E R Bates, F M Aueron, V Legrand, M T LeFree, G B Mancini, J M Hodgson and R A Vogel
transluminal coronary angioplasty on regional coronary flow reserve.
Comparative long-term effects of coronary artery bypass graft surgery and percutaneous
Print ISSN: 0009-7322. Online ISSN: 1524-4539
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SURGERY
Comparative
long-term
effects of coronary artery
bypass
graft surgery and percutaneous transluminal
coronary angioplasty on regional coronary flow
reserve
ERIC R. BATES,M.D., FRED M. AUERON, M.D., VICTORLEGRAND,M.D.,MICHAEL T. LEFREE, B.S.,
G. B. JOHN MANCINI, M.D., JOHN M. HODGSON, M.D., AND ROBERT A. VOGEL, M.D.
ABSTRACT Toevaluate the relative long-term improvement in coronary artery hemodynamics after revascularization by coronary artery bypass graft surgery (CABG) or percutaneous transluminal coro-nary angioplasty (PTCA), regional coronary flow reserve (CFR) was measured, by digital computer analysis of 35mmcine film, in 50 menundergoing cardiac catheterization. CFR (mean ± SEM) in 12 atherosclerotic arteries before revascularization was 1.02 + 0.05. Mean CFR in 29 normal arteries of men with normal coronary arteriograms was significantly higher (2.59 + 0.11) than that in 16
atheroscleroticarteries of patients revascularized by CABG (2.02 + 0. 17, p< .01) or in 14 atheroscle-rotic arteries of those revascularized by PTCA (1.97 + 0.12, p< .01). NodifferenceinCFR between the CABG and PTCA groups was found and variables known to influence CFR were similar between groups. Equivalent and significant long-term improvement in coronary artery hemodynamics is pro-vided by CABG or PTCA. We postulate that the difference in CFR in the men with normal arteries and
thosewho underwentrevascularizationwasrelatedtothe effects of thegeneralatherosclerotic process,
which remain despite successful treatment by these techniques.
Circulation 72, No. 4, 833-839, 1985.
MYOCARDIAL REVASCULARIZATION can now
beaccomplishedbyeithercoronary arterybypass graft
surgery (CABG) or percutaneous transluminal
coro-nary angioplasty (PTCA).`- Although symptomatic,
metabolic, hemodynamic, and functional
improve-ment has been demonstrated with each technique,5-'5
little data exist comparing the two. 6. 17 One difficulty
inundertakingcomparativestudies resides in the clini-cal disparities in groups ofpatients undergoing these procedures. While patients who undergo CABG are
more likely to have chronic symptoms, a history of myocardial infarction, and multivessel disease, those
treatedby PTCAcharacteristicallyhaverecentonsetof
symptoms, normal ventricular function, and
single-vessel disease. More importantly, the lack ofa
gener-ally available clinicaltestsensitive enoughtoevaluate
From the Division ofCardiology,VeteransAdministration Medical
Center, AnnArbor.
Supported in part bygrants from the VeteransAdministration, the
MerckFellowshipFoundation of the AmericanCollegeofCardiology,
andthe MichiganHeartAssociation.
Address forcorrespondence:Eric R.Bates,M.D.,Division of Cardi-ology,VeteransAdministrationMedicalCenter,AnnArbor,MI48105.
Received Feb. 7, 1985;revision acceptedJune 20, 1985
subtle regional differences in coronary blood flow or
myocardial function dueto eithertechnique has inhib-ited investigation.
Thecoronaryreactive hyperemicresponse isan
im-portant,reproducible physiologicparameter.l' 1' Itcan
be measuredbydeterminingthe ratioof maximal coro-nary blood flow to resting flow. Increasingly
signifi-cant obstructive coronary artery disease progressively exhausts thiscoronaryflowreserve(CFR) byreducing
peak flow.202 Three techniques have recently been
developedthat allow themeasurementofregionalCFR inman. Thefirstuses apulsed Dopplercoronary artery catheter, which can measure proximal coronary flow velocity in the catheterization
laboratory.2-2
The seconduses a Doppler velocity probe, which can be applied
directlyto selected epicardial coronary arteries at the time of open heart surgery to measure the reactive hyperemic response to transient arterial occlusion.25
Thethirdisadigital radiographic techniqueperformed
during routihe cardiac catheterization that measures
the myocardial reactive hyperemic response to
intra-coronary injection of contrast medium.24 25
The presentstudy, in which we usedthethird
tech-833
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BATES etal.
