Download Effect of Sublingual Nitroglycerin on Regional Flow in

Effect of Sublingual Nitroglycerin on Regional Flow
in Patients With and Without Coronary Disease
JAWAHAR MEHTA, M.D.
AND
CARL J. PEPINE, M.D.
SUMMARY We evaluated the effects of sublingual nitroglycerin on indices of regional coronary flow and
coronary resistance (CR) in 12 selected patients with coronary artery disease (CAD) and eight with normal
coronary arteries (NCA), using continuous thermodilution. Resting total left ventricular flow, reflected by coronary sinus flow (CSF), and anterior regional flow, reflected by great cardiac vein flow (GCVF), in NCA and
CAD patient groups, were similar. However, in a subgroup of six patients, with CAD limited to the anterior
descending artery, GCVF was lower and anterior regional CR (CRANT) higher than the NCA subjects. Nitroglycerin reduced the systolic pressure-heart rate product similarly in both patient groups. CSF and GCVF in
NCA subjects declined 15% and 17%, respectively, as total CR (CRT) and CRANT increased. In the CAD subconsisting of patients with CAD limited to the anterior descending, GCVF increased 48% as CRANT
group,
declined 50%, and CSF was unchanged. In the other CAD subgroup of patients with CAD in the right and/or
circumflex arteries, GCVF declined 32% and CRANT increased 46% as CSF was minimally increased.
These data imply that sublingual nitroglycerin reduces both CSF and GCVF in NCA patients as oxygen
demands decrease. In certain CAD patients, however, nitroglycerin alters regional coronary venous blood flow,
suggesting a redistribution of flow from normally perfused to hypoperfused regions.
Downloaded from http://circ.ahajournals.org/ by guest on August 10, 2017
NITROGLYCERIN REDUCES or prevents clinical
and hemodynamic manifestations of myocardial
ischemia. Because of these beneficial responses, this
agent's potential to decrease ischemic injury and
possibly limit infarct size is under close investigation.'-3 The primary mechanism by which
nitroglycerin may be effective is thought to relate to
potent venodilator properties that reduce left ventricular filling pressure and diastolic wall tension.4 5
Nitroglycerin also lowers systolic pressure through
systemic arteriolar dilation.5 These effects lessen the
myocardial oxygen requirement. The effect of nitroglycerin on coronary flow, however, is controversial.
Some6-8 suggest that nitroglycerin may have a prominent action on collateral channels, thereby increasing
blood flow to ischemic regions. When this response occurs across the myocardial wall, subendocardial flow
may increase at the expense of epicardial flow, and
total flow may remain unaltered. In contrast, others9
have suggested that flow to the ischemic zone may
decline with nitroglycerin as oxygen requirements and
perfusion pressure decline. These seemingly conflicting data may be related to different techniques and experimental designs. Furthermore, data obtained in
animals with acute myocardial ischemia are difficult
to extrapolate directly to man with chronic coronary
disease.
We recently evaluated a thermodilution method to
continuously assess regional left ventricular flow in
man using a multithermistor catheter.10 The purpose
of this investigation was to study the regional cor-
onary venous blood flow responses to sublingual nitroglycerin in patients with and without coronary artery
disease (CAD) using this technique. In patients with
coronary disease, regional flow responses were
analyzed relative to the angiographic location of
significant coronary obstruction.
Methods
Patient Selection
Twenty male patients, age 38-61 years (mean 53
years) who underwent clinically indicated right and
left cardiac catheterization were included in this
study. Informed consent was obtained in each case.
Twelve of these patients had significant coronary
obstruction. The latter was defined as .70% diameter
narrowing in at least one of the three major coronary
arteries. Each of these patients was clinically stable
and was thought to have evidence of transient myocardial ischemia based on a history of typical angina pectoris and the electrocardiographic ST segment
response during stress testing. These patients were
selected because the location of the coronary obstruction conformed to a pattern that allowed evaluation of
the left ventricular region supplied by the anterior
descending branch of the left coronary artery. Six had
significant obstruction limited to the anterior descending branch, while the right or circumflex coronary
arteries had no significant obstruction. The other six
patients had significant obstruction only in the right
and/or circumflex arteries, while the anterior descending had no significant obstruction. The remaining
eight patients had angiographically normal coronary
arteries (NCA) and were undergoing cardiac catheterization to help define a vague chest pain syndrome. No
subjects had evidence for heart failure or other forms
of heart disease.
