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Myocardial infarction in dogs with acute and gradual occlusion of the circumflex or right coronary arteries.

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THE ANATOMICAL RECORD 204:113-122 (1982)
Myocardial Infarction in Dogs With Acute and Gradual
Occlusion of the Circumflex or Right Coronary
Departments of Anatomy (JL.WJ and Physiology and Biophysics (K.W.S.), University
of Tennessee Center for the Health Sciences, Memphis, TN 38163
This study was designed to quantitate and describe the incidence
and magnitude of myocardial infarction in the canine heart following acute and
gradual occlusion of the circumflex or right coronary arteries. In animals with
acute occlusion, the circumflex artery was ligated just distal to the bifurcation of
the left coronary artery for 4 hr (seven dogs). Gradual occlusion was produced by
placing an Ameroid occluder on the circumflex artery for 1 month (nine dogs), 3
months (nine dogs), and 5 months (eight dogs) and on the right coronary artery
for 3 months (nine dogs). Ten dogs served as controls. At the end of the experiments
the dogs were sacrificed, and identification of myocardial infarction was made
with an enzyme-mapping technique in dogs with acute occlusion and with histological methods in dogs with gradual occlusion. The volume of ventricular infarction was determined with the use of an Apple I1 Computer and graphics tablet.
After 3 months, gradual occlusion of the right coronary artery produced a 22%
incidence of infarction which was significantly less (P <.01, x2) than the 67%
incidence observed with 3 months of gradual circumflex occlusion. The average
infarct volume produced by gradual right coronary occlusion was 0.94 + 0.69%.
The average volume of left ventricular infarction in animals with circumflex acute
occlusion was 15.6%+ 6.6 and the incidence of infarction was 100%.With gradual
occlusion of the circumflex artery for 1,3, and 5 months, average left ventricular
infarction was 2.02 ? 1.01%, 3.13 f 1.53%, and 2.96 2 1.35%, respectively.
There were no significant differences in the amount of damage observed among
the three groups with gradual occlusion, and the average incidence of infarction
for these three groups was 76%.In the 1-, 3- or 5-month animals with circumflex
occlusion, no additional areas of necrosis subsequent to the original damage were
found, indicating that infarction is a single event in this model of gradual occlusion. These results suggest that infarct size is determined primarily by factors
at the time of total occlusion and that gradual occlusion allows sufficient time
for collateral growth, thereby limiting the extent of myocardial injury.
Although acute coronary occlusion and the
ensuing development of myocardial infarction
have been studied extensively (Baughman et
al., 1981; Jugdutt et al., 1979; Lowensohn et
al., 1976; Marcus et al., 1976; Miura et al.,
1979; Rose et al., 1976; Willerson et al., 19771,
this type of occlusion is not typical of atherosclerosis in man, which causes a gradual occlusion over a long period of time. Gradual coronary occlusion may allow time for preexisting
collaterals to grow and compensate partially
or completely for the diminished blood flow to
the myocardium of the impaired vascular bed
0003-276W82/2042-0113$03.000 1982 ALAN R. LISS, INC
(Bloor, 1974;Cohen, 1978; Schaper et al., 1967;
Schaper, 1971; Scheel et al., 1976). Thus, gradual occlusion may result in an absence o r a
considerable reduction of myocardial necrosis
as compared to acute coronary occlusion, which
consistently produces myocardial infarction
(Miura et al., 1979; Rivas et al., 1976). Therefore, in the present investigation, our first purAddress reprint requeststo Dr. Jack L. Wilson, Department of Anatomy, University of Tennessee Center for the Health Sciences, 875
Monroe Avenue, Memphis, TN 38163.
Received June 5,1981; accepted June 22,1982.
pose was to determine the incidence and magnitude of myocardial infarction with gradual
occlusion and compare them with infarction
following acute occlusion. The hemodynamic
aspects of gradual occlusion and coronary collateralization have been reported previously
(Schaper, 1971; Scheel et al., 1976,1979). Our
purpose was to provide further evidence concerning the role of coronary collaterals in myocardial damage.
In clinical studies, 17-22% of patients with
myocardial infarction have shown additional
myocardial necrosis 2-17 days following the
original damage (Hutchins and Bulkley, 1978;
Reid et al., 1974). The atherosclerotic disease
process develops slowly with simultaneous involvement of numerous coronary vessels.
Therefore, it is difficult to determine if this
additional myocardial necrosis develops as an
extension from the originally injured myocardium or is due to a progressive occlusion of
other vessels involved in the disease process.
