(Circulation. 1997;96:3346-3352.)
© 1997 American Heart Association, Inc.
Articles |
Effects of Dobutamine at Maximally Tolerated Dose on Myocardial Blood Flow in Humans With Ischemic Heart Disease
From the Departments of Medicine (Cardiac Unit), Radiology, and Nuclear Medicine, Massachusetts General Hospital, Harvard Medical School, Boston.
Correspondence to Henry Gewirtz, MD, Cardiac Unit/Vincent Burnham 3, Massachusetts General Hospital, Boston, MA 02114. E-mail gewirtz.henry{at}mgh.harvard.edu
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Abstract |
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Background This study tests the hypothesis in humans with ischemic heart disease that myocardial blood flow response to dobutamine is linearly correlated with blood flow response to adenosine.
Methods and Results PET with [13N]ammonia was
used to measure myocardial blood flow at rest and during
adenosine and dobutamine at the maximally tolerated
dose. Myocardial segments were defined
physiologically on the basis of blood flow
response to adenosine: normal, 
2 mL ·
min-1 · g-1;
abnormal, <2 mL · min-1 ·
g-1; and "steal," decline versus
baseline 0.15 mL · min-1 ·
g-1. The patient population consisted of 11
men and 2 women. Dobutamine increased heart rate (79±22 to
115±28 bpm) and rate-pressure product (9748±2862 to
15 157±3433 mm Hg/min) significantly (both P<.01).
Myocardial blood flow at rest in abnormal segments (0.50±0.23 mL
· min-1 ·
g-1) was reduced (P<.001) versus
normal (0.90±0.45) and steal (0.92±0.60). Nevertheless, in abnormal
segments, blood flow increased versus rest (P<.001) with
dobutamine (0.83±0.43) and adenosine (0.90±0.49).
In steal segments, myocardial blood flow declined versus baseline
(P<.001) with dobutamine (0.68±0.46) and
adenosine (0.50±0.45). In normal segments, myocardial blood
flow increased (P<.001) with dobutamine
(2.16±0.99) and adenosine (3.10±0.90). Over the range of
flows, the correlation between adenosine and
dobutamine was good (r=.78,
P<.0001). Although flow with dobutamine in
normal segments correlated with rate-pressure product
(r=.81, P<.05), the slope of the line was
2.7±0.8 (P<.02), and normalized blood flow (3.3±2.5
xrest) exceeded normalized rate-pressure product (1.9±0.8 xrest;
P<.05).
Conclusions In humans with ischemic heart disease, myocardial blood flow responses to dobutamine and adenosine are linearly correlated over a wide range. The hyperemic response to dobutamine is in excess of that predicted by rate-pressure product and reflects the unmeasured inotropic, oxygen-wasting, and ß2-agonist effects of the drug. Dobutamine induces coronary steal with a frequency approaching that of adenosine.
Key Words: dobutamine • blood flow • ischemia
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Introduction |
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Previous studies of the effects of dobutamine at maximally tolerated doses on myocardial blood flow in patients with ischemic heart disease have indexed results either to coronary artery anatomy or to regional wall motion during dobutamine stress.1 2 Although both studies provide important information, neither evaluated regional myocardial blood flow responses to dobutamine with respect to directly measured maximal vasodilator capacity with adenosine. Because both regional wall motion and coronary artery anatomy have definite limitations as surrogates for maximal dilator capacity of the coronary circulation,3 4 it is difficult to use results of these studies to directly assess the true myocardial blood flow effects of the drug.
Indeed, a direct, quantitative comparison of myocardial blood flow responses to adenosine and dobutamine has not been reported in humans with ischemic heart disease. Moreover, the ability to categorize myocardial segments physiologically in terms of directly measured maximal vasodilator capacity with adenosine provides the opportunity (1) to quantify the extent to which the inotropic, ß2-adrenergic agonist5 6 and oxygen-wasting7 effects of dobutamine augment myocardial blood flow above and beyond simple elevation of rate-pressure product in myocardial segments with proven normal maximal vasodilator capacity and (2) to address the issue of coronary "steal" with dobutamine, which has been considered to only a limited extent in previous reports.2 8 Accordingly, we tested the hypothesis that regional myocardial blood flow with maximally tolerated dobutamine would approach that of adenosine in segments with preserved maximal vasodilator capacity, whereas segments with evidence of impaired flow response with adenosine would exhibit blunted response to dobutamine as well. Furthermore, we tested the hypothesis that coronary steal, which has been shown to occur with adenosine,9 also may occur with dobutamine because of the potent inotropic and ß2-adrenergic agonist properties of the drug.5 6
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Methods |
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Patient Population
After approval was obtained from both the Radiation Safety and the Human Studies committees of the Massachusetts General Hospital, 13 patients were recruited at our institution between November 1, 1995, and November 30, 1996. Written informed consent was obtained from all patients. Exclusion criteria included any factor that precluded adequate or safe completion of PET with adenosine and dobutamine stress. These included unstable angina, uncontrolled left ventricular failure or atrial fibrillation, severe hypertension, recent (within 1 month of PET study) myocardial infarction, severe chronic obstructive pulmonary disease, and inability to lie supine for sufficient time to allow data acquisition.