nique,
wasdesigned
to evaluate the relativeimprove-ment in
long-term regional
CFR aftermyocardial
re-vascularization
by
CABG or PTCA.Methods
Patientpopulation. The patient population consisted of 50 men undergoing coronary arteriography. These patients were
divided intofour groupsforanalysis. GroupIwas composedof 10
patients
withsymptomaticcoronary arterydisease(atotal of 12diseasedarteries)who subsequentlyunderwent revasculari-zationby
CABG or PTCA. Eleven patients with 16 arteriespreviously
treated byCABGformed group II, and 13 patientswith 14arteriespreviously treated byPTCAformed group III; these
patients
were studied to evaluate postrevascularizationvesselpatency. Ingroup Il patients all grafts were patent and
nonstenotic, and in those in group III there was a residual translesional pressuregradientof 20mmHgorlessatthe time of
angioplasty
and no angiographic evidence of restenosis atfollow-up.
Twenty-nine arteries in 16 patients with atypicalchest
pain
and normal coronaryarteriograms formedgroup IV and servedasthenormalcontrolgroup. Patientswereexcluded ifthey
had valvular heart disease, electrocardiographic evi-denceof leftventricularhypertrophy,morethanmildhypokine-sisdocumentedonthecontrastventriculogram,or
angiographi-cally
visible coronary collateral vessels. Data from 15% of arterial distributions were excluded from analysis because of use ofaninadequate
contrastinjectiontechnique,motionarti-fact, poorvisualization ofthe perfusionbed, orfailure of the
angiographer
toacquire arteriographicdatasuitable fordigitalprocessing.
Prescribed medicationregimenswerenotfollowedthe
morn-ing
of the cardiaccatheterization. Patientswere premedicatedwith 10 mg
diazepam
and 50 mgdiphenhydramine. Thisstudywas
approved
by the institutional committees on humanre-search andinformed consent wasobtained from eachpatient.
Arteriographic
technique. To obtain images for digitalprocessing,
the following arteriographic technique was used. Standard left ventriculography and multiple-view selective coronaryarteriography
were performed by the Judkinstech-nique. Arteriography
for subsequent functional image digitalprocessing
was obtained in the left anteriorobliqueprojection on 35 mm cine film. Fixed parameter (kV, mA, and pulsewidth)
cineradiography
at 30 frames/sec was used. Patients wererequired
toceaserespirationand remainmotionlessduringfilming.
Veingrafts and coronary arterieswereopacifiedby afixed dose of 5to8 mlof sodiummegluminediatrizoate
(Reno-grafin-76)
injected by an electrocardiographically triggeredpower
injector
gated to the R wave of theelectrocardiogram.Refluxofcontrastmedium intotheaorta wasconsideredproof thatamaximal bolus ofcontrastwasdeliveredtothearteryand
that thecatheterwasnotimpedingcoronary blood flow. Base-line studies were performed at least 3 min after the previous
injection
ofcontrast. Studies underhyperemicconditions wereperformed
10 sec afterintracoronary injection ofan identical dose ofcontrastmedium. Cineradiographywasinitiatedatleast onefull cardiaccyclebeforeinjectionofcontrast.Adensitystepwedge
was imaged and checked densitometrically after filmprocessing
toensure that the film gray scale waskeptconstant on aday-to-day
basis.Digital
processingof thefunctionalimage. Digital imageprocessing
wasperformed by a technique similarto thatpre-viously
described.2 27 Threegeneral operationswererequired:digitization,
mask-mode substraction, and functional imagegeneration. Arteriogramsweredisplayedon acine film
projec-tor
(Vanguard
Corporation, XR-35) equipped with aprimary beam splittercoupledtoafixed-gainvideo camera and a videoanalog-to-digital converter. Five toseven end-diastolic frames from consecutive cardiac cycles were chosen, with use ofthe criterion of closest duplication of arterial position, beginning
with the end-diastolic frame just before injection of contrast
medium. Theseframes were digitized into 512 x 512 x 8-bit matrixes. Video-amplified gain andprojector light levels were
adjusted to provide a linearcorrespondence between contrast x-ray absorption and digital scale. The digital images were stored in the disk memory of a digital radiographic computer (DPS-4100C. ADAC Labs, Edenvale, CA) for subsequent
processing.