From the Division of Cardiology, Department of Medicine,
University of Florida and the Veterans Administration Hospital,
Gainesville, Florida.
Presented in part at the Southern Section of the American
Federation for Clinical Research, New Orleans, Louisiana, January
1978.
Catheterization
Address for reprints: J. Mehta, M.D., Box J-277, JHM Health
Center, University of Florida, Gainesville, Florida 32610.
Received April 24, 1978; revision accepted July 7, 1978.
Circulation 58, No. 5, 1978.
No premedication was used, and nitroglycerin was
omitted for at least 8 hours before study. Catheter803
CIRCULATION
804
ization was performed in a postabsorptive state. A #8
Sones catheter was positioned, via the right brachial
artery, in the aorta to measure systemic arterial
pressure using a Statham P23Db transducer. Mean
pressure was obtained by electronic filtration. This
catheter was also advanced to the left ventricle to
record left ventricular end-diastolic pressure at high
amplification. A multithermistor thermodilution
catheter'01'2 was advanced from an antecubital vein
and positioned in the coronary sinus. The distal thermistor was advanced to the great cardiac vein.
Catheter position was localized'0 and frequently
checked using magnification fluoroscopy and injection
of 1-2 ml of Renografin 76 (meglumine diatrizoate).
The position was confirmed at the beginning and end
of each measurement period by comparison with a
videotape recording. Electrocardiographic lead V, was
recorded and monitored continuously.
VOL 58, No 5, NOVEMBER 1978
Where CRANT and CRT = anterior regional and
total left ventricular coronary resistance indices,
respectively.
Statistical analysis
Mean values and SEM were determined before and
after nitroglycerin. Data were compared using the t
test for paired or unpaired analysis where appropriate.
A P value <0.05 was considered significant.
Results
Regional coronary and left ventricular hemodynamic data before and after nitroglycerin are summarized for the NCA subjects in table 1. Data obtained in the CAD patients are summarized in table 2
according to the location of obstruction.
Regional Hemodynamic Data at Rest Before Nitroglycerin
Downloaded from http://circ.ahajournals.org/ by guest on August 10, 2017
Regionalflow
Recording and Measurements
Arterial and left ventricular pressures
recorded during a hemodynamically stable control
period. During this period coronary sinus flow (CSF)
and great cardiac vein flow (GCVF) were measured as
previously described.10 12 These blood flows were
recorded simultaneously as the aortic pressure was
recorded.
After control recording, sublingual nitroglycerin
0.3-0.6 mg was given to produce approximately 10%
decline in mean arterial pressure (MAP). When heart
rate and arterial pressure stabilized (3-4 minutes
after nitroglycerin administration), flow and pressure
recordings were repeated.
were
Calculations
Both CSF and GCVF were calculated by a
modification of the method of Ganz et al.", 12 Venous
flow was measured as room temperature saline solution (indicator) was infused by Harvard pump at a
fixed rate. Temperatures of the indicator and venous
blood were determined from catheter-mounted thermistors. The resultant temperature reduction of both
the great cardiac vein and coronary sinus blood is inversely related to flow, which was calculated as
described elsewhere.10-12
The GCVF was taken as an index of flow draining
from the anterior left ventricular region supplied
predominantly by the anterior descending coronary
artery and the CSF was used to represent the fraction
of venous flow derived from the anterior region.