PET Imaging
PET imaging was performed on a whole-body tomograph (GE Medical
Systems Scanditronix PC4096) in patients after an overnight fast
according to a previously described protocol.4 10 Briefly,
images were acquired in 15 contiguous sections
simultaneously with center-to-center separation of 6.5
mm. After positioning in the scanner, a 10-minute transmission scan was
performed to correct the emission data for attenuation. Next, 
25 mCi
of [13N]ammonia was administered with the patient at
rest, with dynamic tomographic imaging begun just before injection.
Data were collected for the first 3 minutes at 6 seconds per frame and
then at 2 minutes per frame for 6 minutes. After image acquisition,
radioactivity was allowed to decay for 30 minutes, at which time the
count rate seen by the scanner was 7500 cps.
Next, 2 minutes after initiation of an intravenous infusion
of adenosine (140 µg ·
kg-1 · min-1
over 5 minutes), dynamic data acquisition was begun, and several
seconds later, 25 mCi of [13N]ammonia was administered
intravenously over 30 seconds. Images were acquired in the
same fashion as described above.
After another 30-minute period to allow for decay of radioactivity, dobutamine was infused intravenously beginning at 10 mg · kg-1 · min-1 and increasing every 3 minutes to a maximum of 40 mg · kg-1 · min-1. The maximally tolerated dose (34±7 mg · kg-1 · min-1; mean±SD) was maintained for as long as possible (average, 7 minutes; range, 3 to 12 minutes) to permit steady-state conditions during data acquisition. [13N]Ammonia was injected intravenously over 30 seconds at minutes 1 to 6 of the high-dose infusion (mean, 2.3 minutes). Clinical indications for termination of the infusion either before or during the 40-mg · kg-1 · min-1 dose were hypertension or hypotension, progressive angina, high-grade ventricular ectopic activity, attainment of 85% of predicted maximal heart rate, or intolerable discomfort related to forceful or frequent cardiac contraction. ß-Blocker drugs were held for 48 hours before the study in all patients. The patient's ECG and arterial pressure (Dynamap, model 845, Critikon Co) were monitored continuously during the study.
Attenuation-corrected [13N]ammonia images were reconstructed with a conventional filtered back-projection algorithm as 128x128-pixel images in the transverse plane normal to the long axis of the body. Filtering of the projection data was performed with a Hanning filter to yield output resolution of 7.8 mm (full width at half maximum). The [13N]ammonia scans (n=3) for each patient, corresponding to the last 6 minutes of data acquisition, were summed to permit placement of a region of interest over the left ventricular cavity. The region of interest was used to generate the arterial input function for the tracer kinetic model by which regional myocardial blood flow was determined.10 The arterial input function was not corrected for recirculation of labeled ammonia metabolites.11 A computer program developed at our institution was used in conjunction with the dynamic data to generate parametric (K1) images for rest and stress conditions.12 The images obtained provided a pixel-by-pixel representation of K1 and were used for analysis of regional myocardial blood flow.
PET Image Analysis
Three short-axis rings corresponding to the proximal, middle,
and distal thirds of the left ventricle were constructed for each K1
scan as described previously.4 Briefly, circular regions
of interest (8.5-mm radius) were placed over each ring at standard
areas of interest: inferoseptum, midseptum, anteroseptum, anterior,
anterolateral, lateral, posterolateral, and inferior zones.
Regional myocardial blood flow was computed from values of
K1.10 12
Myocardial segments were defined as normal, abnormal, and
coronary steal based on blood flow response to
adenosine. Abnormal segments had adenosine-stimulated
blood flow <2 mL · min-1 ·
g-1, whereas normal segments had
adenosine-stimulated blood flow 2 mL ·
min-1 · g-1.
