THERAPY AND PREVENTION

CONGESTIVE HEART FAILURE

Beneficial effects of dopamine combined with

intravenous nitroglycerin on hemodynamics in
patients with severe left ventricular failure
HENRY S. LOEB, M.D., JAMES P. OSTRENGA, M.D., WILLIAM GAUL, M.D., JEFFREY WITT, M.D.,
GREGORY FREEMAN, M.D., PATRICK SCANLON, M.D., ROLF M. GUNNAR, M.D.

ABSTRACT Hemodynamic effects of dopamine and intravenous nitroglycerin alone, and in combi-
nation, were studied in 27 patients with severe left ventricular failure. Dopamine alone increased
cardiac index from 1.8 to 2.5 1/min/m2 but also increased wedge pressure from 24 to 30 mm Hg and
heart rate from 88 to 101 beats/min. Arterial oxygen saturation fell from 92% to 87% (p < .001).
Nitroglycerin alone had a lesser effect on cardiac index (1.8 to 2.2 1/min/m2) but decreased wedge
pressure from 26 to 16 mm Hg and heart rate from 91 to 86 beats/min. Arterial oxygen saturation fell
from 91% to 90% (NS). Combined dopamine and nitroglycerin administration resulted in optimal
hemodynamics, with cardiac index of 2.9 1/min/m2, wedge pressure of 17 mm Hg, and heart rate of 96
beats/min. Arterial oxygen saturation remained low at 88% in spite of the reduction in left ventricular
filling pressure, which probably reflects increased intrapulmonary right-to-left shunting coupled with
increased pulmonary blood flow. These results suggest that the combination of dopamine with intrave-
nous nitroglycerin should be considered for patients with severe left ventricular dysfunction who
require temporary pharmacologic support.
Circulation 68, No. 4, 813-820, 1983.
Downloaded from http://ahajournals.org by on May 14, 2019

TEMPORARY pharmacologic support of patients congestion or edema.2' 3 The possible mechanisms of

