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Transcript
CY
VOL 57
]
0
JANUARY
NO 1
1978
AN OFFICIAL JOURNAL oftle AMERICAN HEART ASSOCIATION
REVIEWS OF CONTEMPORARY
LABORATORY METHODS
Arnold M. Weissler, M.D., Editor
Precordial Electrocardiographic Mapping
Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017
A Technique to Assess the Efficacy of
Interventions Designed to Limit Infarct Size
JAMES E. MULLER, M.D., PETER R. MAROKO, M.D.,
AND EUGENE BRAUNWALD, M.D.
These experiments demonstrated conclusively that STsegment elevation appears following coronary occlusion; Q
waves appeared in tracings recorded five days postocclusion
but were not discussed. A detailed description of the epicardial QRS changes of infarction was then provided by Wilson
and his colleagues,'3 14 who postulated that a QS wave
results from transmission of the negative cavity potential
through necrotic myocardium. This theory of Q wave
genesis was confirmed by Prinzmetal for some infarcts, but
it was found that in other instances a QS complex resulted
simply from a balance of vectors directed away from the injured area.'5 '1 Prinzmetal also noted that an epicardial QR
complex was produced by a mixture of living and necrotic
myocardium in the subjacent tissue.'7
Conventional capacitor-coupled ECG amplifiers do not
permit differentiation of ST-segment elevation from TQsegment depression. Using a direct coupled ECG amplifier,
Samson and Scher demonstrated in 1960 that the apparent
ST-segment elevation observed following coronary occlusion can result from varying amounts of true ST-segment
elevation and TQ-segment depression producing apparent
ST-segment elevation.'8 Furthermore, recordings from individual cells indicated that the TQ depression was accompanied by a loss of resting membrane potential while the true
ST-segment elevation was accompanied by a shortening of
the action potential. More recent studies have confirmed the
presence of both TQ depressions and true ST-segment
elevations during ischemia but stress the greater contribution of the former.'9 20
Prinzmetal et al. investigated the subcellular events
responsible for alterations in the monophasic action potential in ischemic myocardium. They demonstrated that perfusion of myocardium with a solution containing a high concentration of K+ causes TQ depression, leading to apparent
ST-segment elevation.2' Johnson has recently proposed that
THE QUANTITY OF MYOCARDIUM which
becomes necrotic following coronary occlusion has been
shown to influence both the acute and long-term consequences of myocardial infarction.1 2 Fortunately, experiments now indicate that the size of a myocardial infarct
is not irrevocably determined immediately following a coronary occlusion, but can be altered substantially by a
number of interventions.3-1- However, the clinical assessment of interventions designed to protect ischemic myocardium has posed considerable difficulty. Precordial electrocardiographic mapping, including analysis of both the ST
segment and the QRS complex, which has been developed
over the past several years, is now being used in studies on
patients with acute myocardial infarction. In this review
evidence will be presented which indicates that electrocardiographic mapping, when employed properly and with appropriate awareness of its limitations, can yield valid results
and indicate whether or not an intervention modifies either
the severity of ischemia itself or the eventual size of an infarction.
Epicardial Electrocardiographic Mapping
The electrocardiogram has been used in the study of
myocardial ischemia and infarction for half a century. In
1918, in an effort to establish the utility of the electrocardiogram as an aid in the diagnosis of myocardial infarction,
Smith conducted a systematic study in dogs of the changes
in the electrocardiogram following coronary occlusion.12
From the Department of Medicine, Peter Bent Brigham Hospital and Harvard Medical School, Boston, Massachusetts.
Supported by Contract NOI HV-53000 from the National Heart, Lung and
Blood Institute, Bethesda, Maryland. Dr. Muller is the recipient of an NIH
Research Fellowship #5F32 HL 05110-02 CVB.
Address for reprints: Dr. James E. Muller, Harvard Medical School, 180
Longwood Avenue, Boston, Massachusetts 02115.
I
CIRCULATION
2
ST
6r
I
Jst
OCCLUSION
12nd OCCLUSION
51F
4
NST
8r
3
6
21
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21
11
0
o0
9
9
FIGURE 1. Epicardial ST-segment elevations produced by a 20min occlusion of the left anterior descending coronary artery, a onehour period of recovery and a second occlusion in nine dogs. The
average ST-segment elevation (ST) and the number ofsites with ST
segments exceeding 2 mV (NST) from epicardial sites 15 min
following occlusion are shown. The amount of ST-segment elevation is reproducible and can be used to evaluate the effects of an intervention.
6
OCMr
VOL 57, No 1, JANUARY 1978
the onset of ST-segment elevation, which occurs within seconds of coronary occlusion, could result from an inhibition
of the active transport of K+ with a rapid accumulation of
K+ in the transverse tubular system.22 Although K+ changes
can account for alterations in the action potential of an
ischemic cell, it has recently been shown that venous blood
from an ischemic area contains an unidentified substance
which can alter the electrical behavior of cells.28 Downar et
al. demonstrated that blood from the veins draining an
ischemic area of porcine myocardium shortened the action
potential and reduced resting potential of cells in perfused
cardiac muscle strips. These changes could not be totally accounted for by changes in K+ of the "ischemic" blood even
in combination with hypoxia, acidosis, hypoglycemia or increased lactate.
Both Wilson's and Prinzmetal's groups used epicardial
electrograms from numerous sites (epicardial maps) to study
events following coronary occlusion.13"17 Later, Sayen
reported that elevations occurred in ST-segment maps when
myocardial oxygen tension, determined polarographically,
declined by 35% or more from control values.2' The use of
epicardial ST-segment mapping to evaluate interventions
which could alter ischemic injury and necrosis following coronary occlusion began in 1969.9, 26 Two separate methods of
ST mapping were developed. The first is that in which the
ST segment is used as an index of ischemic injury during
sequential 20 minute coronary occlusions. An occlusion is
placed on the left anterior descending (LAD) coronary
artery of the dog. The ST-segment elevation in multiple
epicardial sites is determined 15 minutes after occlusion.
The occlusion is then released and the myocardium allowed
to recover. Forty-five to sixty minutes later the artery is
reoccluded in the same location but in the presence of the in-
20%02
* 40%o 02
5
4
Ii~~~~
ST(
(mv)3
0
5
10
15
Time (min)
20
20% O
EI 40% 02
FIGURE 2. Example of the effect of respiring 40% 02 on the average ST-segment elevation (S9T) following coronary
occlusion. Right) Schematic representation of the heart. Lined area = area of ST-segment elevation 15 min following
occlusion with F102 of 0.20. Starred area = area of ST-segment elevation 15 min following occlusion with an F102 of 0.40.
LAD = left anterior descending coronary artery. * = sites from which epicardial electrograms were recorded. Left) Com= 7-T
parison between the average ST-segment elevation (g7) in the same animal after two occlusions. o
just before and after occlusion with F102 of 0.20. 0
O= ST just before and after occlusion with F102 of 0.40.
Time = minutes after coronary artery occlusion. (From Circulation 52: 360, 1975.)
PRECORDIAL MAPPING/Muller, Maroko, Braunwald
tervention being tested for its ability to alter ischemic injury.
The mean ST-segment elevation (ST) and the sum of STsegment elevations in all epicardial sites (2ST), as well as
the number of epicardial sites with ST-segment elevation
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greater than 2 mV (NST) are then compared to the same
parameters recorded during the first occlusion8' 26-28 (figs. 1
and 2). The electrical manifestations of injury produced by
15 to 20 minutes of ischemia are reversible and several consecutive occlusions can be carried out in the same animal.
When no intervention is interposed between occlusions the
results are highly reproducible.3 29 The major advantages of
this method are its simplicity and the fact that it permits
each animal to serve as its own control. When animals do
not serve as their own controls, comparison of results
between animals requires large numbers of experiments
because the naturally occurring variability of the coronary
circulation leads to large differences in the size of the
ischemic zone, and ultimately of the infarction following a
"standard" coronary occlusion.
However, this approach has two serious inherent disadvantages: first, it is possible that the intervention being
evaluated has a nonspecific effect on the ST segment and no
effect on the ischemic injury itself; second, this method does
not provide information about the relationship between
ischemic injury occurring shortly after coronary occlusion
and the final amount of myocardial necrosis.
The 24-hour occlusion method in which early ST-segment
mapping is compared to the resultant necrosis overcomes
both of these limitations. As with the first method, the LAD
is occluded and the epicardial ST-segment map recorded 15
min later; the occlusion is maintained, and the chest is closed
for 24 hr, reopened and transmural myocardial specimens
are excised from the sites at which epicardial electrograms
3
had been recorded 24 hr earlier. The biopsies are then coded
and analyzed for histologic evidence of necrosis and
decrease of tissue creatine kinase (CK) activity without
knowledge of the origins of the specimens. In animals which
receive no intervention, there is a predictable, highly significant inverse relationship between the height of the STsegment 15 min after occlusion and the tissue signs of
necrosis, i.e., the histologic, histochemical, electronmicroscopic and biochemical (tissue CK activity) evidence
of infarction 24 hr later.20 32
Thus, with this technique, the epicardial electrogram
serves as a predictor of subsequent tissue viability or infarction and the agent being evaluated is administered after the
ST-segment map has been recorded. Since the ST-segment
map is recorded before the intervention is applied, a nonspecific effect of the intervention on the electrogram can be
excluded. Agents which alter the relationship between the
amount of necrosis predicted (from a control group of
animals) and that observed following administration of the
agent can be said to alter the progression from ischemic injury to necrosis4-7' 10, 28, 30 (figs. 3-5).
Discussion of the limitations and potential difficulties of
epicardial ST-segment mapping has centered on the follow-
ing issues:
1) Does epicardial ST-segment elevation following coronary occlusion correlate with regional myocardial blood
flow?
The experimental results bearing on this issue are mixed
and have recently been summarized.33 Wegria et al., who
were the first to note a relationship between coronary blood
flow and epicardial ST segment elevation, found that a 10 to
OCCLUSION ALONE
EXP. 305
AREA OF ST SEGMENT ELEVATION
SITE OF BIOPSY
SITE
ST
CPK
HISTOLOGY
(mv) I.U./mg prot
O3
0
O
0
3
7
7
8
6
5
is
4G
O
O
0
Q
25.2
21.0
7.2
4.0
3.7
5.9
6.4
4.5
NORMAL
NORMAL
ABNORMAL
ABNORMAL
ABNORMAL
ABNORMAL
ABNORMAL
ABNORMAL
FIGURE 3. Relationship between ST-segment elevation 15 min after occlusion and CK activity and histologic changes
24 hours later in a dog without an intervention. Left) Schematic representation of the anterior surface of the heart.
L.A. = left atrial appendage; L.A.D. = left anterior descending coronary artery. The shaded area represents the area of
ST-segment elevation after occlusion. The circles represent sitesfrom which specimens were obtained. Right) Comparison
of ST-segment elevation with CK activities and histologic analysis 24 hours later in the same sites (from Circulation 45:
1160, 1972).
4
CIRCULATION
2520-
iZ
15-
0
E
E
Ic
10-
80
7-
6A
K
0
4
-
3
-
2
J
-
8 CD E -
2-
0
CONTROL
HYALURONIDASE
PROPRANOLOL
G 50%
GIK
5
10
ST SEGMENT ELEVATION (mV)
15
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FIGURE 4. Relationship between ST-segment elevation 15 min
after occlusion and log creatine kinase (CK) activity from the same
specimens obtained 24 hours later. Line A) control group (occlusion
alone). Fifteen dogs, 101 biopsies. Line B) hyaluronidase. Thirteen
dogs, 94 biopsies. Line C) propranolol. Line D) glucose 50%. Six
dogs, 46 biopsies. Line E) glucose-insulin-potassium infusion. Thirteen dogs, 96 biopsies. All interventions started 30 minutes following coronary artery occlusion, i,e., 15 min after epicardial mapping.
There is a statistical difference (P < 0.01) between the slope ofline
A and the slopes of the other lines, showing less creatine kinase
depression after treatment (from Acta Med Scand Suppl 587: 128,
1975).
35% reduction of coronary blood flow usually failed to
produce electrographic changes while a 35 to 70% reduction
produced 1.0 or 2.0 mV ST-segment elevation with T wave
inversions.34 A reduction in coronary flow greater than 70%
always produced more than 2.0 mV ST-segment elevation
with concomitant T wave changes. When regional myocardial blood flow was measured by the microsphere technique,
VOL 57, No 1, JANUARY 1978
reductions of tissue flow by more than 65% led to a mean
ST-segment elevation of 2.7 mV while flow reductions of 20
to 65% of normal produced a mean ST-segment elevation of
only 0.5 mV.35 Smith et al. found a weak negative correlation between regional myocardial blood flow, as determined
by microspheres and epicardial ST-segment elevation 15
minutes after occlusion.36 The inclusion of sites with severe
ischemia (< 10% of normal blood flow) which had no epicardial ST-segment elevation weakened the correlation. This
could be expected since sites with such severe ischemia often
demonstrate local conduction delay, which invalidates the
ST segment as an index of ischemic injury.37 Becker noted a
great variability in the relation between ST-segment elevation following occlusion and coronary flow but found a correlation between areas of high, medium and low flow and
ST-segment elevation.38 Irvin and Cobb found considerable
scatter in the relationship between ST-segment elevation 15
min postocclusion and blood flow as determined by microspheres 2 hr postocclusion (r = 0.057), but noted that with
only one exception ST-segment elevation exceeding 2 mV
did not occur unless blood flow was less than 50% of
normal.39 Kjekshus40 found a correlation between the
ST-segment elevation 15 min after occlusion and both subendocardial and subepicardial flow 24 hr later, although
the correlation between the ST segment and subendocardial flow was not linear.
