JACC Vol. 14. No.
September
1989:%9
604
3
Significance of Coronary Artery Tone in Patients With
Vasospastic Angina
AKIRA
HOSHIO,
MD, HIROSHI
KOTAKE,
MD, HIROTO
MASHIBA,
MD, FACC
Tottori, Japan
To investigate
the relation
between basal coronary
artery
diameter and development of coronary artery spasm, the
diameters of the proximal, middle and distal segments of
the three major coronary artery branches, together with
that of the left main trunk, were measured on a control
angiogram and after ergonovine and nitrate administration
in 30 patients with vasospastic angina without significant
organic stenosis, and in 35 patients without ischemic heart
disease. The percent change in coronary diameter after
ergonovine and nitrate administration
compared with the
control diameter was used as an index of coronary vasoreactivity.
In patients with vasospastic angina, coronary artery
responses to both ergonovine and nitrate were greater in
the spastic segments than in the other segments(p < 0.05),
and those of the coronary arteries without spasm were
It is well known that coronary artery spasm is a cause of
ischemia in patients with rest angina; however, the causes of
coronary spasm are still unknown. An early report (I I
suggested that significant coronary obstruction could be due
to normal vasomotion in the coronary arteries with organic
stenosis. However. other investigators (2-5) reported that a
localized disorder in coronary vasoreactivity is present in
patients with coronary spasm.
On the basis of the observation that coronary artery
spasm tends to recur in the same coronary segments (3,6)
and that the coronary vasodilation produced by nitrate
administration in patients with variant angina is greater than
that in patients without variant angina (5). we presumed that
local hypersensitivity to vasoconstrictive stimuli and increased basal coronary artery tone might play a major role in
the genesis of coronary artery spasm. In addition, several
From
the Department
Medicine.
Manuscript
March
of Internal
Japan.
received November
Medicme.
8, 1989, accepted
Address
cine, Tottori
for reorints:
University
April
Umverrirq
School
of
29. 1988: revised
by the American
Akira Hoshm. MD.
School of Medicme.
College
manuscript
recwed
4. 1989.
683, Japan.
01989
Tottori
Tottori.
of Cardiology
Department
Niahimachi.
of Internal MediYonapo. Tottori
greater
than those of the coronary
arteries
in patients
without ischemic heart disease (p < 0.01). There were no
significant differences between the coronary artery diameters in the two groups after nitrate administration,
and the
control diameters were less in patients with vasospastic
angina than in patients without ischemic heart disease.
These observations indicate that a coronary vasomotion
disorder, which involves increased basal coronary artery
tone and hypersensitivity
to vasoconstrictive stimuli, not
only at a localized segment but also in the entire coronary
artery tree, is present in patients with vasospastic angina.
Clinically, evaluation of basal coronary artery tone may he
useful for predicting the occurrence and location of coronary artery spasm.
(.I Am Co11Cardiol1989;14:6049)
reports (7-9) have indicated the similarity of spontaneous
and ergonovine-induced attacks of coronary spasm.
The purpose of this study was to quantify coronary artery
responses to ergonovine and nitrate in patients without
significant organic stenosis, and to investigate the significance of coronary artery tone in patients with vasospastic
angina.
Methods
Patient
selection.
A retrospective analysis was performed, involving 159 patients who had undergone diagnostic coronary angiography with the ergonovine provocative
test and who had normal coronary arteries or fixed lesions
with ~40% diameter reduction after nitrate administration.
Sixty-five of these patients were separated into two groups
according to the clinical findings and the results of the
ergonovine provocative test. None of the patients had prior
myocardial infarction. Informed consent was obtained from
each patient.
T/P wso.spnstic ctngina group consisted of 30 patients
(average age 57 years, range 42 to 73) with suspected variant
angina and coronary artery spasm during the ergonovine
0735-I 097!89!S3..(rl
JACC Vol.
September
14, No. 3
198Y:604-9
provocative test. All patients had chest pain at rest. which
was relieved by sublingual nitrate.
