13

Models of Coronary Artery Disease: "Critical" versus "Functional" Coronary Artery Stenosis H. S chad', W. Heim isch, and N. Mendl er Depa rt ment of Ca rdia c a nd Vascular Surge ry. Germa n Heart Cen ter Munich , Munich. FRG

"Critical corona ry stenosis" (reduction of coronary blood now [Q] until rea ctive hyperaem ia following 15s coronary occlusion

is just abolished) an d "functional stenosis" (reduction of Q unt il systolic shortening Idl.)ofpost-sten otlc myocardium is curta iled by 50 %) were compared with resp ect to the reduction in Q necessary and the effect on regional myocardia l and global ventricula r functio n . In 9 ana est hetized (piritr amide) dogs , enddiastolic length Ied l.I and dL of a myocardial area suppli ed by the left descending coronary artery (LAD) wer e meas ured by sonomicrometry. Left-ventricula r end-diasto lic pressure (LVEDP) and dP/dt, aortic pressu re (AoP), stroke volume (SV), and heart ra te (HRJwere monitored . QtADwa s ste pwise re duce d by a sna re . Critical stenosis. present at a 25 % reduction Of QIAD' had no effect on regional and global ventric ular function , but recovery of dL after release of 15s LAD occlusion was significa ntly delayed . Further obstruction of QINJ pro gressively impaired dL, reac hi ng 50 % dL (functio nal ste nosis) by a flow re duction of abou t 50 %. The decrease in dL was accompanied by a n increase in edL. The haemodyna mic effects of the functional stenosis we re rathe r disc rete (LVEDP+5 %, SV - 12%, dP/ dt max -8 %). Models of myoca rdial ischaemia used to study the effect of dr ugs or other ha emodynamically effective interve ntions should be able to show func tional impairment as well a s improve ment of the ischaemic myoca rdium . The crit ical ste nosis does not impair myocardial function and , conse quently. a favourab le influence on the function of ischaemic myocardium by an y intervention ma y not become evident. However , in the presen ce of a functional stenosis the cha nge in systolic shorte ning ofthe isehaem ic myocardium is a very se ns itive response to an y intervention which affects th e ene rgy bala nce of the ischa emic myocard ium . Therefore. this model sho uld be preferred . Key words

xrodette der koro na ren Herzkrunkhei t: ..krit isch e" ve rsus

.Junktto nelte" Koron a rste nose . Kritische Korc rc narsten ose" (Drosselung des Koronarflusses [OJ bis einer 15s-0kklusion gerade keine reakti ve Hypera mie mehr folgtl und ..funktionelle Stenose" (Einschra nkung von Q bis die systclischc Ver ktirzu ng (dl.) des poststenotischen Myokards urn 50 % reduziert istl wur den hin sichtlic h Q sowie der Wirkung auf die reg iona le und gesa rnt-ventrikulare Funktlon vergliche n. Bei 9 Hund en in Piritramid na rkose wu rden enddiastolische La nge (edl.l und dL cines von der linken deszendieren den Koronarar terie (LAD) verso rgten Myokardsegm ent s sono mikrometrisch bestimmt. Llnks-vent rikularer end -diastolischer Druck (LVEDP) und dP/dt, Aortendruck. Schlagvolume n (SV) und Her zfreque nz wurd en fortlau fend gemess en . OIAD wu rde schrittweise eingeschra nkt. Die krit ische Stenose wa r bei Minde rung von QL\tl urn 25% erreic ht. sie ha tte keine Wirku ngen auf die regionale bzw . ventrikulare Funktion , nur die Erholung von dLnach LAD-Okklusio n wa r a uf da s 6fa che verle ngert. Weiter e Einschr anku ng von OL\D verminde rte dL fortschreitend , 50% Reduktlon von dL (funktionelle Stenose ) wa r bet Drosselung von QIAll urn 50 % er re icht . Die Abnahme von dL war von einer Zunahme von edL begleitet . Die fun ktion elle Stenose hatte nur geri nge hamodyna mische Effekte (LVEDP +5% . SV - 12%. dp/dt max -8 %). Modelle der Myoka rdis cham ie zur Unters uchung von Pha rma ka oder ande ren ha modyna misch wirksam en Maflnahm en sollen eine Verbesserung ebens o wie eine Beeintrachtigung der myokardialen Funktion au fzeigen kdnnen . Bei der kritischen Stenose ist das betrofTene Myokard funktionell nicht elngeschra nkt. so da B eine gilnstige Seeinflussung der Funktion des ischa rnischen Myokards verschleiert bleiben ka nn . Bei einer fun ktionellen Stenose rea giert das ischami sch e Myokard empfin dlich mit Anderungen von dL sowo hl auf funktionsmindern de. a ls au ch au f funktio nsverbessernde MaOna hm en . Diesem Mod ell ist des halb der Vorzug zu gebe n .