Indices of vascular resistance in each left ventricular region were derived from the ratio of
simultaneously measured MAP and the respective
flow as:
CRANT
CRT
= GCVF
mm
Hg/ml/min
mm
Hg/mI/min
MAP
In the NCA subject group, CSF averaged 149 ± 15
ml/min and GCVF 59 ± 9 ml/min (table 1). These
values were not significantly different from those obtained in the CAD patients (121 ± 10 ml/min and
55 ± 10 ml/min, respectively) (table 2). In the subgroup of patients with obstruction limited to the
anterior descending artery, GCVF (33 ± 6 ml/min)
was lower than in the NCA group (P < 0.05).
However, CSF (109 ± 7 ml/min) was not significantly
different. In contrast, in the other CAD patient subgroup with disease in the right and/or circumflex
arteries but not the anterior descending, both CSF and
GCVF (132 ± 20 ml/min and 77 ± 14 ml/min,
respectively) were similar to those obtained in the
NCA subjects. The GCVF/CSF ratio in NCA and
CAD patients averaged 41 ± 5 and 45 ± 7%, respectively (P= NS). The GCVF/CSF in patients with
anterior descending obstruction (31 ± 5%) was similar
to that in NCA patients (41 ± 5%), but it was
significantly (P < 0.02) lower than that observed in
the right and/or circumflex obstruction subgroup
(60 ± 9%).
Regional Coronary Resistance
The resistance indices CRT and CRANT were
0.71 ± 0.09 and 1.87 ± 0.25 mm Hg/ml/min, respectively, in NCA subjects, compared to 0.91 + 0.08 and
2.54 ± 0.43 mm Hg/ml/min, respectively, in the
CAD patients. Only CRT was significantly higher
(P < 0.05) in CAD patients. However, CRANT
(3.43 ± 0.66) was higher (P < 0.02) in the CAD subgroup with anterior descending disease than that in the
subjects with NCA.
Regional Hemodynamic Data After Nitroglycerin
Regional Flow
In the NCA group, nitroglycerin effected a decline
(P < 0.02) in both CSF (15%) and GCVF (17%) compared to control (table 1). In the CAD patients, nitroglycerin produced nonsignificant changes in CSF and
CORONARY FLOW AND NITROGLYCERIN/Mehta and Pepine
TABLE 1. Effect of Nitroglycerin on Left
HR
MAP
LVEDP
(beats/min) (mm Hg) (mm Hg)
Pt. C
N
C
NC
N
1 63
72 85 73 11
8
2 90
108 94 85 10 7
3 62
68 115 103
9
6
4 76
92 115 90 12
8
5 70
84 92 88 12
7
6 78
100 95 87
6 6
7 72
84 93 90 12 8
8 90
80 80 75 10
8
Mean
75
86* 96 86* 10 7*
805
Ventricular and Coronary Hemodynamics in Subjects with Normal Coronary Angiograms
SAP X HR
CSF
GCVF GCVF/CSF
CRT
CRANT
(%)
(units)
(units
(ml/min) (ml/min)
(units)
C
N
C
NON
N
C
C
C
N
N
6930 5256 69 52 32 25 46
48
1.23
1.40
2.66
2.92
11250 9936 163 100 60 46
37
46
0.58
0.85
1.57
1.85
9920 8562 127 100 45 40 35
40
0.91
1.03
2.56
2.58
10640 9936 146 129 51 38 35
29
0.79
0.70
2.26
2.37
9100 8232 174 149 115 90 66
60
0.53
0.59
0.80
0.98
9594 10000 199 210 38 32
19
15
0.48
0.41
2.50
2.72
8640 8400 183 157 72 56 39
36
0.51
0.57
1.29
1.61
9450 6720 128 116 61 63
48
54
0.63
0.65
1.31
1.19
9440
8380* 149 127t 59
49*
41
41
0.71
0.78
2.03t
1.87
SEM
4
Downloaded from http://circ.ahajournals.org/ by guest on August 10, 2017
5
4
3 0.7 0.3
463
598 15 17
9
7
5
5
0.09
0.25
0.26
0.11
*P <0.01 N vs C.
tP < 0.02 N vs C.