The normgina group consisted of 35 patients (average
age 49 years, range 32 to 67) without chest pain or ischemic
heart disease. Ten patients had hypertrophic cardiomyopathy, 10 had valvular heart disease, 7 had arrhythmia. 4 had
electrocardiographic (ECG) ST-T changes without chest
pain, 3 had a coronary artery fistula and I had an atrial septal
defect.
Catheterization procedure. Coronary angiography was
performed with the Sones technique. Pharmacologic therapy
was withheld for at least 24 h before cardiac catheterization.
After coronary angiography was performed without premedication as a control, ergonovine (0.05 to 0.20 mg) was
administered as a bolus injection into the ascending aorta.
Heart rate, intraaortic blood pressure and ECG lead II were
continuously monitored, and standard 12 lead ECGs were
recorded at 30 s intervals. Coronary angiography was performed immediately if typical chest pain or ECG changes
indicating myocardial ischemia occurred. In the absence of
these symptoms after ergonovine administration. coronary
angiography was performed 4 min later. Additional ergonovine (0.05 to 0.2 mg) was administered to patients who
did not develop coronary artery spasm after the initial dose
of ergonovinc. The same angiographic procedure was then
repeated. Either nitroglycerin (0.33 mg) or isosorbide dinitrate (5 mg) was administered as a bolus injection into the
ascending aorta after both coronary arteries were visualized.
Coronary angiography was repeated 2 to 4 min after nitrate
administration.
Analysis of coronary angiograms. The 35 mm coronary
angiograms were reviewed on a Vanguard projector. Coronary artery diameter was measured in the proximal, middle
and distal segments of the three major coronary artery
branches. together with that of the left main trunk and in the
spastic segments in which coronary artery spasm was provoked by ergonovine. Right coronary artery diameter was
measured distal to the sinus node artery (proximal), distal to
the right ventricular branch (middle) and distal to the acute
marginal branch (distal). The left main trunk diameter was
measured just before the artery’s bifurcation. The left anterior descending coronary artery diameter was measured at
the artery’s origin (proximal). distal to the first septal perforator (middle) and distal to the second septal perforator
(distal). The left circumflex artery diameter was measured at
the artery’s origin (proximal), distal to the obtuse marginal
branch (middle) and at the origin of the posterior lateral
branch (distal). When the spastic segment was at the same
site as I of the IOdivided nonspastic segments. the segment
was excluded from the measurement of the nonspastic
segment. In addition, when the spastic segment had a
diameter reduction >90% after ergonovine administration.
the distal segments of the vessel were excluded in this study.
To minimize pincushion distortion. measurements were
CORONARY
ARTERY
HflSHIl1
TONE
AND
ET AI
SPASM
605
made near the center of the angiograms. Serial measurements were taken at end-diastole in the 30” right anterior
oblique projection of the left coronary artery and the 60”left
anterior oblique projection of the right coronary artery. The
coronary artery diameter (in millimeters) was calculated
with reference to the Sones catheter tip diameter (I .7 mm).
The reproducibility of these measurements was good, with
an intraobserver correlation of r = 0.93 and an interobserver
correlation of r = 0.93 for 1I I coronary artery segments. The
error in duplicate measurements of the diameter of the
proximal anterior descending segment obtained with this
technique was 0.5 mm (twice the standard deviation of the
difference between the first and second measurements, n =
50 duplicate measurements). The percent vasoconstriction
by ergonovine and vasodilation by nitrate were used to
quantify the degree of coronary artery tone.
The percent change
cul~~lrl~lted
NSfollon’s:
in coronary
artery diameter
IVNS
Percent vasoconstrictionby ergonovine =
Control diameter - Diameter
after ergonovine
Control diameter
x ,oo ,~,.
c
Percent vacodilation by nitrate =
Diameter
after nitrate - Control diameter
Control diameter
- x 100 (rc).
Both control diameters
used in these two equations were
measured on the control angiogram. Dynamic coronary
diameter reduction >50% from the control diameter (focal or
diffuse) was considered to represent coronary artery spasm
(IO).
Statistics. The mean values from control angiograms and
after ergonovine and nitrate administration were compared
with the paired t test. The unpaired t test was used to
compare the mean values of a single variable between the
vasospastic angina and nonangina groups. A probability (p)
value CO.05was considered to be statistically significant. All
grouped data were reported as mean values -+ standard
error.