Imageenhancement was performed bystandard mask-mode subtraction with useof theend-diastolic frame beforeinjection ofcontrastasthemask. Asingle contrastintensityand
appear-ancetime-modulated functional imagewasthengeneratedfrom eachsetofenhancedframes(figure 1).25Theintensityvalueof each pixel corresponded to the maximum contrast density
reachedduringeach acquisition, while theappearance time of
contrastin thepixelwascolormodulated, withadifferentcolor assigned to eachpostinjection cardiac cycle (redfor the first cycle,yellowfor thesecond, etc.).Only pixelswithanintensity aboveapresetthresholdappearedonthe finalfunctionalimage. This thresholdwasmanuallysetatalevel that excludedmostof the background noise intensity. Acquisition and processing
wereidentical for each pairofbasal and hyperemicimages so that eachset was technically comparable.
Analysis offunctional images. Mean myocardial contrast
density and appearance were determined by a computer
pro-gramthataveragedpixelvalues inaregionofinterest definedby
the operator in the basal images and in the same area of the hyperemicimages(figure 1). Large epicardialcoronaryarteries andareasthat overlapped with the aortic root, diaphragm, or
coronary sinus were excluded from analysis. Since contrast
density is directlyrelatedto thevolume ofdistribution in the myocardiumand flow isinverselyrelatedtomyocardialcontrast
appearancetime,digitalestimation ofcoronaryblood flowwas
calculated as
Q Xcvolume/time xCD/AT
whereQ =meanregionalcornaryflow;CD =meanmaximal
contrast density; and AT = mean contrast appearance time.
CFR,the ratio ofhyperemic(H)flowtobasal(B) flow,
correct-ed for heart rate (HR), was calculatedas
CFR= QH/QB = CDH/CDB X ATB/ATH x HRH/HRB
Studies indogshavedemonstratedanexcellent correlation
be-tween CFRmeasured by electromagnetic flow probe and the ratioCD/AT measuredby digital subtractionangiography(r = .92).Thedigitalmeasurementswereaccurate(regressionslope
=.90),reproducible(+-13%),andhad low interobserver(r .99) and intraobserver(r = .98)variability.25
Dataanalysis.Dataareexpressedas mean + SEM.
Statisti-cal comparisons between groups wereobtained withthe
two-tailed, unpaired t test. Significant differences were assumed when confidence limits exceeded 95% (p < .05).
Results
Clinicalcharacteristics.Theclinicalcharacteristicsof
the patients groups are listed in table 1. Nine of 11
patients ingroup II(CABG) had triple-vesseldisease,
while nine of 13 patients in group III (PTCA) had
single-vessel disease. Forty-two of the 48 diseased
arteries in group IIand IIIpatients were successfully
revascularized. Two patientseachin groups II andIII
FIGURE 1.Conit-astmiiediuILIm appearancepictLrCes fanaolt malrigehtcaot00dB atter inthleii ititeitol- obiiuLeCprojectionls at
baselinle(/efit and Linidet l\peIci-ciz tJi conditions. CFR was calculated tobe2.49 in the ecionlat interest.
still had exertional chest pain; the others were pain
free. The hemiioglobin averaged 14.9 + 0.7 gldl in
group II and 15.0 + 0.3 g/dl in group III and the
interval between revascularization and catheterization inthese two groups was 15.4 ± 2.0 and 32.6 ± 4.2 weeks, respectively.
Cardiac
catheteri7zationi.
Data obtained at cardiac catheterization for the fourpatientgroups arelisted in table2. There were nosigniificant dilferences in heart rate, mean aortic pressure, or pressure-rate product between groups.Althougrh
group Ill patients had asignificantly lower left ventricular ejection fraction than the men with normal arteries (group IV) (p <
.01), the value was not statisticallydifferentfromthat in group 11, and was well within normal physiologic limits. No difference in left ventricular end-diastolic
pressuresexisted. Percent luminal stenosis of arteries
was 80 + 4% in group I and 17 ± 3% in group Ill.
CFR. Individual values for CFRfor each group are
plotted in figure 2. CER in five patients who
subse-Vol. 72, No. 4. OctobeI 1985
quently underwent CABG and in five patients who subsequentlyunderwent PTCAaregroupedtogether in
group I becausetheywereequivalent(l.
