REVERSE CORONARY STEAL/Chiariello et al.
809
7. Stein I, Weinstein J: Unusual reaction to ergonovine maleate in a case of
coronary insufficiency. NY State J Med 53: 1454, 1953
8. Heupler F, Proudfit W, Siegel W, Shirey E, Razavi M, Sones FM: The
ergonovine maleate test for the diagnosis of coronary artery spasm. Cir-
culation 51, 52 (suppl II):II-ll, 1975
9. Maseri A, Mimmo R, Chierchia S, Marchesi C, Pesola A, l'Abbate A:
Coronary artery spasm as a cause of acute myocardial ischemia in man.
Chest 68: 625, 1975
10. Maseri A, Pesola A, Mimmo R, Chierchia S, l'Abbate A: Pathogenetic
mechanism of angina at rest. Circulation 51, 52 (suppl II):II-89, 1975
11. Weiner L, Kasparian H, Duca PR, Walinski P, Gottlieb RS, Hanckel F,
Brest AN: Spectrum of coronary arterial spasm. Clinical, angiographic
and myocardial metabolic experience in 29 cases. Am J Cardiol 38: 945,
1976
12. Master AM, Pordey L, Kohler J: Ergotamine tartrate and the two-step
exercise electrocardiogram in functional cardiac disturbances. J Mt Sinai
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13. Innes IR: Identification of the smooth muscle excitatory receptors for
ergot alkaloids. Br J Pharmacol 19: 120, 1962
14. Dieckmann WJ, Forman JB, Phillips GW: The effects of intravenous in-
jection of ergonovine and solution of posterior pituitary extract on the
postpartum patient. Am J Obstet Gynecol 60: 655, 1950
15. Schade FF: Methergine: A study of its vasomotor properties. Am J
Obstet Gynecol 61: 188, 1951
16. Friedman EA: Comparative clinical evaluation of postpartum oxytocics.
Am J Obstet Gynecol 73: 1306, 1957
17. Baillie TW: Vasopressor activity of ergometrine maleate in anaesthetized
parturient women. Br Med J 5330: 585, 1963
18. Baillie TW: Vasopressor activity of ergometrine. Br Med J 5343: 1477,
1963
19. Brooke OG, Robinson BF: Effect of ergotamine and ergometrine on
forearm venous compliance in man. Br Med J 1: 139, 1970
20. Crawford JS: Vasopressor activity of ergometrine. Br Med J 5340: 1285,
1963
"Reverse Coronary Steal"
Downloaded from http://ahajournals.org by on October 19, 2023
Induced by Coronary Vasoconstriction
Following Coronary Artery Occlusion in Dogs
MASSIMO CHIARIELLO, M.D., LAIR G. T. RIBEIRO, M.D.,
MICHAEL A. DAVIS, D.SC., AND PETER R. MAROKO, M.D.
SUMMARY The phenomenon of "coronary steal," i.e., the shunt-
ing of blood from ischemic to normally perfused areas of myocar-
dium, has been described as an effect of the administration of several
vasodilating agents. This study was performed to ascertain whether
the reverse situation can be induced, i.e., whether vasoconstriction of
the vessels supplying the nonischemic zone could increase the
collateral flow to the ischemic area. In 16 open chest dogs, 15 and 30
min after occlusion of the left anterior descending coronary artery,
epicardial electrograms were recorded and regional myocardial blood
"VASCULAR STEAL" may occur whenever a sudden
reduction in the vascular resistance of a given area results in
the shunting of blood to it through collateral channels from
adjacent areas of unchanged resistance. This steal
From the Departments of Medicine and Radiology, Harvard Medical
School and Peter Bent Brigham Hospital, Boston, Massachusetts.
Supported in part by contract NO1-HV-53000 under the Cardiac Diseases
Branch, Division of Heart and Vascular Diseases, NHLBI, and USPHS
grant GM-18674.
Address for reprints: Peter R. Maroko, M.D., Harvard Medical School,
Bldg. A, 25 Shattuck Street, Boston, Massachusetts 02115.
Received May 30, 1977; revision accepted June 20, 1977.
21. Davis ME, Boynton MW: The use of ergonovine in the placental stage of
labor. Am J Obstet Gynecol 43: 775, 1942
22. Wassef MR, Pleuvry BJ: The cardiovascular effects of ergometrine in the
experimental animal in vivo and in vitro. Br J Anaesth 46: 473, 1974
23. Rinzler SH, Travell J, Karp D: Detection of coronary atherosclerosis in
the living animal by the ergonovine stress test. Science 121: 900, 1955
24. Rinzler SH, Travell J, Karp D, Charleson D: Detection of coronary
atherosclerosis in the living rabbit by the ergonovine stress test. Am J
Physiol 184: 605, 1956
25. Karp D, Rinzler SH, Travell J: Effects of ergometrine (ergonovine) on
the isolated atherosclerotic heart of the cholesterol-fed rabbit. Br J Phar-