Results
Nonangina group. The mean dose of ergonovine in these
3S patients was 0.22 t 0.013 mg. and no patient had
coronary artery spasm or transient ST segment shifts during
the ergonovine provocative test.
Vasospastic angina group. The mean dose of ergonovine
in these 30 patients was 0.17 2 0.018 mg, which was
significantly less than that in the nonangina group (p < 0.05).
With ergonovine administration, 25 patients had spasm in
one major coronary
artery, and 5 had spasm in two major
coronary arteries simultaneously. Spasm was observed in
the right coronary artery in 22 patients. the left anterior
descending coronary artery in IO patients and the left cir-
HOSHIO ET AL.
CORONARY
ARTERY
606
Table
1. Coronary
Artery
JACC
Diameter
on the Control
Vol.
14. No. 3
September 19X9:6(14-9
TONE AND SPASM
Angiogram
and After
Nitrate
Administration
in 65 Patients
After Nitrate
Control Angiogram
VSA
(n = 30)
3.76 2 0.16
Nonangina
(n = 35)
VSA
(n = 30)
Nonangina
(n = 35)
RCA
Proximal
3.15 + 0.12
2.55 2 0.1s:
3.75 ? 0.14
Middle
2.88 2 0.11
2.40 ? 0.14*
3.45 + 0.14
3.74 + 0.14
Distal
2.67 2 0.11
2.36 ? 0.13
3.27 * 0.14
3.51 f 0.14
LAD
Proximal
3.40 5 0. IO
2.58 2 O.lli
3.74 * 0.1
I
3.59 + 0.15
Middle
2.27 ? 0.08
0.09+
0.06+
2.61 ? 0.09
2.00 + 0.07
2.57 f 0.10
1.91 ? 0.07
Distal
1.75 2 0.06
1.74i
I.36 =
LCX
Proximal
2.84 2 0.08
2.40 2 0.14:
3.32 ? 0.10
3.22 ? 0.12
Middle
Distal
LMT
2.62 5 0.12
2.00 f 0.10
4.16 2 0.12
1.92 2 0.13:
1.37 * 0.07:
3.59 + O.lli
2.91 2 0.13
2.31 * 0.10
4.43 f 0.14
2.65 z 0.16
2.01 -c 0.11
4.28 t 0.12
*p < 0.05, tp < 0.01 compared with the nonangina group. Values are reported as mean ? standard error.
LAD = left anterior descending artery; LCx = lefl circumflex artery: LMT = left mam trunk; RCA = right coronary artery; VSA = vaaospastic angina.
cumflex coronary artery in 3 patients; it was not observed in
the left main trunk. Thirteen (43%) of the 30 patients with
vasospastic angina had transient ST segment elevation with
chest pain after ergonovine administration. Because nitroglycerin (17 patients in the nonangina group and 8 in the
angina group) and isosorbide dinitrate (18 patients in the
nonangina and 22 in the angina group) produced similar
absolute and percent increases in coronary diameter in the
nonangina and vasospastic angina groups, the results with
the two drugs were pooled for analysis.
Effect of nitrate on diameter in each major coronary artery
(Tables
1 and 2). Excluding the spastic segments, the control diameters of all but the right distal segment were smaller
in the vasospastic angina group than in the nonangina group
(p < 0.05) (Table I). The control diameter of the right distal
segment showed a tendency to be smaller in the vasospastic
angina group than in the nonangina group (p < 0.10). The
Table 2. Percent
Vasodilation
After
Nitrate
Administration
in
Proximal,Middleand Distal Segmentsin 65 Patients
% Vasodilatlon by Nitrate
Proximal
Middle
Distal
20 2 3
10 * 2
I7 t 2
20 + 2
16? 3
I! ? 2
23 2 3
IS ? 3
I7 2 3
51 ?6
41 +4
39 ? 4
63 ? 8
51 +6
42 ? 4
52 ? 4
43 ? 5
49 ? 5
Nonangina (n = 35)
RCA
LAD
LCX
VSA (n = 30)
RCA
LAD
LCX
Values are reported
Table I.
as mean 2 standard error.