The model of gradual coronary occlusion used
in this study (Ameroid technique) is a pure
form of single-vessel occlusion without involvement of other arteries. Therefore, it was
possible to determine if this single-vessel type
of coronary occlusion produces time-delayed
infarctions. Previous studies have shown that
collateralization in dogs is an active process up
to 5 months followingAmeroid occlusion (Scheel
et al., 1976, 1980). In the second aspect of this
study, we observed animals after 1, 3, and 5
months of occlusion to determine whether, during this time when collaterals are growing,there
are any additional areas of myocardial infarction that might develop following the original
In the final aspect of this study, we investigated the extent of infarction in right versus
left gradual coronary occlusion. Because the
work load of the right ventricle is less than
that of the left ventricle, which pumps against
a higher pressure a t the same cardiac output
(Lowensohn et al.,1976; Peter et al., 1972;Ram0
et al., 1970; Ratliff et al., 19701, this comparison was expected to reveal whether a difference in work load could alter the susceptibility
to infarction.
In this study, 53 young adult male dogs
weighing between 15 and 18 kg were used. All
chronic dogs were examined for a normal electrocardiogram (leads I, 11,111)and negative microfilariae before being accepted into a conditioning program in which they were treated
for intestinal parasites and vaccinated for distemper and hepatitis.
Gradual Circumflex and Right Occlusion
The basic protocol for animals with gradual
occlusion was to place an Ameroid constrictor
on the circumflex or right coronary artery of
the dogs and allow them to remain caged for
either 1, 3, or 5 months. In these groups the
Ameroid constriction was placed close to the
origin and proximal to any branches of the respective vessels. The Ameroid constrictor consists of a plastic material encased in a stainless
steel ring that is slipped onto the artery. The
Ameroid plastic is a hygroscopic material that
swells with the absorption of tissue fluids and
results in total occlusion of the vessel in 17-18
days (Schaper, 1971). Surgical placement of the
Ameroid constrictor on the circumflex artery
followed careful sterile procedures previously
described in detail (Scheel et al., 1976, 1977).
At the termination of the study the animals
were sacrificed for histopathological examinations.
The animals were divided into five groups.
Group I consisted of ten control dogs. Gradual
circumflex occlusion was produced by placing
an Ameroid constrictor on the circumflex artery in group I1 (nine dogs) for 1 month, in
group I11 (nine dogs) for 3 months, and in group
IV (eight dogs) for 5 months. In group V gradual occlusion of the right coronary artery was
produced by placing an Ameroid occluder on
the right coronary artery (nine dogs) for 3
Following the above periods of Ameroid occlusion, the hearts were removed from the animals, and the aorta was attached to a constant-pressure (100 mmHg) reservoir filled with
normal saline. In animals with Ameroid occlusion, a cannula was placed in the circumflex
or right artery just distal to the occluder and
connected by tubing to the reservoir. The coronary vessels were flushed with normal saline
and then perfused with 1 liter of McDowell’s
fixitive for 20 min (McDowelland Trump, 1976).
After fixation, each heart was examined for
complete coronary occlusion by the Ameroid.
The hearts were cut into 7.5-mm thick transverse slices with a Hobart meat slicer. The slices
were stored in 1 liter of fresh McDowell’s fixative for an additional week, dehydrated, and
embedded in paraffin. From each slice, 7 p.m
sections were cut with a sledge microtome. The
sections were stained with hematoxylin-eosin,
Movat’s pentachrolhe (Russell, 1972), and Gomori’s one-step trichrome (Wells, 1966) con-
nective tissue stains to identify areas of myocardial infarction.
Using whole heart histologic sections from
each of the transverse slices described above,
the endocardial outlines of the left ventricle
including the septum were traced on drawing
paper. The free wall of the right ventricle was
traced separately. The necrotic regions from
each slice were projected with a B&L microprojector and traced separately on drawing paper. Depending on the size of the infarct, a
x 2.7, x 5, or x 12 low-power objective was used.
A careful effort was made to include all necrotic and infarcted regions in the drawings.
This was accomplished by constantly changing
to higher-power magnification to determine the
borders and location of infarcts of all sizes.