Coronary steal segments had a decline in myocardial blood flow
with adenosine 0.15 mL ·
min-1 · g-1
versus baseline.
Statistical Analysis
All data are expressed as mean±SD. Group mean values of
continuous variables were compared by ANOVA with an appropriate
post hoc multiple comparison test using commercially available software
(Fisher's protected least significant difference test, StatView V4.0,
Abacus Concepts). Paired t tests also were used for
comparison of myocardial blood flow at each intervention within segment
type if repeated-measures ANOVA demonstrated a significant treatment
effect. Wilcoxon signed-rank test for paired data was used to
compare normalized rate-pressure product with normalized myocardial
blood flow because the data were not normally distributed.
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Results |
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Patient Population
Thirteen patients (11 male and 2 female) 63±11 years old (range, 39 to 76 years) were studied (Table 1
).
Previous myocardial infarction was present in 11 patients and was
anterior in 5, inferior in 3, lateral in 1, and both
anterior and inferior in 2. Four patients had previous
coronary bypass surgery or coronary angioplasty. Study
patients included 2 diabetics (1 insulin-dependent). Triple-vessel
coronary artery disease was present in 8 patients,
double-vessel disease in 1, and single-vessel disease in 3
(coronary angiography was not available in 1 patient).
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Hemodynamic and Clinical Response to
Dobutamine
Under baseline conditions, heart rate was 79±22 bpm,
systolic arterial pressure 124±14 mm Hg, and
rate-pressure product 9748±2862 mm Hg/min (Table 2). In response to adenosine,
there was no significant change versus baseline in heart rate,
systolic arterial pressure, or rate-pressure
product.
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The maximal dose of dobutamine was 34±7 mg · kg-1 · min-1 and was given for 7±3 minutes. No patient had angina during dobutamine infusion, and only 1 had ECG evidence of myocardial ischemia, which resolved after the drug was discontinued. Ventricular ectopic activity was observed in 5 patients during dobutamine and also resolved when the drug was discontinued. Heart rate and rate-pressure product increased (P<.001) versus baseline in response to dobutamine, although systolic arterial pressure was unchanged. The peak heart rate attained with dobutamine was 74±19% of age-predicted maximum. No patient was given atropine.
Regional Myocardial Blood Flow
A total of 303 myocardial segments were available for
analysis (Table 3; Figs 1 through 4). Nine segments from 1 patient could
not be analyzed because of positioning problems such that the
segments were off the field of view.
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Comparison of Dobutamine and Adenosine Blood
Flow Responses
Under basal conditions, myocardial blood flow in abnormal segments
(n=177; 13 patients) was reduced (P<.001) versus that of
normal segments (n=84; 8 patients) and coronary steal (n=42; 6
patients). Similarly, blood flow responses to both
dobutamine and adenosine were substantially reduced
(P<.001) in abnormal versus normal segments. It should be
noted, however, that in abnormal segments, myocardial blood flow with
dobutamine and adenosine increased
(P<.001) versus rest and that the absolute increments were
virtually identical with each. Furthermore, when abnormal segments were
considered by themselves, there was a good correlation
(r=.75, P<.0001) over the entire range of blood
flows (0.2 to 2.0 mL · min-1 ·
g-1) between the absolute response to
adenosine and that to maximally tolerated
dobutamine (Fig 1
).
In normal myocardial segments, blood flow increased substantially
versus rest (P<.001) both with dobutamine and
with adenosine. The increment with dobutamine,
however, was less (72±30%) than that with adenosine
(P<.001). Finally, when all segments were considered
together, there was a strong correlation between absolute myocardial
blood flow with dobutamine and adenosine (Fig 2).
Dobutamine and Rate-Pressure Product
The correlation between the blood flow response to
dobutamine and the rate-pressure product attained was
examined for normal segments. All normal segments from an individual
patient were averaged together because all were normal, and only one
value of rate-pressure product was applied for each patient.
Normalized (xrest) myocardial blood flow with dobutamine
was plotted as a function of normalized (xrest) rate-pressure
product (Fig 3). A strong correlation
was observed (r=.81, P<.02). More important,
however, is the fact that the slope of the regression line was 2.7±0.8
(P<.02) and that normalized blood flow response to
dobutamine (3.3±2.5 xrest) was greater than that of
normalized rate-pressure product (1.9±0.8 xrest;
P<.05, Wilcoxon paired signed-rank test).