Reactive hyperaemia - Critical coron ary stenosis - Funct iona l cor ona ry stenosis - Regiona l myoca rdial functio n - Ventri cula r function

Introduction The pat hop hysiology of myocardial ischaemia and th e resp onse of ina dequately per fused m yocardium to drugs includin g anaes thetics or to haemodynamic interventions is usually studied in an imal expe riments by one of the following three m od els: 1. Complete occlusion of a corona ry artery . Although the haemodynami c consequences of this man oeuvre might

be rat her slight depending on the extent of the ischaemic area , the active function of the non-perfused myocard ium is completely abolished. i. e. the ischaemic area shows only par adoxical motion with systolic lengt hening an d diastolic shortening (e.g. 23, 29, 30. 33). This myocardium can resp ond neither with further functional deteriora tion nor with functional improvement to any intervention except reper fusion.

* H. Scha d was awarded th e lIa ncock-Edition-Prize 1989 for this

pape r Thora e. cardiovasc. Surgeon 39 (1991) 13- 18 © Georg Thieme Verlag Stuttgart New York

Received for Publication: July 19. 1990

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Summa r)'

Thorac. cardiovas c. Su rgeon 39 (l991 )

II. Schad. W lleimisch, and N. Mendler

2. Th e "critical stenosis" , whi ch was first defined by Gould and coworkers (8) as "a const riction sufficient to pre vent an increas e in flow over restin g values in response to increased myocardial oxygen demands". A numbe r of other definitions of the critical ste nosis have also been used , ran ging from an unlikely suppres sion of reactive hyper aemi a by coro nary const riction witho ut redu ction in base-line flow (6) to coro nary narrowing , which abolishes systolic wall thick ening (and thu s syst olic contraction [27, 29 ]) of the myocardium dist ally to the stenosis (1 5) . Accord ingly, th er e is no agre eme nt on the functional conseq ue nces of a "critical ste nosis". 3. "Fu nctional ste nos is" , i. e. redu ction of corona ry blood flow by vessel cons triction to a level at which the systolic shorte ning of the myocardium distally to the ste nos is is significan tly redu ced . This hypo-perfu sed myocard ium was shown to respond sensitively to very differ ent int er ventions, e.g. cha nges in ha ema tocrit (101,intermitte nt coronary sinus occlusion (14), or drugs (9, 18, 28). A comparison of th e "functiona l" and "critica l" ste nosis is lacking, however , and thus, there is the question which degree of ste nos is is mor e appro priate to st udy the efTects of drugs and oth er interventions on inad equat ely perfused myoca rdiu m. The aim of the pr esent st udy was to compa re the "critical stenosis" (defined according to Gould et a), (8) as that ste nosis, which jus t aboli shes reactive hyperaemia following sh ort coronary occlusion) and th e "funct iona l stenosis" (defined as th at vessel cont riction, which causes a 50 % redu ction of systolic shortening distall y to th e sten osis) with resp ect to the redu ction in restin g corona ry blood flow, and th e efTect on regional myocardial function an d globa l ventri cular performan ce.