macol 15: 333, 1960
26. Varma DR, Melville KI: Cardiovascular responses to hypoxia and ergo-
novine in rabbits and dogs with normal or impaired coronary circulation.
Rev Canad Biol 20: 683, 1961
27. Prinzmetal M, Kennamer R, Merliss R, Wada T, Bor N: Angina pec-
toris: 1. A variant form of angina pectoris: Preliminary report. Am J
Med 27: 375, 1959
28. Browning DJ: Serious side effects of ergometrine and its use in routine
obstetric practice. Med J Austral 1: 957, 1974
29. Wright EN, Graiewski SJ: Ergonovine sensitivity and/or toxicity; Report
of a case. Obstet Gynecol 6: 347, 1955
30. Baillie TW: Ventricular ectopic activity following intravenous
ergometrine. Anaesthesia 24: 253, 1969
31. Canning BSJ, Green AT, Mulcahy R: Coronary heart disease in the
puerperium. A case report. J Obstet Gynecol Br Cwlth 76: 1018, 1969
32. Forman JB, Sullivan RL: The effects of intravenous injection of ergo-
novine and methergine on the postpartum patient. Am J Obstet Gynecol
63: 640, 1952
33. Editorial: Ergometrine - hypertensive drug? Br Med J 5330: 560, 1963
34. Ringrose CAD: The obstetrical use of ergot: A violation of the doctrine
"Primum non nocere." Canad Med Assoc J 87: 712, 1962
35. Casady GN, Moore DG, Bridenbaugh LD: Postpartum hypertension.
JAMA 172: 1011, 1960
flow (RMBF) was measured with radiolabeled microspheres.
Methoxamine was infused intravenously between 17 and 30 min, the
mean arterial pressure being kept constant. The results indicate that
while the coronary arterial flow to the normal myocardium fell from
90.6 ± 4.3 to 77.7 ± 3.2 ml/min/100 g (P < 0.01), the collateral
blood flow to the ischemic area increased from 21.4 + 3.5 to
41.0 ± 4.2 ml/min/100 g (P < 0.01), and thereby reduced acute
myocardial ischemic injury. This favorable redistribution of blood
flow might be considered a "reverse coronary steal."
phenomenon has been observed in the subclavian,' aor-
toiliac,2 mesenteric3 and coronary4 '2 vascular beds. In dogs
with coronary artery occlusions or patients with ischemic
heart disease, coronary vasodilator agents may increase the
total coronary blood flow, but they may do this at the ex-
pense of reducing the collateral blood flow to the ischemic
area already maximally dilated as a result of metabolic
stimuli. This phenomenon has been described with car-
bochromen,7 dipyridamole,4 6 8, 10,11 isoproterenoll and
minoxidil.'2 Since drugs which cause arterial dilatation in
normal myocardium also reduce the arterial flow to
ischemic areas, interventions which cause arterial constric-
 810
tion in normal myocardium might be expected to improve
the blood flow to the ischemic areas. Accordingly, this study
was designed to determine whether the administration of a
coronary constrictor that reduced blood flow in the normal
myocardium would increase the flow to the ischemic areas,
thus producing a "reverse coronary steal."
Materials and Methods
Sixteen mongrel dogs weighing between 20 and 30 kg were
anesthetized with sodium thiamylal 25 mg/kg intravenously
and ventilated with a Harvard respirator. A polyethylene
cannula was placed in the carotid artery and connected to a
Statham P23Db transducer to monitor arterial pressure.
Lead aVF of the electrocardiogram was recorded con-
tinuously. A left thoracotomy was performed in the fifth in-
tercostal space and the heart exposed and suspended in a
pericardial cradle. The mid portion of the left anterior
descending coronary artery was isolated from the adjacent
tissue and occluded permanently with a silk suture. In eight
of the dogs, 17 min after occlusion (control period) methox-
amine (20.0 ± 0.5 ,gg/kg/min) was infused intravenously for
15 min, while mean arterial pressure (AP) was maintained
constant by bleeding through a femoral artery catheter into
a constant pressure chamber. This protocol was chosen in
order to render the changes in coronary blood flow indepen-
dent of changes in perfusion pressure which would rise with
an increase of AP.
The regional myocardial blood flow (RMBF) and cardiac
output (CO) were measured at 15 and 30 min after occlusion
using 7-10 u carbonized microspheres labeled with a
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gamma-emitting radionuclide (14'Ce or "5Sr) according to