1u
± 0.05 vs0.95 + 0.06). Mean values for CFR for grcoups 1,11, Ill, and IV were 1.02 ± 0.05, 2.02 + 0.17, 1.97 +
0.12, and 2.59 ± 0.11, respectively. While CFR in
patients withatheroscleriotic arteriesrevascularized by
CABGorPTCA was significantlyhigherthan in those with arteries not revascularized (p < .0001), it was
significantlylower thanCFRin men withnormal
arter-ies (p< .(01). NodifferenceinCFRingroupsII and III
was found. Discussion
Autoregulatory changes maintain basal coronary
blood flow in arteries with flow-limiting stenoses by
decreasing distal coronary resistance, but this limits
potential further increases in flow. In arteries with
high-grade stenoses suitable for revascularization by
CABGorPTCA, CFR isexhausted. An improvement
835
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BATESetal.
TABLE 1
Characteristics of the 50studypatients
Group I Group II Group III Group IV (n = 10) (n = 11) (n = 13) (n = 16)
Age(yr)A 56+3 57+2 55+3 48+2
No. of diseased vessels 19 31 17 0
No. ofvessels revascularized 18 27 15 0
No. of vessels studied 12 16 14 29
LAD 7 5 6 9
Diagonalbranch 0 3 0 0
Leftcircumflex 2 6 2 8
RCA 3 2 6 12
Medications beforetesting
Nitrates 10 3 3 10
,f-blockers 2 9 0 11
Ca+ +-blockers 6 2 9 3
LAD = left anteriordescendingartery;RCA AMean ± SEM.
rightcoronary artery.
inindividual arterial CFR several months after CABG andimmediatelyafterPTCA,asmeasuredbycoronary
radiography, has been demonstrated previously.26 27 Wehave since modifiedour image analysis algorithm
andusecontrastdensityinformationtoreflectregional vascular volume and the CD/AT ratio to more
accu-rately estimatecoronary blood flow.25 While the CFR
values found for vessels without severeobstructionare
higher when CD/AT ratios than when AT ratios are
used,2 27findingswithbothmethodsindicatethatCFR is absent in vessels with high-grade stenoses suitable forrevascularization. In this report, the long-term ef-fects ofrevascularization as determined bythese two
techniques werecompared with this refined image
al-gorithm. Equivalent and significant long-term
im-provements in regional CFR were found in arteries
revascularized byeither CABG orPTCA.
Additional-ly, eventhough revascularization wasquitesuccessful in each artery, normal CFR was not restored.
Clinicalimplications.CABGhas been themost
popu-larmeansofrestoring regional myocardialblood flow
to perfusion beds distal to coronary stenoses for 15
years. More recently, PTCA has emerged as an
alter-native revascularizationtreatmentfor single-vessel ob-structive coronary artery disease. It has clearly been demonstrated that successful revascularization by CABG or PTCA produces symptomatic, metabolic,
hemodynamic, and functional improvement.'-" The
current investigation is the firstto suggestthat
equiv-alentimprovementinindividualcoronaryartery
hemo-dynamicsisachievedbythetwotechniquesandfurther justifies the use of revascularization by CABG or
PTCA in properly selected patients.
Theoreticalimplications.The failure of successful
re-vascularizationto restorenormalCFRto
atherosclerot-ic coronary arteries is probably the most interesting findingofthis study andoneforwhich anexplanation
isnotreadilyapparent.Thepatients in eachgrouphad
equivalent basal oxygen demands, as estimated by
pressure-rateproduct, and normal global left
ventricu-larfunction. Patientswith severeregionalwall motion
abnormalities, collateral blood flow,orleft ventricular
hypertrophy were excluded becausethese factors can
haveaneffecton CFR independentof that ofcoronary
TABLE 2
Cardiac catheterization data
GroupI GroupII Group III Group IV (n = 10) (n = 11) (n = 13) (n = 16)
Heart rate(beats/min) 75+2 75+3 74+3 71 3
Mean aortic pressure (mmHg) 92 3 95 4 97 3 93 3
Pressure-rateproduct (x10 ') 99 + 4 96+ 5 98 ± 5 90+ 6 Left ventricularejection fraction (%) 65 ± 4 67+ 3 59 + 3A 73 ± 3 Left ventricular end-diastolic pressure (mm Hg) 13 ± 2 10+2 14 ± 2 13+1
Data expressed as mean + SEM.