Abbreviations: HR = heart rate; MAP = mean arterial pressure; LVEDP = left ventricular end-diastolic pressure; SAP X
HR = systolic arterial pressure-heart rate product; CSF = coronary sinus blood flow; GCVF = great cardiac vein flow; CRT
= total left ventricular coronary resistance; CRANT = anterior regional coronary resistance; C = control, before nitroglycerin;
N = after nitroglycerin.
TABLE 2. Effects of Nitroglycerin on Coronary and Left Ventricular
MAP
LVEDP SAP X HR
HR
CSF
(beats/min) (mm Hg) (mm Hg)
(units)
(ml/min)
N
N
NC
C
C
ON
Pt. C
N
Patients with disease limited to the LAD
84
1 78
6
9282 7392 140 110
95 70 13
2 96 110
8 10560 10450 98 115
95 78 10
74
3 68
9
85 80 10
7480 7400 111 110
4 60
4
72 110 90 11
9300 7920 100 68
5 72
78 100 85 14
7
9360 8580 112 80
92 80 16 10
6 67
77
8576 7700 95 94
Mean
74
7$ 9093 8240t 109 96
83t 96 81$ 12
*SEM
5
6
3
3
1 0.9
415
477
7
8
Hemodynamics in Coronary Disease Patients
GCVF GCVF/CSF
CRT
(A/mi)
(%)
CRANT
(units)
(units)
C
N
C
N
C
N
C
N
31
32
13
39
56
27
55
55
42
53
56
31
22
33
12
39
50
28
50
48
38
78
70
33
0.68
0.97
0.77
1.10
0.89
0.97
0.64
0.68
0.73
1.32
1.06
0.85
3.06
2.97
6.53
2.82
1.78
3.41
1.27
1.42
2.10
1.70
1.52
2.58
33* 49§
31
53t
0.90
0.88
3.43t
1.77§
4
5
7
0.06
0.11
0.66
0.20
84 66 45
128 40 20.
95 107 68
214 71 32
281 130 102
118 46 46
85
29
86
47
62
52
54
16
72
15
36
39
1.54
0.67
0.94
0.70
0.50
1.25
1.37
0.66
0.92
0.41
0.32
0.89
1.82
2.30
1.10
1.48
0.80
2.39
2.56
4.25
1.28
2.72
0.88
2.28
10t 12969 10533 132 153 77
52t 60*
39t
0.93
0.76§
1.65
2.33
0.6
6
Patients with disease limited to RCA and/or LCX
1 72
2 72
3 150
4 72
5 84
6 80
78
78
150
78
96
85
120 115
92 85
118 87
105 87
105 90
110 105
23
15
14
18
35
13
10
10
8
10
12
8
11376
10080
23250
9720
10750
12640
10080
8424
14700
8190
10272
11650
78
138
125
150
211
88
Mean
88
94t 108
95t 20
SEM
13
12
4
5
3
All coronary patients (n = 12)
Mean
81
881 102 88t 16
2099
9t 11031
32
14
12
9
9
0.16
0.16
0.26
0.49
9396t 121 125
55
50
45
46
0.91*
0.82
2.54
2.05
980
20
SEM
0.43
0.09
7
6
6
3
2 0.6 1176
7
0.08
0.26
3
6
626 10 18 10
*P < 0.05 compared to normal coronary artery (NCA) group.
tP < 0.02 compared to NCA group.
tP < 0.01 N vs C.
§P < 0.02 N vs C.
Abbreviations: HR = heart rate; MAP = mean arterial pressure; LVEDP = left ventricular end-diastolic pressure; SAP X
HR = systolic arterial pressure-heart rate product; CSF = coronary sinus blood flow; GCVF = great cardiac vein flow; CRT
= total left ventricular coronary resistance; CRANT = anterior regional coronary resistance; C = control, before nitroglycerin;
N = after nitroglycerin; LAD = left anterior descending artery; RCA = right coronary artery; LCX = left circumflex artery.
