausesofclinicalarrhythmias.Itoccurswhenawaveof
depolarizationtravelsinanapparentlyendlesscircle.Reentryhasthreerequirements:(1)a
closedconductionloop,(2)aregionofunidirectionalblock(atleastbriefly),and(3)asufficiently
slowconductionofactionpotentialsaroundtheloop.

Beforefurtherconsideringreentry,weneedtodiscussaconductiondefectthatisessentialforre
entryunidirectionalblock.Unidirectionalblockisatypeofpartialconductionblockinwhich
impulsestravelinonedirectionbutnotintheoppositeone.Unidirectionalblockmayariseasa
resultofalocaldepolarizationormaybeduetopathologicalchangesinfunctionalanatomy.
Normalcardiactissuecanconductimpulsesinbothdirections(Fig.2115A(f15)).However,after
anasymmetricanatomicallesiondevelops,manymorehealthycellsmayremainononesideofthe
lesionthanontheother.Whenconductionproceedsinthedirectionfromthemanyhealthycells
tothefewhealthycells,thecurrentfromthemanymaybesufficienttoexcitethefew(righttoleft
inFig.2115B(f15)).Ontheotherhand,whenconductionproceedsintheoppositedirection,the
fewhealthycellscannotgenerateenoughcurrenttoexcitetheregionofmanyhealthycells(leftto
rightinFig.2115B(f15)).Theresultisaunidirectionalblock.
Figure2115
Abnormalconduction.

Wereturnnowtotheproblemofreentry.Imaginethatanimpulseistravelingdownabifurcating
Purkinjefiberandisabouttoreachagroupofventricularmyocytesaclosedconductionloop(
Fig.2115C(f15)).However,therefractoryzonespreventthereentryofimpulsesfromtherightto
theleft,andviceversa.Wenowintroducealesionthatcausesaunidirectionalconductionblockin
theleftbranchofthePurkinjefiber.Whentheimpulsereachestheforkintheroad,itspreadsin
bothdirections(Fig.2115D,step1(f15)).However,theimpulsecannotcontinuepastthe
unidirectionalblockintheleftbranch.Theimpulsetravelingdowntherightbranchstimulatesthe
distalconductingcells(Fig.2115D,step2(f15)),leavingtheminaneffectiverefractoryperiod.
Whentheimpulsereachestheventricularmuscle,itbeginstotravelbacktowardthedamagedleft
branch(step3).Atthispoint,thecellsinthenormalrightbranchmaystillberefractoryto
excitation.Theimpulsefinallyreachesthedamagedleftbranchandtravelsinaretrogradefashion
upthisbranch,reachingandpassingthroughtheregionoftheunidirectionalconductionblock
(step4).Finally,theimpulseagainreachesthebifurcation(step5).Becauseenoughtimehas
elapsedforthecellsatthebifurcationaswellasintherightbranchtorecoverfromtheir
refractoryperiod,theimpulsecannowtravelretrogradeupthemainpartofthePurkinjefiberas
wellasorthogradedowntherightbranchforasecondtime.

Ifthisreentrantmovement(steps252,andsoon)continues,thefrequencyofreentrywill
generallyoutpacetheSAnodalpacemaker(frequencyofstep1)andisoftenresponsiblefor
diversetachyarrhythmiasbecausethefastestpacemakersetstheheartrate.Reentryexcitation
mayberesponsibleforatrialandventriculartachycardia,atrialandventricularfibrillation,and
manyotherarrhythmias.Reentrycanoccurinbigloops(Fig.2115D(f15))orinsmallloops
consistingentirelyofmyocardialcells.

AccessoryConductionPathways
AccessoryConductionPathways
TheWolffParkinsonWhite(WPW)syndrome,brieflymentionedearlier,isacommon
exampleofanaccessoryconductionpathway,whichinthiscaseprovidesashortcircuit(i.e.,
bundleofKent)aroundthedelayintheAVnode.Thefastaccessorypathwayiscomposednotof
Purkinjefibersbutinsteadofmusclecells.Itconductstheactionpotentialdirectlyfromtheatria
totheventricularseptum,depolarizingsomeoftheseptalmuscleearlierthanifthedepolarization
hadreacheditbytheslower,normalAVnodalpathway.Asaresult,ventriculardepolarizationis
morespreadoutintimethanisnormal,givingrisetoabroaderthannormalQRScomplex.The
generaldirectionofventriculardepolarizationisreversed,sothattheeventsnormallyunderlying
theQwaveoftheQRScomplexhaveanaxisoppositetothatnormallyseen.Thisearly
depolarization,orpreexcitation,appearsasasmall,positivedeltawaveatthebeginningof
theQRScomplex(Fig.2114G(f14)).Inaddition,becausethetimebetweenatrialdepolarization
andventriculardepolarization(i.e.,beginningofdeltawave)isshortened,theintervalbetweenthe
PwaveandtheQRScomplexisshortened.