with chronic severe left ventricular dysfunction is fre-
quently required either during episodes of deteriora-
tion or before definitive diagnostic or therapeutic pro-
cedures. Although a variety of intravenous inotropic
and vasodilator drugs are available for this purpose,
the selection of a specific drug or combination of drugs
remains largely empiric.
Dopamine, a catecholamine with significant inotro-
pic activity, has potential advantages for use in patients
with advanced low-output cardiac failure because of its
selective effect on promoting blood flow to renal and
splanchnic beds via stimulation of nonadrenergic vaso-
dilator receptors in these areas.1 Although dopamine
infusion may reduce an elevated left ventricular filling
pressure in some patients with heart failure, other pa-
tients may show a significant increase in filling pres-
sure associated with the development of pulmonary
From the Section of Cardiology, Department of Medicine, Loyola
University Stritch School of Medicine, Maywood, IL, and the Veterans
Administration Hospital, Hines, IL.
Supported in part by the Research Service of the Veterans Adminis-
tration and a grant from American Critical Care Division of the Ameri-
can Hospital Supply Corp., McGaw Park, IL.
Address for correspondence: Henry S. Loeb, M.D., Program Direc-
tor in Cardiology, Veterans Administration Hospital, Hines, IL 60141.
Received April 14, 1983; revision accepted June 23, 1983.
Vol. 68, No. 4, October 1983
dopamine-induced elevation of left ventricular filling
pressure, particularly at higher doses, are many and
include increased preload and afterload due to exces-
sive a-receptor-mediated vasoconstriction, excessive
tachycardia, and/or myocardial ischemia in patients
with severe coronary artery disease. In addition, in
patients with chronic heart failure, the inotropic re-
sponse to dopamine may be diminished by prior myo-
cardial catecholamine depletion4 or by "down regula-
tion" of myocardial fl-receptors secondary to
prolonged compensatory sympathetic stimulation.' In
such patients the high doses of dopamine required to
obtain an adequate inotropic effect may be associated
with excessive and undesirable a-receptor stimulation.
Nitrates have been shown to be effective venodila-
tors and are particularly useful in lowering left ventric-
ular filling pressure in patients with severe left ventric-
ular failure.9 Since intravenous nitroglycerin has
recently been approved for clinical use, it seemed rea-
sonable to evaluate the use of dopamine combined with
intravenous nitroglycerin in a group of patients with
advanced chronic left ventricular failure. Our results
suggest that this combination offers significant advan-
tages over either drug administered alone and may be
ideally suited for patients with severe left ventricular
813
 LOEB et al.
dysfunction who require temporary pharmacologic
support.
Methods and materials
The patients studied were all men who were hospitalized for
symptoms of chronic low-output cardiac failure (NYHA class
III or IV) in spite of treatment with digitalis and diuretics. Ages
ranged from 33 to 66 years and averaged 57 years. Informed
consent was obtained from each patient before the study. Nine
patients had arteriosclerotic heart disease documented by coro-
nary arteriography (six patients) or postmortem examination
(three patients). Nine patients had no-or insignificant coronary
artery disease as determined by angiography and were consid-
ered to have primary myocardial disease. Of the remaining nine
patients who did not undergo angiography, six were considered
to have primary myocardial disease on the basis of clinical
findings. In no patient was valvular heart disease considered to
be the major cause of heart failure.
On the morning of the study all patients, who had fasted and
had not received any drugs, were brought to a special hemody-
namic research unit. A No. 7F thermal dilution Swan-Ganz
catheter was inserted in an antecubital vein and was advanced
under fluoroscopic control until the catheter tip was situated in
the right or left pulmonary artery. The tip was positioned to
yield a reliable wedge pressure (WP) waveform when the bal-
loon was inflated and pulmonary artery systolic (PASP) and
diastolic (PADP) pressure waveform when the balloon was de-
flated.' Right atrial pressure (RAP) was measured from the
proximal lumen. Cardiac output (CO) was determined by aver-
aging three or more thermal-dilution curves obtained by inject-
ing 10 ml of 0°C saline into the right atrium. A Model 9500
Edwards Laboratory cardiac output computer was used to give
on-line readout of CO. Arterial systolic (ASP) and diastolic
Downloaded from http://ahajournals.org by on May 14, 2019
(ADP) pressures were measured from an indwelling catheter in
the radial or brachial artery. All pressures were obtained from
Statham 23Db transducers leveled at the midchest position.
Mean pulmonary (MPAP) and mean systemic arterial (MAP)
pressures were determined by electrical damping. Heart rate
(HR) was determined from a standard electrocardiographic
(ECG) lead that was monitored continuously. Pressures and
ECGs were recorded on a multichannel photographic recorder
run at various paper speeds. Arterial (ART 02) and pulmonary