dia stolic pressure (LVDEP) an d dlvdt . Resp irat ory p ressure was monito red (Statham , P23 1D) to enable the assignment of th e haem odyn amic a nd myocard ial pa ra meters to th e res piratory phase . Th e perica rdium an d the chest remai ned ope n. Experimental protocol: Card iac performance a nd haemodynam ics were allow ed to stabilize for at least 30 min after th e p reparation was acco mplished . Th en the control data were collected . The reafter th e LAD was gradu ally na rrowed by the s na re to re duce QI.\Dstepwise. At each level OfQIADthe LAD was occluded for 15. the reactive hyperaem ic res ponse was measured and the functional recovery of the tr ansien tly ischae mic myoca rd ium wa s followed . In three experime nts th e stenosis was re leased . reg ional and global ventricular fun ction were allowed to re cover a nd to stabilize. a nd the n the w hole pr ocedure was repeated. Data analysis and statistics: All va riables were recorded on multi -ch an nel chart record er s (Gould Bru sh 481) a nd on mag netic tape Iftacal Sto re 70) for late r pla ybac k an d a nalysis. Mean Qu P a nd mean ao rt ic pressure were com puted elect ro nica lly. Hea rt rate (HR) was cou nte d fro m the left ve ntricular pressu re trace . Fro m the tr ace of the myocard ial seg ment length the end- diastolic length (edl. l an d the systolic s ho rte ning (dl.l wer e read. The latt er w as defined as shortening during left ve ntricula r ejection from the opening to th e closu re of the ao rti c valve as given by th e aortic pressure trace, and it is expre sse d as % of th e end -diastolic segmen t len gth . Three consecutive cardiac cycles were sa mp led and ave raged . All varia bles were read in the end -exp irato ry phase . Data a re given as mean ± SEM. Signi ficance of differ en ces was evaluated by the wllcoxon match ed-pair sig ne d ra nk test: p < 0.0 5 was de fined to indicate significa nce.

Met hods

Table 1 Control dataand the effect of critical and functional stenosisof the left descending coronary artery (LAD) on LAD blood flow (QLAo), end-diastolic length (ed L) and systolic shortening (dL) of an LAD-supplied myocardia! seg· rnent, left ventricularend-diastolic pressure (LVEDP), aorticmean pressure (PAo ) stroke volume (SV),heart rate (HR),and maximalrateinchange in left ventricula r pressure (dP/dt)

Animals and anaesthesia: Th e ex periments we re pe rfo r med in 9 mo ngre l dogs of both sexes. bod y wei ght 17 -36 kg. The a nimals were pretr eated with a phenothiazine derivative i. m. n mgk g'" Combelen" . Ba yer). Anaesthesia was indu ced by pe nto ba rbital i. v. (12mg kg'" Nemb uta l>. Abbot) an d mai ntained by a n infusion of piritramide (0.6 mg kg" h- I Dipido lors'. Jan ssen). Th e pa ral yzed a nimals Il. v. infusion of'Pancu ronlumw. Organo n. O.l mg kg' "p riming . 0 .1 mg kg' " h - 1 sust a ining dose) were artificially ventilated (f = 15 min - I) via an en do trac heal tube with O2 : N20 = 1 : 1 at a t idal volume (Vl = 12 -1 5 ml kg- I) approp riat e to maintain arterial pC0 2 at 35 - 40 m mHg. NallC OJ (1 mol I- I) was substituted as ne cessa ry to keep the base excess above - 3 010101 r'. Hinger 's solution w as infuse d co ntinuo usl y (3 ml kg" h - I ) . Preparation and instrumentation: The left external jugular ve in and the rig ht femor al arte ry we re ca n nulated for application of drugs a nd fluids an d for blood sam pling. The heart wa s exposed from the left 5 lh inte rcostal space. Per ivas cular electromagnetic flow pro bes (Statham ) we re placed arou nd the ascending aorta (18 - 220101) an d the left descend ing coronary artery (2- 30101, LAD)to mea sure st roke volume (SV)and coro na ry bloo d flow (QL\P) ' A to urn iquet adj ustable by a micro-dr ive was placed around the LAD dist al to th e flow-prob e to reduce QI..\ P' A seco nd snare was place d distally to the tou rni que t to occlude the LAD inte r mittently for eva luation of coro nary flow reserve by the re act ive hyper aemic response. The perform an ce of the myocard ium s up plie d by the LAD distal to th e tou rni qu et as assessed by measuri ng the cyclic varia tions in len gth of a subendoc ardial wall segme nt by sono mlcro me try as describ ed pr eviously (11) . Cat heter tip ma nomete rs (Milla r. PC 350) we re adva nced from the left femor al arte ry to the asce nding aorta to measu re aortic pressure (PAn), and fro m' the left at rial a pp endage into the left vent ricle to reco rd left ventric ular end -

Results The contro l data obtain ed befor e obstruction of LAD blood flow as well as the chan ges indu ced by a "critical" and a "functiona l" stenosis of th e LAD are summarized in Table s 1 and 2.

