The Biomechanics of Arterial Aneurysms - MAE

29 Pages·2007·0.48 MB·English

by  Juan C. Lasheras

ANRV294-FL39-13 ARI 12December 2006 6:5
The Biomechanics of
Arterial Aneurysms
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s.or Juan C. Lasheras
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als.annonal us 92093-0411;email:[email protected]
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319. an Di Annu.Rev.FluidMech.2007.39:293–319 KeyWords
007.39:293-alifornia - S aTTthhflieusAiadrn.taninculnaelu’sRadleroveiiv:eiwewofs.FolrugidMechanicsisonline ainbtdeoramcitnioanl,aeonrtliacrgaenmeuernyts,mrus,pctuerreebralaneurysms,flow-structure
2C
Rev. Fluid Mech. by University of 1CA000lol.6p1r61yi-gr44hi6g1t/h8sa9trn/e(cid:2)n0csue7rr2/ev00ve10.dfl175ub-idy0.23A99n3.n0$u52a00l9.0R005e.v1i1ew01s2.8 ATfawaachbclteoslotmrafrionpaardllcmetaxtanhtdieinotnpherereompdfloaoaydmnyibnanearattmnwetrielciyeanlsdtaiebmngieoeuunllorieygrosiamnctaivltiehsperpborevcoleiecsessevseseelsd’s,sritwneoasulbtlhl.eteiOnaganmrctfeeurrolatimain-l
nu. aneurysm forms, the repetitive pressure and shear stresses exerted
n
A 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
g thetwoposteriorcerebral
or approximately70timesperminute,100,000timesperday,oralmost3billiontimes
s. arteries
w throughouttheexpectedlifetime(McDonald1974).Witheachperiodicejectionof
e
viy.
ualree onl bthloatodpraocpraogssattehsethaorortuigchvoaulvtethinetoeltahsteicasnceetnwdoinrkgoaforatrat,eraiepsreinssduurceinpgulasepiuslsgaetnileerflatoewd
als.annonal us wfuinthctiaomnoeafnthfeorowrgaardnmthoattiiotns.uDppelpieesn,deiancghoanrteitrsyphraosxaimdiitfyfertoentthdeehgereaertoafnedlaostnictihtye.
ded from arjourn5/07/07. For pers TTtthhhhaeteeesseletalpiasfatsfintrciaecittsieytsytiohsifseptadwhreaettilealarlfrlmrytoeicmrnoieantdlhtwreboaybllllletohdiosebdcsyosttrtnrhusecetatamrunert.gelTyualhaanitddsojurfceysoetamedcdbptaiobvcsyiktitytcihoooennfttrorheofegltuehslnyeasdttoaoerrtmtyheerwfliuiahanllecwrcteeiaoblllnlys.
nloaon 0 of the endothelial cells is remarkably stable, and allows the circulatory system to
wo accommodateinashorttimethelargechangesinthecardiacoutputdictatedbythe
og
19. Dn Die ianncdreoatshinegr edxetmraannedouosfnacuttirviietnietss.aAnrdteorxieysgecnantoaltshoeatdisasputetaondloonrgg-atnersmduprhinygsioexloegrcicisael
3a
293-a - S conditions by thinning or thickening the muscular layer, and altering the relative
9:ni composition and organization of the various assemblies of structural proteins in a
007.3alifor processgenerallyknownas“remodeling.”