Dobutamine and Coronary Steal
Myocardial segments that exhibited coronary steal with
adenosine had rest blood flow nearly identical to that of
normal segments and significantly greater (P<.001) than
that of abnormal segments. By definition, myocardial blood flow
declined versus rest in response to adenosine. The magnitude of
the decline was substantial (45%). Myocardial blood flow also
declined versus rest in response to dobutamine in these
segments (P<.001). The magnitude of the decline, however,
was less (P<.001) than that observed with adenosine
(Fig 4).
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Discussion |
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Principal Findings
This study tested the hypothesis in humans with ischemic heart disease that myocardial blood flow response to maximally tolerated dobutamine is linearly correlated with blood flow response to adenosine. In fact, we demonstrated in myocardial segments with well-preserved maximal vasodilator capacity that myocardial blood flow with dobutamine also was substantial, although less (
25% on average) than that of adenosine. In
abnormal myocardial segments, defined as those in which MBF failed to
increase above a level 2 mL ·
min-1 · g-1
with adenosine, a range of flow responses was observed, from
essentially no increase versus rest to as much as 1.9 mL ·
min-1 · g-1
with adenosine. In these same segments, myocardial blood flow
with dobutamine exhibited similar behavior (Fig 1). Because
most patients in this study had advanced ischemic heart
disease, similar myocardial blood flow responses to vasoactive drugs
with dissimilar mechanisms of action and potency are perhaps not
surprising in segments exhibiting very limited flow reserve. However,
as shown in Figs 1 and 2, dobutamine flow responses
paralleled those of adenosine in segments with milder
degrees of flow restriction as well as those with none at all.
Moreover, as will be discussed in more detail below, in segments
demonstrating steal with adenosine, there was a similar, albeit
less potent, effect of dobutamine (Fig 4). Accordingly,
across the entire range of myocardial blood flow responses to
adenosine from steal to hyperemia,
dobutamine at maximally tolerated doses elicited a
proportional, albeit less potent, response. The fact that blood flow
responses to the drugs tended to parallel one another over the entire
range suggests that conclusions derived in the present
investigation, which included primarily patients with advanced
ischemic heart disease, may apply to patients with less severe
disease as well, although additional studies are required to establish
this point. We recognize, moreover, that adenosine causes dilation of the coronary circulation by a direct action on vascular smooth muscle and possibly endothelium as well. In contrast, dobutamine elicits coronary dilation primarily by indirect mechanisms related to its chronotropic and inotropic effects, although it too may cause primary dilation by means of its ß2-agonist effects.5 Differences in mechanism of action between adenosine and dobutamine, especially in the setting of coronary steal, may translate into very different effects on left ventricular function, notwithstanding directionally similar effects on myocardial blood flow. Thus, even though proportional and in some instances very similar flow responses to the drugs were observed in the present study of patients with severe ischemic heart disease, important differences between the mechanisms of action of adenosine and dobutamine should not be overlooked in terms of the potential to cause myocardial ischemia (see below).