806
CIRCULATION
GCVF (table 2). In the CAD subgroup with disease
limited to the anterior descending, GCVF increased
(48%, P < 0.02), while- CSF fell (10%, P = NS). In
the patient subgroup with right and/or circumflex
CAD, CSF was not significantly increased (15%,
P = NS) while GCVF declined (32%, P < 0.01). In
subjects with and without coronary disease,
GCVF/CSF was unchanged (table 1 and 2) with nitroglycerin. However, in the CAD patient subgroup with
anterior descending disease, GCVF/CSF increased
(66%, P < 0.01), whereas in the subgroup with right
and/or circumflex disease, it declined (36%,
P < 0.01).
Downloaded from http://circ.ahajournals.org/ by guest on August 10, 2017
Regional Coronary Resistance
In the NCA subjects, CRT was not significantly
altered, but CRANT increased (9%, P < 0.02). In the
CAD patients, both CRT and CRANT declined, but the
change was not significant. The patient subgroup with
CAD localized to the anterior descending had a
CRANT decline (48%, P < 0.02), whereas in the subgroup with right and/or circumflex obstruction, CRT
declined (18%, P < 0.02).
Systemic Hemodynamic Effects of Nitroglycerin
(tables 1 and 2)
Nitroglycerin increased heart rate (14%) and
decreased MAP (10%) in the NCA group and 9% and
14%, respectively, in the CAD group (all P < 0.01).
The systolic pressure-heart rate product declined
(P < 0.01) in both groups. One patient (#3) in the
CAD subgroup with right and/or circumflex artery
disease had persistent atrial tachycardia unaltered by
nitroglycerin. Otherwise, similar changes in heart
rate, MAP and systolic pressure-heart rate product
were seen in the two CAD subgroups. Left ventricular
end-diastolic pressure declined (10 ± 0.7 to 7 ± 0.3
mm Hg, P < 0.01) in theNCAand(16 ± 2to9 i 0.6
mm Hg, P < 0.01) in the CAD patient groups.
Discussion
Resting total and anterior regional left ventricular
blood flow values found in this study are similar to
those reported by others using the same'"'4 or
different techniques.", 16 Coronary flows at rest in coronary disease patients were not significantly different
than in subjects with normal coronary arteries, supporting observations in other patient groups."-"' Indices of coronary resistance were slightly higher in the
coronary disease patients than in normal coronary
subjects, as expected.15
In the patient subgroup with angiographic evidence
of obstruction limited to the anterior descending,
anterior regional flow was lower and resistance index
higher than in the patients with right and/or circumflex obstruction. Similarly, these anterior regional
hemodynamic values found in the anterior descending
obstruction subgroup were altered significantly from
NCA subjects. The fraction of total left ventricular
flow derived from the anterior regional flow was also
VOL 58, No 5, NOVEMBER 1978
reduced compared to the other CAD subgroup or
patients with NCA. In contrast, patients with obstruction limited to the right and/or circumflex arteries had
anterior regional flow and resistance indices similar to
normal coronary subjects. These observations suggest
that measurements of regional venous flow provide the
potential for functional evaluation of the significance
of regional coronary artery obstructive disease. This
type of functional evaluation is not necessarily apparent from the arteriogram alone.
Nitroglycerin was administered in a dose sufficient
to evoke a comparable change in arterial pressure and
heart rate in the patient groups studied. This approach
resulted in a similar systolic arterial pressure-heart
rate product and left ventricular end-diastolic pressure
reduction in these patients. Alterations in coronary
blood flow and resistance patterns, however, were
strikingly different. In patients with normal coronary
angiograms, both total and anterior regional flow
declined and resistance increased as indices of
myocardial oxygen demand fell. These observations
are similar to those reported by Cohn et al.1" In contrast, both coronary flow and resistance were unaltered considering all the coronary disease patients
together. But in those with obstruction limited to the
anterior descending, there was a significant increase in
anterior regional flow associated with a reduction in
the index of anterior coronary resistance. Total coronary blood flow, however, was unchanged, suggesting
redistribution of flow from areas supplied by the right
and/or circumflex arteries to the region supplied by
the anterior descending. Similarly, in the subgroup
with disease limited to the right and/or circumflex
arteries, nitroglycerin produced a decline in flow and
an increase in resistance indices related to the anterior
region without changing total left ventricular flow.