TheaberrantconductionpathwayinWPWsyndromealsoestablishesaloopthatmaymeetthe
requirementsforreentryandmaythereforebeassociatedwithasupraventricular
tachycardia.Althoughingeneralabenigncondition,WPWsyndromeisassociatedwithatleast
oneattackofsupraventriculartachycardiainatleast50%ofaffectedindividuals.Thetwomost
commonsupraventriculartachycardiasseeninthispopulationareparoxysmalsupraventricular
tachycardiaandatrialfibrillation(describedlater).Paroxysmalsupraventricular
tachycardia(PSVT)isaregulartachycardiawithaventricularrateusuallyexceeding150beats
perminute.Becauseventriculardepolarizationstilloccursthroughthenormalconducting
pathways,theQRScomplexappearsnormal.

If,duringanepisodeofPSVT,theconductiondirectionforreentryisinthereversedirection(i.e.,
downtheaccessorypathwayandbackupthroughtheAVnode),theQRSshapemaybeunusual.
ThisarrangementmayproduceaPSVTwithwideandbizarreQRScomplexesbecauseventricular
depolarizationdoesnotoccuralongthenormalbundlebranches.Asmallnumberofpeoplewith
WPWsyndromehavemorethanoneaccessorypathway,sothatmultiplereentryloopsare
possible.

Fibrillation
Infibrillation,manyregionsofreentrantelectricalactivityarepresent,creatingelectricalchaos
thatisnotassociatedwithusefulcontraction.Atrialfibrillation(Fig.2114H(f14))iscommonly
foundinelderlypatients,sometimeswithmitralvalveorcoronaryarterydisease,butoften
withoutanyevidenceofunderlyingcardiacdisease.Thereentryloopwithintheatriamoves
wildlyandrapidly,generatingarapidsuccessionofactionpotentialsasmanyas500perminute.
Thiswanderingreentrycircuiteasilybecomesthefastestpacemakerintheheart,outpacingthe
SAnodeandbombardingtheAVnode.Fortunately,theAVnodecannotrepolarizefastenoughto
passalongalloftheseimpulses.Onlysomemakeitthroughtotheventricles,resultinginthe
irregularappearanceofQRScomplexeswithoutanydetectablePwaves.Thebaselinebetween
QRScomplexesmayappearstraightormayshowsmall,rapidfluctuations.Althoughonlysome
atrialimpulsesreachtheventricles,theventricularratecanstillbequitehigh.
Becausetheatriafunctionmainlyasaboosterpump(seetheboxonatrialcontractioninChapter
22),manypatientstolerateatrialfibrillationwithoutharmandmayevenbeunawarethatthey
haveit.Othersmaysuffergreatlyfromthelossofacoordinatedatrialcontraction,particularlythe
elderlyorthosewithcoexistingcardiacdisease.Ifpossible,attemptsshouldbemadetoconvert
mostindividualsbacktonormalsinusrhythmbyeitherelectricalorchemicalmeans.Ifthisisnot
possible,thenattemptscanbemadetoatleastslowconductionthroughtheAVnode.For
example,digitaliscompoundsincreaseparasympatheticanddecreasesympatheticstimulationto
theAVnode,decreasingthespeedofAVconductionandthusreducingtheventricularrate.
AdrenergicblockersorCa2+channelblockersarealsousedtocontrolventricularrate.

Ventricularfibrillation(Fig.2114I(f14))isalifethreateningmedicalemergency.Theheart
cannotgeneratecardiacoutputbecausetheventriclesarenotabletopumpbloodwithouta
coordinatedventriculardepolarization.

Alteredautomaticitycanoriginatefromthesinusnodeorfromanectopic
locus
Theautomaticityofanycardiactissuecanchange.Pacemakercellscanexperienceanalterationor
evenacompleteabsenceofautomaticity.Conversely,othercellsthatnormallyhaveno
automaticity(e.g.,ventricularmuscle)canbecomeectopicpacemakers.Thesedisturbancesof
automaticitymakeupthesecondmajorcategoryofcardiacarrhythmias.

DepolarizationDependentTriggeredActivity
ApositiveshiftinthemaximumdiastolicpotentialbringsVmclosertothethresholdforanaction
potentialandcaninduceautomaticityincardiactissuethatotherwisehasnopacemakeractivity.
ThedevelopmentofdepolarizationinducedtriggeredactivitydependsontheinteractionoftheCa
2+
current(ICa)andtherepolarizingK+current(IK).Thismechanismcanproduceamore
rapidpacemakerdepolarizationintheSAorAVnodalcells,causingthemtoacceleratetheir
pacemakers.ItcanalsoincreasetheintrinsicpacemakerrateinPurkinjefibercells,which
normallyhaveaveryslowpacemaker.

