Microcirculation and O Systemic Vascular Changes
Dallaetalstudiesin2004theeffectsofacuteandchronicsmokingonskinmicrovas- cularpropertiesofyounghealthysubjects.Inthisobservationalstudy,usingatotallynon-
invasiveapproach,employingcontinuouspalmarmicrovascularlowlaserDopplerand arterialpressuremeasurements,atotalof20healthymalesubjectsninehabitualsmokers
and11non-smokers;aged27±1and29±2years,respectivelywereexamined [150]
. Measureswereobtainedatbaselineandafteriontophoreticadministrationofacetylcholine
ACh, an endothelium-dependent vasodilator and of sodium nitroprusside NP, an endothelium-independentvasodilator.Thestudyshowedthatsmokersshowedsigniicant
lowerbaselinemicrovascularresistiveZ0andoscillatoryimpedance,i.e.ZCproperties thannon-smokers.Inthenon-smokersgroup,AChandNPiontophoresisinducedasignii-
cant decrease of both Z0 and ZC, before and after smoking one cigarette p 0.02. Conversely,inthesmokersgroup,bothZ0andZCwerenotaffectedbyAChiontophoresis
beforeacutesmoking,while,aftersmoking,asigniicantdecreaseofbothZ0andZCp 0.02wasdetectedafterAChchallenge.Thestudyindicatesthatsmokershaveacomplex
disruptionofperipheralmicrocirculatoryregulation,includinginappropriaterestingvaso- dilation, impaired endothelium-dependent and independent vasodilation, paradoxical
recoveryofendothelium-dependentvasodilationinresponsetoacutesmoking [151]
. Inafurtherstudy,theacuteeffectsofsmokingonmicrovascularfunctioninhealthy
smokerswasstudiedusingmeasuresofHR,bloodpressure,capillaryrecruitmentduring peakreactivehyperaemiaandendothelium-dependentandendothelium-independentvaso-
dilatation of the skin microcirculation with iontophoresis of acetylcholine and sodium nitroprussiderespectivelycombinedwithlaserDopplerluxmetry
[151] Itwasfoundthat
incomparisonwithshamsmoking,acutesmokingcausedincreasesinHRsmoking,9.3± 4.1beatsmin;sham,−1.3±3.0beatsmin;p0.001andsystolicbloodpressuresmok-
ing,6.3±8.8mmHg;sham,0.8±4.4mmHg;p0.05.Also,decreasesinabsolutesmok- ing,−4.9±6.9permm
2
;sham,0.8±2.1permm2;p=0.01andrelativesmoking,−13.8± 21.4;sham,1.9±6.9;p=0.02capillaryrecruitmentduringpeakreactivehyperaemia;
anddecreasesinabsolute[smoking,-62.4±47.7perfusionunitsPU;sham,−30.8±32.6 PU;p=0.04]andrelativesmoking,−147±163;sham,32±225;p=0.07vasodilata-
tioncausedbyacetylcholineweredemonstrated.Fromthisstudyitcanbeconcludedthat acute smoking is associated with impaired capillary recruitment during peak reactive
hyperaemia and impaired microvascular endothelium-dependent vasodilatation. These indingsmayalsoexplaintheincreasedbloodpressureanddecreasedinsulinsensitivity
thathavebeenobservedafteracutesmoking [151]
. VascularresponseandO
2
supplyoftheskinanddeepertissuelayerscanbemeasured bylaserDopplerlowmetryandbydeterminingtranscutaneouspartialO2pressurewith
platinumelectrodes,asourownresearchhasdemonstrated [9]
.Attentionwasdrawnlong agotothedifferencesbetweenthereactionsproducedbycigarettesmokeandbynicotine
[152] .Reactivehyperaemiaoccurringafter1–3minocclusionoftheupperarmwitha
bloodpressurecuffanditsnormalisationhavebeenfoundtodifferbetweensmokersand non-smokers
[9,153,154] ,withreactivehyperaemiainsmokersbeinglessthanthatin
non-smokersseeFig. 6.6
:thereasonsforthisarecertainlytobesoughtinvasorespon- sivenessNOproductionandintheviscosityoftheblood,whichinluencesitslowprop-
erties [9]
. The differences in vasoreactivity were still detectable even after a 6-month observationperiodFig.
6.7
[8] .Forasummaryoftheindingsonthistopic,readersare
referredto [155]
.Simultaneousphotoplethysmographicrecordingsofbloodlowatdiffer- enttissuesitesrevealedaconsiderablevasocontrictiveresponseintheingersandamore
modestresponseinthetoes;theresponsewasabsentintheforeheadandearrecordings [154]
.Themagnitudeofthevascularresponseintheingersdidnotcorrelatewiththe nicotineyieldofthecigarettes.