oxygen saturations were determined with an American Optical
oximeter.
Calculations were made with the following formulas: cardiac
index' (CI) = CO/body surface area, stroke index (SI) = CIf
HR, left ventricular stroke work index (LVSWI) = (MAP
WP) x SI x 13.6/1000, systemic arteriolar resistance (SAR)
= (MAP - RAP)/CO, and pulmonary arteriolar resistance
(PAR) = (MAP WP)/CO.-
Two sets of control measurements were obtained 15 min apart
in 10 of the 27 patients. In these 10 patients differences between
the first and second control measurements were not significant.
In the remaining 17 patients, a single" set of control measure-
ments was obtained before drug infusion. The order of drug
infusion was randomized by drawing from a sealed envelope.
Dopamine was given first in 17 patients and nitroglycerin was
first in 10 patients. Both drugs were administered with an auto-
mated (IVAC) infusion system after dilution of the drug with
5% dextrose in water'to concentrations of 800 ,ug/ml for dopa-
mine and 400'gg/ml for nitroglycerin. Each drug was titrated
separately as follows: dopamine was started at 2 fxg/kg/min with
dose increments of 1 /tg/kg/min every 10 min until WP was
greater than 28 mm Hg, HR was greater than 120 beats/min, or a
maximum dose of 6 ,ug/kg/min was given. In our experience3
doses above 6 iig/kg/min frequently lead to undesirable tachy-
814
cardia and/or elevation of arterial pressure when given to pa-
tients with advanced cardiac failure. Nitroglycerin was started
Aug/min
at 20 with increases of 20 ;g/min every 2 min until WP
fell bymore than or equal to 50%, ASP fell by more than 20mm
Hg, HR was greater than 120 beats/min, or a maximal dose of
400,ug/min was given. This maximal dose of nitroglycerin is
considerably higher than that commonly used for the treatment
of patients with unstable angina, and it seems unlikely that
doses above 400,ug/min would have resulted in significant
additional hemodynamic improvement. Measurements were
made during a steady state 15 min after final dose adjustment.
After measurements had been completed, the first drug infusion
was stopped and control measurements were made after 15 min.
The second drug was then evaluated in similar fashion. Studies
were then repeated during combined drug administration at full
dose of drug 2 plus a half dose of drug 1, a full dose of both
drugs, and a half dose of drug 2 plus a full dose of drug 1.
Statistical analysis was performed with Student's t test for
paired numerical data. Both dopamine and nitroglycerin infused
alone at full doses were compared with respective control values
obtained immediately before the infusions (table 1). Dopamine
alone at full dose was compared with a full dose of dopamine
combined with a half dose and a full dose of nitroglycerin, and
nitroglycerin alone at a full dose was compared with a full dose
of nitroglycerin combined with a half dose and a full dose of
dopamine (table 2).
Results
Effects of dopamine and nitroglycerin alone (table 1).
Before infusion of either drug, all patients had eleva-
tion of WP equal to or greater than 20 mm Hg (average
28 ± 1 mm Hg) and a reduction of CI less than 2.5 1/
min/m2 (average 1.7 + 0.1 I/min/mn2).
Dopamine. Infusion of dopamine (4.5 ± 0.3,uglkgl
min) resulted in significant increases in the following
variables: ASP, 118 to 131 mm Hg; MAP, 83 to 89
mm Hg; PASP, 50 to 58 mm Hg; MPAP, 37 to 44 mm
Hg; PADP, 29 to 34 mm Hg; WP, 24 to 30 mm Hg;
HR, 88 to 101 beats/min; CI, 1.8 to 2.5 1/min/m2; SI,
21 to 26 ml/beat/m2; and LVSWI, 16 to 20 g/m2. Dopa-
mine resulted in significant decreases in the following:
PAR, 4.1 to 3.3 mm Hg/l/min; SAR, 22 to 18 mm Hg/
1/min; ART 029 92% to 87%; and arterial minus pul-
monary arterial oxygen saturation (AVO2A), 36% to
27%.
Nitroglycerin. Infusion of nitroglycerin (3.2 ± 0.3
,g/kg/min) resulted in significant decreases in the fol-
lowing: ASP, 117 to 111 mg Hg; MAP, 84 to 75 mm
Hg; ADP, 68 to 61 mm Hg; PASP, 50 to 38 mm Hg;
MPAP, 40 to 28 mm Hg; PADP, 31 to 21 mm Hg; WP,
26 to 16 mm Hg; RAP, 12 to 7 mm Hg; PAR, 4.5 to
3.2 mm Hg/l/min; SAR, 22 to 17 mm Hg/lfmin; and
AVO2A, 37% to 32%. Nitroglycerin resulted in sig-
nificant increases in the following: CI, 1.8 to 2.2 1/
min/m2; SI, 20 to 26 ml/beat/m2; and LVSWI, 16 to 21
g/m2.
Effects of dopamine alone vs dopamine combined with
nitroglycerin (table 2). Values obtaCinedduRng a full
CIRCULATION
 THERAPY AND PREVENTION-CONGESTIVE HEART FAILURE
TABLE 1
Measurements during control periods and during single infusions (mean ± SEM)
Control D p (<) Control N p (<)
ASP (mm Hg) 118 131 .001 117 111 .01
+3 +3 ±3 +4
MAP (mm Hg) 83 89 .01 84 75 .001
+2 ±2 +2 ±2
ADP (mm Hg) 66 69 NS 68 61 .001
+3 ±3 ±2 ±2
PASP (mm Hg) 50 58 .001 50 38 .001
-+-2 ±3 ±3 ±3
MPAP (mm Hg) 37 44 .001 40 28 .001
±2 ±2 ±1 ±2
PADP (mm Hg) 29 34 .01 31 21 .001
+1 ±1 ±1 ±2
WP (mm Hg) 24 30 .01 26 16 .001
±2 +1 +1 ±2
RAP (mm Hg) 11 13 NS 12 7 .001
+1 ±2 ±1 ±1
HR (beats/min) 88 101 .001 91 86 .01
±2 ±3 ±2 ±2
CI (Irmin/m2) 1.8 2.5 .001 1.8 2.2 .001
+0.1 ±0.1 ±0.1 ±0.1
SI (mi/beat/M2) 21 26 .001 20 26 .001
+-1 ±2 ±1 ±1
LVSWI (g/m2) 16 20 .01 16 21 .001
+1 ±2 ±1 ±1
PAR (mm Hg/l/min) 4.1 3.3 .01 4.5 3.2 .001
+0.5 ±0.4 ±0.5 ±0.3
SAR (mm Hg/l/min) 22 18 .001 22 17 .001
Downloaded from http://ahajournals.org by on May 14, 2019