Since myocardial oxygen consumption varies from dog to
dog, and in the same dog from moment to moment, and
since coronary blood flow correlates very closely with
myocardial oxygen consumption, it would be surprising if a
close correlation existed between local blood flow and
epicardial ST-segment elevation. The latter, of course, does
not reflect a reduction in blood flow per se, but rather an imbalance between the supply of oxygen provided by the coronary circulation and myocardial oxygen demand. If, at any
level of coronary blood flow, oxygen demand rose, myocardial ischemia would be intensified and ST segments would be
expected to rise.
15 min
24 hours
ECG
CPK
histologic
grade
-t
----i
--l
1i
Tt.i
4,1-
35.6
0
21.3
34
10.6
4+
,
w
FIGURE 5. A schematic representation of the heart and its arteries. The left anterior descending (LA D) was occluded at
its midportion (occl). The shaded area represents the zone of ST-segment elevation 15 min after occlusion. Right) Examples of epicardial electrograms, myocardial CK values (in IU/mg protein), and histologic grades from a control dog.
Site A (from nonischemic myocardium) exhibited no ST-segment changes 15 min after occlusion and 24 hr later showed a
normal QRS configuration, normal CK activity, and appeared normal histologically. Site B (border zone) showed
moderate ST,,m while at 24 hr there was a significant Q wave and partial loss of R wave voltage. The CK activity was
moderately depressed, and the histologic section was graded 3+ (51-75%) necrosis. Site C (center of the ischemic zone)
had marked ST,6m and at 24 hr demonstrated a total loss of R wave with a QS complex. The myocardial CK activity was
greatly depressed, and the histologic section was graded 4+ (> 75%) necrosis (from Circulation 54: 591, 1976).
PRECORDIAL MAPPING/Muller, Maroko, Braunwald
5
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On the other hand, numerous studies have demonstrated a
close linkage between epicardial ST-segment elevation and
ischemic injury. Scheuer and Brachfeld studied the
relationships between myocardial production of lactate and
ST-segment elevation in dogs with externally controlled coronary flow.4" They observed that whenever ST-segment
elevation was present, myocardial lactate was produced. As
ischemia was made progressively more severe, the ST-segment changes generally lagged behind the onset of lactate
production. Karlsson et al. noted that sites with ST-segment
elevations had much higher tissue lactate concentrations in
either the inner half (14.8 ± 2.5 vs 1.6 ± 0.5 , moles/g wet
weight) or the outer half (12.5 ± 1.9 vs 1.6 ± 0.4 ,u moles/g
wet weight) of the ventricular wall. The sites with STsegment elevations also showed significantly less adenosine
triphosphate and creatine phosphate.42
Sayen et al. compared changes in the epicardial electrogram with myocardial oxygen availability as determined
by the polarographic method.24'" ST-segment elevation
appeared in the center of ischemic zones when the oxygen
availability fell to less than 65% of the control level. Angell
et al., using polarographic techniques, also found a significant correlation between intramyocardial oxygen tension
and epicardial ST-segment elevation and concluded that
"minute to minute variations in local myocardial oxygen
balance thus appear to reflect the magnitude of epicardial
ST elevation."" Khuri et al. have utilized a mass spectrometer to study the relationships between intramyocardial STsegment changes and local intramyocardial oxygen and carbon dioxide tensions in dogs with coronary artery occlusion.
Reductions of oxygen tension and elevations of carbon dioxide tension were both found to correlate with local ST-segment changes.4' Thus, while some uncertainty over the
precise relationship between ST-segment elevation and
ischemia persists, there is impressive evidence linking elevation of the epicardial ST segment to various well accepted
markers of ischemic injury.
As a corollary to the latter observation, it has been
reported that ST-segment elevation is lowest in the center of
an area of ischemia and increases as the electrode is moved
from the center to the periphery.49 This diminution of STsegment elevation in the center of an ischemic zone has not
been noted in most studies of the spatial distribution of STsegment elevation.10' 11, 87 60 However, it might be accounted
for by local conduction delay in the center of the ischemic
area leading to a paradoxical decline in ST segment
elevation.37
2) When an area of ischemia is enlarged, does epicardial
ST-segment elevation increase or decrease?
In several studies epicardial ST-segment elevation has
been observed to increase when the area of ischemia is enlarged.3 27 36 46 In canine experiments the epicardial STsegment elevation produced by occlusion of a branch of the
LAD increased when a proximal LAD occlusion was
added.37 However, in a subset of animals in which the area of
ischemia was enlarged, local intraventricular block occurred and ST-segment elevations decreased. These changes,
which are analogous to the well known secondary STsegment changes produced by left bundle branch block, occur in accordance with the ventricular gradient theory.47
When the QRS duration in the dog exceeds 65 msec or the
interval from the Q to the onset of the intrinsic deflection exceeds 40 msec, the relationship between the ST segment and
ischemic injury is altered and the height of the ST segment
no longer varies with the severity of ischemia in the subjacent myocardium. In similar studies in dogs in which occlusion of a branch of the LAD was followed by occlusion of
the proximal LAD, ST-segment elevation was reported to
decrease when the area of ischemia increased but changes in
QRS duration were not considered.'48 49
4) Does reduction in ST-segment elevation indicate a
salvage of ischemic myocardium or an accelerated
progression from ischemic injury to necrosis?
A distinction must be made between a reduction in the
height of ST-segment elevation during a second temporary
occlusion in the same dog, and a decrease in ST-segment
elevation following a sustained occlusion. In experiments
with two sequential occlusions the development of a reduced
amount of ST-segment elevation on the second occlusion
may be taken to indicate a reduction of ischemic injury if
nonspecific effects of the intervention on the electrocardiogram can be excluded. In experiments with a single
fixed occlusion, it is impossible to determine from the early
ST-segment changes alone if a reduction in ST-segment
elevation indicates salvage of myocardium or accelerated
necrosis. However, if the animal survives 24 hr and the
amount of necrosis is determined from the myocardial CK
activity and histologic appearance of myocardial biopsy
specimens, salvage of ischemic myocardium can be differentiated from accelerated necrosis.
The experiments of Ergin et al. provide an opportunity for
comparison of results of acute ST-segment mapping with
direct measurement of completed infarct size.29 The LAD
3) What is the relationship between subendocardial
ischemia and changes in the epicardial ST segment?
This relationship has recently been clarified by the work
of Guyton et al.51 Circumflex coronary flow was gradually
diminished in dogs instrumented with endocardial and
epicardial electrodes. When coronary perfusion pressure was
reduced to 70 mm Hg, ST-segment elevation occurred in the
endocardial lead. When the perfusion pressure was further
diminished, the endocardial ST-segment elevation increased
and reciprocal epicardial ST-segment depression appeared.
This change occurred when epicardial flow remained unchanged from control values. Only when coronary perfusion
pressure was reduced below 40 mm Hg did ST-segment
elevation appear in the epicardial recordings. It is apparent,
therefore, that epicardial ST-segment elevation reflects a
balance of unknown amounts of subendocardial ischemia
producing reciprocal epicardial ST-segment depression and
subepicardial ischemia producing epicardial ST-segment
elevation. However, the fact that epicardial ST-segment
elevation cannot be dissected into its component parts
(primary epicardial ST-segment elevation minus reciprocal
epicardial segment depression) does not invalidate its use to
assess interventions since the recorded epicardial STsegment elevation has been found to correlate well with the
amount of necrosis found in myocardial biopsy specimens 24
hr later.' 7 10 30-32
CIRCULATION
6
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was temporarily occluded in dogs and ST-segment elevation
was measured 15 min postocclusion. One hour later the
LAD was permanently occluded and ST-segment elevation
was again measured 15 min postocclusion. In control
animals the ST-segment elevation was not significantly
different after each occlusion, while in animals given
propranolol after the first occlusion the ST-segment elevation was markedly lower following the second. These STsegment mapping results agreed with the results of direct
measurement of the infarcted area several days later 10.5 ± 2.2% by weight of the left ventricle in the propranolol
group vs 18.5 ± 4.4% in the control group.
Additional support for the validity of ST-segment mapping as an index of alteration in myocardial damage is now
available from the use of other techniques to evaluate infarct
size. A method developed by Jennings et al.8' 52 is based on
histologic analysis of the amount of necrosis in the posterior
papillary muscle of the dog following occlusion of the circumflex artery. Studies of the effect of propranolol on infarct size8 with this method produced results identical to
those in a study of beta-blockade with the ST-segment mapping technique.53 A rat model of myocardial infarction has
been developed in our laboratory which permits a quantitative assessment of infarct size totally independent of the
electrocardiogram. In this model the left coronary artery of
the rat heart is occluded and the size of the infarct measured
48 hr or 3 weeks later by analysis of the total CK activity of
the left ventricle and the percent of the ventricle
demonstrating histologic evidence of infarction. Studies in
this model have demonstrated the effectiveness of
hyaluronidase,5 cobra venom factor, an anticomplement
agent,55 and glucocorticoids5" in limiting infarct size. These
results are similar to and confirm those obtained in the dog
with epicardial ST-segment mapping.
In summary, when appropriate attention is paid to its
limitations, epicardial ST-segment mapping is a valuable
technique which can be used to evaluate ischemic injury. It
cannot be used in the presence of ischemia severe enough to
produce local ventricular conduction delay. When
accelerated necrosis or a nonspecific effect of the intervention on the electrogram is a possibility, the 24 hour method
with subsequent analysis of the subjacent myocardium must
be employed along with acute ST-segment mapping.
Finally, with the availability of totally different methods for
assessing the efficacy of interventions designed to protect the
ischemic myocardium, such as the rat model, results which
support those obtained from ST-segment mapping in the
dog have been obtained.
Epicardial QRS Mapping
It has been known since the work of Wilson'3, 14, 57 and
Prinzmetall5l'7 and their respective collaborators that
alterations in the epicardial QRS complex generally signify
permanent changes in the subjacent myocardium. Kaiser et
al.58 sought an electrographic method capable of detecting
nonviable myocardium to assist with resection of scar tissue
in patients with a ventricular aneurysm. Epicardial electrograms were recorded in 10 dogs from 10 days to one
month postocclusion; the changes in the form of the electrogram were localized tc tissue that demonstrated
VOL 57, No 1, JANUARY 1978
pathologic features characteristic of myocardial infarction.
When it became evident that the extent of necrosis
resulting from coronary occlusion could be modified, the
relationship between early ST-segment elevations (an index
of ischemic injury) and late QRS changes (an index of
necrosis) was evaluated. It was found that the ST-segment
elevation recorded 15 minutes following coronary occlusion
was an excellent predictor of the development of epicardial
Q waves 6 and 24 hr later (fig. 6).69 It was also demonstrated
that these changes in the QRS complex could also be used to
detect salvage of ischemic myocardium.60 The experiment
was similar in design to the 24 hr ST-segment mapping
method described previously, the sole difference being the
recording of epicardial electrograms 24 hr following coronary occlusion, in addition to the analysis of myocardial
histologic appearance and CK activity. In control (untreated) dogs there was a predictable relationship between
the ST-segment elevation 15 min after coronary occlusion,
and the development of Q waves and the loss of R waves
(AQ + AR) 24 hr following occlusion (r = 0.81). A dose
correlation was also present between ST-segment elevation
15 min after coronary occlusion and the development of Q
waves 24 hr later (r = 0.83). Animals which received
hyaluronidase or propranolol (agents shown in other studies
to limit infarct size) demonstrated significantly less change
(AQ + AR) than the control group. In addition, an extremely close correlation was present between the electrographic indices (AQ + AR) and tissue CK and histologic
ST1, in mV
FIGURE 6. The relationship between ST-segment elevation at 15
min following occlusion (ST,,,) and changes in QRS configuration
at 24 hr/(AR + AQ)24hJ. The regression line for eight controls (continuous line) is: (AR +AQ)24h = (3.39 + 0.75) ST,5m,. + (8.8 ± 1.9);
N = 8, r = 0.81 ± 0.06. The regression line for eight hyaluronidase-treated dogs (dotted line) is: (AR + AQ).h = (1.35 ±
0.37)STi5m + (5.4 ± 1.7); N = 8, r = 0.60 ± 0.14. The regression
line for the eight propranolol-treated dogs (dashed line) is: (AR +
AQ)24h = (1.79 ± 0.41)ST5sm + (9.0 ± 2.5); N = 8, r = 0.68 ± 0.08.
