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Restoration of Regional Wall Motion by
Nitroglycerin Therapy in Patients with Left
Ventricular Asynergy*
Allan D. Sniderman, M.D.;"' Peter Herscooitch, B.Eng.;
Derek Marpole, M.D.;t and Ernest L. Fallen, M . D S
Abnormalities in regional wall motion are not uniformly
improved following aortocoronary bypass operation. This
study demonstrates that regional wan motion abnormalities may be reversed with nitroglycerin therapy. Eighteen
asynergic regions in seven patients with coronary artery
&ease were studied before and after sublingually administered nitroglycerin. Although none of the normal
areas became abnormal after nitroglycerin therapy, there
were marked changes in the asynergic regions. Of the
seven hypokinetic areas, three became normal. Of the 11
dyskinelic areas, 4 showed a normal reduction in area after nitroglycerin treatment. The stndy illustrates that because ereas of regional dysfunction may not exist as fixed
lesions, their recoverability can be realized by changing
the loading conditions of the ventricle. Identification of
such potentially viable areas of asynergy may prove helpful in the selection of cases for aortocoronary bypasa o p
eration.
ortocoronary bypass operation has a variable
e£€ect on the function of the left ventric1e,l4
This may be due, in part, to inability to predict the
behavior of regional wall abnormalities following
revascularization. Areas of asynergy may have pronounced influence on left ventricular fun~tion,4.~
and yet traditional hemodynamic techniques measure the integrated response of the left ventricle as
though all segments made a uniform contribution to
total function. Previous investigations show that abnormal wall motion occurs in zones supplied by
those arteries with critical stenosi~.~,'
It is pertinent therefore to inquire whether these
regional areas of malfunction are due to irreversibly
damaged tissue or to viable but ischemic myocardial
fibers, which under different loading conditions may
be recruited in the contractile process. A demonstration that an asynergic segment supplied by an obstructed artery may be recoverable would help in
case selection for bypass operation.
This study examines the question by quantitating
regional wall motion before and after the administration of nitroglycerin (NTG) in patients with
coronary artery disease.
years. Selective coronary arteriograms revealed occlusive
disease in all cases. Each patient received premeditation of
10 mg of diazepam orally. Through the right antecubital
vein, a 7 F Goodale-Lubin or Zucker bipolar pacing catheter
was directed into the coronary sinus and advanced to the
obtuse margin of the left ventricle. In this position, the
catheter outlined the msterior arc of the atrioventricular
groove. By continuous monitoring of phasic undamped coronary sinus pressure, care was taken to avoid wedging of the
catheter. A transfernoral approach was used to pass a 100-cm
multiple-hole catheter retrograde across the aortic valve and
position it in the midleft ventricular cavity. After recording
the heart rate and left ventricular pressures, a resting left
ventricular angiogram was performed at 30' right anterior
oblique, using 45 to 60 ml of meglumine diatrizoate
(Renograb 76 percent) over 4 sec at 80 frames per sec. At
least 15 min were allowed to elapse before the left ventricular enddiastolic pressure ( LVEDP ) either returned to levels
before angiogram was performed or stabilized for another 5
min. At this juncture, 0.6 mg of nitroglycerin was administered sublingually. Five minutes following complete absorption of the pill (the time at which maximum decrease in left
ventricular volume occurs)f+lo the heart rate and pressure
were once again recorded, and a left ventricular an&ogram
repeated in a manner identical to that previously described.
A
Data Reduction and Analysh
The method for quantifying regional contraction patterns
has been detailed in a previous report.6 The ventriculographic images selected for analysis were among the first four sinusconducted beats following contrast injection. No postextraSeven patients undergoing diagnostic cardiac cathetersystolic beats were analyzed. The left ventricle was visualization for anterior chest pain were selected for this study on
ized as a truncated ellipsoid of revolution subtended by the
the basis of their abnormal ventriculograms. They included
atrioventricular ring, which in turn (outlined by the coronary
six men and one woman and ranged in age from 46 to 60
sinus catheter) served as an intracardiac plane of reference.
The enddiastolic and end-systolic silhouettes were aligned
'From McCill University Clinic, Division of Cardiology,
and the junction of the aortic and mitral valves superimposed.