The extent of myocardial infarction was
quantitated utilizing an Apple I1 computer and
its associated graphics tablet. After the tracings were completed, the following calculations were made: (1) The area of the left ventricle, including the septum, was calculated as
the area within the borders circumscribed by
the epicardial surface of the ventricular wall
and the right side of the septum (A1)and the
ventricular endocardial border (A2). The total
area of the left ventricle in each slice was defined as A1-A2. The area of each slice was multiplied by the slice thickness (7.5 mm) to obtain
volume measurements (Ginks et al., 1974). The
volumes of the slices were summed to give the
total volume of the left ventricle, VT. (2) The
total volume of infarction, VYI,for each heart
was determined separately as the sum of all
necrotic regions traced for each slice, corrected
for magnification factors, and multiplied by slice
thickness. (3)The magnitude of infarction was
expressed in percent volume of the left ventricle, and calculated as the ratio of total infarct volume and total left ventricular volume
x 100). Right ventricular areas and
volumes were determined in a similar manner.
age was determined by the TTC (triphenyl tetrazolium chloride) enzyme-mapping technique
(Lie et al., 1975). The hearts were sliced transversely at a thickness of 1 cm. The slices were
washed in cold water and incubated at 37°C in
a solution of 'M'C for 45 min. The ischemic
myocardium was grayish in color and normal
myocardium was bright red.
The quantitation of acute myocardial damage followed the technique described for animals with gradual circumflex occlusion. The
normal and damaged areas of the slices were
traced on clear mylar, and the calculations were
made with the use of the Apple graphics tablet
as described above.
This study was designed to describe and
quantitate myocardialinfarction followingacute
and gradual occlusion of the coronary arteries.
In this section the histopathological changes
observed with these two types of occlusion will
be presented separately.
Control Animals
Group I
There was no evidence of myocardial infarction or ischemia observed in any of the control
Gradual Circumflex and
Right Coronary Occlusion
Group I1 (circumflex occlusion, 1 month)
There was a 77% incidence of myocardial
infarction of the left ventricle in this group of
dogs (Table 1).The average volume of damaged
left ventricle in animals with infarction was
2.02%,with most animals (five dogs) showing
less than 1.0%volume of infarction (Table 1).
Infarcts in the five animals with least damage consisted of small, focal (1-2 mm2) areas
of fibrosis located in the endocardial and midAcute Circumflex Occlusion
myocardial levels at the posterior papillary and
A 4-hour acute occlusion of the circumflex posteriolateral aspeds of the left ventricle (Fig.
artery was produced in eight dogs (group VI) 1). Histologically, these infarcts were a t least
and the extent of myocardial necrosis was de- 1 week old, and the necrotic muscle had been
termined with an enzyme-mapping technique. replaced by collagen tissue with elongated fiThe general surgical procedure was similar to broblasts scattered evenly throughout.
In the two animals with greater than 1%left
that used in Ameroid application. A suture was
placed around the circumflex artery and li- myocardial damage, infarction involved the
gated for a period of 4 hr. No drugs or external portion of the left ventricle typically supplied
methods were used to control fibrillation. One by the circumflex artery. This included the posanimal died from ventricular fibrillation dur- terior papillary muscle, adjacent septum, and
the posteriorlateral and lateral wall of the left
ing the experiment.
At the end of 4 hr the dogs were sacrificed, ventricle (Fig. 2). The areas of damage were
and the anatomical extent of myocardial dam- found in the sections taken midway between
TABLE I . Myocardial infarction
Infarction volume as percent' of total left or right ventricle
Number of dogs within infarct range
II (circumflex, 1mo Ameroid)
I11 (circumflex,
3-mo Ameroid)
IV (circumflex,
5-mo Ameroid)
V (right 5-mo
VI (circumflex
2.02 * 1.01
2.96 k 1.35
2.70 2 0.35
0.94 2 0.69
15.6 f 6.6**
'Percent = values based only on do with infarction.
*Different from group V, P < .01
**Differentfmm groups XI, 111, IV, P < ,001, (analysis of variance).
base and apex of the hearts. They were limited
to the inner half of the myocardium with no
epicardial involvement. In both animals histological examination indicated that a large
core of necrotic muscle was in the process of
being removed. Surrounding the necrotic muscle was a large cellular band of numerous fibroblasts and macrophages with few lymphocytes and eosinophils (Fig. 3). Peripheral to the
necrotic core, we observed a large area of collagen fibers and fibroblasts with an active vascular proliferation typical of reparative tissue
at this stage. These vessels were very numerous and evenly dispersed throughout the infarcted area (Fig. 3).
Group I11 (circumflex occlusion, 3 months)
In this group the incidence of infarction was
67%, and the average volume of infarction was
3.13% (Table 1). The small infarcts consisted
of areas of subendocardial fibrosis older than
that observed at one month (group11).The larger
infarcts also showed further aging changes from
those observed at 1 month and were found in
the inner half of the myocardium. All remnants of necrotic muscle within the infarct had
been removed at 3 months, and the collagen
fibers and fibroblasts were beginning to arrange themselves into parallel bundles (Fig.
4). No recent infarcts were observed. There was
a general reduction in the degree of vascularization within the infarct compared to that seen
in group 11. However, there were areas within
the infarcts in which vascularization was still
prominent and concentrated.