Physiological Implications
Coronary Artery Stenosis Anatomy and
Regional Wall Motion as Surrogates for Myocardial Flow Reserve
Although the effects of maximally tolerated dobutamine
infusion on myocardial blood flow have been investigated in humans with
ischemic heart disease and compared with results of either
coronary angiography or regional wall motion,1 2 8
potential limitations of both modalities for assessing the
physiological status of the coronary
circulation3 4 make it important to evaluate the
coronary effects of dobutamine in terms of a
physiological gold standard. We used
adenosine for this purpose. The value of this approach is
illustrated by the fact that previous studies that have investigated
the relationship between coronary artery stenosis
severity and myocardial blood flow response to
dobutamine1 2 14 have shown substantial
scatter and only weak correlations (r2=.24
to.39) between the two. Moreover, in another report, the correlation
between myocardial flow fractional reserve, an invasive measure of
stenosis severity, and regional wall motion response to
dobutamine also was noted to be weak, with wide scatter in
the data.14 Accordingly, efforts to predict regional wall
motion or blood flow response to dobutamine based on
detailed knowledge of coronary stenosis anatomy
generally have not been reliable, especially in individual cases. Data
from our own laboratory support this view.4 In contrast,
failure of myocardial blood flow to increase with
dobutamine was more predictive of development of a new or
worsening wall motion abnormality with
dobutamine2 and also is consistent
with data previously reported from our laboratory.4
Myocardial Blood Flow With Dobutamine and
Rate-Pressure Product
An important aspect of the blood flow response to
dobutamine concerns its relationship to rate-pressure
product in myocardial segments capable of an unrestricted flow
response to adenosine. Although we observed a linear
correlation between relative increment (versus baseline) in myocardial
blood flow with dobutamine and relative increment in
rate-pressure product similar to that reported by
others,1 13 the slope of the regression line in the
present study was 2.7 versus 1.0 reported by
others.1 In the present investigation, moreover, in
normal segments there was a significant difference between the
increment in myocardial blood flow with dobutamine
(3.3-fold, patient-based analysis, see Fig 3) and the
increment in rate-pressure product (1.9-fold). The difference in
results between the present study and earlier
ones1 2 13 may be related in part to longer total duration
of dobutamine infusion at maximal dose in the present
study as well as longer interval (5 minutes on average) between
tracer injection and discontinuation of the drug. The excess in blood
flow relative to rate-pressure product reflects the unmeasured
contribution of contractility, oxygen
wasting,7 and primary vasodilative effects5 6
of dobutamine. The present study is the first, to the
best of our knowledge, to demonstrate these effects in myocardial
segments with preserved maximal dilator capacity in patients with
ischemic heart disease and provides insight into limitations of
rate-pressure product as an index for assessing appropriateness of
blood flow response to a drug or intervention, particularly
catecholamines.
The extent to which myocardial blood flow increases in response to
dobutamine in normally perfused myocardium of
either normal volunteers or patients with ischemic heart
disease also has been considered in relation to myocardial oxygen
consumption measured by PET.7 13 In one study,
dobutamine in normal volunteers increased rate-pressure
product 2.4-fold, with comparable increases (2.5-fold) in
myocardial blood flow and oxygen consumption. In the same study,
however, myocardial blood flow and oxygen consumption in normal zones
of patients with coronary artery disease increased in excess of
rate-pressure product, although the difference (2.0-fold versus
1.6-fold, respectively) failed to reach statistical significance. A
disproportionate increase in myocardial oxygen consumption (2.4-fold)
relative to rate-pressure product (1.2-fold), however, has been
reported by others7 in normal volunteers and is
consistent with data obtained in the present
investigation.
Dobutamine and Coronary Steal: Incidence and
Clinical Implications
Previous studies1 2 8 13 provide only limited
information concerning coronary steal with
dobutamine. In two of the reports,1 13 steal
was not observed. In the others,2 8 a decline in
myocardial blood flow with dobutamine was observed in 3
patients, 2 of whom2 also had abnormal wall motion with
dobutamine. Although comparison with an absolute measure of
maximal dilator capacity was not made in either study, the decline in
blood flow observed in previous reports2 8 to 60% to
80% of baseline was similar to that in the present study, in which
6 of 13 patients exhibited steal to 74% of baseline with maximally
tolerated dobutamine. It is likely that differences in dose
and duration of dobutamine infusion as well as patient
population account for differences in frequency of occurrence. In
animal models, dobutamine may15 or may
not6 16 17 cause coronary steal, depending on
species, stenosis severity, dose and duration of drug infusion,
and other details of experimental design. Whether or not
coronary steal occurs at therapeutic doses of the drug in
humans with ischemic heart disease cannot be determined from
the data obtained in the present study but should be considered
especially if doses above the usually recommended therapeutic range
(2.5 to 10 mg · kg-1 ·
min-1) are used.
Coronary steal has a number of important clinical implications. First, the data obtained in the present study demonstrate that defects in clinical, single-photon, myocardial perfusion images obtained after dobutamine stress may reflect not only a relative but rather an absolute reduction of myocardial blood flow. Because dobutamine, as shown in the present study, is generally a less potent coronary vasodilator than adenosine, the fact that it nevertheless is capable of inducing coronary steal is important to understand. This is particularly so because an absolute reduction in regional blood flow relative to baseline will obviously improve image contrast and hence defect recognition in clinical single-photon myocardial perfusion images.