+1 ±1 ±1 ±1
ART 2(%) 92 87 .001 91 90 NS
+1 ±1 +1 ±1
AVO2A (%) 36 27 .001 37 32 .01
+1 ±1 ±2 ±1
D = dopamine; N = nitroglycerin.

dose of dopamine alone were compared with a full
dose of dopamine combined with a half dose of nitro-
glycerin. This combination resulted in a significant
reduction in all measured pressures and resistances, a
significantly lower HR (p < .02), and higher CI, SI,
and LVSWI. Neither ART 02 nor AVO2A were
changed.
A full dose of dopamine alone when compared with
a full dose of dopamine combined with a full dose of
nitroglycerin yielded similar results, except that HR
was no longer significantly lower than that with dopa-
mine alone while AV02A was lower (p < .02).
Effects of nitroglycerin alone vs nitroglycerin combined
with dopamine (table 2). Values obtained during a full
dose of nitroglycerin alone were compared with values
obtained during a full dose of nitroglycerin combined
with a half dose of dopamine. This combination result-
ed in significantly higher mean values for HR, SI, and
CI, and lower values for SAR, PAR, ART 02 and
Vol. 68, No. 4, October 1983
AVO2z, while both systemic and right-sided pressures
were similar. When compared with a full dose of nitro-
glycerin alone, combined nitroglycerin and dopamine
at full doses yielded significantly higher mean values
for ASP, CI, SI, and LVSWI, and lower mean values
for SAR, PAR, and AVO2A, while MAP, ADP, and
right-sided pressures were not increased. The ART 02
of 88% during nitroglycerin plus dopamine was sig-
nificantly less (p < .02) than the mean value of 90%
during nitroglycerin alone.
Discussion
The desired hemodynamic goals of short-term intra-
venous drug therapy in patients with advanced low-
output cardiac failure includes augmentation of for-
ward output and peripheral perfusion plus reduction in
backward failure and pulmonary congestion. An addi-
tional important goal, particularly in patients with
coronary disease, is the maintenance of an adequate
815
 LOEB et al.

TABLE 2
Measurements during drug combinations (mean ± SEM)
D + N/2 p <A D + N p <A p <B D/2 + N p <B

ASP(mm Hg) 126 .05 121 .001 .01 113 NS

±3 ±4 +4
MAP (mm Hg) 82 .001 78 .001 NS 73 NS
±2 +2 +2
ADP(mm Hg) 65 .001 62 .001 NS 59 NS
±2 ±+2 ±2
PASP (mm Hg) 45 .001 41 .001 NS 38 NS
±3 ±3 ±3
MPAP (mm Hg) 33 .001 29 .001 NS 28 NS
±2 ±2 +2
PADP (mm Hg) 26 .001 22 .001 NS 20 NS
±2 +2 +2
WP(mmHg) 21 .001 17 .001 NS 17 NS
+2 ±2 ±2
RAP (mm Hg) 9 .001 8 .001 NS 7 NS
+2 1 1
HR (beats/min) 95 .02 96 NS .001 90 .01
+3 +3 +3
CI (1/min/m2) 2.7 .01 2.9 .001 .001 2.6 .001
+0.1 +0.1 +0.1
SI (ml/beat/M2) 28 .001 30 .001 .001 29 .001
±2 ±2 ±2
LVSWI (g/m2) 24 .01 25 .001 .001 22 NS
+1 +1 +1
PAR (mm Hg/l/min) 2.7 .01 2.4 .001 .001 2.5 .001
±0.3 ±0.3 ±0.3
SAR (mm Hg/l/min) 15 .001 13 .001 .001 14 .001
Downloaded from http://ahajournals.org by on May 14, 2019

+1 +1 +1
ART02(%) 88 NS 88 NS .01 87 .001
+1 +1 +1
AVO2A (%) 26 NS 25 .02 .001 32 .001
±+ +l ±+
D + N/2 = dopamine plus half dose nitroglycerin; D + N = dopamine plus nitroglycerin, full doses; D/2 + N half dose
dopamine plus nitroglycerin.
AValue vs dopamine alone.
BValue vs nitroglycerin alone.