Group IV (circumflex occlusion, 5 months)
The incidence of left ventricular infarction
in this group was 88% with a 2.96%average
volume of ventricular damage (Table 1). Microscopically, the infarcts were located in the
subendocardium and inner half of the myocardium and were older than those observed in
the previous groups. The smaller lesions (four
dogs) were comprised of compact bundles of
collagen with few scattered fibroblasts. The
larger infarcts (three dogs) consisted of an almost acellular scar tissue of dense collagen in
the septal, posterior, and posteriolateral areas
of the left ventricle. The cellular content was
limited to fibroblasts, and the increased vascular growth observed in earlier infarcts had
disappeared except at the periphery of some of
the large scar areas (Fig. 5).
Group V (right coronary occlusion, 3
Myocardial infarction was found in 22% of
the animals (Table 1).The average volume of
infarction was 0.94%of the right ventricle. The
infarcts were found exclusively in the free wall
of the right ventricle; and although the right
ventricular free wall was thin, the pathological
changes were located in the inner half of the
Fig. 1. Group 11 (circumflex, 1-moAmeroid). An example
of a small, focal area of subendocardial fibrosis (F)frequently found in the posterior papillary muscle. Hematoxylin and eosin. x 40.
Fig. 2. Group I1 (circumflex, 1-mo Ameroid). A midlevel,
transverse section through the entire heart showing a large
myocardial infarct in the posterior and posteriolateral aspects of the left ventricle (arrows). Note large core of necrotic
muscle (N) in posterior papillary muscle. Right ventricle
(R).Movat’s pentachrome stain. x 1.
myocardium. The infarcts consisted of small
(approximately 1 mm2)collagen scars with few
fibroblasts and, histologically, appeared similar to the small lesions observed with three
months of circumflex occlusion. There were no
lesions in the septum or the left ventricle.
Acute Occlusion
Group VI
Infarcts were found in all of the seven animals that survived 4 h r of acute circumflex
occlusion (Table 1).The average volume of left
ventricular infarction was 15.6%,ranging from
8% to 26%. In each animal, the infarcts involved very large areas of the lateral, posterior, and the adjacent septa1 aspects of the left
ventricle. The lesions were found in all slices
from the apex to the base of the hearts (Fig.
6). The color intensity of the TTC staining consistently was prominent after 4 hr of occlusion,
and infarcts could be outlined by the unaided
Statistical Observations
Using an analysis of variance, no significant
differences were found between the volumes of
infarction with 1, 3, or 5 months of circumflex
occlusion (groups 11,111, IV, see Table 1).Also,
there was no significant difference in the volume of infarction between animals with right
occlusion (group V) and animals with 3 months
of circumflex occlusion (group 111). However,
there was a significant difference (P <.01, x2)
between the incidence of infarction found in
animals with right coronary occlusion (group
V) compared to animals with gradual circumflex occlusion (group 111).There was also a significant difference (P <.001) between the volume of infarction found in animals with acute
circumflex occlusion (group VI) and animals
with gradual circumflex occlusion (groups 11,
111, or IV).
In this study, we were able to compare myocardial damage following acute and gradual
coronary occlusion using similar quantitative
methods. The results show a large reduction
in the extent of myocardial infarction of the
left ventricle following gradual circumflex occlusion (2.7%)when compared to acute circumflex occlusion (15.8%), and a lower incidence
of infarction with gradual occlusion (70%)than
acute occlusion (100%).Following gradual right
occlusion, the average amount of right ventricular infarction (0.94%)was less than with
left myocardial infarction but was not statis-
tically different from 3 months of gradual circumflex occlusion. However, the incidence of
infarction was considerably less with right occlusion (22%)as compared with circumflex occlusion (67%, P <0.01, x2).
To our knowledge, this is the first study to
quantitate and compare myocardial infarction
following acute and gradual occlusion of the
circumflex artery using similar procedures.
Other studies with gradual occlusion referred
to the incidence of infarction but have not
quantitated the magnitude of infarction (Flameng et al., 1973, 1975a,b, 1979; Schaper et
al., 1967).