These alterations again suggest redistribution of blood
flow from areas perfused by the nonobstructed
anterior descending to the hypoperfused region
supplied by the right or circumflex arteries.
Redistribution of blood flow from nonischemic to
ischemic zones appears related to the effects of nitroglycerin on the large coronary arteries.6 17-19 Our
observations also support other patient studies
suggesting redistribution of blood flow to a hypoperfused area.6 15 16 Although intracoronary nitroglycerin can increase total left ventricular blood
flow7"12 without changing systemic arterial pressure, a
beneficial effect on pacing-induced angina was not
demonstrated by Ganz and Marcus. 12 Intravenous
nitroglycerin in the latter study, however, reduced
myocardial oxygen demand indices and relieved
angina. Regional blood flow responses were not
reported by these investigators. In our patients, sublingual nitroglycerin decreased systolic arterial
pressure-heart rate product and was associated with
apparent redistribution in left ventricular blood flow.
The decrease in left ventricular end-diastolic pressure
with nitroglycerin could contribute to increased blood
flow to regions with obstructed vessels. This increase
in blood flow to potentially ischemic areas induced by
sublingual nitroglycerin may complement the reduc-
CORONARY FLOW AND NITROGLYCERIN/Mehta and Pepine
Downloaded from http://circ.ahajournals.org/ by guest on August 10, 2017
tion in myocardial oxygen demand, providing additional beneficial actions.
Bache et al.8 suggested that nitroglycerin improves
perfusion of ischemic subendocardium by dilating
penetrating arteries. This would deliver blood from
epicardial to subendocardial layers. In contrast, Forman et al.9 indicated that nitroglycerin may not dilate
subendocardial vessels that are already "fully dilated"
during ischemia. This dilation of vessels in nonischemic subepicardial layers may result in hemodynamic conditions that favor a "steal" of blood flow
from ischemic regions. The thermodilution technique
used in our study cannot differentiate between flow in
subepicardial and subendocardial layers. Our study
was not designed to examine the coronary flow effects
of nitroglycerin during acute ischemia when the
hypothesis of "'fully dilated collaterals and fixed blood
flow" may be operative. However, the flow increase
and resistance decrease in zones supplied by
obstructed vessels was striking in selected CAD
patients who were probably not ischemic at rest or
during nitroglycerin study. These observations
demonstrate the presence of flow reserve in potentially
ischemic regions, and raise the possibility that some
degree of ischemia may have been present at rest.
In summary, our study implies that sublingual
nitroglycerin decreases coronary flow in subjects with
normal coronary arteries as oxygen demands decline.
In selected patients with coronary disease, nitroglycerin appears to produce a redistribution of coronary flow manifested by an increase in venous blood
flow from hypoperfused regions. This is interpreted as
an increase in flow to potentially ischemic zones
associated with a reduction in determinants of oxygen
demand. The change in coronary flow distribution
may be related to alterations in regional resistance
and could contribute to nitroglycerin's beneficial action in patients with coronary disease. Although the
data indicate that sublingual nitroglycerin may
redistribute flow to hypoperfused areas, further
studies are warranted. These studies should define: 1)
the normal ratio limits of GCVF to CSF in larger
numbers of CAD patients; 2) the ratio limits in
patients with varying CAD patterns at rest and with
stress; and 3) possible errors in measuring total and
regional coronary flows.
