The Biomechanics of Arterial Aneurysms

29 Pages·2013·0.48 MB·English

by  Juan C. Lasheras

ANRV294-FL39-13 ARI 12December 2006 6:5
The Biomechanics of
Arterial Aneurysms
org Juan C. Lasheras
s.
w.annualreviewsonal use only. DB92ieo0pm9a3re-td0mi4cea1nl1tE;oenfmgMianieel:celhraiasnnhgiec,[email protected],eSrainngDaniedgoW,LhiataJkoellra,InCsatiltifuotrenoiaf
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93-3San Annu.Rev.FluidMech.2007.39:293–319 KeyWords
07.39:2ornia - aTthfleuAidn.annunaluRalerveiveiwewofs.FolrugidMechanicsisonline ainbtdeoramcitnioanl,aeonrtliacrgaenmeuernyts,mrus,pctuerreebralaneurysms,flow-structure
h. 20Calif Thisarticle’sdoi:
Fluid Mecversity of 1CA0lol.p1r1yigr4hi6gt/hsatrne(cid:2)ncsuerr2ev0ve0.dfl7ubidy.3A9n.n0u5a0l9R05e.v1i1ew01s2.8 ATfachbtesotrfrioaarlcmtaantdionpreodfoamnianratnetrliyaldaengeeunreyrsamtivies pbreoliceevsesd, rteosubletinagmfuroltmi-
ev. Uni 0066-4189/07/0115-0293$20.00 a complex interplay between biological processes in the arterial
Ry
u. b wall and the hemodynamic stimuli on the vessel’s wall. Once an
n
An aneurysm forms, the repetitive pressure and shear stresses exerted
bythebloodflowontheweakenedarterialwallgenerally,butnot
always,causeagradualexpansion.Asthewallgeometry,composi-
tion, and strength progressively degrade through the enlargement
process,theaneurysmruptureswhenthewallofthedistendedartery
failstosupportthestressesresultingfromtheinternalbloodflow.
Thisreviewsurveysrecentprogressinthisareaandprovidesacrit-
icalassessmentofthecontributionmadebyhemodynamicsstudies
tothecurrentunderstandingofthepathogenesisofthediseaseand
toitsclinicalmanagement.
293
ANRV294-FL39-13 ARI 12December 2006 6:5
1.INTRODUCTION
Blood is periodically pumped by the heart into a complex branching network of
CircleofWillis: aroughly muscularelasticarteriesthatcarrynutrientsandoxygentothetissuesandorgansin
circularconnectionof the body. During each cardiac cycle, the heart ejects 70 ml of blood at a pressure
arterieslocatedatthebase of 120 mm Hg into the aorta where the mean pressure is approximately 80 mm
ofthebrainandformedby
Hg.Thepressurepulsegeneratedbythehearttravelsalongthenetworkofarteries,
theanteriorcommunicating
partiallyreflectsateachbranchingpoint,andisdampedbythetimeitreachesthe
artery,thetwoanterior
cerebralarteries,thetwo capillaries that irrigate the tissues. The blood then returns to the heart through a
internalcarotidarteries,the networkofveinsthatareequippedwithacomplexsystemofvalveswhosefunction
twoposterior isregulatedbysecondarymuscularactivityandtheactionoftheheartitself(Nichols
communicatingarteries,and
&O’Rourke1990).Inanormal,healthyindividual,thepumpingprocessisrepeated
thetwoposteriorcerebral
org arteries approximately70timesperminute,100,000timesperday,oralmost3billiontimes
s. throughouttheexpectedlifetime(McDonald1974).Witheachperiodicejectionof
w.annualreviewsonal use only. btwfuhlionathtoctdpiaoraomncproeaoafgsnsathttfeehoserotwrhagaorarordntuigcmthhvoaoattuliviottentshi.uneDptopeellptiaehessten,icdeaisannccegehtnwoadnoritnreikgtrsyoapfohrraaotrsaxta,eimradieiiptfsyfreeirntsoesdunutrthcedienpeghguerlaseaeerptiuosalfsngaedetlnailoseetnriflacttiohetwyde.