Ap< .01,ascompared with the control group(group IV).
4.0 - 35-0 H 3.0 Cc W G 2.5-W U) W cc 200 LAL >- 1.5 z 0 g 1.0o o5 p<O.OOO1 I p<O.01 N.S. 0 0 0 0 0 a a GROUP CAD n:12 GROUP II CABG n 16 0 a to GROUPIlIl PTCA nfl 14 0 0
L
GROUPIV NORMAL n:29FIGURE 2. Long-term CFRvalues for thepatientgroupsasdetermined
by digitalcoronary radiography. CAD = coronaryartery disease.
stenoses.28-31 By using contrast medium as a direct
vasodilator stimulus, ratherthan depending onthe
is-chemic stimulation ofvessel occlusion often used in
the operating room, we avoided measurement ofany
influence dualblood supply mayhave hadon
determi-nations of graft CFR. Also, the arteries subjected to
PTCA had very mild residual luminal stenoses and
wouldthusnotbe expectedtobeassociated with limi-tations of peak coronary blood flow.20 21 In the early postrevascularization period patients were receiving
antianginal medications prescribed by their referring physicians for prophylactic reasons, not because of persistentischemia;nonereceivedantianginal
medica-tions on the day of the catheterization.
Itisunlikelythatuseofasaphenousveingraftasthe
proximal conduit for coronary blood flow influences coronary artery hemodynamics. No change in timing
ofthe resting pulse wave, pressure contour, or distal
blood flow was found by Kakos et al.32 in bypassed
normal canine coronary arteries. Others have shown
graft CFR to be normal in the canine model.`
Like-wise, Brandtet al.34 have demonstrated restoration of
normal CFRbyCABG ina nonatherosclerotic human
right coronaryartery originating fromthe left sinus of Valsalva.
It is postulated that the difference in CFR in men
with normal arteries and those who underwent
revas-cularization is related to the atherosclerotic disease process. First, although obstructive coronary artery
disease, as defined by the coronary arteriogram, is
Vol. 72, 4,
often detected as discrete proximal luminal stenoses
treatable by CABG or PTCA, anatomic descriptions have repeatedly demonstrated the diffuse nature of atherosclerotic plaque in diseased epicardial coronary
arteries.5"- Secondly, local vasomotorreactivity may notbe normal in atherosclerotic arteries. Neovascular-ization in theregion of atherosclerotic plaque has been visualized by cinematography after silicone polymer injections into the arteries ofisolated human hearts.38 These transmural vascular networks potentially pro-vide higher concentrations of vasoconstrictor sub-stances and theproliferation of autonomic nerve termi-nals known to accompany neovascularization may enhance localcatecholaminelevels.38 Also, endotheli-al damage due to mechanical injury oratherogenesis
hasbeenshown to inhibit arterial smoothmuscle relax-ation.39 40 Finally, vascular reactivity at the arteriolar level may be affected by the atherosclerotic disease
process through intimal thickening and fibrosis,41
al-tered a-adrenergic tone,42 or chronic
microemboliza-tion of platelet aggregates.43
The effect of experimental atherosclerosis on CFR hasbeen studied in thecynomolgus monkey.44 Afteran
atherogenicdiet wasgiventoinducelesionsproducing
anaverageof60% luminal stenosis,anormal diet was
givenfor aregression period of 18months. Whilethe
degreeof stenosis wasreducedto25%,intimal fibrosis was increased and CFR was only partially restored.
The authors concluded thatintimal fibrosis substantial-ly limited arterial hemodynamic improvement.
Studylimitations.Thelimitations of the digital radio-graphictechnique we used have been previously sum-marized and include those relatedtospecific hardware requirements, motion artifact, use of contrast medium
as the hyperemic stimulus, and the mathematic as-sumptions necessary for calculation of blood flow.2-27 45 Despite these difficulties, a good correla-tion between electromagnetic flowmeter and digital
radiographic determinations of relative regional CFR has been demonstrated.29 Also ofconcern is the fact that aboutaquarterof the normal CFR valueswereless than 2. We have recently shown that patients with
chest pain, normal coronary arteriograms, and low regional CFR frequently have associated regional ab-normalities onradionuclide exercise tests.46 These pa-tients probably have ischemic heart disease without
epicardial coronary stenoses.47 48 Since this normal
group was defined only by the arteriogram, without radionuclide exercise test data, it is likely that the
difference in CFR in the group with normal arteries
and the group undergoing revascularization is larger than stated.49 The widerange ofCFR values found in at UNIV MEDECINE LEIG 228272 on May 27, 2014
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BATES etal.