Abbreviations
as in
coronary artery diameters of all segments after nitrate administration were similar in the two groups (p = NS).
The percent vasodilation after nitrate administration was
similar in all segments in each major coronary artery branch
(p = NS) (Table 21. Because the percent vasodilation by
nitrate was not related to location (proximal, middle and
distal segments) in each of the three major coronary artery
branches, results in the three segments in each major coronary artery branch were combined for subsequent analysis.
Comparison of group responses to nitrate (Fig. 1). Excluding the spastic segments, the percent vasodilation after
administration of nitrate of the right, left anterior descending
and circumflex coronary arteries, together with that of the
left main trunk, was 21 2 1%. 14 2 2%, 15 ? 1% and 7 f I%,
respectively. in the nonanginagroup, and 56 ? 4%, 45 +- 3%.
43 * 3% and 20 2 3%, respectively, in the vasospastic
angina group. In both groups, the percent vasodilation of the
left main trunk was less than that of the other three major
coronary artery branches (p < 0.01). and the percent vasodilation of the right coronary artery was greater than that of
the left anterior descending (p < 0.05) and circumflex
coronary arteries (p < O.Ol), whereas that of the left anterior
descending and circumflex coronary arteries was similar
(p = NS). The responses to nitrate in the three major
coronary artery branches (p < 0.01) and left main trunk (p <
0.05) were all greater in the vasospastic angina group than in
the nonangina group.
Effects of ergonovine and nitrate on diameter of the spastic
and nonspastic segments (Fig. 2). The percent vasoconstric-
tion after administration of ergonovine in the spastic segments, adjacent segments and segments of the coronary
arteries without spasm in the vasospastic angina group and
the combined segments in the nonangina group was
JACC Vol. 14. No. 3
September 3989:6049
CORONARY
**
I
1
r___l___,
+*
r------1
L.
f
I
h
LAD
LCX
LMT
Figure 1. Coronary artery response to nitrate shown as the percent
vasodilation by nitrate. Excluding the spastic segments, the percent
vasodilation by nitrate was compared among the three major coronary artery branches together with the main trunk, and between the
nonangina (openbars) and vasospastic angina (WA) (hatchedbars)
groups. *p < 0.05; **p < 0.01. LAD = left anterior descending
coronary artery; LCX = left circumflex coronary artery: LMT = left
main trunk: NS = not significant: RCA = right coronary artery.
76 ? 3%,
Percent
24 t 2%,
vasodilation
13 t
after
1% and 8 2
nitrate
I%,
respectively.
administration
in those
segments was 64 ? 5%. 51 i 3%. 42 5 2% and 16 ? I%,
respectively.
The coronary artery responses to ergonovine
and nitrate were greater in the spastic segments than in the
adjacent segments and segments of the coronary arteries
without spasm (p < 0.05). The responses in the nonangina
group were less than those in the segments of the coronary
arteries without spasm (p < O.OI), which were less than
those in the adjacent segments (p < 0.05).
Discussion
Previously, coronary vasomotion disorder in response to
ergonovine or nitrate in patients with vasospastic angina has
been documented with quantitative angiographic techniques.
Previous studies (2,4) using ergonovine distinguished between the segments with and without spasm. In contrast, a
study (I 1) using nitrate did not show data relative to segments with and without spasm. In other studies the number
of patients was small (6) or the location of coronary artery
spasm was unclear (5). Furthermore, there were few studies
that dealt with differential coronary responses to ergonovine
and nitrate in patients with vasospastic angina compared
with the control patients. Therefore, using quantitative coronary angiography, we investigated in detail responses to
ARTERY
HOSHIO
TONE AND
ET Al_.
SPASM
607
ergonovine and nitrate in patients with vasospastic angina
and compared them with responses in control patients.
In describing variant angina in 1959. Prinzmetal et al. (12)
suspected that the disease resulted from temporary occlusion of a coronary artery with significant organic stenosis
due to a normal increase in coronary artery tone. Similarly,
MacAlpin (1) suggested that significant coronary obstruction, even complete occlusion, could be dynamically produced by physiologic degrees of vasoconstriction at the site
of the stenosis. Therefore, we selected patients without
significant organic stenosis to rule out the possibility that
coronary artery spasm could be a result of normal vasomotion in the coronary arteries with significant organic stenosis.