wer
oaded from w2/05/13. For p TTtthhhhaeteeesseletalpiasfatsfintrciaecittsieytsytiohsifseptadwhreaettilealarlfrlmrytoeicmrnoieantdlhtwreboaybllllletohdiosebdcsyosttrtnrhusecetatamrunert.gelTyualhaanitddsojurfceysoetamedcdbptaiobvcsyiktitytcihoooennfttrorheofegltuehslnyeasdttoaoerrtmtyheerwfliuiahanllecwrcteeiaoblllnlys.
wnln 0 of the endothelial cells is remarkably stable, and allows the circulatory system to
Doo o accommodateinashorttimethelargechangesinthecardiacoutputdictatedbythe
19. Dieg increasingdemandofnutrientsandoxygentothetissueandorgansduringexercise
93-3San and other extraneous activities. Arteries can also adapt to long-term physiological
07.39:2ornia - ccoonmdpiotisointisonbyanthdinonrginagniozartitohnickoefntihnegvtahreiomususacsuselamrbllaiyeesro,fanstdruaclttuerrianlgprtohteeirneslaitnivea
h. 20Calif proTcehsrsoguegnheorualtlythkeneonwtnireasli“freetimmoedoeflinagh.e”althyindividual,thelivingcomponentsof
Mecy of thearterialwallmustregenerateandremodelcontinuouslytomaintaintheintegrity
Fluid versit andfunctionofthesystemandtowithstandtherepetitivewallstresses.Unfortunately,
ev. Uni insomecases,thisotherwiseremarkablystablesystemdestabilizes,whetherdueto
Ry disease or other complex processes, and a portion of the arterial wall weakens and
nu. b distendspermanently,formingananeurysm(fromtheGreekword“aneurusma,”“ana”
n
A throughoutand“eurus”wide).Althoughthesepathological,blood-filledpermanent
dilatations form in many blood vessels, and even in the heart, they mainly appear
inarteries,primarilyintheabdominalandthoracicportionsoftheaortaandinthe
intracranialarteriessurroundingtheCircleofWillis.
Although the precise cause of this disease is still unknown, it is believed to be
multifactorial and predominantly degenerative, arising through a complex interac-
tion among several biological factors as well as from some specific changes in the
hemodynamicstimulionthevessel’swallthatmightdestabilizetheabove-mentioned
regulatory system. Once the aneurysm forms, the hemodynamic forces exerted by
the pulsatile blood flow on the weakened arterial wall generally, but not always,
294 Lasheras
ANRV294-FL39-13 ARI 12December 2006 6:5
causeagradualexpansion.Asthewallgeometry,composition,andstrengthprogres-
sively degrade through the enlargement process, the aneurysm ruptures when the
wall of the distended artery fails to support the stresses resulting from the inter-
Pathogenesis: the
nal blood flow. The rupture of an aneurysm often leads to sudden death or severe
mechanismbywhichcertain
disability. factorscauseadisease
Oneofthemostdetrimentalfeaturesofthisdiseaseisthataneurysmsareseldom
detectedatearlystages(Pokrovskiietal.2003,Szilagyi1982).Inthevastmajority
ofcases,theyremainlatentuntilsymptomsoccurastheirsizegreatlyincreases,or
theyarefoundinanincidentalexam.Oncedetected,duetothelackofknowledge
oftherolethatthevariousfactorsplayintheexpansionprocess,thereiscurrently
noaccuratetechniquetopredicttheaneurysm’sexpansionrate,nortodetermineits
criticalsize(orshape)atthepointofrupture.Owingtoalackofanyotherreliable
g
or method,aneurysmdiameteranditsobservedexpansionratearethecurrentstandard
s.
w.annualreviewsonal use only. p2tsoi0azr0eaad4mh,aieUgntheejiuerisreryrbesitymskaswlo.hhf1airc9vuhe9p9bpt)ueh.eryPensoi(fcpEoiuaunnlngastdliueotnsnodt-irmbeuatapstaeteuld.rt1esht9,ea9wt8rihsi,tseikLrcesaoawsfshoreouttwhpaetltu.rhsr1aeh9t9a(iNv4ne)ca.rbdHeeeaeros-niwSnoeegvpbseasirehz,reivsmeeletdaaaldtllo-s.