coronary perfusion pressure and avoidance of myocar-
dial ischemia.
Of the inotropic drugs available for continuous in-
travenous infusion, both dobutamine and dopamine
have been shown to significantly augment CO in pa-
tients with advanced heart failure. However, when
these drugs are used alone, an elevated left ventricular
filling pressure may fall only slightly or, in the case of
dopamine, may actually increase.2' Additionally,
both dobutamine and dopamine may increase net myo-
cardial oxygen demand unless preload and myocardial
wall tension are concurrently reduced sufficiently to
offset the direct inotropic and chronotropic actions of
these drugs.
As an alternative to inotropic therapy, intravenous
vasodilators have become popular for short-term man-
816
agement of patients with severe left ventricular failure.
Sodium nitroprusside, which acts on both the venous
and arterial systems,'0 has been shown to result in
significantly lower WP and HR when compared with
dobutamine at doses that augmented CO to the same
extent."'1112Recently, intravenous nitroglycerin has be-
come commercially available; however, its role in the
management of patients with severe left ventricular
failure has yet to be defined. Theoretically nitroglycer-
in may offer certain advantages over nitroprusside,
particularly when used in combination with inotropic
drugs. Its more potent action on venous vs arterial
smooth muscle'3 should make it possible to effectively
reduce preload without causing excessive hypoten-
sion, which could compromise coronary and peripher-
al perfusion. Nitroglycerin dilates the large conduit
CIRCULATION
 THERAPY AND PREVENTION-CONGESTIVE HEART FAILURE
coronary vessels'4, 15 and may augment flow to areas mmHg
supplied by stenotic coronary vessels'6; this is in con- 130r
trast to nitroprusside, which dilates coronary resis-
tance vessels and may reduce flow to ischemic myo- 120k
cardium.17 Additionally, prolonged nitroprusside
administration may cause accumulation of toxic levels 1101-
of thiocyanate, IB whereas intravenous nitroglycerin
can be given safely for extended periods.'3 1ok0
Leier et al.9 compared intravenous nitroglycerin
with nitroprusside in 10 patients with congestive fail- 90k
ure. At doses that exerted a similar reduction in left
ventricular filling pressure, nitroprusside resulted in a 801
greater increase in CO and reduction in arterial pres- MAP
sure than did nitroglycerin. Effects on limb and hepatic 70>
blood flow were similar and renal blood flow, which
fell significantly during nitroglycerin treatment, was 60
unchanged with nitroprusside. Thus, although intrave-
nous nitroglycerin is well tolerated and is very effec- 50
tive in reducing elevated pulmonary and left-sided fill-
ing pressures in patients with severe acute or chronic 401_
heart failure, it is generally less effective than inotropic
drugs or sodium nitroprusside in augmenting CO and 30_ T
M AMPAP
P
systemic blood flow. PADP
To achieve optimal hemodynamic effects, combined 20k_
intravenous therapy with inotropic and vasodilator
1OLL
_Ir -.1
HWP
drugs has been advocated. The combination of dobuta- w
Downloaded from http://ahajournals.org by on May 14, 2019