In this regard, it should be recalled that clinically available myocardial perfusion tracers are diffusion limited and tend to plateau in the myocardium at blood flow levels >2 to 3 mL · min-1 · g-1.18 19 Thus, because tracer activity does not increase in proportion to blood flow above these levels, a region with flow of 2 to 3 mL · min-1 · g-1 may have no more tracer than one having flow of 4 to 5 mL · min-1 · g-1, and so they may be indistinguishable. A decline in blood flow in an abnormal area, however, would enhance image contrast and so facilitate defect recognition. Accordingly, the fact that dobutamine may induce coronary steal and the fact that clinical single-photon myocardial perfusion imaging is insensitive to blood flow >2 to 3 mL · min-1 · g-1 most likely account for results of a previous study that demonstrated similar sensitivity of adenosine and dobutamine as stressors for detection of coronary artery disease by SPECT imaging with 99mTc MIBI.20
Echocardiographic recognition of regional wall motion abnormalities during dobutamine stress, however, may be enhanced by coronary steal. This is true because myocardial oxygen demand is enhanced by dobutamine at the same time that it is responsible for an absolute decline in blood flow. The result will be more severe ischemia9 and hence more marked contraction abnormality,21 which in turn should be more easily detected in the clinical echocardiogram. Furthermore, even when adenosine induces steal, the degree of ischemia produced may not be sufficient to cause a detectable wall motion abnormality in transthoracic echocardiograms, as indicated by the fact that adenosine is less sensitive than dobutamine for detection of patients with ischemic heart disease when the diagnostic end point is development of a new regional wall motion abnormality.20
Critique of Methods
The limitations of coronary angiography for assessing
physiological significance of coronary
stenosis are becoming increasingly well known.3
Thus, we deliberately chose to index myocardial blood flow responses
with dobutamine to an appropriate gold standard, namely,
blood flow responses to adenosine. Accordingly, because the
present study focused on the physiological
status of the coronary circulation, detailed coronary
angiographic data were not considered.
The definitions of normal, abnormal, and steal segments were based on
the following considerations. A previous study of normal volunteers
demonstrated with only one exception that myocardial blood flow
response to adenosine was 2 mL ·
min-1 · g-1 in
all vascular territories.12 Thus, to ensure that only
segments having well-preserved maximal vasodilator capacity were
included, we used that level to define segments with normal maximal
dilator capacity. Abnormal segments, therefore, had values <2 mL
· min-1 ·
g-1. Coronary steal was defined as an
absolute reduction versus baseline myocardial blood flow of 0.15
mL · min-1 ·
g-1 with adenosine. In a previous
study, we observed that 1 SD for a given blood flow measurement was 0.1
mL · min-1 ·
g-1 in our laboratory,10 and so a
minimum decline of 0.15 mL · min-1
· g-1 was selected as a cutpoint. The fact
that segments defined this way on average exhibited a decline of nearly
50% from baseline flow of 0.9 mL ·
min-1 · g-1
indicates that the criteria were effective in selecting myocardial
segments that truly had a reduction in blood flow with
adenosine. Moreover, the fact that these same segments
exhibited a statistically significant decline in blood flow of 25%
versus baseline with a second independent measurement made during
dobutamine infusion (Fig 4) strongly supports the
physiological validity of the observation, argues
persuasively against technical artifact or statistical noise as the
cause, and represents new information not available in previous
reports.1 2 8 13
Summary
The data obtained in the present study of patients with severe
ischemic heart disease demonstrate that (1) myocardial blood
flow response to maximally tolerated dobutamine is linearly
correlated with absolute blood flow response to adenosine over
the entire range of adenosine responses from steal to
hyperemia but is 25% less potent at the extremes; (2) in
myocardial segments with preserved vasodilator reserve,
dobutamine induces a substantial hyperemic response
that is out of proportion to elevation of rate-pressure product and
reflects combination of inotropic, ß2-agonist, and
oxygen-wasting effects; (3) dobutamine at maximally
tolerated doses is capable of inducing coronary steal and does
so with a frequency approaching that of adenosine, albeit with
lesser potency; and (4) although flow effects of the drugs may be
directionally similar, mechanisms of action are very different, and as
a result, rather different effects on left ventricular
function may occur, particularly in the case of coronary
steal.
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Acknowledgments |
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Edie Sinagra assisted with preparation of the manuscript and coordination of patient scheduling. We wish to express our appreciation to the technical personnel of the PET and nuclear cardiology laboratories for dedicated and skilled assistance in the performance of these studies.
Received April 14, 1997; revision received June 27, 1997; accepted July 15, 1997.
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