%change by LAD stenosis control before LAD stenosis

0''0 edL dL

LVEDP

P" HR

SV

dP/dt ~,

dP/dt ml~

51 ± 10 14.7 ± 1.0 18.1 ± 1.7 7.4 ± 1.2 89 ± 4 0.89 ± 0.08 123 ± 5 +2600 ± 340 - 2140 ± 200

(ml/miOl (mm)

(%edLI (mmHg) (mmHg) (ml/ kg) (l /m in)

(mm Hgls) (mmHglsl

critical

-25 ± 3' 0 ±1 0 ±2 +5 ± 2 +1± 1

-3± 2 0 ±2 - 1± 2 +1± 2

functiona l

- 47 ± 3' +5 ± I" - 46 ± 3' + 12 ± 5" +1 ± 1 - 12 ± 3' +1 ± 2 - 8 ± 2' - 4 ± 3"

mean ± SEM (n = 12); ' sign ificantly different fromcontrol, P < 0.05

Table 2 Peak reactive hyperaemia (x-times baselineflow), duration of hyperaemic response, and recovery timeof systolic shortening{dL)of the myocardial area supplied by the left descending coronary artery(LAD) following 15 s LAD occlusion, when the LADwas not stenosed. critically stenosed , and functionally stenosed

peak reactivehyperaemia duration of hyperaemia (s) dL recovery time(s) mean ± SEM (n

=

no stenosis

critical

3.45 ± 0.45 122 ± 17 14 ± 2

1.01 ± 0.01' 90 ± 9'

functiona l

1.00'

> 140'

12); ' significantly different fromcontrol. p < 0.05

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14

Models a/Coronary Artery Diseas e

Theme. eardievase. Surgeon 39 (1991)

before LAD stenosis

100

before LAD occlusion

(mlfmin)

30s reperfusion QlAD ~ (ml/min)

JJ

OlAD

,

o

I

(m~~ [ r""~'I"'~""'"",r""~f'IIII'!!~:""" 15 " ...

~"l.iIlII.".i.lWI.""...