eachpatient group probablyreflects the multiplicity of factors that can influence arterial CFR.49 5
In summary, revascularization by CABG or PTCA
restores equivalent CFR to individual coronary
arter-ies. Although normal CFR is not
achieved,
this im-provementincoronary arterialhemodynamics is suffi-cient to reverse clinically detectable myocardial ischemia. The difference in CFRin normal andrevas-cularized arteries requires further evaluation. Confir-mation that physiologic perturbations accompany the
previously documented anatomic changes caused by the presence of coronary atherosclerosis, despite suc-cessful revascularization of angiographically visible
proximal
stenoses, would be of importance inunder-standing the pathophysiology of obstructive coronary
disease.
We areindebted toMr. GlennBeauman for technical assis-tance and to Ms. Diane Bauer forassistance in preparing the manuscript.
References
1. Favaloro RG: Saphenous vein graft in the surgical treatment of
coronary arterydisease.Operative technique. J ThoracCardiovasc
Surg 59: 178, 1969
2. FavaloroRG:Directmyocardial revascularization: A ten year jour-ney. Mythsand realities. Louis F. BishopLecture. Am JCardiol 43: 109, 1979
3. Gruentzig AR, SenningA,SiegenthalerWE: Nonoperative
dilata-tion ofcoronaryartery stenosis: Percutaneous transluminal coro-nary angioplasty. N Engl J Med 301: 61, 1979
4. Gruentzig AR: Percutaneous transluminal coronary angioplasty: sixyears' experience. Am Heart J 107: 818, 1984
5. PeduzziP,HultgrenHN:Effect ofmedicalvs surgical treatment on
symptomsin stableangina pectoris. TheVeteransAdministration
CooperativeStudy of SurgeryforCoronaryArterial Occlusive
Dis-ease. Circulation 60: 888, 1979
6. Kent KM, Bentivoglio LG. Block PC. Cowley MJ. Dorros G.
GosselinAJ, GruentzigA, Myler RK, Stertzer SH, Williams DO, FisherL,Gillespie MJ,DetreK.KelseyS,MullinSM,Mock MD: Percutaneous transluminal coronary angioplasty: report from the
Registry ofthe National Heart. Lung. and Blood Institute. Am J
Cardiol 49: 2011, 1982
7. KlosterFE, KremkauEL,RitzmannLW,RahimtoolaSH,RoschJ,
Kanarek PH: Coronary bypass for stable angina: a prospective
randomized study. N Engl J Med 300: 149. 1979
8. Williams DO,RileyRS, SinghAK,Most AS: Restorationof
nor-malcoronaryhemodynamicsandmyocardialmetabolism after
per-cutaneoustransluminalcoronaryangioplasty. Circulation 62:653.
1980
9. Barry WH, Pfeiffer JF, Lipton MJ, Tilkian AG, Hultgren HN: Effectsofcoronary arterybypass grafting on resting and exercise
hemodynamics inpatientswithstable angina pectoris: a prospec-tive randomized study. Am JCardiol 37: 823, 1976
10. Rothman MT, Baim DS, Simpson JB, Harrison DC: Coronary
hemodynamicsduringpercutaneous transluminalcoronary
angio-plasty. AmJ Cardiol 49: 1615, 1982
11. RahimtoolaSH:Postoperative exercise responsein the evaluation of thephysiologicstatusaftercoronary bypass surgery.Circulation
65(suppl II): 11- 106. 1982
12. RitchieJL,Narahara KA.TrobaughGB,WilliamsDL.Hamilton GW: Thallium-201myocardial imaging before and after coronary revascularization. Assessmentofregional myocardial blood flow and graftpatency. Circulation 56: 830, 1977
13. SchollJM, Chaitman BR, DavidPR,DuprasG. BreversG, Val
PG,CrepeauJ, LesperanceJ. Bourassa MG: Exercise electrocar-diography andmyocardial scintigraphyin the serial evaluation of
838
theresults ofpercutaneoustransluminalcoronaryangioplasty. Cir-culation 66: 380, 1982
14. Kent KM, Borer JS, Green MV, Bachrach SL, McIntosh CL. Conkle DM. Epstein SE: Effects of coronary artery bypass on
global and regional left ventricular function during exercise. N
EnglJ Med298: 1434, 1978
15. Kent KM, Bonow RO. Rosing DR, EwelsCJ, Lipson LC. Mcln-toshCL, Bachrach S, Green M. Epstein SE: Improvedmyocardial functionduringexercise aftersuccessfulpercutaneoustransluminal
coronary angioplasty. N EnglJ Med 306: 441. 1982