References
1. Hirshfeld JW, Borer JS, Goldstein RE, Barrett MJ, Epstein
SE: Reduction in severity and extent of myocardial infarction
when nitroglycerin and methoxamine are administered during
807
coronary occlusion. Circulation 49: 291, 1974
2. 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
3. Flaherty JT, Reid PR, Kelly DT, Taylor DR, Weisfeldt ML,
Pitt B: Intravenous nitroglycerin in acute myocardial infarction. Circulation 51: 132, 1975
4. William DO, Amsterdam EA, Mason DT: Hemodynamic
effects of nitroglycerin in acute myocardial infarction. Decrease
in ventricular preload at the expense of cardiac output. Circulation 51: 421, 1975
5. Miller RR, Vismara LA, Williams DO, Amsterdam EA,
Mason DT: Pharmacological mechanisms for ventricular unloading in clinical congestive heart failure. Differential effects of
nitroprusside, phentolamine and nitroglycerin on cardiac function and peripheral circulation. Circ Res 39: 127, 1976
6. Fam WM, McGregor M: Effect of nitroglycerin and
dipyridamole on regional coronary resistance. Circ Res 22: 649,
1968
7. Cappuro NL, Kenneth KM, Epstein SE: Comparison of nitroglycerin, nitroprusside and phentolamine induced change in
coronary collateral function in dogs. J Clin Invest 60: 295, 1977
8. Bache RJ, Ball RM, Cobb FR, Rembert JC, Greenfield JC Jr:
Effects of nitroglycerin in transmural myocardial blood flow in
the unanesthetized dog. J Clin Invest 55: 1219, 1975
9. Forman R, Kirk EF, Downey JM, Sonnenblick EH: Nitroglycerin and heterogeneity of myocardial blood flow. Reduced
subendocardial blood flow and ventricular contractile force. J
Clin Invest 52: 905, 1973
10. Pepine CJ, Mehta J, Webster W, Nichols WW: In vivo validation of a thermodilution method to determine regional left ventricular blood flow in patients with coronary disease. Circulation 58: 795, 1978
11. Ganz W, Tamura K, Marcus HS, Donosa R, Yoshida S, Swan
HJC: Measurement of coronary sinus flow by continuous thermodilution in man. Circulation 44: 181, 1971
12. Ganz W, Marcus HS: Failure of intracoronary nitroglycerin to
alleviate pacing-induced angina. Circulation 46: 880, 1972
13. Pepine CJ, Schang SJ, Bemiller CR: Effects of perhexiline on
coronary hemodynamic and myocardial metabolic responses to
tachycardia. Circulation 49: 887, 1974
14. Schang SJ, Pepine CJ: Effects of propranolol on coronary
hemodynamic and metabolic responses to tachycardia stress in
patients with and without coronary disease. Cathet Cardiovasc
Diagn 3: 47, 1977
15. Cohn PF, Maddox D, Holman BL, Markis JE, Adams DS, See
JR, Idoine J: Effect of sublingually administered nitroglycerin
on regional myocardial blood flow in patients with coronary
artery disease. Am J Cardiol 39: 672, 1977
16. Horwitz LD, Gorlin R, Taylor WJ, Kemp HG: Effects of nitroglycerin on regional myocardial blood flow in coronary artery
disease. J Clin Invest 50: 1578, 1971
17. Fam WM, McGregor M: Effects of coronary vasodilator drugs
on retrograde flow in areas of myocardial ischemia. Circ Res
15: 355, 1964
18. Winbury MM, Howe BB, Hefner MA: Effects of nitrate and
other coronary dilators on large and small coronary vessels. A
hypothesis for the mechanism of action of nitrates. J Pharmacol
Exp Ther 168: 70, 1969
19. Schang SJ, Pepine CJ: Effects of nitroglycerin on coronary
sinus blood flow in patients on propranolol. Br Heart J 1978. In
press
Effect of sublingual nitroglycerin on regional flow in patients with and without coronary
disease.
J Mehta and C J Pepine
Downloaded from http://circ.ahajournals.org/ by guest on August 10, 2017
Circulation. 1978;58:803-807
doi: 10.1161/01.CIR.58.5.803
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1978 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on
the World Wide Web at:
http://circ.ahajournals.org/content/58/5/803
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally
published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the
Editorial Office. Once the online version of the published article for which permission is being requested is
located, click Request Permissions in the middle column of the Web page under Services. Further
information about this process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Circulation is online at:
http://circ.ahajournals.org//subscriptions/