Myocardial Znfarction With Circumflex
Magnitude of Infarction
Acute occlusion. In a number of recent studies, investigators have reported a wide range
in magnitude of infarction with acute coronary
occlusion. Reimer and Jennings (1979) reported that 31% of the left ventricle was infarcted with permanent circumflex occlusion in
dogs after 4 days. In conscious dogs, average
left ventricular infarct sizes of 10.6%(Jugdutt
et al., 1979),19%(Rivaset al., 1976),and 21.3%
(Baughman et al., 1981) have been reported
2-6 days after permanent acute occlusion of
the circumflex artery. In animals with acute
occlusion of the circumflex artery followed by
reperfusion, infarction of 10%(Lowe et al., 1978)
and 15.4%(Baughman et al., 1981) of the left
ventricle has been observed. Other studies that
investigated acute occlusion of the anterior descending artery, reported infarction of 21%
(Willerson et al., 1977) and 22% (Miura et al.,
1979) of the left ventricle.
In this study, 4 hr of acute circumflex occlusion produced a 15.6% infarction of the left
ventricle. This result is within the range observed by other investigators. The variability
of infarct sue between the various studies could
be due to the conditions and methodologiesunder which the experiments were performed
(consciousdogs, anesthetized dogs, permanent
occlusion, occlusion followed by reperfusion, and
site of ligation).
Gradual Occlusion. The results from the animals in this study indicate that a considerably
smaller volume of myocardial infarction (2.7%)
occurs with gradual occlusion. The size of myocardial damage could be limited because collaterals are given sufficient time to grow and
provide blood flow to the impaired vascular bed
during the time the gradual occlusion occurs
(Bloor, 1974; Schaper, 1971).
Fig. 3. Group 11(circumflex 1-moAmeroid). Higher magnification at edge of necrotic core of muscle (N) observed in
Figure 2. Note the large cellular band ( C ) of fibroblasts and
macrophages surrounding the necrotic muscle and the adjacent large area of scar tissue and vascular proliferation.
Hematoxylin and eosin. x 40.
Fig. 4. Group 111 (circumflex, 3-mo Ameroid). Infarcted
area from animal showing condensation and parallel arrangement of collagen fibers and fibroblasts with a reduction
of vascularization within the infarct from that observed in
group II. Hematoxylin and eosin. x 40.
Fig. 5. Group N (circumflex, 5-mo Ameroid). Portion of
a large infarct showing a dense area of scar tissue with
vascularization restricted to the periphery (p) of the infarct.
Hematoxylin and eosin. x 40.
Fig. 6. Group N (circumflex, 5-mo Ameroid). Transverse
slices from a heart of an animal with acute circumflex coronary occlusion for 4hr. Slices are labeled a-g from apex to
basal end of the heart. Posterior edges of the hearts are to
the right of the illustration. Infarcted areas appear white
and normal myocardium appears dark with the TTC staining technique. Infarcted areas were consistently found in
the septa], posterior, and posteriolateral aspects of the left
Our results also showed that with gradual
occlusion of a single vessel no additional areas
of infarction were found subsequent to the original damage. Although the exact time of myocardial infarction can not be pinpointed, the
histological evidence suggests the occurrence
to be coincident with total Ameroid occlusion.
Using the classical, sequential, and characteristic pathological events of infarction described
in dogs (Barrie and Urback, 1957; Bing, et al.,
19561, our careful examinations of the slides
made it possible to differentiate new infarcts
that might have occurred after the initial time
of occlusion in the 1-, 3-, and 5-month animals.
In group 11, studied a t 1 month (12-14 days
after total occlusion), no recent necrotic areas
were observed. In groups I11 and IV, studied a t
3 and 5 months, the infarcts were found in
various stages of healing and repair, which became progressively more advanced in the 5month group. This indicates that the extent of
infarction was related to the hemodynamics of
the vasculature a t the time of occlusion. In this
single-vesseltype of gradual occlusion, no new
areas of infarction developed beyond the original injury. This suggests that the additional
myocardial necrosis reported in clinical studies
of atherosclerosis (Hutchins and Bulkley, 1978;
Reid et al., 1974) probably develops from the
simultaneousprogression of the disease in other
vessels and/or branches of the same vessel.
Incidence of Infarction
Acute Occlusion. Infarction was found in all
animals with acute (4-hr) occlusion of the circumflex, which is consistent with previous
studies (Miura et al., 1979; Rivas et al., 1976).
Gradual Occlusion. Schaper and colleagues
have reported an incidence of infarction ranging from 15%to 50%following gradual (Ameroid) occlusion of the circumflex artery of the
dog (Flameng et al., 1973, 1975a,b; 1979
Schaper et al., 1967; Schaper, 1971). The lesions were described as small, subendocardial
infarcts in the posterior left ventricular wall.
Schaper (1979)has reported recently that, with
improved techniques, a higher incidence of infarction was observed than previously reported. In other studies, the incidence of patchy
subendocardial fibrosis of the posterior papillary muscle was reported in 17% of the dogs
after 6 months of Ameroid occlusion (Lambert
et al., 1977) and in 28% of dogs with 5 and 8
weeks of Ameroid occlusion (Neil1 and Oxendine, 1979). The present results indicated a
higher incidence of left ventricular infarction
(6748%).The higher incidence observed in this
study probably is due to the fact that smaller
infarcts were found by using ~ 4 3 0magnification.