the technique previously described.13 14 Before the injection,
a 50 ml vial containing the microspheres suspended in a
solution of 50% sucrose with two drops of Tween 80 added
to avoid aggregation was ultrasonicated for 45 min and then
mechanically agitated for an additional 5 min. For each
measurement 1.5 X 10' of one type of labeled microsphere
(selected randomly), suspended in an aliquot of 4 ml of the
solution contained in the 50 ml vial, was injected over a
period of 15 sec through a left atrial catheter; during the
following 15 sec the catheter was flushed with 5 ml of saline.
Random samples were taken from the vial after the injection
for microscopic examination and these did not show
aggregation of the beads. Simultaneously with the atrial in-
jection a reference sample was -collected from a femoral
TABLE 1. Hemodynamic and Electrocardiographic Changes
AP HR CO TVR CR
Before methoxamine
95.6 150.1 2.432 3,625 9.3 X 104
6.2 9.4 -0.433 = 486 = 0.74 X 104
15 Minutes
106.9 155.5 1.621 5,651 10.9 X 104
=8.4 -4.8 -0.184 -660 1.0 X 104
*P <0.05.
**P <0.01.
Abbreviations: AP = mean arterial pressure in mm Hg; HR = heart rate in beatsSin; CO = cardiac output in L/min; TVR = total vascular resistance
in dyne x sec/cm5; CR = coronary resistance in dyne x sec/cm5/g of myocardium; ST = average ST-segment elevation in mV.
CIRCULATION VOL 56, No 5, NOVEMBER 1977
artery catheter using a 50 ml heparinized plastic syringe
placed in a Harvard withdrawal pump operating at a con-
stant speed of 15.3 ml/min. The collection of the reference
blood sample lasted one minute, starting 15 sec before the
beginning of the microspheres injection and ending 15 sec
after the catheter flushing. No changes in aortic pressure or
heart rate were observed during this procedure. Thirty-five
minutes after the occlusion the heart was excised and 7 to 10
transmural biopsies each weighing 3 to 4 g were taken from
the anterior and posterior ventricular walls. These biopsies
contained all of the ischemic tissue as well as portions of the
normal myocardium. Each biopsy was then divided into en-
docardial, middle and epicardial layers, and the radioac-
tivity of each section and that of the reference sample
measured in a gamma-scintillation well counter (Nuclear
Chicago model 4233). Finally, the RMBF and the cardiac
output were calculated as described by Utley et al.'5 Since
the goal of this study was primarily to examine changes in
flow, the RMBF of the endocardial, middle and epicardial
layers and the transmural blood flow were calculated
separately for the ischemic and normal sites, the ischemic
sites being defined as those with a blood flow below 50
ml/min/100 g. Transmural RMBF for each biopsy was
calculated as a weighted mean of the corresponding endo,
mid, and epicardial layer RMBFs.
Total vascular resistance (TVR) (in dyne X sec X cm-,)
was calculated according to the formula: TVR (AP X
=
80)/CO where AP (mean arterial pressure) is in mm Hg and
CO (cardiac output) in L/min. Coronary resistance (Cor
Res) in dyne X sec X cm-,/ I00 g of tissue, was calculated as
follows: Cor Res = (AP X 80)/RMBF where RMBF (in
L/min/100 g of tissue) was the mean blood flow of the non-
ischemic sites.
Epicardial unipolar electrograms were recorded at 15 min
and at 30 min after occlusion, i.e., just prior to the injection
of microspheres, from 13 to 17 sites on the anterior left ven-
tricular wall as previously described.16 The input impedance
of the recorder amplifier was 100 megohms, and the frequen-
cy response of the system was ± 0.5 db from 0.14 to 70 Hz.
The impedance of the electrode was maintained constant, as
reflected in the reproducibility of the tracings. The electrode
employed was a 15 mm2 copper cylinder with a saline soaked
wick connected to the precordial V-lead and held by a cable
perpendicular to the electrode, thus minimizing mechanical
stress. Because of the large area of the electrode, small
variations in location did not change the configuration of the
ST AP HR CO TVR CR ST
Treated Dogs
Ajter methoxamine
3.4 95.6 142.2 1.200** 7,928** 10.5 X 104* 2.2
0. =7.7 ==11.9 0.226 1,374 = 0.82 X 104 -
0.8
Nontreated Dogs
30 Minutes
4.9 110.0 156.4 1.687 5,487 10.7 X 104 4.6
1.0 -8.2 6.7 -0.176 -525 =1.1 X 104 1.1
 REVERSE CORONARY STEAL/Chiariello et al. 811