Depolarizationinducedtriggeredactivityisparticularlydramaticinnonpacemakertissues
(e.g.,ventricularmuscle),whichnormallyexhibitnodiastolicdepolarization.Factorsthat
significantlyprolongactionpotentialdurationcancausedepolarizationdependenttriggered
activity.Duringtherepolarizationphase,INaremainsinactivatedbecausethecellisso
depolarized(Fig.2116A(f16)).Ontheotherhand,ICahashadenoughtimetorecoverfrom
inactivationandbecausethecellisstilldepolarizedtriggersaslow,positivedeflectioninVm
knownasanearlyafterdepolarization.Eventually,IKincreasesandreturnsVmtowardthe
restingpotential.Suchearlyafterdepolarizations,iftheyarelargerthantheoneshowninFigure
2116A(f16),maytriggeranextrasystole.Isolatedventricularextrasystoles(knownbymany
names,includingprematureventricularcontractions,orPVCs)mayoccurinnormalindividuals.
AlterationsincellularCa2+metabolism(discussedinthenextsection)mayincreasethetendency
ofaprolongedactionpotentialtoproduceanextrasystole.Ironically,aclassofdrugsusedtotreat
arrhythmiascanbecomearrhythmogenicbyproducingearlyafterdepolarizations.Forexample,
quinidinecanproducethisdangerousadverseeffect,presumablybyinhibitingNa+channelsand
someK+channelsandthusprolongingtheventricularmuscleactionpotential.

Figure2116
Abnormalautomaticityinventricularmuscle.Therecordsinthisfigureareidealized.A,Theprolongedaction
potentialkeepsINainactivatedbutpermitsICaandIKtointeractandtherebyproduceaspontaneous
depolarizationtheearlyafterdepolarization.B,Theafterdepolarizationreachesthreshold,triggeringa
sequenceofseveralslowpacemakerlikeactionpotentialsthatgenerateextrasystoles.

Morethanoneextrasystolearunofextrasystoles(Fig.2116B(f16))ispathological.Arunof
threeormoreventricularextrasystolesistheminimalrequirementfordiagnosisofventricular
tachycardia.Thisarrhythmiaislifethreateningbecauseitcandegenerateintoventricular
fibrillation(Fig.2114I(f14)),whichisassociatedwithnomeaningfulcardiacoutput.Theheart
rateinventriculartachycardiaismuchfasterthannormal,usuallybetween120and150beatsper
minute(orfaster),andthepacemakerdrivingtheheartbeatislocatedintheventricleitself.The
heartrateinventriculartachycardiamaybesofastthattheheartcannotpumpbloodeffectively.

LongQTSyndrome(LQTS)
PatientswithLQTShaveaprolongedventricularactionpotentialandarepronetoventricular
arrhythmias.Inparticular,thesepatientsaresusceptibletoaformofventriculartachycardia
calledtorsadesdepointes,ortwistingofthepoints,inwhichtheQRScomplexesappearto
spiralaroundthebaseline,constantlychangingtheiraxesandamplitude.LQTScanbecongenital
oracquired.ThecongenitalformcaninvolvemutationsofcardiacNa+channelsorK+channels
(seetheboxesonNa+channelandhumanheartdefectsinChapter7).Theacquiredformof
LQTS,whichismuchmorecommon,canresultfromvariouselectrolytedisturbances(especially
hypokalemiaandhypocalcemia)orfromprescribedoroverthecountermedications(e.g.,several
antiarrhythmicdrugs,tricyclicantidepressants,andsomenonsedatingantihistamineswhenthey
aretakentogetherwithcertainantibiotics,notablyerythromycin).

Ca2+overloadandmetabolicchangescanalsocausearrhythmias
Ca2+Overload
Ca2+overloadinthehearthasmanypotentialcauses.Onefrequentfactorisdigitalisintoxication.
Anotherisinjuryrelatedcellulardepolarization.Ca2+overloadoccurswhen[Ca2+]iincreases,

causingtheSRtosequestertoomuchCa2+.Thusoverloaded,theSRbeginstocyclicallyand
spontaneouslydumpCa2+andthentakeitbackup.TheCa2+releasemaybelargeenoughto
stimulateaCa2+activatednonselectivecationchannelandtheNaCaexchanger(seeChapter5).
ThesecurrentsourcescombinetoproduceIti,atransientinwardcurrentthatproducesa
delayedafterdepolarization.Whenitislargeenough,Iticandepolarizethecellbeyond

thresholdandproduceaspontaneousactionpotential.

MetabolismDependentConductionChanges
Duringischemiaandanoxia,manycellulareventstakeplace,includingafallinintracellularATP
levels.Thisfallin[ATP]iactivatestheATPsensitiveK+channel(KATP),whichisplentifulin
cardiacmyocytes.Thus,when[ATP]ifallssufficiently,KATPislessinhibitedandthecellstendto
becomelessexcitable(i.e.,KATPhelpskeepVmclosetoEK).Theactivationofthischannelmay
explain,inpart,theslowingorblockingofconductionthatmayoccurduringischemiaorinthe
periinfarctionperiod.

ElectromechanicalDissociation
Rarely,patientsbeingresuscitatedfromcardiacarrestexhibitaphenomenoncalled
electromechanicaldissociation,inwhichtheheart'sECGactivityisnotaccompaniedbythe
pumpingofblood.Inmanycases,thebasisofelectromechanicaldissociationisnotunderstood.
However,inothercases,thecauseisobvious.Forexample,theheartofapatientwithalarge
pericardialeffusionmaymanifestnormalelectricalactivity,butthefluidbetweentheheartand
thepericardiummaypressinontheheart(cardiactamponade)andpreventeffectivepumping.

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