Coronaryvasomotiondisorderin responseto ergonovinein
vasospasticangina. Although ergonovine produces mild diffuse coronary vasoconstriction in patients with atypical
chest pain (8,13-16) or a transplanted heart (141, a localized
disorder in which the spastic segments in patients with
spasm shows greater sensitivity to a vasoconstrictor than
other segments has been suggested as a mechanism of
coronary artery spasm (2-4). Similarly, our data show that
the spastic segments were more sensitive to ergonovine than
were the nonspastic segments of the patient with vasospastic
angina and the coronary arteries of the control patients.
However, excluding the spastic segments, coronary artery
responses
to ergonovine were greater in the vasospastic
angina group than in the nonangina group; even coronary
arteries without spasm in these patients showed greater
sensitivity to ergonovine than did the coronary arteries of
the control patients. Consequently. coronary arteries of
patients with vasospastic angina are hypersensitive to ergonovine, not only in the spastic segments, but also in
arteries without spasm.
Coronary vasomotion disorder in response to nitrate in
vasospastic angina. Like the ergonovine response (Fig. Z),
coronary vasodilation after nitrate appears much more
prominent in spastic segments than in other segments, and in
coronary arteries without spasm than in the coronary arteries of control patients. The actual control baseline diameter
measurements were significantly smaller in patients with
vasospastic angina than in the control patients, excluding the
spastic segments. However, the diameter measurements
after nitrate administration were similar in both groups.
Thus, in contrast to observations by Hill et al. (5), who
suggested that a localized disorder in coronary vasodilation
after nitroglycerin is present in patients with spasm, our
findings suggest that the entire coronary artery tree rather
than a localized segment may have increased basal coronary
tone and may exhibit a smaller control diameter and increased basal coronary tone and sensitivity to vasoconstrictive stimuli.
This finding may explain the following
observations.
Coronary artery spasm may not be in the same location
during every angina1 attack, may involve an entire coronary
608
HOSHIO ET AL.
CORONARY
ARTERY
JACC
TONE
AND
El
Non-angina
artery
group
Without
SP~(LIII
adJacent adgment
70.
;
60.
{
so.
r;
c
40.
:
c
0
30,
2
z
Vol.
I?. No. 3
September 1989:60&9
SPASM
20.
which is reflected by a smaller control diameter. Some
patients with chest pain syndrome selected by those investigators may have had vasospastic angina, as evidenced by
the fact that the frequency of provoked coronary artery
spasm during coronary angiography was only 38% in patients with rest angina (29). Simonetti et al. (28). examining
responses to isosorbide dinitrate, suggested that the reason
for these different responses in arteries of varying sizes may
be increased basal coronary artery tone or hypersensitivity
to coronary vasodilators, or both, of small compared with
large coronary arteries. Our data show that coronary artery
responses to nitrate are not related to location in each major
coronary artery branch, and indicate that, clinically, coronary artery diameter after nitrate administration should be
regarded as a standard diameter for making comparisons
between patients with vasospastic angina and control patients.
Coronary
right coroncrry
10
Figure 2. Percent vasoconstriction after ergonovine (left i and vasodilation after nitrate (right) compared among the spastic segments.
adjacent segments and segments of the coronary arteries without
spasm in the vasospastic angina group and the combined segments
in the nonangina group. *p < 0.0s; **p < 0.01.
artery diffusely, even into smaller branches without focal
vasoconstriction (17) and may occur in multiple segments in
a “migratory fashion” from one artery to another or from
one site to another within one artery (IS). Spontaneous
coronary artery spasm during coronary angiography has
been documented (I9-21), and is probably more common
than generally recognized (22,23).