Note that for any level of ST,5m (AR + AQ)24h is less in the treated
dogs than in the controls (P < 0.05), reflecting less myocardial
necrosis. The r values, which rangefrom .81 to .60, indicate that the
use of the technique should be confined to comparisons ofgroups of
animals (from Circulation 54: 594, 1976).
PRECORDIAL MAPPING/Muller, Maroko, Braunwald
30O
7
20-
(AR+AQ)24h
in mV
T
101
0'
.1
U
1+
L+
"Al+
HISTOLOGIC GRADE
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FIGURE 7. The relationship between Q wave development and R
wave fall 24 hr after coronary artery occlusion [(AQ + AR)24hl and
the extent of necrosis demonstrated histologically at the same time
in myocardial biopsy specimens. Histologic grade 0 = no visible
necrosis; grade I + = 1-25% necrosis; grade 2+ = 26-50%
necrosis; grade 3+ = 51-75% necrosis; and grade 4+ = > 75%
necrosis. Note that (AQ + AR)24h increases progressively as
necrosis becomes more pronounced. The standard error of the mean
is indicated (from Circulation 54: 591, 1976).
appearance, the previously used markers of myocardial
necrosis (fig. 7). The average correlation coefficient between
(AQ + AR) and tissue CK activity in eight dogs was found
to be - 0.86. Ergin et al. have also demonstrated a close
relationship between changes in the QRS complex four days
following occlusion and the histologic evidence of cellular
damage in the underlying myocardium.29
The significance of epicardial QRS changes has also been
studied in man. Kaiser et al. observed at operation that "in
every instance in which the electrograms were clearly abnormal, excision of the tissue produced no bleeding from the cut
surface."61 Bodenheimer et al. studied the significance of the
epicardial QRS recorded during cardiac operations in 25 patients who had previously undergone cardiac catheterization.62 During the catheterization two ventriculograms were
obtained to identify segments of myocardium with asynergy
which could be reversed by nitroglycerin. At the time of
operation eight of nine dyskinetic segments which had improved with nitroglycerin showed initial R waves in the electrogram. Q waves were present in eight of the 11 dyskinetic
segments which failed to improve with nitroglycerin. A close
relationship between epicardial Q waves and the presence of
fibrosis in myocardial biopsy specimens has been
observed.62' 63 Local myocardial fibrosis, in turn, has been
found to correlate well with the regional contraction
pattern."' This conclusion was reached after comparison of
the amount of fibrosis in myocardial biopsy specimens obtained during coronary artery bypass surgery with the
regional wall motion previously determined by ventriculography.
A potential difficulty in the analysis of R wave loss is the
occurrence of a dramatic increase in R wave height sec-
7
ondary to a local conduction delay in areas of severe
ischemia.87 In animal studies this difficulty can be overcome by use of the preocclusion R wave height for comparisons with the R wave height 24 hr later. If postocclusion
QRS complexes are used as a baseline it is necessary to limit
the application of this technique to sites at which such conduction delay does not occur or to record the height attained
by the R wave prior to a fixed time (e.g., 60 msec) after the
onset of the QRS complex. Sites excluded from R wave
analysis should be analyzed for changes in Q wave development. If these sites were excluded entirely it would limit the
utility of this method in detecting the effect of an intervention on the most severely ischemic areas.
The principal importance of these observations on the
epicardial QRS complex is its validation as a marker of
myocardial necrosis. They form a basis for the consideration
of the use of surface leads.
Precordial Electrocardiographic Mapping
The exploration of the changes in precordial electrical
potential produced by the heart began with the recording of
the first electrocardiogram in man by Augustus Waller in
1889.68 The use of the surface electrocardiogram to
characterize ischemia began with the observation by
Pardee8" that a patient with acute myocardial infarction
demonstrated ST-segment elevations in the standard limb
leads. The correlation of a large Q wave in lead III with
myocardial infarction was described by Fenichel and Kugell
from a study of 35 autopsied cases.70
The experimental and clinical basis for the use of the
precordial electrocardiogram was presented by Wilson and
colleagues in 1944.71 This classic paper presented the results
of experiments in dogs and demonstrated "the close relation
between the potential variations of a precordial electrode
and the potential variations of the underlying ventricular
surface." The electrocardiographic changes of anteroseptal, lateral and high lateral myocardial infarction were
described, but no autopsy correlations were made. The relationship between the electrocardiographic changes and
changes in the myocardium was studied by Myers et al. in a
series of 161 autopsy cases. Patients who had developed Q
waves in leads V2-V4 were found to have anteroseptal
necrosis.72 Patients with Q7 waves in V2-V, had necrosis in
the anterolateral portion of the heart and those with pathologic Q waves in V5 and V. only, were found to have necrosis
in the lower lateral portion of the ventricle.73 74
Another development in precordial electrocardiography
of relevance to the need to assess changes in infarct size was
the development of surface potential mapping. In 1963 Taccardi utilized 240 precordial leads to demonstrate that multiple maxima and minima can exist on the precordium at
any instant during the cardiac cycle.75 This finding supported
Wilson's claim that the precordial leads yield information
about local electrical events. Further development of
isopotential surface maps permitted description of the
movements of wavefronts through the heart78 and of the
changes in the QRS complex following myocardial infarction.77' 78 Thus, extensive experience with the precordial electrocardiogram and its close relationship to changes in the
myocardium has been available to investigators searching
8
CIRCULATION
for a method to evaluate agents which could potentially limit
infarct size.
Precordial ST-Segment Mapping
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Early claims for the beneficial effects of an agent during
myocardial infarction were made on the basis of the rapid
normalization of ST-segment elevations in the standard 12
lead electrocardiogram,79' 80 even before the explicit development of the concept of the limitation of infarct size. The experimental foundation for the use of ST-segment elevations
recorded from multiple precordial leads was established in
1972 in experiments in dogs with coronary artery
occlusion.8" Interventions which caused an increase or
decrease in epicardial ST-segment elevations produced
similar directional changes in precordial maps. A 35 lead
electrode blanket was devised to record precordial maps
from patients with acute infarction. Several interventions,
such as propranolol or intra-aortic balloon counterpulsation, resulted in rapid resolution of the precordial STsegment elevation.8' The features of surface maps obtained
with multiple precordial leads in patients with acute myocardial infarction were described and a reduction in STsegment elevation following the administration of practolol
was reported.82 83
Recently, studies in dogs with simultaneously recorded
epicardial and precordial maps have confirmed the presence
of an extremely close relationship between changes in
epicardial and precordial 2ST.37 Evidence indicating the
sensitivity of precordial maps has also been obtained. In
pigs, Capone et al. occluded the LAD in its midportion with
a balloon-tipped catheter and recorded the total ST-segment
elevation produced in a precordial map.84 They then
withdrew the catheter an average of 1.6 cm to a more proximal location and again occluded the artery. The increase in
the area of ischemia was reflected in a statistically significant
increase in precordial ST-segment elevation.
In dogs, Abildskov and collaborators studied the precordial form of ventricular ectopic beats induced by stimulation
of the heart with an epicardial electrode. Movement of the
epicardial stimulation site by 1.5 cm produced easily
recognizable changes in the form of VPBs in the precordial
electrocardiogram.88
Since patients with acute myocardial infarction ordinarily
demonstrate progressive reductions of ST-segment elevation
as a function of time alone, it is essential that results in a
treated group be compared to results in a separate group of
untreated control patients. This approach was employed in
an investigation which demonstrated that patients with acute
myocardial infarction who received hyaluronidase showed a
significantly more rapid fall of ST-segment elevation than a
control group.86
Alternatively, the patient may be used as his own control;
by this approach a control period is employed prior to the
application of the intervention under investigation. Using
this method it has been demonstrated that accelerated
reductions in ST-segment elevation occur following intraaortic balloon counterpulsation,26 propranolol plus intraaortic balloon counterpulsation,87 propranolol alone,81 88
nitroglycerin with and without phenylephrine,88 82 and in-
VOL 57, No 1, JANUARY 1978
haled oxygen.93 An infusion of nitroprusside in patients with
acute myocardial infarction was found to increase STsegment elevation.82 The results of this approach are most
persuasive when a postintervention control period is
employed and the ST segments revert to their previous
elevations. However, since it is possible that the beneficial
effects of an intervention can persist after the intervention is
terminated,84 it is not essential for a demonstration of
efficacy that ST-segment elevation increase after cessation
of treatment. ST-segment mapping has also been useful in
detecting extensions of the original area of ischemic inj .81, 95,896
Since the technique of precordial ST-segment mapping
has many limitations, it is not surprising that its use has led
to differing assessments of its validity. Discussion has
centered on a number of questions.
1) How does the normal variability of the course ofprecordial ST-segment elevation during acute myocardial infarction affect the method?
Large, rapid fluctuations in ST segment may occur in the
course of infarction in individual patients without obvious
cause97, 98 and in a group of patients there is a progressive
fall in the average ST-segment elevation as a function of
time. The occurrence of these spontaneous changes in MST
precludes generalization from changes of ST-segment elevation in a single patient. However, conclusions can be drawn
from comparison of ST-segment changes in groups of
patients randomly assigned to control or treatment protocols. Alternatively, pre and postintervention control periods
can be compared with the intervention period, as described
above. Madias and Hood demonstrated the relative stability
of mean ZST in a group of 28 patients with acute myocardial infarction. From 6 to 7 hours after onset of pain, mean
2ST changed only slightly (from 65.8 ± 8.4 to 63.8 ± 8.7
mm).99
2) Does the sensitivity of precordial ST-segment elevation
to stimuli other than a change in ischemic injury invalidate the method?
Events which alter the conducting properties of the chest,
such as the development of a pneumothorax, or which alter
the relationship of the ST segment to ischemic injury, such
as a change in plasma [K+] or the development of pericarditis, can cause nonspecific changes in precordial STsegment elevation. These events must be actively searched
for and when identified, the use of ST-segment mapping
must be discontinued. Thus, frequent examinations can
eliminate most cases of pericarditis, while inattention to this
detail will tend to invalidate the results of ST-segment mapping. It is likely that the few remaining cases of nonspecific
variation in ST-segment elevation which cannot be identified
will occur in a random manner in both the control and the
treated groups. When a specific intervention causes a change
in ST-segment elevation unrelated to a change in ischemic
injury (as may occur with glucose-insulin-potassium), the
ST-segment mapping method should not be used.
The major value of precordial ST-segment mapping is to
provide an index of changes in ischemic injury that can occur
PRECORDIAL MAPPING/Muller, Maroko, Braunwald
within minutes of an intervention. When its use is confined
to brief intervals of time, the effects of pericarditis or
changes in plasma [K+] may be minimized.
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3) How do differences in chest geometry affect the height of
precordial ST-segment elevation?
The distance between the exploring electrode and the
ischemic zone, and variations in chest thickness and configuration weaken the correlation between ST-segment
elevation and other markers of infarct size. However, the
precordial ST-segment mapping method has not been
proposed as a method to measure infarct size, but rather as a
method to determine if an intervention alters ischemic injury. The objective is to detect differences in the rate of
resolution of ST-segment elevation between treated and untreated patients,86 or the immediate effects of the intervention using pre and postintervention control periods.93 These
applications of the method largely negate the variations in
ST-segment elevation due to variations in chest thickness
and configuration.
4) What is the effect of changes in ST-segment elevation in
other parts of the heart on precordial ST-segment elevation produced by anterior ischemia?
The surface electrocardiogram results from a balance of
diversely oriented electrical forces.'00 The posterior extension of an anterior infarct will reduce the ST-segment elevation in anterior leads. This difficulty can be avoided by
restricting the use of ST-segment mapping to infarcts in
which the boundaries of the ischemic injury can be encompassed. Thus, patients with concomitant acute anterior and
posterior wall myocardial infarctions should be excluded
from study by this method. A 35 lead precordial map
utilized in several clinical studies8l extends from the left mid
axillary line to the right sternal border horizontally and the
length of the sternum vertically. This map generally completely encompasses the zone of ST-segment elevation of
anterior infarctions.
5) Do initial or peak precordial 2ST correlate with other indices of infarct size?
Morris found that ST-segment displacement in the
anterior or inferior leads 48 hr after the onset of the infarct
correlated directly with maximum SGOT.'0' In addition, a
significant correlation was observed between ZST and the
area of an infarct as determined by pyrophosphate scan,
although the relationship was curvilinear.'02 However,
Thompson et al. found poor correlations between 2ST and
peak or estimated total CK released.103 A close quantitative
relationship between ZST and other indices of infarct size
does not exist and would not be expected for several reasons.
First, precordial ST-segment elevation is influenced
primarily by one part of the heart (i.e., the anterior wall).