O
2
supplyisassociatedwithtissueperfusion.Aftersmokingorchewingnicotine-con- taininggum,digitalbloodlowwasreduced,andthiseffectoccurredearlieraftersmoking
after5minthanafterchewingnicotinegumafter45min [137]
.Bycontrast,nochanges intcpO
2
weremeasuredeitheraftersmokingorafternicotine [156,157]
.Theseindings standincontrasttoourownlong-termresultsfromtheNiveSStudyFig.
6.8 wherea
changeintcpO
2
couldstillbedetectedevenafter6months’smokingcessation,incompari- sonwithsmokers
[8] .InvestigationoftcpO
2
insmokingandnon-smokingmothershas revealedalesspronouncedhyperaemicreactioninsmokingmothersthaninnon-smoking
motherssee Chap.8
.WhenaninvasivemethodwasusedtomeasureO
2
,areductioninO
2
supplylastingfor30–50minwasdetectedafterasinglecigarettehadbeensmoked
[158] .
Inoverallterms,accordingtotheresultsofthe6-monthNiveSStudy [9]
,theinhaledcom- bustionproductsoftobaccohavegreatersigniicanceforthepathogenesisthannicotine.
Whilenicotinedoespossessvasoconstrictorpropertiesofitsown,thesearenotresponsible for the hypoxaemic reactions, as also conirmed by clinical trials in angina patients
18 16
14 12
10 8
6 4
2 1
2 3
4 5
6 7
8
Time [min]
Arbitrary units
Fig. 6.6
Post-ischaemic reactivehyperaemiaonthe
skin,measuredbylaser Dopplerlowmetryin16
smokersbeforestraightline andafterdashedline
smoking.Theverticalbars indicate±standarderrorof
themean [210]
–2 2
6 10
14 18
22 26
13 12
11 10
9 8
7
Reactive Capillary Flow t -pmax [sec]
Relapsers 70 Smokers 30
Abstainers 50 Weeks
Fig. 6.7
Changesinmaximal rateofincreaset-p
max
insin intracapillarylowofredcells
after3minofforearm ischaemia.Ex-smokers,
relapsersandsmokersover the26-weekstudyperiod.
Theverticalbarsindicatethe standarddeviationsateach
measuringtime [9]
see Table 6.3
[55]
. Ultimately, the facial colouring of a person who has smoked for decadesspeaksforitself
[159] .
Bloodlowdefectswererecordedby
82
rubidiumemissiontomographyin8outof13 patientswithCHDundergoingbicycleergometerexercise;in6ofthese8patientsthe
bloodlowdefectswerealsorecordedatthesamesiteswhenasinglecigarettewassmoked. Acausalrelationshipwithsmokingmaybeassumed,withreducedO
2
availability [95,
103] ,increasedplateletaggregationtogetherwithraisedplasmaibrinogenconcentrations
[5,109,160] ,reducedNOandEDRF
[49,50,113] andincreasedbloodCOlevels
[161, 162]
contributingtomyocardialischaemia.In63patientsnon-smokerswithstableangina andwithproven70stenosisforatleastonecoronaryartery,ergometerexercisepro-
ducedST-segmentdepressionafterexposureto2or4carbonmonoxideseeFig. 6.9
. Simultaneously,thetimetoonsetofangina,timetoST-segmentdepressionaswellas
exercisetimewererecordedasendpointsFig. 6.9
[162]
.Theeffectswereverymuch morepronouncedafterexposureto4COthanto2CO.SmokerswithCO-Hblevels
5shouldgiveupsmokingbecauseofthedangerassociatedwiththeconsequencesof existingischaemicheartdisease.
60 50
40 30
TcpO2 [mm Hg]
−2 2
6 10
14 18
22 26
Week
Abstainers 51 Relapsers 72
Smokers 33
Fig. 6.8
Changesintranscutaneouspartialoxygenpressurebasevaluemean±standarddeviation; 95CIbetweenbaselineand26weeks.p0.001betweenbaselineandthevarioustime
pointsinabstainersandrelapsers.Signiicancep=0.0339top0.001alsobetweensmokersvs. abstainersorrelapsersatalltimepoints
[9]
Controls n=36
14mgnicotine patchn=36
21mgnicotine patchn=36
p-value PerfusiondefectLV
–Total 17.5±10.6
12.6±10.1 11.8±9.9
0.001 –Ischaemia
10.1±8.5 7.2±6.7
6.7±6.3 0.036
COppm 23.3±10.5
13.8±9.6 12.4±8.8
0.001 Nicotinengml
15.8±8.3 24.2±12.0
30.4±10.8 0.001
Cotininengml 290±137
338±186 422±224
0.002 Cigaretteconsumption
daily 31±11
11±10 8±7
0.001
Table 6.3
Effectofnicotinepatchesonperfusioninthedamagedmyocardiumofpatientswith CAD
[55]
Measurementsby201Tl-SPECT3and6daysafterdailyapplicationofanicotinepatch