ech. 2y of C theTarhtreoruiaglhwoaulltmthuesetnretigreenleifreattiemaenodfraemheoadlethlycoinndtiinvuidouuasll,ytthoemlivaiinngtaicnomthpeoinnetengtsriotyf
Rev. Fluid Mby Universit aidnnisdseoafumsenecotcriaoosnetsho,eftrthhciesosmoytsphtleeemrxwapisnreodcrteeosmwseaisrt,hkaastnbadlnydasttpahoberlreteiospynesttoietfimvtehdweeasaltrlatsbetirrlieiazslesesw,sa.wlUlhnwefteoharektruenndsauteaenltyod,
u. distendspermanently,formingananeurysm(fromtheGreekword“aneurusma,”“ana”
n
n throughoutand“eurus”wide).Althoughthesepathological,blood-filledpermanent
A
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,
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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
org criticalsize(orshape)atthepointofrupture.Owingtoalackofanyotherreliable
ws. method,aneurysmdiameteranditsobservedexpansionratearethecurrentstandard
e
viy. parameters by which physicians estimate the risk of rupture (Nader-Sepahi et al.
ualree onl 2004, Ujiie et al. 1999). Population-based statistics show that increasing size leads
als.annonal us tsoizeadhaignheuerryrsimsksohfarvuepbtueeren(fEounngdlutnodreutpatul.r1e9,9w8h,eLreaawsoetthael.rs1h99av4e).bHeeonwoevbesre,rvsmedaltlo-
aded from arjourn05/07/07. For pers gicsasuenrrbodctjwuaecriconrttoemiennvxpgtepllyirpacynaartestliaiiceoorongnnmtessrmsoawitrzeeietn,thsodlewesaamdinvtiahfnuololgnruakptannnheroueyuwuspriyrntcuys,imasriminnnsscsgtrto.eeoDxaafcsaeeeccpdeoeedmrnitinphdsgkleienxotaghfsmeourrnuraagxppteihtemrueuyriaterilwcl(dioSdtichatialrmehtinimeioggtnmehfe,ra,lmtlroaoeonwfardtebme/iitotdherianetlyart.
nloon 1987,Taylor&Porter1987).
wo
Doeg Overthepast30years,thestudyofthepathogenesisandprogressionofaneurysms
19. n Di hasbecomeamultidisciplinaryeffortinvolvingawiderangeofareasspanningfrom
3a
9:293-nia - S mmoolteivcautleadrcbeylltbhieolnoegeydtotosoplriodvainddeflanusidwmerescthoatnhicesc.rTithiceasleqstuuedsiteiosnhsavtheabteaernegeesnseenratlilayl
007.3alifor toclinicallymanagingthedisease:
2C 1. Whatistheexactpathogenesisofthearterialaneurysms?Whydosomepeople
ech. y of developaneurysmswhereasothersdonot?Whyareaneurysmsmorecommonly
Rev. Fluid Mby Universit 23.. sOiIteneneenncaelcfaoahrrngsmepasine?ncegMiufiraocytrscsemapsiemefco,iprficomacrnsst,aitthwneetshlyarin,itscakcarenoerftitathrsiuenepfnataurlcatrtereogrribeesmest?hpearntetcdrieasteteelyrbmqeiunpaernettdhifiiecetrdea?dte?atwhich
u.
n 4. Finally,whatisthepatient-specificoptimaltreatmenttechniquetopreventits
n
A
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
g
or theirwallsarecomposedofacomplexstructureoflivingcellsandastructuralnetwork
ws. ofsheetsandfibersofpolymerizedproteinscapableofnotonlyactivelymodifying
e
viy. theirmechanicalpropertiesinresponsetochangesinthemechanicalstimulifromthe
ualree onl internalbloodflow,butmoreimportantly,ofundergoingpermanenttransformations
als.annonal us (arnedmeovdeenlianggi)nags.aresultofinflammatoryprocesses,infection,degenerativeprocesses,
aded from arjourn05/07/07. For pers eotaudafncvtThiehcnhealatseiy)ot:weiratrgah)alve(lnasFtrouuyofnnrdaiglcetlia1pts9hesinun9eted3liam)isnr(ugagsp,eeoptevhnleFieestisdthgeueulnbsrpiyiecnraot1thxmh)ei.emeTvhdietiuhaysmes(teotaolhr.ntimAchbkeoruntdsheecyresuisaaelrraasetrna)acd,rnoaesdmntgrdopuenotnchstteeeuhrdreatauolsllnfypctieochtcahmrieifiecpexckotleefasurryi,tnneimoarcsltnoi((oooronerrf
wnloo on muscular,andmoreelasticthanveins.Theintimalayerismadeupofasinglelayerof
Doeg vascularendothelialcells(VECs)thatadheretoabasallamina(80nmthick)covering
19. n Di asubendotheliallayercomposedofconnectivetissue,elasticfibrils,andcollagenous
3a
293-a - S bundles.