before LAD occlusion

..J

~~~~~",","

155 occlusion

myocardial segment length l

o

critical LAD stenosis

15

(mm)

o

18

Fig. 1 Effect of transient occlusion of theleft descendingcoronary artery(LAD) on LADblood flow (QLAD), onlength (Ll of an LAD·suppliedmyocardialsegment. and on the pressure- lengthloop ofthismyocard ial area (lVP:leftventricular pressu re)

The non-obst ructed LAD: The efTect of transient LAD occlusion on the function of the dependent myocardium is de monstrated by pressur e-length loops in Fig. 1. The pressure-len gth loop of a myocardial seg ment rep resents the regiona l analogon to the pressur e-volume diagram of the wh ole ventricle. The instantaneous ventricular pressure during one cardiac cycle is given on the ordinate and the cor respon ding length of the myocardial segment on the abscissa . Ventricular filling starts at the lower left of th e loop , a nd the loop ru ns counte r-clockwise. Cha nges in the functiona l sta te of the explored myoca rdial region can be a pproximated at -a-glance from changes in th e area and shape of the pressure-length loop (13). Interru ption of th e LAD blood flow for 15s was sufficient to abolish completely the active function of the myocardium in the LAD territor y. The myoca rdial segment did not contrac t duri ng th e ejection ph ase, but showed shorteni ng during relaxati on. Such a pattern of paradoxical wall motion was obse rved in all experiments within 15s of coronary occlusion . After release of the occlus ion, systolic shortening of the myocardium recovered with in about 15s to pre-occlusion value and was usuall y followed by a tran sien t hyper kinesia . LAD blood flow showed a pronounc ed hyperaemi c response with coronary reperfusion. Peak reactive hyperaem ia was 2-6 (mea n: 3.5 ) times the pre-occlusion flow. The hypera emia lasted about 120 s until LAD blood flow had returned to the pro-occlusion level. The "critica l" s te nos is: Gradual narrowin g of the LAD reduced th e LAD blood flow and the reactive hyperaemic resp onse to th e 15s occlusion. At a Q'AOof about 75% of control the reactive hyperaemic response was just abolished, i.e. peak reactive hyperaemia was less th an 10 % of control flow. This de gree of coronary cons tr iction was defined as "critical stenos is". It was not accompanied by a cha nge in the performance of the post-stenotic myocardial are a (Fig. 2). The observed variat ions in systo lic shorten ing remained within ± 10 % of th e control value (Fig. 3) and showed no correlation to the reduction in Q I.AP' The mean values of d LL, o a nd edL'ADat critical stenosis were just th e

QlAD

28

-

- - -

, , --

functional LAD stenosis

150

QlAD

18

~

15, 15 L(mm)

18

Fig.2 Effect oftransient occlusionof theleftdescendingcoronary artery(LAD) onLAD bloodflow(QLAD)andthepressure-lengthloop of anLAD·supplied myocardial segment atdifferent degrees of LAD stenosis (L: myocardial segment length; LVP: left ventricular pressure)

sa me as they were before obstructing the LAD. Global ventricular function was also not affected by the critical stenosis. The only significant myocardial efTect of the increasing LA D constriction up to the critical stenosis was a pro gressively delayed recovery of systolic s horte ning followin g the 15s LAD occlusion (Fig. 2, 4). At critica l ste nosis, the recovery time was prolonged to 90s equivalent to a 6fold increase as compared to the non-obstructed state. The "f unctional" stenosis: Narrowing of the LAD beyond the critical ste nosis increasingly affected the function of the hypo-perfused myoca rdium : the en d-diastoli c length increased (Fig. 2) and the systolic shortening declined syste mat ically with decreas ing Q,,\n (Fig. 3). The red uction in dL was closely correlated to the impairment of corona ry blood flow (r - 0.84). A decrease of svstolic shorten ing to about 50 %of control was achieve d by ~ reduction ofQ I..\ 1l to a similar extent. The obstruction of coronary blood flow required to reduce dL by 50 % was defined "funct ional ste nos is". This stenos is retarded the recovery of dLL.\ 1l following LAD occlusion to > 140s. The efTect on tota l ventricular function, howeve r, was rather small. Stroke volume, dP/ clt max and dP/dtmin we re slightly reduced as compared to control, end-diastolic pressu re was increased , whereas aortic pressure and heart rate were not affected by the functiona l stenosis of the LAD. Discus sion

Duration of coronary occlusion: The degree of coronary reactive hype rae mia is well known to depend on the du ra-

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L

15

II. Sc had. W lteimisch. and N. Mendler

Thom e. cardiotlasc. Su rgeon 3 9 (I991) lAD stenosis

0

0

0

u

'0 75

0

Ii 0

0

• . ~ «l

0

0

0

o

o

i

0

o·

~

QQ...... .

cg ~

•o : 0

100

0

0

Fig.3 Correlationof lettdescendingcoronary artery (LAD) bloodflow andsystolic function of myocardiumsuppliedbythe LAD duringprogressive LAD constriction upto"criticalstenosis" (right part.y - 1.04- 0.05x) and furtherconstriction beyond"critical stenosis'(lettpart. y"" IID-440e [- 0 016-1. • 'entreat stenosis"

75

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~ ~

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-e