wer growtoverylargesizeswithoutrupturing.Dependingontheirlocation,treatment
m wor p is currently recommended for aneurysms exceeding a maximal diameter, and/or a
Downloaded froo on 02/05/13. F csa1uen9rbd8tj7aeci,conTtmiaenyxpgplloipacrnaat&stiiieoonPnntossrroawttereirt,th1ole9saa8mnv7ia)nul.lgnakpnnheoyuwsriyncs,imainnssctrtoeoaafsaeccdoemrtiphskleexothfseurruragppeteruuyrteiwc(iSdthtilrehinmiggmhfealmlooowfrebeiittdhiaetlyr.
19. Dieg Overthepast30years,thestudyofthepathogenesisandprogressionofaneurysms
93-3San hmaoslbeceucolamrceeallmbiuolltoidgiysctoipsloinliadryanedffflourtidinmvoelcvhianngicasw.Tidheerseansgtuedoiefsahreaavsesbpeaennnginengefrraolmly
07.39:2ornia - mtooctliivnaitceadllybymtahneagnienegdtthoepdriosevaidsee:answerstothecriticalquestionsthatareessential
h. 20Calif 1. Whatistheexactpathogenesisofthearterialaneurysms?Whydosomepeople
Mecy of developaneurysmswhereasothersdonot?Whyareaneurysmsmorecommonly
Rev. Fluid y Universit 2. sOiteenenncelfaoarrngmeasin?negMuraoytrssempiemfcoiprfiomcrsst,aitwnetshlyain,tcacarenertitathsienefnaarlcatterogrrieesmst?heanttdreatteerbmeinperetdhiectreadte?atwhich
u. b 3. Ineachspecificcase,cantheriskofrupturebepreciselyquantified?
n
n
A 4. Finally,whatisthepatient-specificoptimaltreatmenttechniquetopreventits
rupture?
Duringthepastthreedecades,awidelyproposedhypothesishasbeenthatspe-
cific changes in the hemodynamic forces acting on the vessel wall could be a key
contributingfactortotheoriginandprogressionofthedisease(Fox&Hugh1996,
Glagov et al. 1988, Hademenos 1995, Ku et al. 1985, Lei et al. 1995, Malek et al.
1999,Pedersenetal.1993,Soliman2001).Thus,muchattentionhasbeendevoted
toanalyzingthecharacteristicsofthebloodflowinsideaneurysmsaswellastoclas-
sifyingthespecificfeaturesoftheflowinthearterialsegmentswhereaneurysmsare
predominantlyknowntoform.Thisreviewsurveysrecentprogressinthisareaand
www.annualreviews.org • BiomechanicsofArterialAneurysms 295
ANRV294-FL39-13 ARI 12December 2006 6:5
providesacriticalassessmentofthecontributionthatthesestudieshavemadetothe
currentunderstandingofthepathogenesisofthediseaseandtoitscurrentclinical
management.