125 r 175r

look 1501-
AP HR
(mm Hg) (bpm)
75 1251-

0o
4 5

r-n
3
T
OFT
4
T
( /min ) 2 (mV ) ;h

FIGURE 1. Effect of vasoconstriction and simultaneous bleeding on mean arterial pressure (AP), heart rate (HR), car-
diac output (CO) and average ST-segment elevation (ST). The striped columns represent the control values at 15 min, the
dotted columns the values at 30 min during vasoconstriction. All values are mean ± I standard error. * = different from
control, P < 0.05, ** = different from control, P < 0.01.

recordings.16 The sites, clearly recognizable for their relation
with vascular crossings, were chosen in the area supplied by
the occluded vessels as well as in regions of the left ventricle
far away from this area. For each electrographic map, the
average ST-segment elevation (ST) was obtained by dividing
Downloaded from http://ahajournals.org by on October 19, 2023
15 min after occlusion, was reduced by the intervention to
77.7 ± 3.2 ml/min/100 g (P < 0.01) at 30 minutes (fig. 3
and table 2). The analysis by layer is shown in figures 3 and 4
and table 2. In the normal myocardium the calculated cor-
onary resistance per gram of tissue increased in all three

the sum of the ST-segment elevations in all sites by the layers and when calculated for the transmural samples it in-
number of sites. ST-segment elevations were measured from
the T-P line to the J point. Nine percent of sites exhibited
10.0 r TOTAL VASCULAR RESISTANCE
focal intraventricular conduction defect as reflected in QRS
duration exceeding 0.065 sec and were excluded from the
study.'7 The other eight dogs did not receive any drug and 7.5 -
served as controls; all measurements in these dogs were
TVR x 103 :: - :, .....-...-
made at the same times as in the treated dogs. ...C.:...:...
Comparisons between values obtained at 15 and 30 min in (dyne x sec/cm 5) 5.0 Iee--....:....
the same dogs were made using Student's paired t-test, and
between treated and control dogs by Student's t-test for 2.5 -
group observations.'8
Finally, an additional 12 open chest dogs were in- OL
strumented to evaluate the hemodynamic changes induced
by the same dose of methoxamine. They were instrumented 12.5r CORONARY ARTERY RESISTANCE
with ECG leads and cannulae in the left ventricle, aorta and
left atrium for the recording of pressures. 10.0

Results CR x 104
7.5
(dyne x seckmr(/c
5g
In the eight treated dogs the infusion of methoxamine
with concomitant bleeding from 15 to 30 min after occlusion 5.01-
did not change the mean systemic arterial pressure (fig. 1,
table 1). Systolic and diastolic pressures did not change
(from 126.5 + 9.3 to 125.4 ± 9.8 and from 79.9 + 5.8 to 2.5 _
81.0 ± 5.4 mm Hg, respectively). Heart rate fell, but not
significantly (fig. 1, table 1). Cardiac output decreased by OL _
50.7 ± 6.1% (P < 0.01) (fig. I, table 1). The calculated total FIGURE 2. Effect of methoxamine plus bleeding on total vascular
peripheral resistance thus incrfased by 122 + 22% resistance (TVR) and coronary resistance (CR). Note the increase
(P < 0.01) (fig. 2, table 1). The transmural RMBF in the of both parameters following the intervention. * = different from
nonischemic zones, which was 90.6 ± 4.3 ml/min/100 g at control, P < 0.05, ** = different from control, P < 0.01.
 812 CIRCULATION VOL 56, No 5, NOVEMBER 1977

