Circulation. 2000;101:e205-e206
(Circulation. 2000;101:e205.)
© 2000 American Heart Association, Inc.
Circulation Electronic Pages |
Endothelium-Dependent and -Independent Perfusion Reserve and the Effect of L-Arginine on Myocardial Perfusion in Patients With Syndrome X
Stuart D. Rosen, MA, MD, MRCP, FESC, FACC;
Paolo G. Camici, MD, FRCP, FESC, FACC
MRC Cyclotron Unit,
Imperial College School of Medicine,
Hammersmith Hospital,
Du Cane Road,
London W12 0NN,
SDandA.Rosen@btinternet.com
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Introduction
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To the Editor:
We read the recent article by Bøttcher et al1 with
interest. Unfortunately, the authors do not discuss their findings in
the light of a previous study by our group.2 This study is
quite relevant to their work and was published in
Circulation 5 years ago. In our experiment, we also used
positron emission tomography to measure myocardial blood flow (MBF) at
rest and after the administration of intravenous
dipyridamole in patients with syndrome X (n=29) and in
a substantial control group (n=20). Our principal finding was that no
significant differences existed between patients and controls with
respect to myocardial blood flow (Figure 1
). With a broader range of controls,
Bøttcher et al’s corresponding figure (Figure 2) would probably not be distinguishable
from ours.
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Figure 1. Graph shows myocardial blood flow at rest
and after dipyridamole (Dip.) in syndrome X patients
and normal control subjects. Reproduced with permission from Reference
2.
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Figure 2. Resting myocardial blood flow in mL ·
g-1 · min-1 and hyperemic
myocardial blood flow after infusion of dipyridamole
(DIP) 0.56 mL · kg-1 · min-1 in
patients with syndrome X (n=25) and normal controls (group A,
age-matched [n=15]; group B, young [n=15]). *P<0.05
rest vs DIP; +P<0.05 vs control group A;
¤P<0.05 vs control group B. Reproduced with
permission from Reference 1.
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Although Bøttcher et al’s data are quite consistent with ours
in a number of respects, their interpretation of the data is
perplexing. For example, on 2 occasions in the article, they state that
basal MBF was elevated; however, their table shows that no significant
difference was found for basal MBF between their patients and the
age-matched controls. It is then suggested that an accumulation of
adenosine in the extravascular component (caused by patchily
distributed prearteriolar constriction or inadequate dilatation) offers
a unifying hypothesis for the generation of pain and for the ECG
changes observed. In our study, there were no demonstrable
relationships among MBF, chest pain, or the
dipyridamole-induced ECG changes; the clinical use of
aminophylline has been, for the most part, disappointing.
Although ultimately the authors offer "differences in patients’
characteristics" and the "heterogeneous nature of the
disorder" as an explanation for discrepancies with other studies in
the literature, more fruitful avenues for research on this topic, other
than MBF, deserve attention (for example, Cannon’s3
recent work).
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References
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Bøttcher M, Bøtker HE, Sonne H, et
al. Endothelium-dependent and -independent
perfusion reserve and the effect of L-arginine on
myocardial perfusion in patients with syndrome X.
Circulation. 1999;99:1795–1801.[Abstract/Free Full Text]
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Rosen SD, Uren NG, Kaski J-C, et al. Coronary
vasodilator reserve, pain perception, and gender in patients with
syndrome X. Circulation.. 1994;90:50–60.[Abstract/Free Full Text]
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Cannon RO III. The sensitive heart: a syndrome of
abnormal cardiac pain perception. J Am Med Assoc. 1995;273:883–887.zkey[Medline]
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Response
Morten Bøttcher, MD;
Hans Erik Bøtker, MD, PhD;
Helle Sonne, MD;
Torsten Toftegaard Nielsen, MD;
Johannes Czernin, MD
Department of Cardiology B,
University Hospital of Aarhus (SKS),
DK-8200 Aarhus N, Denmark
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Introduction
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We thank Drs Rosen and Camici for their interest in our article.
They
raise several issues regarding the interpretation of our
findings.
We acknowledge that a reference to their previous article could
have been made. An important difference exists between the control
group used in their study and the one in our study. Rosen et al’s
population consisted of patients undergoing angiography due to atypical
chest pain symptoms. The angiography and the ensuing exercise test were
normal. In contrast, our control group consisted of healthy subjects
with no chest pain symptoms. The difference is nicely illustrated in
the figures provided by Rosen and Camici. In the control group of Rosen
et al’s study, several controls have extremely low hyperemic
flow values. This was not the case in our study. We hypothesize that
some of the controls in Rosen et al’s study may have subdetectable
disease, which "dilutes" the difference in hyperemic blood
flow between the patients and controls.
Like Rosen et al, we did not find any difference in basal blood flow
between the syndrome X patients and the age-matched control group.
However, in the group B controls, resting perfusion was lower than that
observed in the syndrome X patients. Because the 2 groups were not
matched, we did not elaborate on this finding. Compared with the
age-matched controls, the important finding is—as explicitly written
in our article—reduced coronary blood in patients with
syndrome X seems to be caused by a reduction of the increase in blood
flow after dipyridamole and not by elevated basal
myocardial blood flow.
The ECG changes referred to in our study occurred during exercise
testing and not during dipyridamole administration,
which rarely causes ECG changes even in severely ischemic
patients. Regarding the effect of aminophylline treatment, several
newer studies have documented an effect on at least some
parameters.R1 R2
We agree with Rosen and Camici that measures other than myocardial
perfusion may contribute to the understanding of the severe chest pain
symptoms experienced by this patient group. Although the majority of
the patients do not show metabolic or functional evidence
of myocardial ischemia,R3 R4 R5 
40% have impaired
coronary flow reserve.R5 The mechanisms underlying
this abnormality are not known, and it was the aim of our study to
evaluate this particular point.
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References
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Inobe Y, Kugiyama K, Morita E, et
al. Role of adenosine in pathogenesis of syndrome
X: assessment with coronary hemodynamic
measurements and thallium- 201 myocardial single- photon emission
computed tomography. J Am Coll Cardiol. 1996;28:890–896.[Abstract]
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Elliott PM, Krzyzowska-Dinckinson K, Calvino R, et al.
Effect of oral aminophylline in patients with angina and normal
coronary arteriograms (cardiac syndrome X). Heart. 1997;77:523–526.[Abstract/Free Full Text]
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Camici PG, Marraccini P, Lorenzoni R, et al.
Coronary hemodynamics and myocardial
metabolism in patients with syndrome X: response to pacing
stress. J Am Coll Cardiol. 1991;17:1461–1470.[Abstract]
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Nihoyannopoulos P, Kaski JC, Crake T, et al. Absence
of myocardial dysfunction during stress in patients with syndrome X.
J Am Coll Cardiol. 1991;18:1463–1470.[Abstract]
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Bøtker HE, Sonne HS, Bagger JP, et al. Impact of
impaired coronary flow reserve and insulin resistance on
myocardial energy metabolism in patients with syndrome X.
Am J Cardiol. 1997;79:1615–1622.[Medline]
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Introduction
References