9:ni
007.3alifor Figure1
2C
ech. y of Smturusccutularreaorftearmy.eUdsiuedmw-siitzhe
Rev. Fluid Mby Universit pMIneccr.mGirsaswio-nHoilflTChoempanies,
u.
n
n
A
296 Lasheras
ANRV294-FL39-13 ARI 12December 2006 6:5
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
org ofgroundsubstances,collagenfibers,bloodvessels(vasavasorium,thevesselsthat
ws. supplythevessel),andnervesthatextendintothemedianlayer.
e
viy. TheVECsformapermeablebarrierthatpreventssomesubstancesfromenter-
ualree onl ing the arterial wall. VECs as well as blood cells (platelets and erythrocytes) are
als.annonal us sbheeeanr-ksnenoswitnivteo.Irnegpuarlatitceulmara,nflyuiodfsthheearVfEorCcesfuinmcptiaorntesdabnydthacetbivliotoydthflroowughhavaelpornog-
aded from arjourn05/07/07. For pers ce“flaemftofseaweslcc.gtfhs1eoa9nrenc8enoe4rdssi,oceaTatnnhlrsldaeyoulrirt”barelafs&ensuresrrlcBfaeraetdecertesktioort1nhea9ceso9em“f8pm)tpi.onerTroctohsh(tpaeaaenpcgroyphetcranrloapienpnsr,rasaidlaaniuztveeciaodtbsinooihodnycci”hplhaao(etBntomhlnraeieccaslkai)nslmdiirnsaeatnsetphpgeooarttantaetsalene.nsst2.ut0ihFnn0ehli2odie,bwexDnittsteoahirvfirenieoaeadrsfl
nloon plateletaggregation,andnitricoxide,whichisthoughttoreduceleukocyteadhesion,
wo
Doeg andmoreimportantly,tocausechangesinthe“contractiletone”oftheSMCsinthe
19. n Di mediallayer(BenDrissetal.1997;Chiuetal.2003,2004).
3a
9:293-nia - S conTsthiteurteivheaevqeubaeteionnmqaunayntcilfiyniincgalthanednolanbloinreaatorrryelsattuiodniesshaipimbeedtwaetecnhtahraecwtearlilzsitnrgestshees
2007.3Califor a1n9d78t,hGersetreaniwnarldesp&onBseerroyf2b0lo0o0d, Lveesvsyel1s9(9fo9r, MrecvVieewigshseeetCala.m20e0ro2n, V1i9t9o9&, DDoibxroinn
ech. y of 2003).Althoughsomeofthemodelsthathavebeenproposedhavebeenextremely
Rev. Fluid Mby Universit vspmtarielolulcpahrebearlmnteiieacinsianloassfnttiatomhlyeuozlbwiintaaagnlilncdaetsmrhtiaeotidbnreeioamlsslopocgedacipectlaassblouplfenrtodhoceefermpstsrheeescedhtipacaoktniionincrggslyopthuflaentchdeceeharvtasanttshogceoeudswlaiacrnlosl.yutAhsptesleiwnmmgi,leltbcbhheeetacwnnoeeimceeandel
nu. apparentinthefollowingsections,thecurrentinabilitytopreciselycharacterizethe
n
A 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
or Environmental factors: Permanent thinning of the muscular
s.