2.PATHOGENESISOFARTERIALANEURYSMS
Mechanically,theformationofanarterialaneurysmresemblesthefamiliarproblem
foundinstructuralengineeringoftheplasticdeformation,permanentbulging,and
subsequent rupture of a pipe under the effect of an oscillatory internal pressure, a
processthatofteninvolvesfailureduetofatigue.However,inthecaseofarteries,the
problem is dramatically more involved and difficult to analyze due to the fact that
theirwallsarecomposedofacomplexstructureoflivingcellsandastructuralnetwork
g
s.or ofsheetsandfibersofpolymerizedproteinscapableofnotonlyactivelymodifying
w.annualreviewsonal use only. ti(anrhnetedemirreonmvdaeleenbclihalnogagoni)ndiacgflsa.loapwrre,osbupulettrmotifeoisnrieflniamrmepsmpooartntaosnreyttloyp,rcoohfcauensngsdeeess,riginnotfiehncegtmipoeenrc,mhdaeanngieecnnaetlrstartiatminvsueflopirrfmroocametsiostehnses,
wer Thewallsofallthelargevesselsinthehumanbodyarecomposedofthreelayers(or
m wor p tunicas):thetunicaintima,thetunicamedia(ormuscular),andthetunicaexternal(or
wnloaded fron 02/05/13. F eoadafcvthehnelatiyoteirarg)av(naFruyonrdgeti1ps9esun9ed3)isn(ugspeopenlFietidhgeubrpyerot1hx)ei.mTviethysestetolh.tiAchkerntheeresisaerastnaadrnesdtgrouennctteuhrreaalsllypceotchmiificpckoefsuri,tnimoctnoioronef
Doo o muscular,andmoreelasticthanveins.Theintimalayerismadeupofasinglelayerof
19. Dieg vascularendothelialcells(VECs)thatadheretoabasallamina(80nmthick)covering
07.39:293-3ornia - San abusnubdelensd.otheliallayercomposedofconnectivetissue,elasticfibrils,andcollagenous
h. 20Calif Figure1
Mecy of Smturusccutularreaorftearmy.eUdsiuedmw-siitzhe
ev. Fluid Universit pMIneccr.mGirsaswio-nHoilflTChoempanies,
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296 Lasheras
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Themedianlayerconsistsprimarilyoflayersofsmoothmusclecells(SMCs),a
variednumberofelasticsheets,acomplexnetworkofelasticfibrils,andbundlesof
collagenousfibersembeddedinanextracellularmatrix(ECM).TheSMCssynthesize
Elastin: alsocalled
theproteinandproenzymesoftheECM,whichinturninfluencetheproliferation,
elasticin,aproteinoften
differentiation,andmigrationofthecells.Themedianlayeraccountsformostofthe presentintheformofsheets
mechanicalpropertiesofthewallandthroughitsactive(SMC)andpassive(struc- andfibersinconnective
turalproteins)componentsdeterminestheelasticityofthewall.Elastinfibershavea tissue
modulusofelasticityof0.6MegaPascals(MPa)(6×106dynes/cm2)andcanstretch Collagen: themainprotein
inexcessof250%ofitsoriginallength.Collagenfibersaremuchstifferwithamod- ofconnectivetissueandthe
ulusofelasticityof500MPa(5×109dynes/cm2),whichisalmost1000timeslarger mostabundantproteinin
mammals
thanelastin(Dobrin1978).Theoutermostlayeristheadventitiaconsistingmainly
ofgroundsubstances,collagenfibers,bloodvessels(vasavasorium,thevesselsthat
g
or supplythevessel),andnervesthatextendintothemedianlayer.
s.
w.annualreviewsonal use only. isbnhegeeTantrhh-kseenenVoarswEittenCirvisteao.lfoIwrnremagplual.arlatVpitceeEurClmmarsae,naaflbysuleiowdfbeslathlhreraeaiserVrbfEotlhorCcoaetdsfpucirnmeeclvpltseiaonr(nttpsesldasatobenmyldeetthassceuatbinbvlsdiottaoyendrtcyhfletrshoorwfuorogchmyhatveaeesn)lpotraenorrge--
wer cessgenericallyreferredtoas“mechanotransduction”(Blackmanetal.2002,Davies
m wor p etal.1984,Traub&Berk1998).Thegeneralizedhypothesisisthatanunidentified
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19. Dieg andmoreimportantly,tocausechangesinthe“contractiletone”oftheSMCsinthe
93-3San medTiahlelraeyherav(eBebneeDnrmisasneytcalli.n1i9ca9l7a;nCdhliaubeotraatlo.r2y00st3u,d2i0es04a)im. edatcharacterizingthe
07.39:2ornia - caonndsttihteutsivtreaeinquraetsipoonnqsueanotfifbylionogdthveenssoenlslin(feoarrrreevlaiteiwonsssheiepbCeatmweeeronnth1e9w9a9l,lDstroebsrsiens
h. 20Calif 1978, Greenwald & Berry 2000, Levy 1999, McVeigh et al. 2002, Vito & Dixon
Mecy of 2003).Althoughsomeofthemodelsthathavebeenproposedhavebeenextremely
Fluid versit vstaillularbelmeaininasntaolyozbintagincemrtaoidnealsspceacptasbolfethoefmpreecdhicatninicgsothfethcehvaansgceuslairnsythsteemm,etchheanneiceadl
ev. Uni propertiesofthewallasitremodelsunderthepoorlyunderstoodcouplingbetween
Ry
u. b mechanicalstimuliandthebiologicalprocessestakingplaceatthewall.Aswillbecome
n
An apparentinthefollowingsections,thecurrentinabilitytopreciselycharacterizethe
mechanicalpropertiesofthevesselasitundergoeslong-termremodelingrepresents
akeystumblingblockprecludingthepredictionofboththeexpansionrateandthe
riskofruptureofaneurysms.