Thus, if varying degrees of infarction occur in the other walls
of the heart, they will not be detected by precordial mapping but will be measured by other methods such as serum
CK activity. Second, as already mentioned, differences in
the geometry of the chest and of the position of the heart
9
within the chest of each patient will lead to varying degrees
of precordial ST-segment elevation for the same degree of
epicardial ST-segment elevation. Third, varying amounts of
tissues with differing electrical resistances lie between the
epicardial surface and the precordium, further weakening
the relationship. Finally, since ST-segment elevations may
decline rapidly with time, variable intervals from onset of
pain to the initial recording of the precordial electrocardiographic map will further diminish the correlation.98
6) What is the relationship between precordial 2ST and
clinical condition or prognosis?
No correlation between 2;ST and radiographic evidence
of pulmonary venous hypertension has been observed in a
group of unselected patients including some with, and others
without, a previous infarction.98 However, in another study
in which patients without a previous infarction were
analyzed separately, patients with higher 2;STs on admission were found to have higher scores by the Killip classification for clinical condition." The division of patients with
anterior infarction into groups with 2ST in the six precordial leads . 0.5 mV or < 0.5 mV revealed that the former
displayed a higher incidence of cardiac arrest, congestive
heart failure, second or third degree A-V block, atrial
fibrillation, shock, death, premature ventricular contractions and ventricular tachycardia.'04 It has also been shown
that increases in ST-segment vector magnitude during the
course of a myocardial infarction presage new ischemic injury and sudden death.'0' Despite these correlations, we
believe that it is unlikely that the absolute value of the ZST
will prove useful as a prognostic indicator since it does not
correlate well with infarct size, as indicated above. It may be
useful, however, in patients in whom myocardial necrosis is
limited to the anterior left ventricular wall.
7) What changes occur in precordial ST-segment elevation
when an area of ischemia enlarges?
In dogs in which multiple epicardial and precordial leads
were recorded simultaneously, the 2STs showed parallel
changes when the area of ischemia was modified.37 In pigs,
on the other hand, it has been reported that epicardial STsegment elevation decreased while precordial ST elevation
increased as an area of ischemia became larger.'08 However,
in that investigation only a single epicardial electrode was
used, and it could have been strongly influenced by local
events. In any event, clinical studies have shown that extension of infarction, as identified by re-elevation of serum CK
and chest pain, is accompanied by an increase in precordial
ST-segment elevation.93'"
8) Does an accelerated rate offall ofprecordial ST-segment
elevation reflect reduction of ischemic injury or
accelerated progression from ischemic injury to necrosis?
As already noted, reductions of epicardial or precordial
IST due to salvage of ischemic tissue cannot be distinguished from accelerated necrosis by ST-segment mapping alone. However, although all the pharmacologic interventions that reduced ST-segment elevations were found
10
CIRCULATION
to reduce necrosis and not to accelerate it, only an independent assessment of myocardial necrosis can confirm tissue
salvage or necrosis. The close relationship between myocardial necrosis and changes in the QRS complex37' 60 suggests
the usefulness of analysis of the QRS complex in the interpretation of rapid resolution of ST-segment elevation.
In summary, when applied with appropriate controls and
with attention to invalidating factors, precordial STsegment mapping can produce helpful information concerning the efficacy of interventions designed to limit infarct size.
Important additional information can be obtained with
precordial QRS mapping, as described below.
Precordial QRS Mapping
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This technique is based on the following three considerations:
1) QRS evolution following coronary occlusion is
predictable;59' 60
2) Changes in the epicardial QRS correlate closely with
the amount of necrosis observed in subjacent myocardial
biopsy specimens;59163
3) Changes in epicardial potentials are closely reflected
by changes in precordial electrical potentials.37
With the use of these relationships, salvage of ischemic
myocardium has been detected in dogs by precordial QRS
mapping.'07 A group of dogs in which an LAD occlusion was
maintained demonstrated a greater loss of R wave voltage in
precordial leads exhibiting ST-segment elevation than did a
group of dogs in which ischemic myocardium was salvaged
by early reperfusion (fig. 8).
The value of this method rests upon the accuracy with
which the precordial QRS complex reflects the actual condition of the myocardium. It is therefore essential to review
(A)
CONTROL
CONTROL (7)
(7)
PARTIAL
REPERFUSION (7)
1.3 -1.3
9
X
T
.7~~~~~~~~~~~~~~~~~~X
.9
Precordial
R
.5~~~~~~~~~~~~~~~~~~~~.
.3-3
15
60
15
60
MINUTES POST OCCLUSION
FIGURE 8. Retention of R wave voltage as a sign of salvage of
ischemic myocardium. In seven control dogs permanent occlusions
were placed on two branches of the LAD and 30 lead precordial
maps were obtained 15 and 60 minutes later. In the seven partially
reperfused dogs, identical measurements were made but one of the
two occlusions was released after the 15 minute map, salvaging a
portion of ischemic myocardium. The mean fall of R wave voltage
(R) of sites with ST-segment elevations of 0.15 m V or greater 15
minutes after occlusion is shown. From 15 to 60 minutes postocclusion the group in which ischemic myocardium was salvaged, as
documented by retention of myocardial CK activity and histologic
appearance 24 hr later, showed significantly greater retention of R
wave
voltage (P
<
0.05).
VOL 57, No 1, JANUARY 1978
the evidence that the development of Q waves or loss of R
wave voltage in the precordial leads indicates the development of myocardial necrosis. It is theoretically possible, and
has been reported, that Q wave development may be reversible.108- "' In such instances, the Q wave cannot, by definition, serve as an index of necrosis. However, reversal
generally occurs in Q waves which are present only a short
time, i.e., less than several hours. In addition, in many instances Q waves may be lost when left anterior hemiblock or
other conduction abnormalities develop.'09' "' The number
of instances in which early Q wave reversal occurs in the
absence of a conduction change is extremely small and unlikely to influence mapping results in a large group of patients. Finally, it is well known that Q waves may disappear
months or years after an infarction."2 This disappearance
would not affect the use of QRS mapping as proposed here
since the last ECG would be recorded only one week postinfarction, before this type of change could have occurred.
As has already been noted, epicardial R wave height may
increase in severe ischemia secondary to local conduction
delay. A similar though attenuated increase in R wave
height also occurs in precordial leads,"3 but can be
recognized by a delay in the onset of the intrinsicoid deflection. Therefore, intraventricular conduction disturbances invalidate, or at the least cloud, the interpretation not only of
the ST segment but also of the QRS complex.
Clinicians have long been aware of the close relationship
between QRS changes in the precordial electrocardiogram
and the condition of the underlying myocardium. In 1945
Rosenbaum, Wilson and Johnston"14 described a patient
with recurrent chest pain several days after an anteroseptal
infarction; simultaneously QS complexes were noted to
appear in leads V, and V4, and the R wave height fell in V,.
They reasoned that "since the changes in the QRS complexes are now recorded from a much larger area, it is evident
that the initial zone of infarction has grown larger by lateral
extension." There is abundant autopsy evidence that abnormal Q waves are related to myocardial necrosis and scarring. As already mentioned, Myers et al. described an excellent correlation between the development of Q waves in
specific precordial leads and the pathologic evidence of infarction in the corresponding regions of the heart.72 74 In a
similar study comparing autopsy and electrocardiographic
findings in 1184 patients, Horan et al."" found 51 patients
with Q waves > 0.03 sec in leads I, V,-V6. Forty-eight of
these patients had autopsy evidence of infarction in the
anterolateral myocardium, indicating the high specificity of
Q waves in these leads for myocardial damage. Savage et al.
recently compared QRS changes with infarct size as
measured by planimetry in 24 patients who were found to
have a myocardial infarction at autopsy."" A loss of R wave
voltage in V4-V6 was found to indicate increasingly extensive infarction of the apex of the heart.
Correlations have also been noted between precordial Q
waves and ventricular performance in patients with coronary artery disease. Miller found that patients with
pathologic Q waves had significantly higher left ventricular
end-diastolic pressures than patients without pathologic Q
waves. "' Williams compared the location of asynergy as
determined by ventriculogram with the QRS signs of
transmural anterior infarction and concluded that the electrocardiogram can be used as an index of the location and
PRECORDIAL MAPPING/Muller, Maroko, Braunwald
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severity of ventricular wall lesions.118 In a similar study
Miller found that the electrocardiogram reliably predicted
the presence or absence of dyssynergy in 88% (108 of 123) of
patients with coronary disease."" Furthermore, they found
that in patients with anterior myocardial infarction, the
most lateral precordial lead to which pathologic Q waves extended was related to the severity of dyssnergy. In patients
undergoing cardiac surgery it has been shown that precordial Q waves generally overlie epicardial Q waves and that
epicardial Q waves indicate the presence of myocardial
fibrosis.68 Awan et al. recently found a correlation coefficient
of - 0.87 between the number of Q waves in a 35 lead
precordial map and the angiographically determined ejection fraction.120 In addition, a correlation with one year mortality was found: less than 15 Q waves-9%, 15 to 25
Qs- 19% and 26-35 Qs-60%. An intervention which
reduced the number of Q waves appearing in a precordial
map could by inference be expected to have an effect on ventricular function and mortality. Although less attention has
been directed to the relationship between the loss of R wave
and ventricular function, the sum of R wave voltage in the
precordial V leads has been demonstrated to correlate with
the ejection fraction.'2'
These considerations led to a study in patients with acute
myocardial infarction of the relationship between STsegment elevation in precordial leads on admission to the
coronary care unit and subsequent changes in the QRS complex (R wave loss and Q wave development).'22 Precordial
leads with ST-segment elevation 0.15 mV on admission
exhibited a 63.7 ± 3.8% loss of R wave voltage over the
ensuing five days. Four-fifths of this fall occurred during the
first 24 hours after admission.
From these observations the following method of precordial QRS mapping is proposed for use in patients with acute
myocardial infarction. First, precordial electrocardiograms
from 35 sites on the patient's chest (a precordial map) are
obtained as soon as the patient comes under observation.
The patient is then randomly assigned to a control or treatment group. A second precordial map is recorded one week
later in order to evaluate the changes of the QRS complex in
the sites at risk (i.e., those sites which had exhibited STsegment elevations on the first map), and the extent of the
change in the control and treatment groups is compared.
This method has been used to evaluate the effect of
hyaluronidase in limiting myocardial necrosis in patients
with acute myocardial infarction.'23 Ninety-one patients
with an anterior myocardial infarction who were studied
within 8 hr of the onset of chest pain were randomly assigned
to control or hyaluronidase treatment groups. Sites with STsegment elevation (> 0.15 mV) on the initial ECG which exhibited an R wave were considered vulnerable for the
development of electrocardiographic signs of necrosis. The
sum of R wave voltages of vulnerable sites fell more in the
control group than in the hyaluronidase group (70.9 ± 3.6%
vs 54.2 ± 5.0%, P < 0.01). Q waves appeared in
59.3 4.9% of the vulnerable sites in the control patients vs
46.4 ± 4.9% in the hyaluronidase patients (P < 0.05). Sites
with ST-segment elevation < 0.15 mV on the first map also
showed more favorable evolution in the treatment group.
With hyaluronidase there was diminished loss of R wave
voltage (30.7 ± 4.3% vs 39.7 ± 4.0%).
Derrida et al. have also used this method of QRS analysis
I
to study the effect of nitroglycerin on the electro-
cardiographic signs of necrosis in patients with acute myocardial infarction.'2' Forty-six patients with acute anterior
myocardial infarction were randomly assigned to control or
nitroglycerin treatment groups 10.1 ± 0.9 hr after the onset
of ischemia. The nitroglycerin group lost less R wave
(32.4 ± 8.1% vs 64.0 ± 12.7%) and developed fewer Q
waves (30.0 ± 7.3% vs 56.2 ± 14.0%) than the control
group. An additional value of these studies is the demonstration that even with relatively small sample sizes, QRS mapping can be used to detect protection of ischemic myocardium.
In summary, it is possible to predict the evolution of the
QRS complex of patients observed in the early phases of
an acute myocardial infarction. Differences in evolution
between a treated and control group can then be sought.
There is strong evidence indicating that these changes in the
QRS complex reflect changes in the extent of necrosis and
viability of the underlying myocardium. These changes are
related to localized wall motion, ventricular function, and
less directly to morbidity and mortality.
Technical Aspects of Precordial Mapping
At the present time the use of mapping is so varied that
each group of investigators using the technique can be identified by the number or types of electrocardiographic leads
employed. Since improvement in the method is needed, this
pluralistic approach is desirable and likely to aid its development. In the following section we will describe the mapping
technique which we utilize, not to urge its universal acceptance, but to present an example of a method which has
already been tested in a group of patients with acute
myocardial infarction.122
Patient Selection
The use of the method is restricted to patients with all of
the following conditions: 1) an acute transmural myocardial
infarction by clinical, standard electrocardiographic and enzymatic (determined retrospectively) criteria; 2) an interval
of less than 8 hr from the start of the pain signaling the onset
of ischemia; 3) acute anterior or lateral myocardial
ischemia, as indicated by a total ST-segment elevation of at
least 2.5 mV (25 mm at normal electrocardiographic standardization) in 35 precordial leads with at least five leads
each having 0.15 mV or more of ST-segment elevation; 4) no
evidence of left bundle branch block or QRS duration exceeding 0.10 sec on the initial ECG; 5) no record of preexisting "persistent" ST-segment elevation; 6) no significant
abnormalities of serum electrolyte concentration.