w smoking, diet, lack of median layer
e
viy. exercise
ualree onl Age and gender Rupture
als.annonal us Figure2
ded from arjourn5/07/07. For pers PpthraoethcUaeorsngsteteeinsrl.eitashilsewopfaalalsrttdefueriewaltdaonesecyuaprdyhesisml,istsh.,Itenhmteerolposltdaycgoibnmegtwmoeofennbacmcaetuecsrheiaaon(ifcmaanlosestutimrcyouslmmiamsnwdonapslhyiynsCifoellecomtgioiecnanlcoina
a0
nloon Pneumonia)fromaninfectedheartvalve,orfrombloodletting.Today,theseprimary
wo
og causes of wall degradation have been greatly diminished and other factors such as
De
19. n Di geneticdisorders,mycoticinfection,highbloodpressure,effectsofcigarettesmoking,
293-3a - Sa atheTrwoosclheerroesdisi,taarnydcsoimllapgleynagviansgcuhlaarvedbiseocrodmeresdaorme iknnaonwt.n to cause aneurysms: the
9:ni
007.3alifor Mtoaarbfanno’rsmanadlittiheseiEnhtlheerss-yDnatnhleossis’saSnydndorrogmaneisza(Wtioinlmoifntkheetsatrl.u2c0tu0r0a)l.pBroottheicnosn(terliabsutitne
2C
ech. y of andcollagen),andthustoapathologicalweakeningofthewall.Thesetwoconditions
Rev. Fluid Mby Universit aintnoroetbtrvaeyeceirrntyavbnoreialaevrlnee)dhdanaiinssdcbcoarevloetehsnrsoe-eudlxig.tnehCkniaansnifgvadefmioldyrialrctieaeoprlgloaaerggntgeeerndse,fagoonatrtdhiaoeennlraessuoptrfieynscsoiomfimrc’oseptpthoyresepsrdeisbistslropeufogcasetinunteireouatnlricycaosframmecstepox(omrpnseaehcinatnetvlsdye.
nu. Severalpredisposingriskfactorshavebeenstatisticallyshowntoplayanimpor-
n
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
298 Lasheras
ANRV294-FL39-13 ARI 12December 2006 6:5
Figure3
Aneurysmclassification
basedontheshapesofthe
aneurysms.
g
or
s.
w
e
viy.
ualree onl
als.annonal us
ded from arjourn5/07/07. For pers cwdheitaphlolesninotgsaeatdrheeovrveoersryclFtreharureoesslpiiyfsaotsdhrtmiestewsaiotseesd,weacnhadedreaerstaeanrseiaualnryseisutmersysswSfmoiartshmcactr(hueLeleaomefrteoetnstaloc.ob1ns9ec9re7vn)e.tdrTaithneedpcpautlriareqenuntest
a0
nloon thoughtisthatatherosclerosismayaidtheprogressionofthediseaseinsomecases,
wo
Doeg butitaloneisnottheprimarycauseoftheweakeningofthewall.
19. n Di Aneurysmsareoftenclassifiedaccordingtotheirshapeandlocationinthehuman
293-3a - Sa b(sopdinydinlet-oshtwapoemd)aianngeuroryuspms:sfuasriefomrmostancdomsamccounlalyrafonueunrdysinmtsh(eseaebFdiogmurinea3l)a.oFrutasifoorrimn
9:ni
007.3alifor tfohuenpdopinlittehaelamrtaeirnyabretehriinedstohfethkneecee,rwebhrearlecaisrcsauclcautiloanr,(beesprreyc-ialilklye)aalorengprtehdeoCmiirncalnetolyf
2C
ech. y of Willis.