mine with nitroprusside, 1l 19 20 dobutamine with nitro-

glycerin,2' and dopamine with nitroprusside22' 23 or
sublingual isosorbide dinitrate24 have each been report-
ed to result in more favorable hemodynamics than
achieved with the inotropic or vasodilator drugs ad-
ministered separately.
Our experience with 27 patients with severe low-
output cardiac failure clearly demonstrated that the
combination of intravenous nitroglycerin with dopa-
mine resulted in major hemodynamic improvement not
obtainable with either drug used alone. Figure 1 shows
that dopamine increased both systemic and right-sided
pressures. WP increased in two-thirds of our patients
from a mean of 24 to 30 mm Hg for the group. We3' 25
have previously reported increases in filling pressure
during dopamine administration in some patients with
left ventricular failure, cardiogenic shock, or septic
shock, which appears to be a reflection of a-adren-
ergic-mediated vasoconstriction of resistance and/or
capacitance vessels that dopamine can exert, particu-
larly at higher doses.2&28 We believe this feature of
dopamine markedly limits its usefulness as a single
drug for inotropic support of patients with impaired left
ventricular function, and if a single inotropic drug is
desired dobutamine would be preferable. On the other
hand, dopamine, unlike dobutamine, has unique non-
Vol. 68, No. 4, October 1983
C D D+N/2 D+N W2+N N
FIGURE 1. Pressure measurements (mean + SEM) during the initial
control period and during infusion of dopamine and nitroglycerin alone
and in combination. The order of drug administration was different than
illustrated in the figure. C = control; D - dopamine; N = nitroglycer-
in; N/2 = half dose nitroglycerin; D/2 half dose dopamine.
adrenergic-mediated renal and mesenteric vasodilator
properties' that might be highly desirable in patients
with low-output states and reduced renal blood flow.
As can be seen in figure 1, the combined use of intrave-
nous nitroglycerin with dopamine markedly reduced
the high WP and right-sided pressures to levels essen-
tially the same as with nitroglycerin alone. Arterial
pressures, although also reduced, remained well above
hypotensive levels. Therefore, nitroglycerin would
seem to have advantages over nitroprusside in patients
with borderline hypotension.
The fact that intravenous nitroglycerin resulted in
major reduction of left ventricular filling pressure, pul-
monary artery pressure, and RAP with only a modest
fall in systemic arterial pressure probably reflects the
greater relative effect nitroglycerin has on venous vs
arterial smooth muscle, and to some extent distin-
guishes it from most other vasodilators used for treat-
ment of patients with heart failure. Since patients with
817
 LOEB et al.
advanced heart failure have a depressed Starling func-
tion curve, CO will be minimally affected by even
large changes in preload. Nitroglycerin, therefore,
would not be expected to markedly lower systemic and
coronary perfusion pressures in such patients. To the
contrary, reduction of elevated intracavitary diastolic
pressures could augment subendocardial perfusion,
and reduction in wall tension should reduce myocardi-
al oxygen demand with a net effect of improving the
myocardial oxygen supply and demand relationship.
Although the hemodynamic responses we observed are
compatible with these concepts, we did not measure
myocardial blood flow or oxygen consumption in our
patients, nor was it possible from clinical or electrocar-
diographic observations to demonstrate effects of the
drugs alone or in combination on the relationship be-
tween myocardial oxygen supply and demand. Such
studies should be undertaken in the future.
In figure 2, changes in HR, CI, SI, and resistances
are illustrated. During single drug administration,
dopamine was more effective than nitroglycerin in
augmenting CO; however, the maximal increases in
120 _
HR 100 _ T
beats/min
Downloaded from http://ahajournals.org by on May 14, 2019
80_
3.0 _
i The overall effect of the infusions on left ventricular
CI 2
L/min/m
m2- re--.
SI 2
cc/rn
m
30
20
20
SAR
mmHg/L/min
10-
PAR F 10
mmHg/L/min
C D D+N/2 D+N D/2+N
FIGURE 2. Measurements (mean + SEM) during the initial control
period and during infusion of dopamine and nitroglycerin alone and in
combination. C = control; D = dopamine; N = nitroglycerin; N/2 =
half dose nitroglycerin; D/2 = half dose dopamine.
818
CI, SI, and LVSWI, and reductions of SAR and PAR
occurred when dopamine and nitroglycerin were ad-
ministered together in full doses.
The chronotropic effects of dopamine resulted in an
increase in HR from 88 to 101 beats/min. Although
most patients with chronic heart failure tolerate such
increases in HR, and none of our patients experienced
angina or ischemic ECG changes during dopamine
infusion, tachycardia would generally be considered
undesirable in patients with heart failure and coexistent
coronary artery disease. When nitroglycerin was com-
bined with a full dose of dopamine, mean HR tended to
be lower than with dopamine alone, although the dif-
ference was significant only for dopamine plus a half
dose of nitroglycerin (101 vs 95 beats/min, p < .02). It
was also of interest that nitroglycerin alone reduced
mean HR from 91 to 86 beats/min (p < .01). The
tendency for nitroglycerin alone or in combination
with dopamine to reduce HR could be the result of
reduced work of breathing secondary to reduction of
central blood volume and left ventricular filling pres-
sure. Additional mechanisms related to autonomic re-
flexes under the influence of pulmonary vascular or
cardiac chamber stretch receptors must also be consid-
ered, but their role in modifying HR in response to
drugs such as nitroglycerin remains speculative. What-
ever the mechanism, it appears that in some patients
with heart failure the addition of nitroglycerin can sig-
nificantly reduce potentially undesirable tachycardia
that occurs when dopamine is given alone.
performance is shown in figure 3, which is a plot of left
25 D+NN
cU
0
E
E
0I
z
w
:
20 L D/2+N
N
_
D+N/2
CONTROL
D+
15 _
C,
I-
~~I
Iu~
15 20 25 30
LEFT VENTRICULAR FILLING PRESSURE -mmHg
N FIGURE 3. Ventricular performance is illustrated by plotting left ven-
tricular filling pressure against LVSWI. During dopamine (D) alone the
plot moves up but to the right, whereas with nitroglycerin (N) alone or in
combination with dopamine (D + N), the plot moves up and to the left,
suggesting a major improvement in left ventricular performance.
CIRCULATION
 THERAPY AND PREVENTION-CONGESTIVE HEART FAILURE
ventricular filling pressure vs LVSWI. With dopamine 95 r
alone the plot moved up but to the right, whereas with
nitroglycerin alone or in combination with dopamine
the plot moved up and to the left, suggesting maximal
improvement in left ventricular performance. H[_
In a previous study,3 we compared the hemodynam- co9
ic effects of dopamine with those of dobutamine in 0

patients with severe chronic heart failure. We observed cc85

a fall in ART 02 during dopamine infusion in associ- 4

ation with elevation of WP to above 30 mm Hg. Al-

though increased CO per se may result in arterial hy-
poxemia by increasing flow to nonventilated or poorly 80H
ventilated lungs,29' 30 ART 02 did not fall during
dobutamine infusion in spite of similar increases in
CO. In view of this, plus the fact that WP rose with 40
dopamine but not with dobutamine, we felt that pulmo-
nary congestion best explained the arterial hypoxemia
we observed during dopamine infusion.
In the present study, we again observed a significant 1 30 H[
0.
reduction in ART 02 from 92% to 87% during dopa- U-
mine infusion. Of 25 patients in whom ART 02 was
measured immediately before and during dopamine 20H
infusion, 12 had a reduction in ART 02 of 5% or more.
Comparing these 12 patients with the remaining 13 C D D+N N
patients (figure 4), it was again apparent that as a group FIGURE 5. Arterial oxygen saturation (ART 02) and left ventricular
the patients having the greatest fall in ART 02 during filling pressure (LVFP) in 12 patients having reduction of ART 02 bY
Downloaded from http://ahajournals.org by on May 14, 2019