Thus,theperennialquestionbeingdebatedis:Doesananeurysmformasaresult
ofadegradationprocessinthewall,orbyanomalouschangesinthehemodynamic
stimulithatcouldresultinanunstabledegenerativeresponseonthevesselwall,or
byacombinationofboth?Thecurrentconsensusisthatthecauseismorelikelythe
resultofacomplexinterplaybetweendegenerativebiologicalprocessestriggeredby
inheritedbiochemicalorstructuraldefects,aging,infectionordisease,andspecific
hemodynamicfactors(seeFigure2).
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ANRV294-FL39-13 ARI 12December 2006 6:5
Risk factors Pathophysiological processes Mechanical factors
Genetics Vascular endothelium response
Biochemical disorders of Damage to the intima artherogenesis
collagen metabolism
Enzymatic destruction Media defects
of arterial tissue
Elastic degeneration Hemodynamic stresses
Hypertension, obesity, (pressure and shear)
diabetes, atherosclerosis Bulging of the arterial wall
g Environmental factors: Permanent thinning of the muscular
s.or smoking, diet, lack of median layer
w.annualreviewsonal use only. eAxgeer caisned gender Figure2Rupture
m wwor per Ppraothceosgseens.esisofarterialaneurysms.Interplaybetweenmechanicalstimuliandphysiological
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Downlo on 0 Pneumonia)fromaninfectedheartvalve,orfrombloodletting.Today,theseprimary
93-319. San Dieg cgaatehuneseertosicsocdflieswrooarsdlilse,drsae,ngmdraysdciamottipioclnyinahfgeaivcntegiobhnea,evhneiggbhreebcaolotmloyeddpdimroemisnsiuinsrahene,tde.ffaencdtsootfhceirgafraectttoerssmsuockhinags,
07.39:2ornia - MaTrfwano’shaenrdedtihtearEyhcloerllsa-gDeannvloass’csuSlayrnddriosomrdeser(sWairlemkinnkowetnalt.o20ca0u0s)e.Baontehurcyosnmtrsi:btuhtee
h. 20Calif toabnormalitiesinthesynthesisandorganizationofthestructuralproteins(elastin
Mecy of andcollagen),andthustoapathologicalweakeningofthewall.Thesetwoconditions
Fluid versit ainretrvaecrryanriaarle)hanasdbaelethnoeuxgtehnasifvaemlyilrieaproargtgerde,goatthioenrsopfescoifimceptoyspseibsloefgaenneeutricysfamcsto(mrsahianvlye
ev. Uni notyetbeendiscovered.Candidategenesforaneurysm’spredispositionareexpected
Ry
u. b tobeinvolvedincross-linkingforcollagenandelastinorotherstructuralcomponents.
n
n Severalpredisposingriskfactorshavebeenstatisticallyshowntoplayanimpor-
A
tant role in the formation of aneurysms: cigarette smoking, alcohol consumption,
hypertension,andatherosclerosis(Juvelaetal.2001,Krexetal.2001,Singhetal.