According to Epstein and Talbot (24), mild to moderate
increased coronary artery tone could predispose to coronary
spasm. Ross et al. (25) speculated that an alteration in
activational mechanisms from tonic to phasic might play a
role in spasm. Furthermore, Yasue et al. (II) showed that
the percent vasodilation after nitroglycerin was significantly
higher in the early morning than in the afternoon, and this
observation was interpreted as showing increased basal
coronary artery tone in the morning in patients with variant
angina.
artery
to nitrate
were greater
in the
than in the other arteries;
specifically.
basal coronary artery tone was higher in the former than in
the latter. This finding may support our observation that the
right coronary artery is more prone to spasm than the other
arteries, although coronary artery response to ergonovine in
the former was similar to that in the latter. Similarly, Higgins
et al. (19) reported that most cases of documented coronary
artery spasm involved the right coronary artery, and ST
segment elevation was observed most often in the inferior
ECG leads in patients with variant angina and “normal”
coronary arteries. A similar distribution was found in several
other reports (29-31). Chahine et al. (22) suggested that it
may be caused by a difference in innervation.
Clinical implications. The ergonovine provocative test is
highly sensitive and specific for the detection of coronary
artery spasm @,9,13-16), but some risks to its use do exist
(8,15,16,32). If coronary artery spasm could be identified
without the provocative test, prediction of vasospastic angina would be safer. When patients have not taken nitrate,
the initial coronary angiograrns will presumably reflect the
basal state of coronary artery tone (5). Evaluation of basal
coronary artery tone may be useful for predicting the occurrcnce and location of coronary artery spsam in patients who
have not been previously recommended for the provocative
test of spasm, such as with coronary spasm in significant
organic stenosis.
We are very grateful to Hiroyuki
for their constructive criticism.
Different coronary responses to nitrate in the three major
coronary artery branches and left main trunk. Several investigators (26-28) observed that during coronary angiography.
the smaller the control diameter. the greater the coronary
vasodilation after nitrate administration. The reason for this
observation may be increased basal coronary artery tone,
cwtety responses
Miyakoda.
MD and Junichi Hasegawa, MD
References
I. MacAlpin
RN. Contribution of dynamic vascular wall thickening to
luminal narrowing during coronary arterial constriction. Circulation 1980:
hl:296-301.
JACC Vol.
September
14. No. 3
19X9:60&9
2. Freedman B. Richmond DR. Kelly DT. Pathophyaiology
artery spasm. Circularlon 1982:66:705-9.
CORONARY
of coronary
ARTERY
HOSHICJ
t-ONE AND
ET AL.
SPASM
609
17. Mnseri A. Severi S. De Nes M. et al. “Variant” angina: one aspect of a
contmuous spectrum of basospastic myocardial ischemia. Am J Cardiol
1978:41:1019-3s.
3. Kaski JC. Crea F. Meran D. et al. I,ocal coronary supewnsitivity
ro
diverse vasoconstrictive stimuli in patients with variant angina. Circulation 1986:74:1255-&S.
18. Hrupler FA Jr. Bott-Silverman
In Ref l&49-75.
4. Matsuda Y. Moritam K. Ogawa H. et al. Response ofthe coronary artery
to a small dose of ergonowne in variant angina. Am Heart J 1986.
112:947-52.
19. H~ggms CB. Wexler L. Sdverman JF. Hayden WG, Anderson WL,
Schroeder JH. Spontaneously and pharmacologically provoked coronary
arterial spasm in Prinzmetal variant angina. Radiology 1976;119:521-7.
5, Hill JA. Feldman RL. Pepine CJ. Conti CR. RegIonal coronary arter)
dilation response in variant angina. Am Heart J 198!:101:??6-33.
20. Oliva PB. Potts DE. Pluss RG. Coronary artenal spasm in Prinzmetal
anplna’ documentation by coronary arteriography N Engl J Med 1973:
288:745-5 I.
6. MacAlpin RN. Relation of coronary arterial spasm to she9 of organic
stenosis. Am J Cardiol 1980:46:143-53.
7. Curry RC. Pepine CJ. Sabom MB. Conti CR. Simdaritiec of ergonovineinduced and spontaneous attacks of variant angma. Clrculatmn 1979,
59:307--12.
8. Heupler FA Jr. Proudfit WL. Razavi M. Shire) EK. Greenstreel R.
Sheldon WC. Ergonovine maleate provocative test for coronary arterial
spasm. 4m J Cardiol 1978:41:631-40.