Mapping Technique
A commercially available* 35 lead electrode blanket is
used to facilitate recording (fig. 9). Electrodes (HewlettPackard 14057) with felt attached are located in fixed
positions in a grid of five horizontal rows with seven leads in
each row. The electrode nearest the patient's head and right
arm is placed in the second right intercostal space at the
-*Manufactured by Mr. Richard Peters, 5 Janice Road, Stoughton, Mass.
02702.
CIRCULATION
12
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FIGURE 9. Schematic representation of the 35 electrode map on a
patient's chest (from Am J Cardiol 29: 223, 1972).
right parasternal line. The distance between the first two vertical columns is 7 cm, and the distance between the other
adjacent vertical columns is 4.5 cm. The distance between
adjacent horizontal rows is 4 cm. The electrodes lead to a
switch box which in turn is connected to a commercial electrocardiographic recorder through the "V" lead. The limb
leads are connected in the routine manner. Since results are
based on comparison between maps it is of the utmost importance that all maps be recorded from the same location
of the individual patient's chest. To minimize shifts of location an outline of the borders of the map is drawn on the
patient's chest.
A 0.1 mV standardization is placed at the beginning and
end of each tracing. The six limb leads are recorded to detect
changes in axis and conduction of the depolarization wave
which could affect the precordial QRS complex. Each of the
35 precordial leads is then recorded sequentially. Three to
four complexes which have a stable baseline and are free of
interference are recorded from each lead; at least one complex is recorded at a paper speed of 50 mm/sec to facilitate
analysis of Q wave width and the timing of the intrinsicoid
deflection. Immediately after the first map is recorded the
patient is randomized and treatment or placebo administered. One week later a second precordial map is
recorded in identical fashion.
Analysis of the Electrocardiographic Maps
Patients who demonstrate an increase in QRS duration of
sec between the two tracings or the
greater than 0.02
VOL 57, No 1, JANUARY 1978
appearance of fixed left anterior hemiblock or bundle branch
block are excluded from analysis.
1) ST-segment elevation. The difference between the
baseline (the TQ segment) and the ST-segment height
(recorded 40 msec after the end of the QRS complex) in
millivolts is recorded for each of the 35 sites.
2) R wave loss. The sum of R wave voltage (2R) is determined for sites with ST-segment elevation > 0.15 mV, for
sites with ST elevation < 0.15 mV, and for all 35 sites in
both tracings. The percentage fall in ZR between the two
electrocardiograms is then determined for each of these
three groups of leads.
3) Q wave development. The precise quantification of increases in Q wave depth is more complex for precordial than
for epicardial leads because of occasional discontinuity in Q
wave changes. In leads recorded from the area of V, and V2,
the total loss of a very small R wave can convert a deep S
wave into a deep Q wave. This increase in Q wave depth is
not directly comparable to an equivalent Q wave increase in
V5 or V,. This difficulty can be minimized by the use of the
scoring system described below. Another approach is to
record the changes in the maximum negative deflection, be it
an S wave or a Q wave.
The following scoring system has been developed to
categorize and weigh the relative degree of necrosis indicated by various QRS configurations:120
Score 0 = a QRS complex with normal appearance, i.e.,
Q wave < 0.2 mV and < 40 msec.
Score 1 = a decline in R wave amplitude by > 0.2 mV
and > 50% from that recorded on the first
map; Q wave < 0.2 mV and < 40 msec. By
definition this score cannot be applied in
analyzing the initial map.
Score 2 = a QRS complex with Q wave amplitude . 0.2
mV, duration . 40 msec, and a Q/R ratio
. 1.0.
Score 3 = a QRS complex identical to that defined for a
score of 2, except for a Q/R ratio > 1.0.
Score 4 - a QS complex.
The QRS complex from each of the 35 sites is assigned a
score from 0 to 4 for the initial and final maps. The number
of sites which demonstrate an increase in score by 1 or more
and by 2 or more are determined for each patient. As with
the percentage fall in ZR, this calculation is made for sites
with and without 0.15 mV ST-segment elevation on admission and for all sites regardless of the ST-segment elevation.
The final results of this analysis are expressed as a percentage fall in ZR and a percentage of sites with a change in
score of 1 or more or 2 or more. These three indices are
analyzed separately for sites with 2 0.15 mV or < 0.15 mV
ST-segment elevation on admission and without regard to
ST-segment elevation (fig. 10). It is then possible to compare
these quantitative descriptions of the QRS signs of necrosis
for control and treated groups.
Limitation of Method
The greatest disadvantage of electrocardiographic mapping (ST and QRS) is its restriction to patients with
transmural anterior or lateral myocardial infarction. In addition, patients must be free of significant intraventricular
conduction defects. For QRS mapping the patient must sur-
PRECORDIAL MAPPING/Muller, Maroko, Braunwald
13
CONTROL
1
2
Admission
3 4
5
6
7
1
2
After 1 Week
3 4 5
6
7
., tL
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I
-
II
I 11
III aVR aVL aVFcaI.....
....
111 ~~~~~~~~~~~aVR
aV{L aVF cal
%+ERI100.0
i11
%Ascorek1=100.0
111 aVR aVL aVF cal
% Ascore2I=10OD
L
FIGURE 10. An example of the use of 35 lead precordial electrocardiographic mapping to evaluate the development of
myocardial necrosis in a patient with an anterior myocardial infarction. Thesites with ST-segment elevation > .15 m Von
admission are outlined. Note the unfavorable progression from ischemic injury to necrosis with 100% loss of R wave
voltage by I week of sites within the outline.
vive one week without developing a conduction abnormality
so that the posttreatment map can be obtained but survival
is not required for ST-segment mapping. In addition, QRS
mapping should be used primarily to assess efficacy by comparing results between treated and control groups. In contrast, with ST-segment mapping it is possible to use the patient as his own control and determine at the bedside if
deleterious or beneficial effects are occurring. QRS mapping can indicate whether an individual patient has experienced favorable or unfavorable consequences of his initial ischemia; since all patients in the control group of the
recently completed study of hyaluronidase'l23 lost more than
20% of their total R wave voltage of sites with ST-segment
elevation 0.15 mV, loss of less than 20% of such R wave
voltage in a given patient may be an indication of a
favorable response to therapy.
Another limitation of both QRS and ST mapping is that
they provide information only about the response of the
epicardial half of the anterior left ventricular wall to an intervention, and provide no direct information concerning the
>
effect of an intervention on the subendocardium or of the
posterior and diaphragmatic walls of the ventricle. This
limitation may not be a serious one since interventions
beneficial to one portion of the heart are likely to be
beneficial to isehemic myocardium regardless of its location.
Finally, electrocardiographic mapping in its present form
does not yield quantitative results in terms of grams of
myocardium infarcted or salvaged. Therefore, the
demonstration of a difference in QRS evolution between two
groups of patients cannot be translated into the actual
amount of myocardium preserved. However, it can be concluded that an intervention which produces a favorable
change in mapping results is more beneficial than one which
fails to do so.
Future Development of Precordial Electrocardiographic
Mapping
The precordial mapping method is still in an early stage of
its development and numerous improvements are likely to
14
CIRCULATION
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be made. First, it is probable that additional information
can be gained from greater experience with the method as it
is presently applied. For instance, multiple maps could
be obtained after the onset of pain to define the rate of
evolution of the QRS complex. It may also prove useful to
compare the results of QRS measurements in patients with
infarction with the known QRS variation in a normal population as has recently been reported for changes in the R/S
ratio.'25 In addition, analysis of absolute changes may well
strengthen the linkage of QRS changes with measurements
of ventricular function, and with morbidity and mortality
from myocardial infarction.
Second, certain relatively straightforward modifications
of the method are needed. For instance, it may well be that a
substantial reduction in the number of leads will result in
only a minimal loss of information. It must be determined if
the inferior leads (II, III, aVF) are adequate for evaluation
of diaphragmatic infarctions. Also, the value of computer
techniques to measure the ST segment and the QRS complex and to analyze these measurements must be investigated. The use of a computer to analyze precordial STsegment elevation has already been demonstrated.'26
Third, two approaches to mapping which differ from that
described in this review may be of great value in the future.
The ST-segment vector in the vectorcardiogram has been
shown to correlate with 2ST derived from the scalar electrocardiogram in dogs and in patients with acute myocardial infarction.'27' 128 This would offer a simplified method of
following changes in 2ST. The vectorcardiogram has been
shown to be superior to the scalar ECG in detecting
asynergy of the anterior wall of the heart.129 Indeed, the vectorcardiogram has been shown to be capable of detecting a 1
cm area of akinesia, as determined by ventriculography with
a sensitivity of 85 %.130 Therefore, it is logical to study the use
of analysis of changes in the QRS loop of the vectorcardiogram as a method of assessing the amount of myocardium infarcted.
An interesting use of precordial mapping has been the
recording by McLaughlin et al.'3' of the difference in the
precordial isopotential distribution map before and one
week following experimental coronary occlusion. This
difference represents an electrical picture of the infarct. In
clinical studies a pre-occlusion map is usually unavailable,
but these investigators are now obtaining control maps on a
large number of patients at high risk of developing a
myocardial infarction. If appropriate serum CK measurements could be obtained during infarction, the maps obtained in these patients postinfarction could yield valuable
information concerning the relationship between the electrical deficit produced by the infarction and the extent of loss
of myocardial tissue.
Comparison of Precordial Mapping with other Techniques
Two approaches other than precordial electrocardiographic mapping have been taken to assess changes in infarct size: the analysis of serum creatine kinase (CK) curves,
as developed by Sobel and colleagues'32 137 and radionuclide
imaging of ischemic and infarcted myocardium.138 130 Both
methods have certain advantages over electrocardiographic
mapping, but also have certain limitations which hinder
their use in clinical studies.
VOL 57, No 1, JANUARY 1978
Serum CK curves can be used to measure or to predict infarct size. Infarct size can be calculated from a knowledge of
the level of serum CK activity, the rate of release of CK
from the necrotic myocardium, the CK distribution space
and the rate of disappearance of CK activity from the
serum. However, a recent study in dogs with experimental
myocardial infarction does not confirm the results of earlier
investigators.'40 In man it has been shown that infarct size
calculated from CK curves conforms closely to infarct size
measured morphologically at autopsy in patients who died
of acute myocardial infarction.'36
Even if the conflict in the results of animal studies is disregarded two problems remain with the clinical use of this
method to assess the effect of an intervention on infarct size:
1) the biologic variation in size of infarcts is so great that
large numbers of control and treated patients are needed
since patients do not serve as their own controls; and 2) interventions may alter the amount of CK released from infarcting tissue, giving a falsely elevated serum CK."'1
The number of patients required for a study can be
markedly reduced by a modification of the serum CK
method - the prediction method. With this method serum
CK samples are collected for 7 hr prior to intervention. Each
patient can then be used as his own control to project future
changes in serum CK activity. Since serum CK levels do not
begin to rise for about 3 hr after the onset of myocardial
ischemia and since a delay of 7 hr from the start of CK
elevation is required to permit prediction of the entire curve,
the intervention to be evaluated cannot be applied until at
least 10 hr after the onset of ischemia. By that time it is
likely that most of the injured cells would have progressed to
necrosis. An improvement in the CK method which is of
benefit when a noncardiac cause of CK elevation is
suspected is the measurement of the MB isoenzyme of CK
which is specific for myocardial tissue.'35' 142
The CK method may also be used to assess the presence
and size of extensions of infarction. It has recently been
shown that propranolol attenuates the late rise in CK
observed in approximately 50% of patients with infarction.'43
The advantages of the CK method over precordial mapping as are follows:
1) The CK method can yield quantitative results (if the
intervention can be shown not to alter the fraction of CK
released from infarcting myocardium) while mapping cannot.
2) The CK method can be applied to more patients than
mapping, including those with diaphragmatic, posterior or
subendocardial infarctions.
On the other hand, electrocardiographic mapping has certain advantages over the CK method:
1) With mapping, the intervention can be applied immediately after the initial electrocardiogram is recorded.
2) Each patient serves as his own control for the amount
of necrosis expected, radically decreasing the sample size
needed to detect significant differences between control and
treatment groups.
3) Since the ECGs are recorded before and long after the
intervention is administered, it is possible to prevent a temporary nonspecific effect of the intervention on the electrocardiogram from invalidating the results.
On the other hand, with the CK method samples could be
PRECORDIAL MAPPING/Muller, Maroko, Braunwald
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affected by the intervention since they are collected while it
is being administered. The possibility that an intervention
such as reperfusion during the collection period could alter
the amount of CK released from infarcting tissue has been
mentioned above.