Royal Victoria Hospital, Montreal, Canada
The longitudinal axis, which was drawn only for end-diastole
'*Assistant Professor. ExDerimental Medicine: Fellow. Canadian Heart ~ssociatio;.
from apex to midpoint of the aortic valve, was quadrisected
?Assistant Professor, Medicine.
by six transverse chords, producing eight regional areas each
*Associate Professor, Experimental Medicine.
(Fig 1 ) at end-diastole ( D ) and end-systole (S). Each
M ~ ~ received
~ ~ january
~ , 15;+revision
~ ~accepted
8,
Reprint requests; Dr. Sniderman,~~~~l victoria ~ ~ ~ ~ 687
i t a l , regional area was integrated by an electronic planimeter in
Pine Avenue West, Montreal, Quebec, Canada
which output was plotted by a PDP 11/20 computer as the
CHEST, 66: 5, NOVEMBER, 1974
RESTORATION OF REGIONAL WALL MOTION 545
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Table M f f e c t of Nitro#lycerin on Regional Areor
Before NTG
38
38
-
Hypohetic
7
3
2
2
Dyakinetic
11
4
3
4
Normal
FIGURE1. Left-hand &tion shows end-diastolic ventricular
silhouette divided into eight regions, as described in text.
Right-hand section shows end-systolic silhouette, divided into
ameqnmding areas, werlaid on enddiastolic outline.
After NTG
Normal Hypokinetic Dyakinetic
Regional Dynamics
Of the 56 regions examined, 38 had a normal
systolic decrease in area prior to treatment with
nitroglycerin (Table 2); that is, the fractional
change in systolic dimensions was greater than 20
percent. None of these areas became abnormal following use of the nitrate. Of the seven hypokinetic
areas, three contracted normally after NTG, two
remained hypokinetic, and two became frankly
dyskinetic. Of the 11 dyskinetic areas, 4 showed a
normal reduction in area after therapy with the
drug, 3 became hypokinetic, and 4 were unchanged.
Therefore, 3 of 7 hypokinetic areas and 7 of 11
W o x i c segments improved in their contraction
pattern with administration of nitroglycerin. Eight
of 18 abnormal segments either did not change or
worsened with nitroglycerin treatment.
Figure 2 (A, B ) illustrates one example of the
effect of nitroglycerin therapy on regional wall motion in a patient with dyskinesis of the posterior wall.
This does not represent the most dramatic amelioration of ventricular asynergy in the study, but it does
demonstrate the reversibility of systolic expansion of
a ventricular segment with use of nitroglycerin. The
m i d valve prolapse indicated by the shaded area
in Figure 2A was completely corrected in association
with improvement in posterior wall motion.
fractional change for each area during systole. A total of 56
regional areas in seven patients were analyzed before and
after administration of nitroglycerin.
Two types of abnormalities were distinguished. Dyskinesis
was dehed as "a net systolic expausion of a regional area"
and hypokinesis as "less than a Wpercent reduction of a
regional area during systole." A comparison was then made of
identical regions before and after treatment with nitroglycerin. Left ventricular volumes were calculated by the
area-length method of Dodge et 4 1 1 and ejection fraction
was derived from the ratio of angiographic stroke volume to
end-diastolic volume.
The effect of nitroglycerin therapy on hemodynamics is presented in Table 1. At the time that
measurements were made, that is, 5 min following
administration of nitroglycerin, there was a slight,
insignificant increase in the average heart rate (77 to
82lmin) and a small, insignificant decrease in the
average left ventricular peak systolic pressure (142135 mm Hg ). The mean resting LVEDP and ejection fractions were also unchanged. There was,
however, a significant reduction in the end-diastolic
volume, from 101 to 81 ml Ma( p < .01). A change
in loading conditions was therefore produced with
the nitrate, and since no appreciable effect in heart
rate, peak systolic pressure, or ejection fraction was
noted, the reduction in volume was presumably
mediated by a preload mechanism.
This study shows that the contraction pattern of
asynergic wall segments was m&ed by altering
Table 1--Effect of Nitroglycerin on E d Patient,
NO.
LVSP*
Hg)
Heart Rate
LVEDP**
(= Hg)
(=
CO
NTGl
C
*Peak left ventricular systolic preeeure.
**Left ventriculsr end-diaatolic pmmm.
tEnd-dhtolic volume.
NTG
C
NTG
EDVt
(ml/ms)
C
NTG
EFtt
C
NTG
ttEjection fraction.
§Control &ate.
INitroglyceriu.