Rev. Fluid Mby Universit ssTiuthgioTigsnehhseoytpftmohthatahrteketesahidrsetehdpraiaifseftehsbroeweegnhnecenferuesesriittsnhheoetrhfysettfhiroreerssnmehgatpp(hrmeeonucaeesscdswsubeleasylrlitshaeeslmaftsoahtsciecttdtlaihikosaerttitlnyathcsvetosismntcrceeuirwdcetehbunarrtcaaeldlaoicfrfofteAmerrAepienAost-s).
nu. (themostcommonfusiformaneurysm)increasesdramaticallywithage(Singhetal.
n
A 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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Figure4
Abdominalaortic
aneurysm(AAA)
g
or
s.
w
e
viy.
ualree onl
als.annonal us arenneaulrayrstmeriinestahnedhuupmsatrneabmodoyffiotsrmbisfuinrctahteioanbidnotmotinhaeliplioacrtaiortneroifest.hBeealoorwta,,wbeealonwalythzee
aded from arjourn05/07/07. For pers tAicanhonAcindsrAdeAisuanAscveAt2ees.rda2yds%irarnaarsroNeteifpcloryawrelwlosayepmanpyaetteainantarigov1eiev9nec95rai45ns6–eda10oin9vfydi9dte5hupaeraseshlfasukoosswufifnieoanddgremettrhh(te5aSyt0ipenAeaygr.AehlLyaAriekss8te0aoartsfhle..eaAp2gor0eeln0a,ser1ebgsn)uh.ettoIsitwtnchrhn8eeaii.esrn9n%aFiinnliscggooiudfsbretmueeneedc4nnye,
nloon found that with the gradual increase in life expectancy, the incidence of AAAs has
wo
Doeg increased steadily over the past decades, although this may simply be a result of a
19. n Di largerawarenessofthediseaseinthemedicalcommunityandimprovedscreening
3a
293-a - S methods(Bestetal.2003,Collin1988).
9:ni
2007.3Califor 2se.e1m.1s.Trehaseonagabinlegthoyapsosuthmeesitsh.atBtehceaupsreimagaeryisctahuesemoofstthdeoirmfionramnattfiaocntosrhionulAdAlAies,oint
ech. y of thecouplingbetweenthespecificchangesinthearchitectureofthevessel(length,
Rev. Fluid Mby Universit dttahhbiaeidsmyocmeiontueidnpru,alcailnenagdoinrmwtaatahlydleeslteghraruedamcdtteouosdr,aeyan)nnraudemnsiustitslctasdib.nilaTgemfhrreeeostmepprootngshtrseuaelndawoutheramlelirysaelitbnhaygcaritaneupagsnopedrsrte.oirocnessposefacntifihdcethwceoancllhdoaitfniogthneess
nu. Therehasbeenalargebodyofworkdevotedtotheunderlyingmechanismsof
n
A 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
org of the smooth muscle is then accompanied by a remodeling process whereby the
ws. collagenous content in the muscular layer increases. The end result of the above-
e
viy. mentioned,irreversibleprocessisthecreationofananeurysm.Thisprocesscanbe
ualree onl compoundedandamplifiedbyotherarchitecturalchangesthatoccurintheseelastic
als.annonal us arteIrnietshweipthoratgioen. oflargeelasticarterieslocatedupstreamofabifurcation,suchas
aded from arjourn05/07/07. For pers ttwephhfoafeepevceupatblrianedmtsoitsoahmuyneri.eabnTliawsflouhaareviconeaarittm(tiapioa,puntalleisn(teFaud)nuditdneshgecaoo1cfic9nltie9sahli3ceed,,rea1rfreet9aemfl9be7tloyhc)rt.eameAldf,onoadwrinnmiafidcvaereptdeioaoianspnselitaiothnefreatetlhhsaiaubesrldattaeomnormefipeuitlsnihr,tyaeutlshdmraeeeosflaarmeimtnxapipotillnhinifitceucrodaeeftlaeditsohoeenersf
nloon as the ratio between the cross-sectional area of the bifurcated arteries (iliacs) and