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" 0

~

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50

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.,.

00

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M

:2 25 10'

0 0

0

u 0

~

0

25

0

E

o

0 50

25

100

75

lAD blood flow(X of control)

50

• 75

lAO blood flow(X of control)

co

',. 200

200

0

"

U o 0

a

(5)

(5)

:5

0

~

'""' 150 co '" '"1::" .s: ."'"

0

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0 0

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0 0

100

00

0 0

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lAD blood flow (::I: of control)

Fig.4 Recovery timetocontrol valueof myocardial systolicshorteningafter 15socclusion of the supplying coronary arteryinrelation todifferent degreesof coronary stenosis asmeasured byreduction incoronary bloodflow. Regression line: y _ 4280e l- 0058- 1

tion of coronary artery occlusion as shown for the first time by Coffman and Gregg (3), Peak reactiv e hyperaemia becomes maximal following a coronary occlusion of 10- 20 seconds (2 1, 26). Prolonged coron ary occlus ion does not increase reactive peak flow but rath er the dur ation of the hyper aemi a (21, 26), In th e pres ent study. peak flow was

taken as a measure of coronary flow reserve and therefore a coronary occlusion time of 15 s was chosen. Peak reactive hype raemia of non-obs tructed coronary arte ries was about 3.5 times the baseline-flow in the pr esent experiments. This agrees very well with dat a from th e literature. Peak hyper aemic response to 10-20s corona ry occlusion was rep eat edly describ ed to be abo ut 3-4 times the bas eline flow in anaes thetized dogs (8.1 6. 19.21 , 24) as well as in consci ous dogs (26. 34). and similar values we re also reported for patients with intact coronary circulation undergoing cardiac surgery (20). "Critical ste nos is " was flrs t deflned by Gould an d coworkers (8) as" . . . a const riction sufficient to preven t an increas e in flow over resting values in response to increased myoca rdial oxygen demands, , .". Accord ingly. mechanical na rrowing of the LAD was called "critical" in the present study when reactive hyperaemia following transi ent coronary occlusion was just abolished. i.e, wh en the coronary constriction had caused a maxim al post-stenotic vasodilation . This degree of stenosis was reached when coronary blood flow was decreas ed to 75 % of bas e-line. In the ab ove menti oned study (8). the hyp eraemic resp onse to int racoronary injection of contrast medium \v·as abolish ed wh en bas eline flow was redu ced to ab out 60 %. This difTerence to the present results is possibl y due to the difTerent vasodilating stimuli. Anoth er deflnition has also been given: coro nary constri ction until reactive hyperaemi a is abolished but resting blood flow is not reduced (6) or is redu ced by less than 15 % (25). Accordi ng to the present results . these two prerequisits are incompatible. and indeed. reactive hype raemia was not enti rely abolished at "critical stenosis" in these studies , Similarly. coronary stenosis has bee n considere d as critical when blood flow did not increase in resp onse to atrial pacing at norm al resting flow (7), "Normal flow" was not verified, however . before an d afte r producing the stenosis, but by comparing the myocardial blood flow of two areas supplied by the ste nosed coro nary and a non-sten osed vesse l. The term has also been used when th e narrowi ng of the vesse l just sta rted to redu ce the resting flow (16). However ,

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16

data on reactive hyperaemia in relation to coronary flow were not presented . A quite differ ent definition of "critical ste nosis" is produ ction of post-s teno tic hypo- oder dyskinesia hy coronary na rro wing (9), reduction of the local epicardial Po, hy coronary constriction to a level which induces myocardial hypokinesia (I), and reduction of coronary hlood fiow unt il systolic wa ll thickening (and th us systolic contraction (27, 29]) of the post-s tenotic myocardium is aholished (15). These descriptions sh ow, however , that a "functional" hut not a "critical stenosis" was established in thes e studi es. Elzinga and Skinner (5) defined as "critical stenosis" that vess el constriction at which diastolic coronary flow , aorti c pressu re, and myocardial tissue Po, sh owed a sudd en and pronoun ced decline. This point was reached, when vessel inn er diam eter was reduced by 75% (and a rea hy 93%), Mean coronary blood flow was significantly reduced (about - 20 %) and peak reactive hyperaemia was nearly abolished . This agrees very well with the present results. In summa ry, the most appropriate definition of the critical ste nosis seems to be in accordance with Gould et al. (8) tha t deg ree of vesse l constriction independ ent of change in blood flow, which just exha usts coronary fiow reserve, so that any vasod ilating stimulus like tran sient coronary occlusion or tachycardia may no longer provoke an increase in hlood flow. Regional myocardial fun ction was not affected by the reduction in coronary flow as long as reactive hyperaemia could be