9. Waters DD. Szlachcic J. Bonan R. Miller DD. Dauwe F. Theroux P
Comparatwe sensitivity of exercise. cold pressor and ergonovine testing
m provoking attacks of variant angina in patients with acuve disease.
Circulation 1983:67:31&5.
10. Macdonald RG. Feldman RI.. Pathnphyviologic observaIion~ in patients
with proven coronary artery spasm. In: Conti CR. ed Coronary Artery
Spasm. New York: Marcel Dekker, 19X6:9-22.
I I,
Yasue H. Omote S. Taklrawa A. Nagao M, Mwa K. Tanaka S. Circadian
variation ofexercise capacity in patients with PrinLmetal’$ variant angina:
role of exercise-induced
coronary arterial spasm. Circulauon 1979:
59:938-48.
I?. Prinzmetal M. Kennamer R. Merhss R. Wdda T. Bor N. Angma pectoris
1. A variant form of angina pecforis: prehmindry report. .4m J Med
1959:27:375-X8.
If.
Schroeder JS. Bolen JL. Quint RA. et al. Provocation ofcoronary
with ergonovine maleate. Am J Cardiol 1977:40:4X7-91.
spabm
14. Cipriano PR. Guthaner DF. Orlick AE. Riccl DR. Wexler L. Silverman
JF. The effects of ergonovine maleate on coronary arterial we. Circulation 1979:59:82-9
!I.
C. Angiography of coronary artery spasm.
Schroeder JS. SIlverman JF. HarrIson DC. Rlght coronary artery spasm
causmp Prmrmetal’, variant angina. Chest 1974:65:573-i.
22. Chahme RA. Ralznel AE, lshlmori T. Luchi KJ. McIntosh HD. The
Incidence and clinical implications of coronary artery spasm. Circulation
1975:53:972-x.
23. Wiener L. Kasparian H. Duca PR. er al. Spectrum of coronary arterial
>pacm’ clinical, angiographic and myocardial metabolic experience in 29
CLXS. Am J Cardiol 1976:38:945-55.
24. Epstein SE. Talbot TL. Dynamic coronary tone in precipitation, exacerbation and rehef of angina pectoris. Am I Cardlol 1981:48:797-803.
25. Ross G. Stmson E. Schroeder J, Ginsburg R. Spontaneous phasic activity
of Isolated human coronary arterlec. Cardiovasc Res lY80;14:613-8.
26. Feldmdn RL. Pepme CJ. Conti CR. Magnitude of dilatabon of large and
small coronary arteries by nitroglycerin. Circulation 1981;64:324-33.
27. Feldm,m RL. Marx JD. Pepme CJ. Conti CR. Analysis of coronary
responses to various doses of inlracoronary nitroglycerin. Circulation
19X2:66:3?l-7.
28. Sirnow% I. De Caterina R. Michelassi C. Marrilli M. De Neb M.
L’Ahbate A. Coronary vasodilation by nitrates is not mediated by the
prostaglandin system: a quantitative cineangiographic study. J Am Coil
Catdiol 1986:S: 1263-X).
29. Bertrand ME. LaBlanche JM. Tdmant PY. et al. Frequency of provoked
coronary arterial spasm in 1089 consecutive patlenls undergoing coronary
arteriogrdphy. Circulation 1982:65:12’%306,
30. Botr-Silverman C. Heupler FA Jr. Natural history of pure coronary artery
spasm in patients treated medically. J Am Coll Cardiol 1983:2:200-S.
IS. Conti CR. Curry KC. Christie LG. Pepine CJ. Clinical use of provocative
pharmacoangiograph)
in patients with chest pain. Adv Cardiol 1979:
26:4454.
31. MacAlpin RN. Correlation of the location of coronary arterial spasm with
the lead distribution of S-T segment elevation during variant angina. Am
Heart J 1980:99:555-M.
16. Curry RC. Pepine CJ. Sabom MB. Feldman RL. ChrIstIe LG. Conti CR.
Effeclr of ergonovine m patients with and without coronary artery
disease. Circulation 1977:56:803-9.
32. Buxton A. Goldberg S. Hirshfeld JW, er al. Refractory ergonovineinduced coronary vasospasm: importance of infracoronary nitroglycerin
Am J Cardlol lY80:46:3?Y-34,