wo
Doeg the parent vessel decreases. With aging, these arteries also elongate slightly and
19. n Di gradually change their shape. Over time, the iliac arteries become more tortuous
3a
9:293-nia - S a2n0d00t)h.eActrhoesrsosseccletiroontiocfdtehpeoirsiltusmoefnpmlaqauyedeincrtehaissepcoorntsioidneroafbtlhye(Gilriaecesnwcoauldld&fuBrtehrreyr
2007.3Califor dspeeceredaoseftthheetcrraonsssm-sietctetidonwaalvaerecaauosfetdhbeiyralugminegn,t.oTgheethperrowgritehsstihveecinhcarnegaesesiinntthheewraatvioe
ech. y of ofcross-sectionalareas,maythenresultinanincreaseinpeaksystolicpressureinthe
Rev. Fluid Mby Universit aweinblaadlsalotntimceinrisnrsheiaeovlenetarscosoiribnmtalet,phocienauucmnrsdeiensadgasienaandinnalaictnycheceerrleeadraraestteseecrsirynit’bshteehddieinaimnwitiaetalhttleieosr.tpnrTreaesnhcsdeeedspp.irneOorgpmvapeagarnartateiignmortneaip,onhtfch,crereaaanicsndkecsrriieennsaustthheltdees
nu. arterialdiameterleadstoafurtherdecreaseinthearearatioandthustotheunstable
n
A 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.
org 2.1.2. The vascular endothelium: flow shear–mediated initiation hypothesis.
ws. CulturedVECstudiesshowthat“disturbedflowconditions”andunsteadyturbulent
e
viy. stressesdamagetheendothelium,andthelossormalfunctioningoftheirregulatory
ualree onl processesmayprovideafirststeptothedegradationofthewall(Daviesetal.1984,
als.annonal us 1sh9e8a6r,s1t9re9s5s)e.sSaenvderthalesltousdsioefsphearvmeesahboiwlitnytohfatthteheenredoisthaecloiarlrceelalltimonembebtrwaneeen(Cvehraypploewll
aded from arjourn05/07/07. For pers eic(1tBat9hnaa9ola9m.s,1eoaZt9ld9ashiol8fa.y,o1bCt9eeheh9ten9iaue,lfn.Beod2tul0oaanc0tld.hk22me)t0.lhia0aan3ltc,eheDtilgalahlev.xit2epe0srm0ee0stps,aoiDlor.an1al9vaain8ne6dsd,aeHsftpfaeealclt.mita1tll9hing9erg5irae,dprLireeeotnilatiefslte.or1aafl9.tw9i1o1a9n)l9.la5Fsn,hudNeratmahrgiesgertrlmraeetostisroaeenls,.
nloon These VEC studies have been the basis of an alternative, or even complemen-
wo
Doeg tary,mechanismresponsiblefortheoriginoftheseaneurysms.Asmentionedabove,
19. n Di duringthenormalcourseofaging,theabdominalaorticarterygraduallyundergoes
3a
9:293-nia - S citosnwfoarllm,ealtcc.)h.aOngveesritnimites,gtheeomreeltartyiv(einucnrceoasnisntgricittsedlennagttuhreanodftdhiiasmaertteerr,ytihniscikdeenitnhge
2007.3Califor aicbadlocmhainnaglecsatvhiatyt,minaytulrena,dctroeatthee“fdoirsmtuartbioendoflfowbe”ncdosn,dkiintikosn,sanindsiodtehethremvoerspsehlo(lio.eg.-,
ech. y of unsteady flow separation and weak turbulence). It is then argued that the anoma-
Rev. Fluid Mby Universit lbwaonuautluslonsrshsectesaipalblroaletnsitsnpregersoossgfharetsehassoresicvsVitearEtedeCsdesgewtrsoa,itdahtanhttdeihoethnhsiegeohfdaitnsshhoteuemraabarrletosedturriflseaosltswewemsac,lpolvonaerdnrayidltialotononwdsthcssepohaueftoalidrramlcsogtarnrteaitsodrsniiebesoun,fttlesothwtooef,
nu. aneurysm.
n
A 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