TABLE 2. Alteratioms in Regional Myocardial Blood Flow*

Trans Endo Middle Epi Endo/Epi Trans Endo Middle Epi Endo/Epi
Treated Dogs
Before methoxamine After methoxamine
Normal 90.6 88.5 79.5 91.1 0.99 77.7** 80.3** 75.2 76.5** 1.10
sites *4.3 -4.2 5.7 *5.0 *0.04 *3.2 4.1 *5.5 3.2 *0.06
Ischemic 21.4 15.7 16.5 21.3 0.41 41.0** 23.9** 38.8** 54.9** 0.39
sites *3.5 3.4 *3.7 *3.2 *0.09 *4.2 -3.5 *5.8 -6.7 -0.06
Nontreated Dogs
15 Minutes 30 Minutes
Normal 81.7 88.0 80.0 78.0 1.08 85.8 90.1 86.6 81.6 1.05
sites -3.4 *4.0 *5.0 *3.0 *0.04 *3.6 *4.4 *5.5 *3.7 *0.05
Ischemic 26.5 23.1 25.5 28.8 0.46 26.9 24.8 26.5 29.9 0.49
sites *3.0 *2.8 *5.0 *3.6 0.04 *3.0 *3.0 *5.2 *4.0 0.04
*Sites with regional myocardial blood flows below 50 ml/min/l00 g, at 15 min after occlusion, were considered to be ischemic.
This applies to the regional myocardial blood flow of any layer as well as when it is calculated transmurally as a weighted mean of
the flow in three layers. Thus, a transmural ischemic site (i.e., transmural flow <50 ml/min/100 g) could include a normal (i.e., flow
>50 ml/min/100 g) epicardial component.
**Different from the value before methoxamine, P <0.01.
Abbreviations: Trans = transmural regional myocardial blood flow in ml/min/100 g; Endo = endocardial regional myocardai
blood flow in ml/min/100 g; Middle = middle layer regional myocardial blood flow in ml/min/lOO g; Epi epicardial regional myo-
cardial blood flow in ml/min/100 g; Endo/Epi = endocardial/epicardial flow ratio.

creased from (9.3 ± 0.74)104 to (10.5 ± 0.82)104 dyne
X sec X cm-' (P < 0.05) (fig. 2).
While the blood flow following methoxamine infusion was
reduced in the normal myocardium, it increased significantly
in the ischemic sites, thus showing that blood was shunted
from the normally perfused to the underperfused areas. The
transmural blood flow in the ischemic area rose from
21.4 ± 3.5 to 41.0 + 4.2 ml/min/100 g (P < 0.01) (fig. 3,
table 2) and the endocardial, middle layer and epicardial
blood flows increased from 15.7 ± 3.4, 16.5 ± 3.7 and
21.3 ± 3.2 ml/min/100 g (P < 0.01), respectively (fig. 5,
Downloaded from http://ahajournals.org by on October 19, 2023
the administration of methoxamine (table 2).
As a result of the increase in the collateral blood flow to
the ischemic areas, the average ST-segment elevation, which
was 3.4 + 0.9 mV 15 min after the occlusion, fell
significantly during the intervention to 2.2 ± 0.8 mV
(P < 0.02) (figs. I and 6, table 1), showing a reduction in the
magnitude of the acute myocardial ischemic injury.
In the eight control dogs the AP, HR, CO, ST, RMBF,
and total vascular and coronary resistances did not change
significantly between 15 and 30 min after the occlusion
(tables 1 and 2), showing that there is no spontaneous

table 2). The endocardial/epicardial blood flow ratio in the change in these parameters.
ischemic myocardium did not change significantly during In the 12 dogs evaluated for changes in hemodynamics,

Transmural Flow
Control Intervention
110 103
123 104
86 70
19 32
131 111
38 46
115 109
130 130
187 187
3,827 2,189
2,154 4,934
9.2 x 104 10.9 x 104