16. Williams D, Singh A, Most A: Sustained efficacy of coronary
angioplasty documented by stress testing atoneyear. J Am Coll
Cardiol 1: 644. 1983 (abst)
17. Meier B, Gruentzig AR. Siegenthaler WE, Schlumpf M: Long-term exerciseperformance after percutaneous transluminal coro-naryangioplastyand coronarv artery bypass grafting. Circulation
68: 796. 1983
18. CoffmanJD, Gregg DE: Reactive hyperemia characteristics of the
myocardium. AmJ Physiol 199: 1143, 1960
19. Olsson RA, Gregg DE: Myocardial reactive hyperemia in the una-nesthetized dog. AmJ Physiol 208: 224. 1965
20. Gould KL, Lipscomb K, Hamilton GW: Physiologic basis for
assessing critical coronary stenosis: instantaneous flow response andregional distribution duringcoronaryhyperemiaasmeasureof coronary flow reserve. Am J Cardiol 33: 87, 1974
21. Gould KL. Lipscomb K: Effects of coronary stenoses on coronary flow reserve and resistance. AmJ Cardiol 34: 48, 1974
22. Cole JS, Hartley CJ:Thepulsed Dopplercoronary arterycatheter.
Preliminary report of a new technique for measuring rapid changes in coronary flow velocity in man. Circulation 56: 18. 1977
23. MarcusM,Wright C, DotyD,EasthamC.LaughlinD, Krumm P,
Fastenow C, Brody M: Measurements ofcoronary velocity and
reactivehyperemia inthe coronarycirculation of humans. Circ Res
49: 877, 1981
24. VogelRA,LeFree MT, Bates ER, O'Neill WW, Foster RK, Kirlin
PC.Smith D, Pitt B: Application of digital techniques to selective coronary arteriography: Use of myocardial contrast appearance time to measure coronary flow reserve. Am Heart J 107: 153, 1984
25. HodgsonJMcB.LeGrandV,Bates ER,Mancini GBJ, Aueron FM. O'Neill WW, Simon SB, Beauman GJ, LeFree MT. Vogel RA: Validation in dogs of a rapid angiographic technique to measure relative coronaryblood flow during routine cardiac catheterization. AmJ Cardiol 55: 188. 1985
26. O'Neill WW. Walton JA. Bates ER, Colfer HT. Aueron FM, LeFree MT. Pitt B, Vogel RA: Criteria forsuccessful coronary angioplasty, as assessed by alterations in coronary vasodilator re-serve. J Am Coil Cardiol 3: 1382. 1984
27. Bates ER, Vogel RA, LeFreeMT.Kirlin PC, O'Neill WW. Pitt B: The chronic coronary flow reserve provided by saphenous vein
bypass grafts as determined by digital coronary radiography. Am HeartJ 108: 462, 1984
28. PichardAD. Gorlin R, Smith H, AmbroseJ, MellerJ:Coronary flow studies in patients with left ventricular hypertrophy of the hypertensive type. Evidence for an impaired coronary vascular reserve. AmJ Cardiol 47: 547. 1981
29. Marcus ML, Doty DB, HiratzkaLF. Wright CB, Eastham CL: Decreased coronary reserve: A mechanism for angina pectoris in patients with aortic stenosis and normal coronary arteries.N Engl J Med 307: 1362. 1982
30. Pichard AD, Smith H. HoltJ,Meller J,Gorlin R: Coronary vascu-lar reserve in left ventricuvascu-lar hypertrophy secondary to chronic aortic regurgitation. Am J Cardiol 51: 315, 1983
31. White CW, Wright CB. Doty DB, Hiratzka LF, Eastham CL, Harrison DG, Marcus ML: Does visual interpretation of the coro-nary arteriogram predict the physiologic importance of a corocoro-nary stenosis? N Engl J Med 310: 819, 1984
32. Kakos GS, Oldham HN. Dixon SH, Davis RW, Haggen P-O,
Sabiston DC: Coronary artery hemodynamics afteraorto-coronary
artery vein bypass. J Thorac Cardiovasc Surg 63: 849, 1972 33. FoltsJD, Kahn DR, BittarN.Rowe GG: Effects of partial
obstruc-tion on phasic flow in aortocoronary grafts. Circulaobstruc-tion 51/52
(suppl 1):1-148, 1975
34. Brandt B, Martins JB,MarcusML: Anomolous origin of the right coronary artery from the left sinus of Valsalva. NEnglJ Med 309:
596,s 1982
CIRCULATION
at UNIV MEDECINE LEIG 228272 on May 27, 2014 http://circ.ahajournals.org/
35. AmettEN, Isner JM, RedwoodDR,Kent KM, Baker WP,
Acker-stein H, RobertsWC: Coronary artery narrowing in coronary heart
disease: comparison of cineangiographic and necropsy findings.