2001, Wanhainen et al. 2005). Smoking has long been known to be a factor, al-
thoughtheprecisemechanismofactionisstillbeingdebated(Auerbach&Garfinkel
1980, MacSweeney et al. 1994, Reilly & Tilson 1989). Hypertension is one of the
most frequently studied risk factors because it is found twice as often in patients
withaneurysmsthaninpatientswithout.Hypertensiongraduallydistendstheves-
selandcausesagradualthickeningofthewall.Atherosclerosishashistoricallybeen
attributedasthemostcommoncauseofwalldegradationinsomeaneurysmssuch
asabdominalaorticaneurysms(AAAs).However,thistheoryhasbeencontinuously
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ANRV294-FL39-13 ARI 12December 2006 6:5
Figure3
Aneurysmclassification
basedontheshapesofthe
aneurysms.
g
or
s.
ww.annualreviewersonal use only. Fusiform Saccular
m wor p
oaded fro2/05/13. F cwdheitaphlolesninotgsaeatdrheeovrveoersrycltreharreoeslpiysatsdhtiestewsaiotseesd,weacnhadedreaerstaeanrseiaualnryseisutmersysswfmoirtshmatr(heLeeomefteoetnstaloc.ob1ns9ec9re7vn)e.tdrTaithneedpcpautlriareqenuntest
Downlo on 0 thoughtisthatatherosclerosismayaidtheprogressionofthediseaseinsomecases,
93-319. San Dieg bbuotdAyitnianelutoornyteswmiossmnaoraetintohgfetreopnurcpimlsa:asfsruiyfisicefaoduramscecaoonfrddthisnaegcwctuoelaatkhreeaninriensughraoypsfemthasne(dswelaeolFcl.aigtiuornein3)t.hFeuhsuifmoramn
07.39:2ornia - (tshpeinpdolpel-istehaalpaerdt)eraynbeuehryinsmdsthaereknmeoes,twchoemremasosnalcycfuoluarn(dbienrrtyh-elikabe)daormeipnraeldaoomrtianaonrtilny
h. 20Calif foundinthemainarteriesofthecerebralcirculation,especiallyalongtheCircleof
Mecy of Willis.
Fluid versit sitioTnheofmtharekeadrtedriifefesrwenhceerseitnhethyefiorrsmhap(meuasscwulealrl aeslatshtiecdaiosrtitnacvtsstcreurcetburraallacrotmerpieos-)
ev. Uni suggestthatthepathogenesisoftheseprocessesismostlikelysomewhatdifferent.
Ry
u. b ThishypothesishasbeenfurtherstrengthenedbythefactthattheincidenceofAAAs
n
An (themostcommonfusiformaneurysm)increasesdramaticallywithage(Singhetal.
2001, Wanhainen et al. 2005), whereas intracranial aneurysms do not exhibit such
a strong dependency on aging (Fox 1983, Gibbons & Dzau 1994). Owing to the
above-mentioneddifferencesintheirshapeaswellastheirwallstructure,weanalyze
thepossiblemechanicalandhemodynamicfactorsresponsiblefortheformationof
eachtypeofaneurysmseparatelyinthefollowingsections.
2.1.PathogenesisofFusiformAneurysms
Mostfusiformaneurysmsarefoundinportionsofelasticmusculararteriesinlocations
upstreamofmajorbifurcationsorbranchpoints.Themostcommonlyfoundfusiform
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ANRV294-FL39-13 ARI 12December 2006 6:5
Figure4
Abdominalaortic
aneurysm(AAA)
g
or
s.
w.annualreviewsonal use only. arenneaulrayrstmeriinestahnedhuupmsatrneabmodoyffiotsrmbisfuinrctahteioanbidnotmotinhaeliplioacrtaiortneroifest.hBeealoorwta,,wbeealonwalythzee
wer thisAAAasarepresentativecaseofthefusiformtype.LiketheoneshowninFigure4,
m wor p AAAs very rarely appear in individuals under 50 years of age, but their incidence
wnloaded fron 02/05/13. F icanoncndrdeiuanscet2es.d2d%irnasoNtifcoawrlwloymayaetinnago1ev9e95r456–a10n9yd9e5parseshakooswfieandgetthh(eaStienAagrAhlyAes8t0aarsle..Ap2r0el0asr1egn).etIsitncrh8ea.es9n%ainlsgoofsbtmueeednny
Doo o found that with the gradual increase in life expectancy, the incidence of AAAs has
19. Dieg increased steadily over the past decades, although this may simply be a result of a
93-3San lmaregtherodaws(aBreenstesestaolf.t2h0e03d,isCeaoslelinin1t9h8e8)m. edicalcommunityandimprovedscreening
07.39:2ornia - 2.1.1.Theaginghypothesis. BecauseageisthemostdominantfactorinAAAs,it
h. 20Calif seemsreasonabletoassumethattheprimarycauseoftheirformationshouldlieon
Mecy of thecouplingbetweenthespecificchangesinthearchitectureofthevessel(length,
Fluid versit dthiaemyeintedru,caendinwathllesthruemctoudrey)nraemsuilctsi.nTgfhreompotshteulnaotermisalthagaitnugnpdreorcesspseacnifidcthceonchdaitniogness
ev. Uni thiscouplingmayleadtoanunstableresponsewherebyaportionofthewallofthe
Ry
u. b abdominalaortadegrades,anditsdiametergraduallyincreases.