dopamine infusion had higher mean values for left 35% during dopamine infusion. ART 02 remained well below the
control value during combination dopamine plus nitroglycerin in spite
of the reduction of LVFP from 36 to 25 mm Hg. C = control; D =
40 p<.ol
dopamine; N = nitroglycerin.

ventricular filling pressures both before and during

dopamine. We were surprised, therefore, that the addi-
p<.02 tion of nitroglycerin to dopamine had little effect on
30_ ART 02 in spite of its marked effect on lowering the
2~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

E
1I elevated left ventricular filling pressure. For the 12
patients with 5% or more reduction of ART 02 during
E dopamine (figure 5), the combination of dopamine
1 20 plus nitroglycerin lowered left ventricular filling pres-
0. sure from 36 to 25 mm Hg; however, ART 02 in-
creased only slightly from 84% to 86%. It seems,
therefore, that arterial hypoxemia during combined
I0 dopamine-nitroglycerin infusion is due at least in part
to factors other than pulmonary congestion. In our
patients, nitroglycerin alone resulted in a slight (but
insignificant) reduction of ART 02 from 92% to 90%.
Others have reported arterial hypoxemia during nitro-
C D glycerin therapy3l' 32 and have ascribed it to increased
FIGURE 4. Mean ± SEM for left ventricular filling pressure (LVFP) intrapulmonary right-to-left shunting. It seems likely,
during control (C) and during dopamine (D) infusion in 13 patients therefore, that in the present study, increased pulmo-
(clear bars) who did not have a fall in ART 02 of -5% during dopa-
mine compared with the 12 patients (solid bars) who did. The 12
nary blood flow coupled with increased shunting dur-
patients whose ART 02 fell by B5% had significantly higher LVFP ing combined dopamine-nitroglycerin infusion may
both before and during the dopamine infusion. have offset the beneficial effects on arterial oxygen-
Vol. 68, No. 4, October 1983 819
 LOEB et al.
ation expected from the nitroglycerin-induced reduc-
tion of left ventricular filling pressure.
In summary, in our patients with chronic heart fail-
ure, the combination of dopamine plus intravenous
nitroglycerin resulted in major overall hemodynamic
improvement not obtainable with either drug given
alone and accordingly could be advocated for similar
patients requiring temporary pharmacologic support.
References
1. McNay JL, McDonald RH, Goldberg LI: Direct renal vasodilata-
tion produced by dopamine in the dog. Circ Res 16: 510, 1965
2. Francis GS, Sharma B, Hodges M: Comparative hemodynamic
effects of dopamine and dobutamine in patients with acute cardio-
genic circulatory collapse. Am Heart J 103: 995, 1982
3. Loeb HS, Bredakis J, Gunnar RM: Superiority of dobutamine over
dopamine for augmentation of cardiac output in patients with
chronic low output cardiac failure. Circulation 55: 375, 1977
4. Goldberg LI: Dopamine -clinical uses of an endogenous cate-
cholamine. N Engl J Med 291: 707, 1974
5. Ginsburg R, Esserman LJ, Bristow MR: Myocardial performance
and extracellular ionized calcium in a severely failing human heart.
Ann Intern Med 98: 603, 1983
6. Taylor WR, Forrester JS, Magnusson P, Takano T, Chatterjee K,
Swan HJC: Hemodynamic effects of nitroglycerin ointment in con-
gestive heart failure. Am J Cardiol 38: 469, 1976
7. Franciosa JA, Blank RC, Cohn JN: Nitrate effects on cardiac out-
put and left ventricular outflow resistance in chronic congestive
heart failure. Am J Med 64: 207, 1978
8. Armstrong PW, Armstrong JA, Marks GS: Pharmacokinetic-
hemodynamic studies of intravenous nitroglycerine in congestive
cardiac failure. Circulation 62: 160, 1980
9. Leier CV, Bambach D, Thompson MJ, Cattaneo SM, Goldberg
RJ, Univerferth DV: Central and regional hemodynamic effects of
Downloaded from http://ahajournals.org by on May 14, 2019
intravenous isosorbide dinitrate, nitroglycerine and nitroprusside