FIGURE 3. An example illustrating the changes in regional myocardial bloodflow 15 minfollowing occlusion (Control)
and after 15 min of methoxamine + bleeding (Intervention). Left) Schematic representation of the heart, left anterior
descending coronary artery (LAD), sites of the biopsies (squared areas), sites where ECGs were recorded (dots), and site
of LAD occlusion (occl). Right) Transmural bloodflows in each biopsy in the control period and during intervention are
indicated, as well as ATP, HR, CO, total vascular resistance (TVR) and coronary resistance (Cor Res). Note the reduction
offlow in the nonischemic areas (i.e., with a RMBF over 50 ml/min/J00 g of tissue) (sites 1, 2, 3, 5 and 7) and its increase
in the ischemic areas (sites 4 and 6).
 REVERSE CORONARY STEAL/Chiariello et al. 813

100 NORMAL MYOCARDIUM

RMBF 80
90

(ml/min/100g)
* 7m

T*
70 ,. ..

...:

60

50_

OL
ENDO MID
0W.,.
S EPI
,.:M

FIGURE 4. Effects of coronary constriction on regional myocardial bloodflows (RMBF) in endocardial (endo), middle
(mid) and epicardial (epi) layers of the normally perfused sites. ** = differentfrom control, P < 0.01. Note the reduction
offlow after vasoconstriction.

methoxamine infusion and simultaneous bleeding resulted in
unaltered aortic and left ventricular systolic pressures
(127 ± 6 to 125 ± 6 mm Hg), aortic diastolic pressure
(107 ± 7 to 108 ± 7 mm Hg), left ventricular end-diastolic
and atrial mean pressures (5.3 ± 1.5 to 4.4 ± 1.6 mm Hg)
and heart rate (161 ± 6 to 156 ± 6 beats/min). In contrast,
max LV dp/dt fell significantly by 20.3% from 2,331 ± 133
to 1,857 i 147 mm Hg/sec (P < 0.01).
Discussion
A fundamental aim in the treatment of ischemic heart dis-
Downloaded from http://ahajournals.org by on October 19, 2023
because they may have multiple and complex effects. They
may, for example, affect the ischemic zone not only through
their action on the coronary arteries themselves but also
through their peripheral vascular effects. Their ability to
reduce systemic arterial pressure and pulmonary vascular
resistance may reduce afterload and preload. Drugs such as
nitroglycerin may also reduce preload by causing pooling of
blood in the venous system. Such a decrease in afterload
and/or preload reduces myocardial oxygen requirements
and this has been considered important for limiting the ex-
tent of ischemia.27 SO Moreover, the effects of the coronary

ease is to improve the balance between oxygen supply and
demand in the ischemic region of the heart."' 19-22 This may
be achieved either by increasing the heart's oxygen supply
(i.e., perfusion) or by reducing its oxygen requirements. Cor-
onary artery bypass grafting23 is a typical example of the
former approach and propranolol administration of the lat-
ter.24 26 Coronary vasodilators were introduced with the
hope that they would increase oxygen supply by dilating the
narrowed vessels; however, their role is controversial
vasodilators on the coronary bed itself is not uniform.
Diverse effects have been shown on the degree of ischemia
indicating that coronary vasodilators are pharmacologically
a heterogeneous group of drugs.3"-33
Vasodilators that act on the proximal conductance vessels
are considered beneficial," 36 while those that act on the
peripheral resistance vessels are thought to be detrimental33
because they produce a redistribution of flow similar to a
coronary steal. We postulated that coronary constrictors