Ann Intern Med 91:350, 1979
36. Roberts WC,Jones AA: Quantitation of coronary arterial
narrow-ing atnecropsyinsudden coronary death: analysis of 31 patients
andcomparisonwith 25 control subjects. Am J Cardiol 44: 39, 1978
37. Roberts WC, Jones AA: Quantification of coronary arterial
narrow-ingatnecropsyinacutetransmuralmyocardial infarction: analysis andcomparison of findingsin 27patients and 22 controls.
Circula-tion 61: 786, 1980
38. Barger AC, Beeuwkes R, Lainey LL, Silverman KJ: Hypothesis: vasa vasorum andneovascularizationof humancoronary arteries. Apossible role in the pathophysiology ofatherosclerosis. N Engl J
Med310: 175, 1984
39. Furchgott RF, Zawadzki JV: The obligatory role of endothelial
cells in the relaxation of arterial smooth musclebyacetylcholine.
Nature288: 373, 1980
40. Habib JB, Wells SL, Williams CL, Henry PD: Atherosclerosis impairsendothelium-dependent arterial relaxation. Circulation 70
(suppl II): 11-123, 1984(abst)
41. Saphir 0, Ohringer L, Wong R: Changes in the intramuscular
coronary branches in coronary arteriosclerosis. Arch Pathol 62:
159, 1956
42. CannnonRO,WatsonRM,RosingDR,EpsteinSE:Anginacaused
by reduced vasodilatorreserveof the smallcoronaryarteries.J Am
Coil Cardiol 1: 1359, 1983
43. FoltsJD,Crowell EB, Rowe GG: Plateletaggregation in partially obstructed vesselsand itselimination with aspirin.Circulation 54: 365, 1976
44. ArmstrongML,HeistadDD,MarcusML,PiegorsDJ, Aboud FM: Hemodynamic sequelae of regression ofexperimental
atheroscle-rosis. J Clin Invest 71: 104, 1983
45. Vogel RA: The radiographic assessment ofcoronaryblood flow
parameters. Circulation 72: ?, 1985
46. LeGrandV, HodgsonJMcB,BatesER,AueronFM, Mancini GBJ, Smith JS,VogelRA:Abnormalcoronaryflowreserveand abnor-mal radionuclide exercisetests inpatients with normal coronary
angiograms. J AmColl Cardiol 5:531, 1985 (abst)
47. Opherk D, Zebe H, Weihe E, Mall G,DurrC, Gravert B,Mehmel HC, Schwarz F, KublerW: Reduced coronarydilatory capacity and ultrastructurechanges of themyocardium in patientswith
angi-napectorisbutnormalcoronaryarteriograms. Circulation 63:817,
1981
48. BergerHJ, SandsMJ, Davies RA, WackersFJ, AlexanderJ,
Lach-man AS, Williams BW,Zaret BL: Exercise left ventricular
per-formance inpatients withchestpain,ischemic-appearingexercise electrocardiograms, andangiographically normal coronary
arter-ies. Ann InternMed94: 186. 1981
49. RozanskiA, Diamond GA, ForresterJS,BermanDS, Morris D, Swan HJC: Alternative referent standards forcardiac normality.
Implications fordiagnostic testing.AnnInternMed101:164, 1984 50. HoffmanJIE: Maximalcoronaryflowandthe conceptof vascular
reserve. Circulation 70: 153, 1984