Radionuclide techniques can also be used to assess
myocardial ischemia and infarction. They are conveniently
described as "cold spot" or "hot spot" methods. Following
intravenous injection, cold spot agents, such as radio potassium and its analogs, are distributed in the myocardium in
proportion to regional myocardial blood flow. Since there is
limited distribution of the radioactive material to an
ischemic area, an external detector demonstrates a cold spot
of decreased radioactivity over the ischemic area in comparison to the activity recorded over well perfused areas."3"
Many radiopharmaceuticals can be used to obtain cold spot
myocardial images after intravenous injection.1" 148 Among
these, thallium-201 has emerged as the most promising
because of its energy level, its long half-life, its avidity for
normal myocardium and its ability to delineate a myocardial infarction within 6 hr of the onset of symptoms. Extensive use of thallium-201 has been limited by its high cost and
limited availability.
In addition to potassium analogs, macroaggregated
albumin,'49' 150 radiolabeled microspheres,'15 and xenon1331621-54 have all been used to identify areas of decreased
myocardial perfusion. However, all three of these techniques
require a direct intracoronary injection which limits their
clinical usefulness. Finally, cold spot methods all measure
areas of hypoperfusion rather than damaged myocardium
and therefore are unable to distinguish areas of fresh
ischemia from areas with reduced blood flow secondary to
chronic scarring.
Hot spot imaging is based on the selective accumulation
of an agent in ischemic and/or infarcted myocardium. Both
NmTc-tetracyclinel38s 165 and OOmTc-pyrophosphatelS" 157 have
been used to obtain direct images of myocardial changes
caused by local ischemia. The resolution capabilities of
currently available equipment hinder exact quantification of
ischemic damage. The primary disadvantage of 9OmTctetracycline is the 3-day interval from onset of ischemia to
the optimal period for scanning. The use of 9OmTcpyrophosphate scans is complicated by accumulation of the
agent in bone,'58 false positive scans,'59 accumulation of the
agent in ischemic as well as infarcted myocardiuml" and
poor accumulation in areas of low flow. A major factor
limiting the quality of imaging techniques is the distortion
produced by representing a three-dimensional space on a
two-dimensional plane. All of the cold spot and hot spot
techniques presently available have limitations of resolution,
repeatability, or interpretation which limit their present
value for clinical studies of limitation of infarct size.
Several new imaging techniques have been employed in
experimental animals. These have not yet been applied
clinically but are mentioned here because they hold substantial promise for the future. Radioiodine-labeled antibodies
to myosin selectively accumulate in infarcted myocardium
and can be used to obtain images of the infarction.16' 152
Also, emission computerized tomography (CT) can be used
to obtain images of ischemic or infarcted myocardium.
Positron-emitting monovalent cations with extremely short
half-lives can be used for sequential determination of
15
myocardial blood flow.162 Substrates such as "carbonlabeled glucose,'" octanoate, and palmitate,'" and 13nitrogen-labeled amino acids,'65 can be used to assess the integrity of certain well understood metabolic pathways, if it
can be determined that failure of uptake occurs because of
cellular injury and not because of low flow. A major disadvantage of these techniques is the requirement for cyclotronproduced radionuclides.
Finally, transmission CT may be of great value for the
noninvasive evaluation of infarcting myocardium. In the
nonbeating heart, with the problem of cardiac motion
eliminated, transmission CT can be used to distinguish
between normal myocardium, edematous ischemic myocardium and dense necrotic myocardium.'"'1'7 Transmission
CT or radionuclide techniques'68 169 may also be useful for
obtaining sequential measurements of an index of left ventricular function, such as the ejection fraction in patients
with myocardial infarction.
Acknowledgment
We are grateful for the assistance of Patricia Kadlick in the preparation
of this manuscript.
References
1. Braunwald E (ed): Symposium on Protection of the Ischemic Myocardium. Circulation 53 (suppl 1): 1-1, 1976
2. Sobel BE, Bresnahan GF, Shell WE, Yoder RD: Estimation of infarct
size in man and its relation to prognosis. Circulation 46: 640, 1972
3. Maroko PR, Kjekshus JK, Sobel BE, Watanabe T, Covell JW, Ross J
Jr, Braunwald E: Factors influencing infarct size following experimental coronary artery occlusions. Circulation 43: 67, 1971
4. Maroko PR, Libby P, Sobel BE, Bloor CM, Sybers HD, Shell WE,
Covell JW, Braunwald E: The effect of glucose-insulin-potassium infusion on myocardial infarction following experimental coronary artery
occlusion. Circulation 45: 1160, 1972
5. Maroko PR, Libby P, Bloor CM, Sobel BE, Braunwald E: Reduction
by hyaluronidase of myocardial necrosis following coronary artery
occlusion. Circulation 46: 430, 1972
6. Libby P, Maroko PR, Sobel BE, Bloor CM, Covell JW, Braunwald E:
Reduction of experimental myocardial infarct size by corticosteroid administration. J Clin Invest 52: 599, 1973
7. Kjekshus JK, Mjos OD: Effect of inhibition of lipolysis on infarct size
after experimental coronary artery occlusion. J Clin Invest 52: 1770,
1973
8. Reimer KA, Rasmussen MM, Jennings RB: Reduction by propranolol
of myocardial necrosis following temporary coronary artery occlusion
in dogs. Circ Res 33: 353, 1973
9. Ginks W, Ross J Jr, Sybers HD: Prevention of gross myocardial infarction in the canine heart. Arch Pathol 97: 380, 1974
10. Hirshfeld JW Jr, Borer JS, Goldstein RE, Barrett MJ, Epstein SE:
Reduction in severity and extent of myocardial infarction when nitroglycerin and methoxamine are administered during coronary occlusion.
Circulation 49: 291, 1974
11. Epstein SE, Kent KM, Goldstein RE, Borer JS, Redwood DR: Reduction of ischemic injury by nitroglycerin during acute myocardial infarction. N Engl J Med 292: 29, 1975
12. Smith FM: The ligation of coronary arteries with electrocardiographic
study. Arch Intern Med 22: 8, 1918
13. Wilson FN, Macleod AG, Baker PS, Johnston FD, Klostermeyer LL:
The electrocardiogram in myocardial infarction with particular
reference to the initial deflections of the ventricular complex. Heart 16:
155, 1933
14. Johnston FD, Hill IGW, Wilson FN: The form of the electrocardiogram
in experimental MI. II. The early effects produced by ligation of the
anterior descending branch of the left coronary artery. Ame Heart J 10:
889, 1934
15. Prinzmetal M, Kennamer R, Maxwell M: Studies on the mechanism of
ventricular activity. VIII. The genesis of the coronary QS wave in
through-and-through infarction. Am J Med 17: 610, 1954
16. Maxwell M, Kennamer R, Prinzmetal M: Studies on the mechanism of
ventricular activity. IX. The mural-type coronary QS wave. Am J Med
17: 614, 1954
17. Shaw CMcK Jr, Goldman A, Kennamer R, Kimura N, Lindgren I,
Maxwell MH, Prinzmetal M: Studies on the mechanism of ventricular
activity. VII. The origin of the coronary QR wave. Am J Med 16: 490,
1954
16
CIRCULATION
Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017
18. Samson WE, Scher AM: Mechanism of ST segment alteration during
acute injury. Circ Res 8: 780, 1960
19. Cohen P, Kaufman LA: Magnetic determination of the relationship
between the ST segment shift and the injury current produced by coronary artery occlusion. Circ Res 36: 414, 1975
20. Vincent GM, Abildskov JA, Burgess MJ: The electrophysiologic basis
of ischemic ST displacement. (abstr.) Circulation 54 (suppl II): 11-128,
1976
21. Prinzmetal M, Toyoshima H. Ekmekci A, Mizuno Y, Nagaya T:
Myocardial ischemia: Nature of ischemic electrocardiographic patterns
in mammalian ventricles as determined by intracellular electrographic
and metabolic changes. Am J Cardiol 8: 493, 1961
22. Johnson BA: First electrocardiographic sign of myocardial ischemia.
Circulation 53 (suppl I): 1-83, 1976
23. Downar E, Janse MJ, Durrer D: The effect of "ischemic" blood on
transmembrane potentials of normal porcine ventricular myocardium.
Circulation 55: 455, 1977
JJ, Sheldon EF, Pierce G, Kuo PT: Polarographic oxygen, the
24. Sayen
epicardial electrocardiogram and muscle contraction in experimental
acute regional ischemia of the left ventricle. Circ Res 6: 779, 1958
25. Maroko PR, Braunwald E, Covell JW, Ross J Jr: Factors influencing
the severity of myocardial ischemia following experimental coronary
occlusion. (abstr) Circulation 40 (suppl
III): 111-140, 1969
26. Maroko PR, Bernstein EP, Libby P, DeLaria GA, Covell JW, Ross J
Jr, Braunwald E: The effect of intra-aortic balloon counterpulsation on
the severity of myocardial ischemic injury following acute coronary
occlusion. Counterpulsation and myocardial injury. Circulation 45:
1150, 1972
27. Maroko PR, Braunwald E: Modification of myocardial infarction size
after coronary occlusion. Ann Intern Med 79: 720, 1973
E, Hale SL: Reduction of infarct
28. Maroko PR, Radvany P, Braunwald
size by oxygen inhalation following acute coronary occlusion. Circulation 52: 360, 1975
29. Ergin MA, Dastgir G, Butt MHK, Stuckey JH: Prolonged epicardial
and intramapping in myocardial infarction: the effects of
aortic balloon pumping following coronary artery occlusion. J Thorac
Cardiovasc Surg 72: 892, 1976
30. Hartman J, Robinson J, Gunnar R: Infarct size and chemotactic activity: comparison of decomplementation and enzyme inhibition. Circulation 51 and 52 (supplII): 11-22, 1975
31. Kjekshus JK, Maroko PR, Sobel BE: Distribution of myocardial injury
and its relation to epicardial ST segment changes after coronary artery
occlusion in the dog. Cardiovasc Res 5: 490, 1972
32. Maroko PR, Libby P, Ginks WR, Bloor CM, Shell WE, Sobel BE,
Ross J Jr: Coronary artery reperfusion. Early effects on local myocardial function and the extent of myocardial necrosis. J Clin Invest 51:
2710, 1972
33. Ross J Jr: Electrocardiographic ST segment analysis in the
characterization of myocardial ischemia and infarction. Circulation 53
(suppl I): 1-73, 1976
34. Wegria R, Segers M, Keating RP, Ward HP: Relationship between the
propranolol
I.
reduction in coronary flow and the appearance of electrocardiographic
changes. Am Heart J 38: 90, 1949
Timogiannakis G, AmendeI, Martinez E, Thomas M: ST segment
deviation and regional myocardial blood flow during experimental partial coronary artery occlusion. Cardiovasc Res 8: 469, 1974
36. Smith HJ, Singh BN, Norris RM, John MB, Hurley PJ: Changes in
blood flow and S-T segment elevation following coronary
myocardial
artery occlusion in dogs. Circ Res 36: 697, 1975
37. Muller JE, Maroko PR, Braunwald E: Evaluation of precordial electrocardiographic mapping as a means of assessing changes in myocardial ischemic injury. Circulation 52: 16, 1975
38. Becker LC, Ferreira R, Thomas M: Mapping of left ventricular blood
flow with radioactive microspheres in experimental coronary artery
occlusion. Cardiovasc Res 7: 391, 1973
39. Irvin RG, Cobb FR: Relationship between epicardial ST segment elevation, regional myocardial blood flow and extent of myocardial infarction
in awake dogs. Circulation 55: 825, 1977
40. Kjekshus JK, Maroko PR, Sobel BE: Distribution of myocardial injury
and its relation to epicardial ST-segment changes after coronary artery
occlusion in the dog. Cardiovasc Res 6: 490, 1972
41. Scheuer J, Brachfeld N: Coronary insufficiency: relations between
electrical, and biochemical parameters. Circ Res 18:
hemodynamic,
178, 1966
42. Karlsson J, Templeton GH, Willerson JT: Relationship between epicardial S-T changes and myocardial metabolism during acute coronary insufficiency. Circ Res 32: 725, 1973
43. Sayen JJ, Pierce G, Katcher AH, Sheldon WF: Correlation of incontramyocardial electrocardiograms with polarographic oxygen and Circ
in the nonischemic and regionally ischemic left ventricle.
tractility
Res 9: 1268, 1961
44. Angell CS, Lakatta EG, Weisfeldt ML, Shock NW: Relationship of inchanges
tramyocardial oxygen tension and epicardial ST segment perfusion
acute coronary artery ligation: Effects of coronary
following
pressure. Cardiovasc Res 9: 12,
SF,
45. Khuri
Flaherty JT. O'Riordan JB, Pitt B, Brawley RL. Donahoo
JW, Gott VL: Changes in intramyocardial ST segment voltage and gas
tension with regional myocardial ischemia in the dog. Circ Res 37: 455,
1975
46. Mjos OD, Miller NE, Riemersma RA, Oliver MF: Effects of experimental myocardial ischemic dichloroacetate on myocardial substrate
extraction, epicardial ST-segment elevation, and ventricular blood flow
following coronary occlusion in dogs. Cardiovasc Res 10: 427, 1976
47. Ashman R, Byer E: The normal human ventricular gradient.
I. Factors
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
59.
60.
61.
35.