70r ISCHEMIC MYOCARDIUM

60-
50s

40
RMBF
(ml/min/100g)
30

201

lO1

0'
ENDO MID EPI
FIGURE 5. Effects of coronary constriction on regional myocardial bloodflows (RMBF) in endocardial (endo), middle
(mid) and epicardial (epi) layers of the ischemic sites. Note the marked increase ofcollateralflow to these ischemic zones
following the vascular constriction of the normal areas. ** = different from control, P < 0.01.
 814 CIRCULATION
5 METHOXAMINE
4
ST 3
(mV)
2
--I
0 -AV I
50
v 20 30 40
ISCHEMIC FLOW (ml/min/100g)
FIGURE 6. Simultaneous changes in average ST-segment eleva-
tion (ST) and ischemic transmural flow. The coronary constriction
produced an increase in collateralflow and consequently a reduction
in ST.
that act on resistance vessels are beneficial while constric-
tors that act on conductance vessels are harmful. Accord-
ingly, the goal of the present study was to ascertain whether
reverse coronary steal can be induced by coronary constric-
tion in the normal part of the myocardium. The constant in-
fusion of methoxamine while the systemic pressure was kept
constant resulted in a reduction of regional myocardial
blood flow to the normal areas. This reduction in flow can be
ascribed both to the lowering in myocardial oxygen con-
sumption and to the presumed constrictive action of the drug
on the coronary arterioles. In contrast, regional myocardial
blood flow in the ischemic areas increased (fig. 7). The
Downloaded from http://ahajournals.org by on October 19, 2023
failure of methoxamine to constrict the arteries in the
ischemic areas may be explained either by a reduced amount
of the drug reaching the underperfused zones or, more
probably, by the more powerful metabolic vasodilation in-
duced by the ischemia itself. Collateral vessels may have
their origin at the level of the arterioles.37 When the pressure
in large arteries is maintained constant despite infusion of
vasoconstrictors, the pressure at the level of the arterioles is
significantly increased.38 This increase in perfusion pressure
at the origin of the collateral vessels may therefore be
responsible for the reverse coronary steal. This augmenta-
tion of collateral flow achieved through the induction of a
reverse steal phenomenon was accompanied by a significant
reduction in acute myocardial ischemic injury as reflected by
the change in the average ST-segment elevation.
The possible multifaceted effects of methoxamine on
regional myocardial blood flow in the normal areas and the
consequent reverse coronary steal should be analyzed closely
since they may help to explain the salutary effects of other
agents which have similar general effects. Methoxamine, as
a result of alpha receptor stimulation, causes coronary con-
striction. However, a reduction in myocardial oxygen con-
sumption will also reduce coronary flow in the normal
myocardium. In the hemodynamic experiments performed
in this study, heart rate, preload and afterload did not
change following drug administration; however, left ventric-
ular dp/dt decreased by 20%, presumably resulting in lower
myocardial oxygen consumption. This fall in dp/dt can be
induced by a beta blocking effect of methoxamine.39 Thus, at
least two factors could have contributed to the coronary
vasoconstriction: the direct effect of alpha receptor stimula-
VOL 56, No 5, NOVEMBER 1977
CONTROL
HEMORRHAGE
NORMAL
MYOCARDIUM
FIGURE 7. Schematic representation of the hypothesis of reverse
coronary steal. The left panel illustrates the distribution of flow
following coronary artery occlusion. Bloodflow in the nonoccluded
vessel is directed mainly to the normal myocardium (larger arrow)
which exhibits a normal resistance; less blood flow (small arrow) is
directed through the collaterals to the ischemic area (diamond
shape) where the coronary resistance is low (loose spring). The right
panel illustrates the alteration due to methoxamine accompanied by
bleeding. There is an increase in coronary resistance in the normal
myocardium (tight spring), producing a decrease inflow to the nor-
mal myocardium (arrow reduced in size). Consequently there is an
increase in blood supply to the ischemic zone (small arrow in-
creases) through the collaterals and the extent of myocardial injury
is reduced (smaller diamond).
tion, and the indirect effect of reduction in myocardial oxy-
gen consumption caused by a decrease in contractility.
The results of this study do not suggest that myocardial
ischemia in patients should be treated with methoxamine
plus bleeding, but this demonstration of the feasibility of
producing a reverse coronary steal phenomenon does
suggest that this principle may provide a useful approach to
the treatment of different forms of regional myocardial
ischemia. By inducing a reverse coronary steal phenomenon
it may be possible to increase collateral blood flow to un-
derperfused zones of myocardium in patients with regional
ischemia. Moreover, the demonstration of the feasibility of
producing a reverse coronary steal phenomenon by methox-
amine may suggest that the reduction of myocardial
ischemic injury obtained by several investigators using nitro-
glycerin plus methoxamine20 40, 41 could be related at least
partially to the reverse coronary steal phenomenon due to
methoxamine.
Acknowledgment
The authors gratefully acknowledge the technical assistance of Mr. Daniel
White, Mr. Joseph Gannon and Ms. Alice Carmel as well as the secretarial
assistance of Ms. Merrilee Spence.
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