Incidence and Magnitude of Myocardial
Infarction With Gradual Right Coronary
The present study found the magnitude of
infarction to be less in right coronary artery
occlusion (0.94%)than in circumflex occlusion
(3.13%)studied after a n equivalent time (Table
1). Because only two animals developed infarctions after right coronary occlusion, it was
not possible to demonstrate that the difference
in magnitude of damage was statistically significant.
There was a significantly greater incidence
of left ventricular infarction when compared
to right (P <.01, x2), as shown in Table 1. A
possible explanation for this observation is that
ventricular work output for the left heart is
greater than for the right, resulting in a decreased susceptibility of the right myocardium
to infarction following coronary occlusion. This
proposal is supported by the observation that
when right ventricular hypertension, induced
by pulmonary stenosis, was produced prior to
right Ameroid occlusion, right infarction was
found in 80%of pigs (Peter et al., 1972; Ratliff
et al., 1970). In the absence of hypertension,
these investigators did not find right ventricular infarction. It could be argued that the work
loadigm of right coronary perfusion territory
is identical to that of the left circumflex; however, it recently has been shown (Scheel et al.,
1982) that the perfusion territory of the right
coronary artery (22.5gm) is about one half that
of the circumflex (52.9gm in 16-18 kg dogs),
while the average pressure in the right ventricle is one fifth to one sixth that of the left
ventricle (Guyton, 1981).
Factors Influencing Infarct Size
Three basic factors that can influence or limit
the size of a n infarct following gradual coronary occlusion have been proposed: (1) the rate
of development of a collateral network from
pre-existing or innate collaterals within the
heart, (2) the number and caliber of collaterals
available a t time of occlusion, and (3) the size
of the occluded vascular bed.
The rate of collateral development stimulated by gradual occlusion is critical in limiting infarct size, since this will determine the
status of the collateral circulation at the time
of total occlusion. This is evidenced by the
greatly reduced infarct size seen in gradual
versus acute occlusion.
In dogs with gradual occlusion, collateral
growth continues beyond the time of total occlusion. There is a very rapid and significant
epicardial collateral growth a t one month which
plateaus after 5-6 months of circumflex occlusion (Schaper, 1971; Scheel et al., 1976). Also,
intramyocardial collateral growth from the
septa1 artery has been shown to contribute approximately 25% of the collateral circulation
to the major coronary arteries (Scheel et al.,
1980). Since the amount of necrosis appears to
be dictated by the rate of growth and number
of collaterals available at the time of total occlusion, continued collateral growth would serve
to increase the coronary reserve to the remaining viable myocardium.
The second factor reported to influence infarct size is the number and caliber of collateral vessels available to provide blood flow to
the impaired vascular bed at the time of occlusion (Maroko et al., 1971; Schaper, 1979;
White et al., 1978).In Ameroid dogs, the number and size of preexisting collaterals was sufficient to reduce the volume of infarcts to about
one sixth of those observed after acute occlusions.
A third influence on the extent of myocardial
infarction has been reported to be the size of
the perfusion territory of the occluded vascular
bed (Lowe et al., 1978). Lowe et al. (1978) examined why occlusion of the same coronary
artery at identical anatomical sites in dogs resulted in a significant variation in the size of
infarcts. Their results indicated a direct correlation between the amount of necrosis and
size of the occluded circumflex bed (myocardium a t risk).
Since coronary flow to the occluded vessel is
supplied via collaterals, the collateral circulation is in series with the impaired vascular
bed. Because of this series connection, flow to
the impaired vascular bed is a function of the
sum of the resistances of the collateral and
coronary vasculature. Therefore, it would seem
more reasonable to propose that infarct size is
determined by the relationship between the
amount of collateral flow available and the size
of the vascular bed supplied by the collaterals.
For example, if there was a large collateral
blood supply perfusing a small vascular bed,
then infarction might not develop. However, if
one assumes the same bed size but a significantly reduced collateral flow, infarction might
occur. Thus, it is not the size of the perfusion
territory, nor the collateral circulation alone,
that determines the magnitude of infarction,
but the ratio of the collateral resistance to perfusion-territory resistance. This principle could
apply to animals with either acute or chronic
occlusions.However, with gradual coronary occlusion, the ratio decreases due to collateral
development which decreases the probability
of infarction (Bloor, 1974; Schaper, 1971). The
results of this study support this concept, since
infarct size with gradual occlusion was considerably less than that seen with acute occlusion.