1975
VOL 57, No 1, JANUARY 1978
62.
63.
which affect its direction and its relation to the mean QRS axis. Am
Heart J 25: 16, 1943
Cohen MV, Kirk ES: Reduction of epicardial ST segment elevation
following increased myocardial ischemia: Experimental and theoretical
demonstration. (abstr) Clin Res 22: 269, 1974
Fozzard HA, Das Gupta PS: ST segment potentials and mapping:
Theory and experiments. Circulation 54: 533, 1976
Prinzmetal M, Toyoshima M, Ekmekci A, Nagaya T: Angina pectoris.
VI. The nature of ST segment elevation and other ECG changes in acute
severe myocardial ischemia. Clin Sci 23: 489, 1962
Guyton RA, Daggett WM: In Cardiovascular Physiology. International
Review of Physiology, vol 9. Edited by Guyton AC, Cowley AW Jr.
Baltimore, University Park Press, 1976, p 310
Jennings RB, Wartman WB, Zuckyk ZE: Production of an area of
homogenous myocardial infarction in the dog. Arch Pathol 63: 580,
1957
Libby P, Maroko PR, Covell JM, Mallock Ross J Jr,
Effect of practolol on the extent of myocardial ischemic injury after experimental coronary occlusion and its effects on ventricular function in
the normal and ischemic heart. Cardiovasc Res 7: 167, 1973
Maclean D, Fishbein MC, Maroko PR, Braunwald E: Hyaluronidaseinduced reductions in myocardial infarct size. Science 194: 199, 1976
Maclean D, Maroko PR, Fishbein MC, Carpenter CB, Braunwald E:
Reduction of infarct size up to 21 days after coronary occlusion in the
rat. (abstr) Circulation 54 (suppl II):II-161, 1976
Maclean D, Maroko PR, Fishbein MC, Braunwald E: Effects of corticosteroids on myocardial infarct size andhealing following experimental coronary occlusion. (abstr) Am J Cardiol 39: 280, 1977
Wilson FN, HillIGW, Johnston FD: The form of the electrocardiogram
in experimental myocardial infarction.
The latter effects produced
by ligation of the anterior descending branch of the left coronary artery.
Am Heart J 10: 903, 1935
Kaiser GA, Waldo AL, Harris PD, Bowman FO, Hoffman BF, Malm
JR: A new method to delineate myocardial damage at surgery. Circulation 39: (suppl I): 1-83, 1969
Radvany P, Askenazi J, Maroko PR, Braunwald E: Predictive value of
ST segment in the development of electrocardiographic signs of necrosis
after experimental coronary artery occlusion. (abstr) Circulation 52
(suppl II):II-14, 1975
Hillis LD, Askenazi J, BraunwaldE, Radvany P, Muller JE, Fishbein
MC, Maroko PR: Use of changes in the epicardial QRS complex to
assess interventions which modify the extent of myocardial necrosis
following coronary artery occlusion. Circulation 54: 591, 1976
Kaiser GA, Waldo AL, Bowman FO, Hoffman BF, Malm JR: The use
of ventricular electrograms in operation for coronary artery disease and
its complications. Ann Thorac Surg 10: 153, 1970
Bodenheimer MM, Vidya SB, Herman GA, Trout RG, Pasdar H, Helfant RH: Reversible asynergy. Histopathologic and electrographic correlations in patients with coronary artery disease. Circulation 53: 792,
1976
Bodenheimer MM, Banka VS, Trout RG, Herman GA, Helfant RH:
Correlation of pathologic Q waves on the standard electrocardiogram
and the epicardial electrogram of the human heart. Circulation 54:213,
CI,
BraunwaldE:
III.
1976
64. Stinson EB, Billingham ME: Correlative study of regional left ventricular histology and contractile function. Am J Cardiol 39: 378, 1977
65. Durrer D, VanLier AAW, Buller J: Epicardial and intramural excitation in chronic myocardial infarction. Am Heart J 68: 765, 1964
66. Rakita L, Borduos JL, Rothman
Prinzmetal M: Studies on the
mechanism of ventricular activity XII. Early changes in RS-T segment
and QRS complex following acute coronary artery occlusion: Experimental study and clinical applications. Am Heart J 48: 351, 1954
67. Hamlin RL, Pipers FS, Hellerstein HK, Smith CR: Alterations in QRS
during ischemia of the left ventricular free wall in goats. J Electrocardiol
2: 223, 1969
68. Waller AD: Demonstration in man of electromotive changes accompanying the heart's beat. J Physiol 8: 229, 1887
69. Pardee HEB: An electrocardiographic sign of coronary artery obstruction. Arch Intern Med 26: 244, 1920
70. Fenichel NM, Kugell VH: The large Q wave of the electrocardiogram.
A correlation with pathologic observations. Am Heart J 7: 235, 1931
71. Wilson FN, Johnston FD, Rosenbaum FF, Erlanger H, Kossman CE,
Hecht H, Cotrim N, Oliveria RM, Scarsi R, Barker PS: The precordial
electrocardiogram. Am Heart J 27: 19, 1944
72. Myers GB, Klein HA, Stofer BE: Correlation of electrocardiographic
S,
I.
PRECORDIAL MAPPING/Muller, Maroko, Braunwald
Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017
and pathologic findings in anteroseptal infarction. Am Heart J 36: 535,
1948
73. Myers GB, Klein HA, Kiratzke T: 2. Correlation of electrocardiographic and pathologic findings in large anterolateral infarcts. Am
Heart J 36: 838, 1948
74. Myers GB, Klein HA, Stofer BE: Correlation of electrocardiogram and
pathologic findings in lateral infarction. Am Heart J 37: 374, 1949
75. Taccardi B: Distribution of heart potentials on the thoracic surface of
normal human subjects. Circ Res 12: 341, 1963
76. Spach MS, Barr RC: Physiologic correlates and clinical application of
isopotential surface maps. Vectorcardiography 2. In Proceedings of the
XI International Symposium on Vectorcardiography, edited by
Hoffman I, Hamby RI, Glassman E. Amsterdam, North Holland
Publishing Co., 1971, pp 131-141
77. Flaherty JJ, Spach MS, Boineau JP, Canent RV Jr, Barr RC, Sabiston
DC: Cardiac potentials on body surface of infants with anomalous left
coronary artery (myocardial infarction). Circulation 36: 345, 1967
Taccardi
78.
B, De Ambroggi L, Viganotti C: Characteristic features of surface potential maps during QRS and ST intervals. Adv Cardiol 10: 248,
1974
79. Oliveira JM, Carballo R, Zimmerman HA: Intravenous injection of
hyaluronidase in acute myocardial infarction: Preliminary report of
clinical and experimental observations. Am Hcart J 57: 712, 1959
80. Poliwoda H: The thrombolytic therapy of acute MI. Angiology 17: 528,
1966
81. Maroko PR, Libby P, Covell JW, Sobel BE, Ross J Jr, Braunwald E:
Precordial ST segment mapping: An atraumatic method for assessing
alterations in the extent of myocardial ischemic injury. The effects of
pharmacologic and hemodynamic interventions. Am J Cardiol 29: 223,
1972
82. Reid DS, Pelides LJ, Shillingford JP: Surface mapping of RS-T segment in acute myocardial infarction. Br Heart J 33: 370, 1971
83. Pelides LJ, Reid DS, Thomas M, Shillingford JP: Inhibition by fblockade of the ST segment elevation after acute myocardial infarction
in man. Cardiovasc Res 6: 295, 1972
84. Capone RJ, Most AS, Sydik PA: Precordial ST segment mapping. A
sensitive technique for the evaluation of myocardial injury? Chest 67:
577, 1975
85. Abildskov JA, Burgess MJ, Lus RL, Wyatt RF: Experimental evidence
for regional cardiac influence in body surface isopotential maps of dogs.
Circ Res 38: 386, 1976
86. Maroko PR, Davidson DM, Libby P, Hagan AD, Braunwald E: Effects
of hyaluronidase administration on myocardial ischemic injury in acute
infarction. A preliminary study in 24 patients. Ann Intern Med 82: 516,
1975
87. Leinbach RC, Gold HK, Buckley MJ, Austen WG, Sanders CA:
Reduction of myocardial injury during acute infarction by early application of intraaortic balloon pumping and propranolol. (abstr) Circulation
48 (suppl IV): IV-100, 1973
88. Gold HK, Leinbach RC, Maroko PR: Propranolol induced reduction of
signs of ischemic injury during acute myocardial infarction. Am J Cardiol 38: 689, 1976
89. Flaherty JT, Reid PR, Taylor D, Kelly DT, Weisfeldt M, Pitt B: Intravenous nitroglycerin in acute myocardial infarction. Circulation 51:
132, 1975
90. Come PC, Flaherty JT, Baird MG, Rouleau JR, Weisfeldt ML, Greene
HL, Becker L, Pitt B: Reversal by phenylephrine of the beneficial effects
of intravenous nitroglycerin in patients with acute myocardial infarction. N Engl J Med 293: 1003, 1975
91. Borer JS, Redwood DR, Levitt B, Cagin N, Bianchi C, Vallin H, Epstein SE: Myocardial ischemia treated with nitroglycerin plus
phenylephrine. N Engl J Med 293: 1008, 1975
92. Chiariello M, Gold HK, Leinbach RC, Davis MA, Maroko PR: Comparison between the effects of nitroprusside and nitroglycerin on
ischemic injury during acute myocardial infarction. Circulation 54: 766,
1976
93. Madias JE, Madias NE, Hood WB Jr: Precordial ST segment mapping.
2. Effects of oxygen inhalation on ischemic injury in patients with acute
myocardial infarction. Circulation 53: 411, 1976
94. Capurro NL, Kent KM, Smith HJ, Aamodt R, Epstein SE: Acute coronary occlusion: Prolonged increase in collateral flow following brief infusion of nitroglycerin. (abstr) Am J Cardiol 39: 263, 1977
95. Reid PR, Taylor DR, Kelly DT, Weisfeldt ML, Humphries JO, Ross
RS, Pitt B: Myocardial infarct extension detected by precordial ST segment mapping. N Engl J Med 290: 123, 1974
96. Madias JE, Venkataraman K, Hood WB Jr: Precordial ST segment
mapping. 1. Clinical studies in the coronary care unit. Circulation 52:
799, 1975
97. Reese L, Scheidt S, Killip T: Variability of precordial ST segment maps
after acute myocardial infarction in man. (abstr) Circulation 48 (suppl
IV): IV-38, 1973
98. Norris RM, Barratt-Boyes C, Heng MK, Singh BN: Failure of ST segment elevation to predict severity of acute myocardial infarction. Br
Heart J 38: 85, 1976
99. Madias JE, Hood WB: Precordial ST-segment mapping. 3. Stability of
17
in the early phase of acute myocardial infarction. Am Heart J 93:
603, 1977
Abildskov JA, Klein RM: Cancellation of electrocardiographic effects
during ventricular excitation. Circ Res 11: 247, 1962
Morris GK, Hampton JR, Hayes MJ, Mitchell JRA: Predictive value of
ST segment displacement and other indices after myocardial infarction.
Lancet 2: 372, 1974
Blomquist CG, Peshock R, Parkey RW, Bonte FJ, Willerson JT: ST
isopotential precordial surface maps in acute myocardial infarction.
(abstr) Circulation 52 (suppl II): II-425, 1975
Thompson PL, Katavatis V: Acute myocardial infarction. Evaluation of
precordial ST segment mapping. Br Heart J 38: 1020, 1976
Nielsen BL: ST segment in acute myocardial infarction. Prognostic importance. Circulation 48: 338, 1973
Kronenberg MW, Hodges M, Akiyama T, Roberts DL, Ehrich DA,
Biddle TL, Yu PN: ST segment variations after acute myocardial infarction: Relationship to clinical status. Circulation 54: 756, 1976
Holland RP, Brooks H: Precordial and epicardial surface potentials
during myocardial ischemia in the pig: A theoretical and experimental
analysis of the TQ and ST segments. Circ Res 37: 471, 1975
Muller JE, Maroko PR, Braunwald E: Use of precordial R wave mapping to detect changes in myocardial ischemic injury. (abstr) Am J Cardiol 35: 159, 1975
Meller J, Conde CA, Donoso E, Dack S: Transient Q waves in
Prinzmetal's angina. Am J Cardiol 35: 691, 1975
Shugold GI: Transient QRS changes simulating myocardial infarction
associated with shock and severe metabolic stress. Am Heart J 74: 402,
maps
100.
101.
102.
103.
104.
105.
106.
107.
108.
109.