546 SNIDERMAN ET A 1
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CHEST, 66: 5, NOVEMBER, 1974
coronary
sim/
PRE
NITROGLYCERIN
POST
NITROGLYCERIN
FIGURE
2A ( Before nitroglycerin therapy). Superimposed enddiastolic and end-systolic ventricular silhouettes. Dyskinesis
of inferior wall is evident, and stippled area represents prolapsed cusp of posterior mitral valve.
FIGURE
2B (After nitroglycerin therapy). Prolapse of mitral
cusp is no longer present, and inferior wall no longer expands
paradoxically.
the loading conditions of the ventricle. Distinct
worsening of wall motion has been demonstrated
following interventions such as atrial pacing and intravenously administered pr~pranolol.'~"In both
cases, the mechanism was said to be due to an
imbalance of the myocardial oxygen demand-tosupply ratio, which immobilized potentially viable
ischemic tissue. In our investigation, most of the
abnormal regions were improved with treatment
with nitroglycerin, suggesting that an abnormal
segment may be recoverable with a more favorable
energy balance. This could imply that such an abnormal but potentially viable area may respond to
the introduction of new blood supply by revascularization.
There are a variety of mechanisms by which nitroglycerin or a reduction in ventricular volume
could affect regional wall motion. First, restoration
of a normal contraction pattern in an asynergic area
may occur by virtue of a reduction in wall tension.
According to Laplace's law, a decrease in ventricular
volume without a corresponding change in intracavity pressure would decrease wall tension or wall
stress, assuming no significant change in mural
thickness. Such a decrease in tension on ischemic but
viable muscle fibers would allow a greater capacity
for fiber shortening. Second, nitroglycerin therapy
may improve the contraction pattern of ischemic
tissue by enhancing collateral blood supply with
redistribution of blood flow through asynergic but
viable zones of muscle.15 If this mechanism were
operative, then improvement in contractile function
and cardiac performance by revascularization would
be all the more likely. Finally, improvement in contraction could occur because of the reflex catecholamine release, which may follow nitroglycerin administration.16 Thare is evidence, albeit sparse, to
suggest that catechols can reverse segmental wall
abn~rmalities.~
In our series, 44 percent of the abnormal segments
either remained the same or became frankly paradoxic following volume reduction with administration of nitroglycerin. One explanation for this occurrence is that a thin akinetic scar, although not
possessing contractile properties, does have certain
compliance characteristics. When studied experimentally, ischemic wall segments show significantly
reduced compliance. After reduction of the total
endocardial surface area of the ventricle, a shift in
the passive length tension curve of the segment may
take place, so that systolic expansion of a segment
could appear during early force development. Another possible explanation for worsening of segmental kinetics is that nitroglycerin could influence
the distribution of coronary flow in such a way that
the ischemic one would be sacrificed in favor of
perischemic and other contractile zones (the socalled coronary steal effect)." Such an imbalance
could result in more dyskinesis of the noncontractible
segment. The cases in which no change in segmental
motion occurred may indicate either a balance of
opposing mechanisms or no discernible effect of the
bg.
We d e h e d hypokinesis as less than a U)-percent
reduction in a regional systolic area. This is based on
studies on normal rentriculograms in our laboratory,
where there was greater than a 30-percent reduction
in all regional areas in each of 12 patients.
We presumed that single-plane angiograms were
capable of tracking an abnormal segment through
systole. Although several recent studies argue for
biplane angiography to detect otherwise hidden
areas of abnonnal m~tion,'~.lOit is generally held
that those aneurysms, which are already identified in
the RAO projection, show little or no rotational
movement from the single-planeview.20
\
CHEST, 66: 5, NOVEMBER, 1974
RESTORATION OF REGIONAL WALL MOTION 547
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Since the initial observation,2l data have already
been presented which support the theory that if
treatment with nitroglycerin improves the motion
and function of regional areas of ischemia, then
bypass of vessels supplying those ischemic zones
results in some restoration of contractile function.22
Our study also suggests that noncontractile ischemic
segments are potentially recoverable under different
loading states, but in addition it demonstrates that
there was an appreciable number of those segments
which remained unchanged or worsened in association with nitroglycerin therapy. The identification
of the contraction patterns in regional zones of
ischemia and the mechanisms underlying their behavior in response to a change in loading state are
important fields for further investigation.
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of direct myocardial revascularisation on left ventricular
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