This study was supported by USPHS grant
HL24323 and Tennessee Heart Association
grant R07-3005-92. We would like to thank
Mrs. Rhonda Williams and Mrs. Hue-ly Guan
for excellent technical assistance and Ms. Bequi Krell for secretarial assistance.
Barrie, H J . , and P.G. Urback (1957)The cellular changes
in myocardial infarction. Can. Med. Assoc. J., 77~100-106.
Baughman, K.L., P.R. Maroko, and S.F. Vatner (1981)Effects of coronary artery reperfusion on myocardial infarct
size and survival in conscious dogs. Circulation, 63:317-323.
Bing, R.J., A. Castellanos, E. Gradel, C. Lupton, and A.
Siege1 (1956)Experimental myocardial infarction: Circulatory, biochemical and pathological changes. Am. J .
Med. Sci., 232:533-554.
Bloor, C.M. (1974)Functional significance of the coronary
collateral circulation. Am. J . Pathol., 76.562-587.
Cohen, M.V. (1978)The functional value of coronary collaterals in myocardial ischemia and the therapeutic approach to enhance collateral flow. Am. Heart J., 953396404.
Flameng, W., W. Schaper, and P. Lewi (1973)Multiple experimental coronary occlusion without infarction. Am.
Heart J., 85.767-776.
Flameng, W.. B. Wusten, and W. Schaper (1975a)Effects of
prindilol on iaoproterenol-induced subendocardial ischaemia in dogs with multiple chronic coronary artery occlusion. Cardiovasc. Res., 3561-568.
Flameng, W., B. Wusten, B. Winkler, S. Pasyk, and W.
Schaper (1975b)Influence of perfusion pressure and heart
rate on local myocardial flow in the collateralized heart
with chronic coronary occlusion. Am. Heart J., 89:51-59.
Flameng, W., F. Schwan, and W. Schaper (1979)Coronary
collaterals in the canine heart: Development and functional significance. Am. Heart J., 97370-77.
Ginks, W., J. Ross, and H.D. Sybers (1974)Prevention of
gross myocardial infarction in the canine heart. Arch.
Pathol., 973380484.
Guyton, A.C. (1981)Textbook of Medical Physiology. W.B.
Saunders Company, Philadelphia, p. 157.
Hutchins, G.M., and B.H. Bulkley (1978)Infarct expansion
versus extension: Two different complications of acute
myocardial infarction. Am. J . Pathol., 41:1127-1132.
Jugdutt, B.T., G.M. Hutchins, B.H. Bulkley,andL.C. Becker
(1979)Myocardial infarction in the conscious dog: Threedimensional mapping of infarct, collateral flow and region
at risk. Circulation, 6031141-1150.
Lambert, P.R., D.S.Hess, and R.J. Bache (1977)Effect of
exercise on perfusion of collateral-dependent myocadium
in dogs with chronic artery occlusion. Clin. Invest., 5931-7.
Lie, J.T., P.C. Pairolero, K.E. Holly, and J.L. Titus (1975)
Macroscopic enzyme-mapping verification of large, homogeneous experimental myocardial infarcts of predictable size and location in dogs. J. Thorac. Cardiovasc. Surg.,
Lowe, J.E., K.A. Reimer, and R.B. Jennings (1978)Experimental infarct size as a function of the amount of myo-
cardium a t risk. Am. J . Pathol., 90:363-377.
Lowensohn, H.S., E.M. Khouri, D.E. Gregg, R.L. Pyle, and
R.E. Patterson (1976) Phasic right coronary artery blood
flow in conscious dogs with normal and elevated right
ventricular pressures. Circ. Res., 39:760-766.
Marcus, M.L., R.J. Tomanek, J.C. Ehrhardt, R.E. Kerber,
D.D. Brown, and F.M. Abboud (1976) Relationships between myocardial perfusion, myocardial necrosis, and
technetium-99m pyrophosphate uptake in dogs subjected
to sudden coronary occlusion. Circulation, 543647453,
Maroko, P.R., J.K. Kjekshus, B.E. Sobel, T. Watanabe, J.W.
Covell, J . Ross, Jr., and E. Braunwald (1971) Factors influencing infarct size following experimental coronary artery occlusions. Circulation, 4336742.
McDowell, D.M., and B.F. Tnunp (1976) Histologic fixatives
suitable for diagnwtic light and electron microscopy. Arch.
Pathol. Lab. Med., 100:405414.
Miura, M., R. Thomas, W. Ganz, T. Sokol, W.E. Shell, T.