1967
110. Pietras RJ, Stavrakos C, Gunnar RM, Tobin JR Jr: Phosphorus
poisoning simulating acute myocardial infarction. Arch Intern Med
122: 430, 1968
111. Fulton MC, Marriott HJL: Acute pancreatitis simulating myocardial
infarction in the electrocardiogram. Ann Intern Med 59: 730, 1959
112. Pyorala K, Kentala E: Disappearance of Minnesota Code Q-QS patterns in the first year after myocardial infarction. Ann Clin Res 6: 137,
1974
113. Prinzmetal M, Kennamer R, Merliss R, Wada T, Bor N: Angina pectoris. 1. A variant form of angina pectoris. Am J Med 27: 375, 1959
114. Rosenbaum FF, Wilson FN, Johnston FD: Changes in the precordial
electrocardiogram produced by extension of an anteroseptal myocardial
infarction. Am Heart J 30: 11, 1945
115. Horan LG, Flowers NC, Johnson JC: Significance of the diagnostic Q
wave of myocardial infarction. Circulation 43: 428, 1971
116. Savage RM, Wagner GS, Ideker RE, Podolsky SA, Hackel DB:
Correlation of postmortem anatomic findings with electrocardiographic
changes in patients with myocardial infarction: Retrospective study of
patients with typical anterior and posterior infarcts. Circulation 55: 279,
1977
117. Miller RR, Bonanno J, Massumi RA, Zelis R, Mason DT, Amsterdam
EA: Usefulness of the electrocardiogram in assessment of ventricular
performance and comparison with coronary arteriography. (abstr) Am J
Cardiol 29: 281, 1972
118. Williams RA, Cohn PF, Vokonas PS, Young E, Herman MV, Gorlin
R: Electrocardiographic, arteriographic and ventriculographic correlations in transmural myocardial infarction. Am J Cardiol 31: 595,
1973
119. Miller RR, Amsterdam EA, Bogren HG, Massumi RA, Zelis R, Mason
DT: Electrocardiographic and cineangiographic correlations in assessment of the location, nature and extent of abnormal left ventricular
segmental contraction in coronary artery disease. Circulation 49: 447,
1974
120. Awan N, Miller RR, Vera Z, Janzen D, Amsterdam EA, Mason DT:
Noninvasive assessment of cardiac function and ventricular dyssynergy
by precordial Q wave mapping in anterior myocardial infarction. Circulation 55: 833, 1977
121. Askenazi J, Freedman WB, Cohn PF, Braunwald E, Parisi AF: The
predictive value of the QRS complex in assessment of left ventricular
function. (abstr) Circulation 54 (suppl II): 11-125, 1976
122. Askenzai J, Maroko PR, Lesch M, Braunwald E: Usefulness of ST segment elevations as predictors of electrocardiographic signs of necrosis in
patients with acute myocardial infarction. Br Heart J 39: 764, 1977
123. Maroko PR, Hillis LD, Muller JE, Tavazzi L, Heyndrickx GR, Ray M,
Chiariello M, Distante A, Askenazi J, Salerno J, Carpentier J Reshetnaya NI, Radvany P, Libby P, Raabe DS, Chazov El, Bobba P,
Braunwald E: Favorable effects of hyaluronidase on electrocardiographic evidence of necrosis in patients with acute myocardial infarction. N Engl J Med 2%: 898, 1977
124. Derrida JP, Sal R, Chicke P: Nitroglycerin infusion in acute myocardial
infarction. N Engl J Med 297: 336, 1977
125. Selwyn AP, Shillingford JP: Precordial mapping of Q waves and RS
ratio changes in acute myocardial infarction. Cardiovasc Res 11:167,
1977
126. Luxton MR, Russell DC, Murray A, Williamson D, Neilson JM, Oliver
MF: Precordial ST segment elevation: new technique for continuous
recording and analysis. Br Heart J 39: 493, 1977
18
CIRCULATION
Downloaded from http://circ.ahajournals.org/ by guest on April 29, 2017
127. Akiyamo T, Hodges M, Biddle TL, Zawrotny B, Vangellow C:
Measurement of ST segment elevation in acute myocardial infarction in
man. Am J Cardiol 36: 155, 1975
128. Foerster JM, Zakauddin V, Janzen DA, Foerster SJ, Mason DT:
Evaluation of orthogonal vectorcardiographic lead ST segment
magnitude in the assessment of myocardial ischemic injury. Circulation
55: 728, 1977
129. Young E, Cohn PF, Gorlin R, Levine HD, Herman MV: Vectorcardiographic diagnosis and electrocardiographic correlation in left ventricular asynergy due to coronary artery disease. I. Severe asynergy of
the anterior and apical segments. Circulation 51: 467, 1975
130. Selvester RH, Wagner JO, Rubin HB, Quantitation of myocardial infarct size and location by electrocardiogram and vectorcardiogram. In
Boerhaave Course in Quantitation in Cardiology, edited by Snellen HA.
The Netherlands, Leyden University Press, 1972, p 31
131. McLaughlin VW, Flowers NC, Horan LG, Killam HA: Surface potential contribution from discrete elements of ventricular wall. Am J Cardiol 34: 302, 1974
132. Shell WE, Kjekshus JK, Sobel BE: Quantitative assessment of the extent of myocardial infarction in the conscious dog by means of analysis
of serial changes in serum creatine phosphokinase activity. J Clin Invest
50: 2614, 1971
133. Shell WE, Lavelle JF, Covell JW, Sobel BE: Early estimation of
myocardial damage in conscious dogs and patients with evolving acute
myocardial infarction. J Clin Invest 52: 2579, 1973
134. Shell WE, Sobel BE: Biochemical markers of ischemic injury. Circulation 54 (Suppl I): 1-98, 1976
135. Roberts R, Henry PD, Sobel BE: An improved basis for enzymatic estimation of infarct size. Circulation 52: 743, 1975
136. Bleifeld W, Mathey D, Hanrath P, Buss H, Effert S: Infarct size estimated from serial creatine phosphokinase in relation to left ventricular
hemodynamics. Circulation 55: 303, 1977
137. Henry PD, Roberts R, Sobel BE: Rapid separation of plasma creatine
kinase isoenzymes by batch adsorption on glass beads. Clin Chem 21:
844, 1975
138. Holman BL, Lesch M, Zweiman FG, Temte J, Lown B, Gorlin R:
Detection and sizing of acute myocardial infarcts with ImTc (Sn)
tetracycline. N Engl J Med 291: 159, 1974
139. Holman BL: Radionuclide methods in the evaluation of myocardial
ischemia and infarction. Circulation 53 (Suppl I): I-1 12, 1976
140. Roe CR, Cobb FR, Starmer CF: The relationship between enzymatic
and histologic estimates of the extent of myocardial infarction in conscious dogs with permanent coronary occlusion. Circulation 55: 438,
1977
141. Manders R, Vatner S, Millard R, Heyndrickx G, Maroko PR: Altered
relationship between creatine phosphokinase release and infarct size
with reperfusion in conscious dogs. (abstr) Circulation 52 (Suppl II): II-
150.
151.
152.
153.
154.
155.
156.
157.
158.
159.
160.
161.
162.
163.
164.
5, 1975
142. Roberts R, Gowda KS, Ludbrook PA, Sobel BE: Specificity of elevated
serum MB creatine phosphokinase activity in the diagnosis of acute
myocardial infarction. Am J Cardiol 36: 433, 1975
143. Pitt B, Weiss JL, Schulze RA, Taylor DR, Kennedy HL, Caralis D:
Reduction of myocardial infarct extension in man by propranolol.
(abstr) Circulation 54 (Suppl II): 11-29, 1976
144. Becker L, Ferreira R, Thomas M: Comparison of 86 Rb and
microsphere estimates of left ventricular blood flow distribution. J Nucl
Med 15(11): 969, 1974
145. Hurley PJ, Cooper M, Reba RC, Poggenburg KJ, Wagner HN Jr:
43KC1: a new radiopharmaceutical for imaging the heart. J Nucl Med
12: 516, 1971
146. Romhilt DW, Adolph RJ, Sodd VJ, Levenson MI, August LS,
Nishiyama H, Berke RA: Cesium-129 myocardial scintigraphy to detect
myocardial infarction. Circulation 48: 1242, 1973
147. Martin ND, Zaret BL, McGown RL, Wells HP Jr, Flamm MD:
Rubidium-8 1: A new myocardial scanning agent. Radiol 11 1: 651, 1974
148. Strauss HW, Harrison K, Langan JK, Lebowitz E, Pitt B: Thallium-201
for myocardial imaging. Relation of thaIlium-201 to regional myocardi-al perfusion. Circulation 51: 641, 1975
149. Ashburn WL, Braunwald E, Simon AL, Peterson KL, Gault JH: Myo-
165.
166.
167.
168.
169.
VOL 57, No 1, JANAURY 1978
cardial perfusion imaging with radioactive-labeled particles injected
directly into the coronary circulation of patients with coronary artery
disease. Circulation 44: 951, 1971
Jansen C, Judkins MP, Grames GM, Gander M, Adams R: Myocardial
perfusion color scintigraphy with MAA. Radiol 109: 369, 1973
Weller DA, Adolph RJ, Wellman FN, Carroll RG, Kim 0: Myocardial
perfusion scintigraphy after intracoronary injection of 99mTc-labeled
human albumin microspheres. Toxicity and efficacy for detecting
myocardial infarction in dogs: Preliminary results in man. Circulation
46: 963, 1972
Cannon PJ, Dell RB, Dwyer EM Jr: Measurement of regional myocardial perfusion in man with "'5Xenon and a scintillation camera. J Clin
Invest 51: 964, 1972
Cannon PJ, Dell RB, Dwyer EM Jr: Regional myocardial perfusion
rates in patients with coronary artery disease. J Clin Invest 51: 978, 1972
Holman BL, Adams DF, Jewitt D, Eldh P, Idoine J, Cohn PF, Gorlin
R, Adelstein SJ: Measuring regional myocardial blood flow with "'3Xe
and the Anger camera. Radiol 112: 99, 1974
Zweiman FG, Holman BL, O'Keefe A, Idoine J: Selective uptake of
9"mTc-complexes and 17Ga in acutely infarcted myocardium. J NucI Med
16: 975, 1975
Bonte FJ, Parkey RW, Graham KD, Moore J, Stokely EM: A new
method for radionuclide imaging of myocardial infarcts. Radiol 110:
473, 1974
Parkey RW, Bonte RJ, Meyer SL, Atkins JM, Curry GL, Stokely EM,
Willerson JT: A new method for radionuclide imaging of acute myocardial infarction in humans. Circulation 50: 540, 1974
Lesch M, Tanaka T, Holman BL: Comparative accuracy of "mTcpyrophosphate, 99mTc-tetracycline, and DBmTc-glucoheptonate for the
scintigraphic diagnosis of acute myocardial infarction. (abstr) Circulation 52 (Suppl II): 11-53, 1975
Ahmad M, Dubiel JP, Verdon TA Jr, Martin RH: Technetium 99m
stannous pyrophosphate myocardial imaging in patients with and
without left ventricular aneurysm. Circulation 53: 833, 1976
Ter-Pogossian MM: Limitations of present radionuclide methods in the
evaluation of myocardial ischemia and infarction. Circulation 53 (Suppl
1): 1-119, 1976
Khaw BA, Beller GA, Haber E, Smith TW: Localization of cardiac
myosin-specific antibody in myocardial infarction. J Clin Invest 58:439,
1976
Beller GA, Smith TW: Radionuclide techniques in the assessment of
myocardial ischemia and infarction. Circulation 53 (Suppl 1): 1-123,
1976
Weiss ES, Hoffman EJ, Phelps ME, Welch MJ, Ter-Pogossian MM,
Sobel BE: External detection of altered metabolism of 'IC-labeled substrates in ischemic myocardium. (abstr) Clin Res 23: 383A, 1975
Ter-Pogossian MM, Hoffman EJ, Weiss ES, Coleman RE, Phelps ME,
Welch MJ, Sobel BE: Positron emission reconstruction tomography for
the assessment of regional myocardial metabolism by the administration of substrates labeled with cyclotron-produced radionuclides. In
Proceedings of Cardiovascular Imaging and Image Processing, Stanford University, July, 1975
Gelbard AS, Clarke LP, McDonald JM, Laughlin JS: Enzymatic synthesis and evaluation of 1'N-labeled amino acids as myocardial scanning
agents. (abstr) J Nucl Med 15: 492, 1974
Adams DF, Hessel SJ, Judy PF, Stein JA, Abrams HL: Computed
tomography of the normal and infarcted myocardium. Am J Roent 126:
786, 1976
Adams DF, Hessel SJ, Judy PF, Stein JA, Abrams HL: Differing
attenuation coefficients of normal and infarcted myocardium. Science
192: 467, 1976
Rigo P, Murray M, Strauss HW, Taylor D, Kelly D, Weisfeldt M, Pitt
B: Left ventricular function in acute myocardial infarction evaluated by
gated scintiphotography. Circulation 50: 678, 1974
Schelbert HR, Henning H, Ashburn WL, Verba JW, Karliner JS,
O'Rourke RA: Serial measurements of left ventricular ejection fraction
by radionuclide angiography early and late after myocardial infarction.
Am J Cardiol 38: 407, 1976
Precordial electrocardiographic mapping. A technique to assess the efficacy of
interventions designed to limit infarct size.
J E Muller, P R Maroko and E Braunwald
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Circulation. 1978;57:1-18
doi: 10.1161/01.CIR.57.1.1
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