Andersons pediatric cardiology 157
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and36hoursatarateof60beats/minandincreasesto220beats/minbythe
eighthdayofgestation.
FIG.6.1 Individualfetalheartrate(FHR)measurements(n=3264data
points)bygestationalageof547normalfetuses.Curvesrepresentingthe
3rd,50th,and97thpercentilesofFHRareshown,asisthestandard
obstetricdefinitionofbradycardia(110beats/min).FHRdecreaseswith
advancinggestationalage.SomenormalFHRmeasurementsare<3rd
percentile,butnoneare<110beats/min.(FromMitchellJL,CuneoBF,
EtheridgeSP,etal.FetalheartratepredictorsoflongQTsyndrome.
Circulation.2012;126[23]:2688–2695.)
Inthehuman,thereislittlevariationofthemeanheartrateatanyparticular
gestationalageupto15weeksbecausetheimmaturecardiovascularsystemdoes
notrelyonheartrateacutelytocontrolcardiacoutput.Themaximumcardiac
outputoccursattheintrinsicheartrateateachembryonicstage,suggestingthat,
asinthechick,cardiacfunctionisoptimizedbythesystolicanddiastolictime
intervals.5
Alterationsinheartratesignificantlyaffectcardiacperformance,6andthereis
nocompensatorychangeincyclelengthinresponsetopreloadasisseeninthe
morematureheart.Humanembryosdieiftheirheartratefallsorifthey
experiencetachycardia.7Thisindicatesthat,duringcardiogenesis,extremesof
heartratearenotcompatiblewithlong-termviability.8
AutonomicControl
Thesubsequentdeclineinheartrateafter10weeks,andtheincreasedvariability
inheartrateafter15weeksofgestation,maybeexplainedbyacombinationof
maturationalchangesthatincludedevelopmentofthenervouscontrolofthe
heart,stressesassociatedwithcardiogenesis,andchangesinthehandlingof
calciumbythemyocyte.
Innervationofthemammalianheartissimilartothatinthechickheart,
consistingofparasympathetic,sympathetic,andsensorycomponents,allof
whichderivefromtheneuralcrest.9Althoughparasympatheticandsympathetic
innervationoftheheartoccursearlyduringcardiacdevelopment,thetimeperiod
betweeninnervation,neuroeffectortransmission,andfunctionalneurotransmitter
reactivityofbothcholinergicandadrenergicreceptorsvariesgreatlybetween
species.Functionaladrenergicandmuscariniccholinergicreceptorshavebeen
detectedintheheartofveryearlychickembryos.10Maturationofautonomic
controlhasbeendifficulttoassessinthehumanfetusuntilrelativelyrecently,
butspectralanalysisofthevariabilityofheartrateinthenormalhumanfetus
demonstratesgestation-relatedchangesascribedtotheimbalancebetween
sympatheticandparasympatheticneuroactivityconsistentwithcardiovascular
maturityofthefetus.