in patients with congestive heart failure. Am J Cardiol 48: 1115,
1981
10. Miller RR, Vismara LA, Williams DO, Amsterdam EA, Mason
DT: Pharmacological mechanisms for left ventricular unloading in
clinical congestive heart failure. Circ Res 39: 127, 1976
11. Mikulic E, Cohn JN, Franciosa JA: Comparative hemodynamic
effects of inotropic and vasodilator drugs in severe heart failure.
Circulation 56: 528, 1977
12. Berkowitz C, McKeever L, Croke RP, Jacobs WR, Loeb HS,
Gunnar RM: Comparative responses to dobutamine and nitroprus-
side in patients with chronic low output cardiac failure. Circulation
56: 918, 1977
13. Hill NS, Antman EM, Green LH, Alpert JS: Intravenous nitroglyc-
erin. A review of pharmacology, indications, therapeutic effects
and complications. Chest 79: 69, 1981
14. Cohen MV, Kirk ES: Differential response of large and small
coronary arteries to nitroglycerin and angiotensin. Circ Res 33:
445, 1973
820
15. Macho P, Vatner SF: Effects of nitroglycerin and nitroprusside on
large and small coronary vessels in conscious dogs. Circulation 64:
1101, 1981
16. Brown BG, Bolson E, Petersen RB, Pierce CD, Dodge HT: The
mechanisms of nitroglycerin action: stenosis vasodilatation as a
major component of the drug response. Circulation 64: 1089, 1981
17. Chiariello M, Gold HK, Leinbach RC, Davis MA, Maroko PR:
Comparison between the effects of nitroprusside and nitroglycerin
on ischemic injury during acute myocardial infarction. Circulation
54: 766, 1976
18. Palmer RF, Lasseter KC: Drug therapy. Sodium nitroprusside. N
Engl J Med 292: 294, 1975
19. Cohn JN, Franciosa JA: Selection of vasodilator, inotropic or com-
bined therapy for the management of heart failure. Am J Med 65:
181, 1978
20. Meretoja OA: Influence of sodium nitroprusside and dobutamine
on the haemodynamic effects produced by each other. Acta An-
aesthesiol Scand 24: 195, 1980
21. Gagnon RM, Fortin L, Boucher R, Gilbert S, Morrisette M, Pre-
sent S, Lemire J, David A: Combined hemodynamic effects of
dobutamine and IV nitroglycerin in congestive heart failure. Chest
78: 694, 1980
22. Miller RR, Awan NA, Joye JA, Maxwell KS, DeMaria AN, Am-
sterdam EA, Mason DT: Combined dopamine and nitroprusside
therapy in congestive heart failure. Circulation 55: 881, 1977
23. Stemple DR, Kleiman JH, Harrison DC: Combined nitroprusside-
dopamine therapy in severe chronic congestive heart failure. Am J
Cardiol 42: 267, 1978
24. Stephens J, Dymond D, Spurrell R: Enhancement by isosorbide
dinitrate of haemodynamic effects of dopamine in chronic conges-
tive cardiac failure. Br Heart J 40: 838, 1978
25. Loeb HS, Winslow EBJ, Rahimtoola SH, Rosen KM, Gunnar RM:
Acute hemodynamic effects of dopamine in patients with shock.
Circulation 64: 163, 1971
26. Black WL, Rolett EL: Cardiovascular adrenergic activity of dopa-
mine in the dog. Am Heart J 75: 233, 1968
27. Cobb FR, McHale PA, Bache RJ, Greenfield JC Jr: Coronary and
systemic hemodynamic effects of dopamine in the awake dog. Am
J Physiol 222: 1355, 1972
28. Mark AL, lizuka T, Wendling MG, Eckstein JW: Responses of
saphenous and mesenteric veins to administration of dopamine. J
Clin Invest 49: 259, 1970
29. Jardin F, Gurdijian F, Desfonds P, Fouilladieu JL, Margairaz A:
Hemodynamic factors influencing arterial hypoxemia in massive
pulmonary embolism with circulatory failure. Circulation 59: 909,
1979
30. Jardin F, Gurdijian F, Desfonds P, Margairaz A: Effect of dopa-
mine on intrapulmonary shunt fraction and oxygen transport in
severe sepsis with circulatory and respiratory failure. Crit Care
Med 7: 273, 1979
31. Mookherjee S, Fuleihan D, Warner RA, Vardan S, Obeid Al:
Effects of sublingual nitroglycerin on resting pulmonary gas ex-
change and hemodynamics in man. Circulation 57: 106, 1978
32. Hales CA, Westphal D: Hypoxemia following the administration
of sublingual nitroglycerin. Am J Med 65: 911, 1978
CIRCULATION