induced, i, e. coronary flow reserve was not exhausted, There was only a significantly delayed recovery of systolic sho rtening following corona ry occlusion, in agreement with a pr eviously described protracted recovery of myoca rdial P'" (32). Beyond the critical stenosis at 75 % of baseline flow, further decrease of coronary hlood flow was accompanied by a progressive steep impairment of systolic contrac tion. Similarly, in anae sthetized dogs it was repeatedly observed that desp ite a significant reduction in coronary flow regional myocardial function remained unimpaired as measured hy systolic tension (2), contractile force (4), systolic sho rten ing (17, 31), patt ern of regional wall motion (23), a nd a rea of epicardia l pressu re-length loops (33). The degree by which flow may be redu ced without functional consequences does not se em to be invariably 25 % of the control value. In conscious dogs , for example, impairm ent of myocardial systolic shortening was observed to begin at flows redu ced by no more than 10% of restin g flow (30), and in ana est hetized pigs regional systolic shortening and wall thickening wer e redu ced by 30 % and 80 %, resp ectively, when coronary blood flow was decreas ed to 75 % of control (29). This difference to the present experiments is prob ably due to the quite different experim enta l condition (awake vs anaesthetized) and to the different species (pig vs dog). Generally the degree of corona ry flow reduction at which the function of the hypo-perfused myoca rdiu m becomes affected can be assumed to depend on the actual ca pacity of coronary flow reserve, Myoca rdial performance can be maintained as long as coronary flow reserve is not entirely exhausted. The reduction in LAD flow by the critical stenosis without any disturbance or regional myocardial an d globa l ventricular function mean s tha t oxygen supply was decr eased while oxygen demand remained unchanged. Consequently, the reduction in a, delivery via the LAD was compensated

Thom e. cardiovasc. Surgeon 3 9 (1991)

for either by collatera l blood flow or by an a ugmented oxygen extraction. Reduction of left circumflex coronary artery blood flow by less than 20 % was described to be associated with a decrease in intra myocardial Po, (5, 25, 32), an d an increase in tissue Pcoa (5, 25). These data suggest that the reduc tion of blood flow was not compensa ted for by collateral blood flow. Global ventricular fun ction was not affected by the critical stenos is of the LAD, becaus e this na rrowing of the coronary did not impair regional contraction. Further reduction of regional myocardi al blood flow had on ly slight effects on global vent ricular function, in agree ment with previous studies (22, 30, 33), becaus e the a rea of impaired performance was too sma ll to result in a deterioration of ca rdiac performance. The significan ce of the small cha nges in ventricular pump function accompanying the severe reduction of regional contraction became evident only by direct comparison of the control value to the value at functional stenosis in each individual experiment, but not by comparing the mean values of all experiments as a lready described (12), Ther efore, global ventricular parameters are not appro priate to study the effects of drugs or othe r haemodynam ically effective interventions on the function of hypo-perfused myocard ial areas. "Functional s tenosis " was defined to be present, when the nar rowing of a corona ry artery yielded a 50 % redu ction in systolic shortening of the hypo-perfused myocardium irrespective of the required reduction in coronary blood flow. The mean reduction in coronary flow was also 50% at this point, but there were considera ble interindividual differences . The functionally impaired myocardium responds very sensitively to any cha nge in oxygen supply and oxygen demand with improvement or further reduction of systolic shortening. At a critical stenos is, however. interventions which are of benefit for hypo-perfused functionally impaired myocardium may not necessarily improve the performance of the functionally intact myocar diu m. For example, an increase in oxygen supply has no effect on systolic sho rtening of the myocardium. On the other hand , occlusion of a coronary artery abo lishes the function of the non- per fused myocardium completely, i. e. the ischaemic area shows only paradoxical motion with systolic lengthening and diastolic shortening (e.g. (23, 29, 30, 33)). The non perfused myocardium, which has lost an y active function , can respond neither with further functional deterioration nor improvement. Therefore, the "functional stenosis" is suggested as the most appropriate model for the study of any interventi ons intended to affect the per forman ce of ischaemic myocardium. Ackn owled gemen ts The skillful technical ass istance and preparation of the figures by Mrs. A. Bernhurd-Abt. Mrs. S. Dorn-Biermeier. and Mrs. C. Scbu tqen are gratefully acknowledged.

References I

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Prof Dr. me d. 11. Sc ha d

Klinik fiir Herz- und Gefabc hirurgte Deutsch es Herzzentrum Miinchen Loths traBe 11 D-8000 Mtmchen 2

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