Toshimitsu, A.C. Kwan, and B.N. Singh (1979) The effect
of delay in propranolol administration on reduction of
myocardial infarct size after experimental coronary artery occlusion in dogs. Circulation, 59;114%1157.
Neill, W.A., and J.M. Oxendine (1979) Exercise can promote
coronary collateral development without improving perfusion of ischemic myocardium. Circulation, 6031513-1519.
Peter, R.H., B.W. Ramo, N. Ratliff, and J J . Morris, Jr. (1972)
Collateral vessel development after right ventricular infarction in the pig. Am. J . Cardiol., 2935640.
Ramo, B.W., R.H. Peter, N. Ratliff, Y. Kong, H.D. McIntosh,
and J.J. Moms, Jr. (1970) The natural history of right
coronary arterial occlusion in the pig. Comparison with
left anterior descending arterial occlusion. Am. J. Cardiol., 26:156161.
Ratliff, N.B., R.H. Peter, B.W. Ramo, W.R. Somers, and J.J.
Morris, Jr. (1970) A model for the production of right
ventricular infarction. Am. J . Pathol., 583471475,
Reid, P.R., D.R. Taylor, D.T. Kelly, M.L. Weisfeildt, J . Humphries, R.S. Ross, and B. Pitt (1974) Myocardial-infarct
extension detected by precordial ST-segmentmapping. New
Eng. J . Med., 2903123-128.
Reimer, K.A., and R.B. Jennings (1979)The “wavefront phenomenon” of myocardial ischemic cell death. 11. Transmural progression of necrosis within the framework of
ischemic bed size (myocardium a t risk) and collateral flow.
Lab. Invest., 40:633444.
Rivas, F., F.R. Cobb, R.J. Bache, and J.C. Greenfield, Jr.
(1976) Relationship between blood flow to ischemic regions and extent of myocardial infarction. Serial mea-
surement of blood flow to ischemic regions in dogs. Circ.
Res., 38:439447.
Rose, A.G., L.H. Opie, and O.L. Bricknell (1976) Early experimental myocardial infarction. Arch. Pathol. Lab. Med.,
Russell, H.K.,Jr. (1972) A modification of Movat’s pentachrome stain. Arch. Pathol., 94:187-191.
Schaper, W., A. Jageneau, and R. Xhonneux (1967) The
development of collateral circulation in the pig and dog
heart. Cardiologia, 51:321-335.
Schaper, W. (1971) The Collateral Circulation of the Heart.
North-Holland Publishing Co., Amsterdam, pp.8, 19-28.
Schaper, W. (1979) The Pathophysiology of Myocardial Perfusion. North-Holland Biomedical Press, Amsterdam, Elsevier, pp.352-360.
Scheel, K.W., T.A. Galindez, B. Cook, R.J. Rodriguez, and
L.A. Ingram (1976) Changes in coronary and collateral
flows and adequacy of perfusion in the dog following one
and three months of circumflex occlusion. Circ. Res.,
Scheel, K.W., R.J. Rodriguez, and L.A. Ingram (1977) Directional coronary collateral growth with chronic circumflex occlusion in the dog. Circ. Res., 40:384490.
Scheel, K.W., E.M. Fitzgerald, R.O. Martin, and R.A. Larsen
(1979) The possible role of mechanical stresses on coronary collateral development during gradual coronary occlusion: A simulation study. In: The Pathophysiology of
Myocardial Perfusion. W. Schaper, ed. North-Holland
Biomedical Press, Amsterdam, Elsevier, p.489.
Scheel, K.W., J.L. Wilson, L.A. Ingram, and L. McGehee
(1980) The septa1 artery and its collateral in dogs with
and without circumflex occlusion. Am. J . Physiol.,
Scheel, K.W., L.A. Ingram, and R.L. Gordey (1982) The relationship of coronary flow and perfusion territory a t maximal vasodilation in the dog. Am. J . Physiol., (in press).
Wells, G.G. (1966) Manual of Histologic Technics. University of Tennessee, Memphis, p. 178.
White, F.C., M. Sanders, and C.M. Bloor (1978) Regional
redistribution of myocardial blood flow after coronary occlusion and reperfusion in the conscious dog. Am. J . Cardiol., 423236243.
Willerson, J.T., R.W. Parkey, E.M. Stokely, F.J. Bonte, S.
Lewis, R.A. Harris, G. Blomqvist, L.R. Poliner, and L.M.
Buja (1977) Infarct size with technetium-99m stannous
pyrophosphate scintigraphy in dogs and man; relationship
between scintigraphic and praecordial mapping estimates
of infarct size in patients. Cardiol. Res., 11:291-298.
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