n
An Therehasbeenalargebodyofworkdevotedtotheunderlyingmechanismsof
aginginthearteriesofhumans(foraverydetaileddescriptionoftheeffectofaging
on the vascular system, see Braunwald 1988, Kissane 1985, Nichols & O’Rourke
1990).Whenelasticsystemicarteriesageovertheyears,theirdiametersincreaseand
becomestiffer,andtheirwallsthicken.However,themajorstructuralchangescaused
byagingoccurinthemedianlayer,whichthinsoutandlosesitsorderlyarrangement
of elastin laminas and fibers, which become fragmented and unorganized (Lakatta
etal.1987).Thedegenerationofelasticfibersisaccompaniedbyanincreaseinthe
collagenous substance (the stiffer structural component). As the ratio of elastin to
collagendecreases,thevesselprogressivelylosesitselasticity.Thestiffeningofthe
wallcausesanincreaseinthespeedofthepulsewave.Forexample,intheaorta,the
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ANRV294-FL39-13 ARI 12December 2006 6:5
wavespeedincreasesfrom6.5m/sina10-year-oldchildtoupwardsof11m/sina
60-year-oldadult(Nichols&O’Rourke1990).
A prevailing hypothesis for the mechanism of arterial degeneration with age is
Smoothmuscle: atypeof
based on the fatigue failure of the wall components. Nichols & O’Rourke (1990)
nonstriatedmuscle,found
suggestthatthefatigueofthecyclestressescausesthefractureoftheload-bearing withinthewallsofhollow
elasticsheets.Elastinsheetsareveryinertandstablewithanestimatedlifetimeofover organs,suchasblood
40years(Rucker&Tinker1977).Underthecyclicfatiguestresses,thepolymerized vessels,thebladder,the
uterus,andthe
structureoftheelastinsheetandfibersreorganizes,causingthemtofailatlevelsof
gastrointestinaltract
tensional stresses below those they were previously able to withstand. The tearing
oftheelastinsheetsandfibers,andtheassociatedlossofsomeoftheelasticrecoil,
cause a progressive permanent dilatation of the vessel. The permanent stretching
of the smooth muscle is then accompanied by a remodeling process whereby the
g
or collagenous content in the muscular layer increases. The end result of the above-
s.
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wer theabdominalaorta,andtheiliac,femoral,andpoplitealarteries,theamplitudeof
m wor p thepressurewave(pulse)isconsiderablymodifiedasaresultofthereflexionofthe
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19. Dieg the parent vessel decreases. With aging, these arteries also elongate slightly and
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h. 20Calif speedofthetransmittedwavecausedbyaging,togetherwiththeincreaseintheratio
Mecy of ofcross-sectionalareas,maythenresultinanincreaseinpeaksystolicpressureinthe
Fluid versit awbadllotmeninsiaolnacoormta,pocauunsdinsganadnaicnccerleeraasteesinthtehienwitiaaltliostnreasnsdesp.rOopvaegrattiimone,otfhceraicnkcsrienasthede
ev. Uni elasticsheetsinthemedianlayerdescribedintheprecedingparagraph,andresults
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u. b in an irreversible increase in the artery’s diameter. The permanent increase in the
n
An arterialdiameterleadstoafurtherdecreaseinthearearatioandthustotheunstable
progressionofthedisease.
The described pathological changes that occur with aging can be compounded
or accelerated by hypertension, excessive alcohol consumption, cigarette smoking,
lack of exercise, and other dietetic or environmental factors. Hypertension can be
viewedasanacceleratedformofaging,causingsimilardegenerativearterialdilata-
tion,stiffeningandincreasedwavespeed,butatanearlierage(Carlsonetal.1970,
Merillon et al. 1982, Nichols & O’Rourke 1990, Ting et al. 1986). The observed
increaseinthepeaksystolicpressureintheabdominalaortainolderpatientswith
hypertensionresultsfromtheabove-describedprocessofafasterwavetravelingdown
thearteryandmergingwithastronger,reflectedwave(O’Rourke1982).Cigarette
www.annualreviews.org • BiomechanicsofArterialAneurysms 301
ANRV294-FL39-13 ARI 12December 2006 6:5
smokingisbelievedtoproducesimilareffectstohypertension(Bonita1986,Juvela
2000).
Theabovehypothesisbasedontheinterplaybetweenthemechanicalstimuliand
thepathologicalchangesinthearterialwallcausedbyagingandotherknownrisk
factorshasnotbeenfullytested,andcertainlyrepresentsanareainneedofresearch.
Studies involving the analysis of the flow-structure interaction in realistic arterial
geometriesusingspecificconstitutivematerialpropertiesofthearterialwallscould
helpshedvaluablelightindeterminingthevariousscenariosofgeometricalchanges
and degradation of the material properties of the wall that could lead to fusiform
aneurysmsupstreamofbifurcations.
2.1.2. The vascular endothelium: flow shear–mediated initiation hypothesis.
g
or CulturedVECstudiesshowthat“disturbedflowconditions”andunsteadyturbulent
s.
w.annualreviewsonal use only. sp1sth9rroe8eacs6res,ess1sst9erdes9as5msm)e.asaSygaeenpvdrteohrtvehailedesneltoudasdosfiitoehrfssetphliesautrvmemep,estaahonboditwlhittnehyetdohelfaogttshrstaehdoeearnrteimdooinastlhafouefcnloticahrtlreiceowelnalailtnilmolgn(eDombfaebtvthriwaeenseireeenrt(eCavglehu.ral1yap9tplo8oer4wlyl,
wer etal.1998,Chiuetal.2003,Daviesetal.1986,Helmlingeretal.1991).Furthermore,
m wor p ithasalsobeenfoundthathightemporalandspatialgradientsofwallshearstresses
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19. Dieg tary,mechanismresponsiblefortheoriginoftheseaneurysms.Asmentionedabove,
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h. 20Calif icalchangesthat,inturn,create“disturbedflow”conditionsinsidethevessel(i.e.,
Mecy of unsteady flow separation and weak turbulence). It is then argued that the anoma-
Fluid versit lbouutsorsecsiplloatnisnegosfhetharesVtrEeCssetso, atnhde thhigehanshoemaarlostursestseems,pvoerrayl alonwd ssphaetairalsgtrreasdsieesn,tlsowof,
ev. Uni wallshearstressassociatedwiththesedisturbedflowconditionscouldcontributeto
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u. b anunstableprogressivedegradationofthearterialwallandtotheformationofthe
n
An aneurysm.
ThisVEC-shearactivationhypothesishastriggerednumerouscomputationaland
experimentalflowstudiesaimedatcharacterizingthespatialandtemporalvariation
of the wall shear stresses characteristic of various arterial configurations (Egelhoff
et al. 1999; Finol & Amon 2001; Finol et al. 2003; Fukushima et al. 1989; Morris
et al. 2004; Peattie et al. 2004; Perktold 1986; Salsac 2005; Salsac et al. 2004,
2006; Scherer 1973; Viswanath et al. 1997; Yip & Yu 2003; Yu et al. 1999, and
manyothers).Unfortunately,duetothelackofspecificmodelsquantifyingthere-
sponseoftheendothelialcellstoeachoftheabove-describedanomaliesintheflow
shear stresses, these studies have been inconclusive and unable to fully prove this
hypothesis.
302 Lasheras