Download Dopamine-lnduced Alterations In Left Ventricular Performance

Dopamine-lnduced Alterations In Left
Ventricular Performance
By William L. Block, M.D., and Ellis L. Rolett, M.D.
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ABSTRACT
Left ventricular responses to dopamine infusion of 1 to 5, 8, and 10 /Ltg/kg
per min for 30 minutes were studied in 14 anesthetized intact dogs. Cardiac
output (dye dilution) and stroke volume increased progressively while the
end diastolic volume (thermodilution) remained constant, signifying more
complete ventricular ejection and resulting in a progressive decline in end
systolic volume. Heart rate remained unchanged as did aortic mean pressure,
but in the presence of a greatly increased systemic blood flow, the calculated
peripheral vascular resistance declined progressively. A linear dose-dependent
increase in both systolic ejection rate and circumferential shortening rate suggested directionally similar changes in myocardial fiber shortening. Isovolumic
contraction was characterized by a marked increase in the peak velocity of left
ventricular pressure rise and presumably in the velocity of force generation
without change in the maximum pre-ejection force. These results indicate that
dopamine increased myocardial contractility. At these infusion doses dopamine differs from norepinephrine and isoproterenol in causing little change in
systemic blood pressure or heart rate in the intact dog. The steady heart rate,
stable blood pressure, and constant end diastolic volume suggest that the inotropic response to dopamine administration was due to a direct myocardial
action which was otherwise unmodified by the preload or afterload of ventricular contraction.
ADDITIONAL KEY WORDS catecholamines
inotropy
myocardial contractility
pressure derivative
cardiac catheterization
• Dopamine (3, 4-dihydroxyphenylethylamine), the immediate biological precursor of
norepinephrine, has pronounced cardiovascular effects which have not been fully defined.
Experimentally produced effects on peripheral vasomotor activity have included (1)
renal and mesenteric vasodilation in the dog
and (2) predominant vasoconstriction in the
extremities of the dog and man.1"4 Augmented renal blood flow and sodium excretion have been described in both species.5' °
Direct cardiac effects of dopamine have
varied, presumably because of differences in
From the Department of Medicine, University of
North Carolina and North Carolina Memorial Hospital, Chapel Hill, North Carolina.
Supported by Grant HE-08580 from the U. S. Public Health Service and Grant 5 T l HE-5486 from the
National Heart Institute.
A portion of this material lias previously appeared
in abstract form in Clinical Research, April, 1965.
Accepted for publication January 17, 1966.
Circulation Resojcb. VoL XIX, July 1966
beta-adrenergic stimulation
thermodilution
anesthetized dogs
dosage and experimental procedure. Using an
open-chest canine preparation and single injections of dopamine (10 to 40 /ig/kg), Eble
showed small and inconsistent changes in
cardiac output.2 Holmes and Fowler, however, demonstrated significant increases in
cardiac output and right ventricular contractile force (strain gauge arch) in a canine
heart-lung preparation following single doses
of 100 to 500 fig.7 McDonald and Goldberg,
studying the intact dog, reported elevated
systolic and decreased diastolic systemic
pressures without change in heart rate following dopamine injections of 2 to 16 fig/
kg.4 Larger doses produced more pronounced
pressor responses. Dopamine infusions in the
human subject (5.9 to 11.6 //.g/kg/min) increased cardiac output with essentially no
change in heart rate.8 Systemic pressure elevations were largely systolic, although diastolic
pressure was also slightly raised.
71
72
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Most administered catecholamines produce
either a substantial pressor response or a
prominent tachycardia with or without an
associated fall in systemic pressure. These
effects are believed to be mediated through
alpha and beta adrenergic receptors respectively.9 Catecholamine-induced increases in
myocardial contractility may be modified by
such changes in blood pressure or heart
rate.10'X1
Because small doses of dopamine do not
produce major changes in heart rate and systemic blood pressure, the following study was
undertaken to define more thoroughly the
effects of dopamine on left ventricular performance in the intact anesthetized dog.
Methods
Fourteen mongrel dogs weighing 16 to 31 kg
were anesthetized with 40 to 70 ml of chloralose
(1.6%) and urethane (16%) 15 minutes after intramuscular administration of 3.0 mg/kg of morphine sulfate. Additional 5 to 10 ml supplements
of the chloralose and urethane solution were administered during the study in order to maintain
a relatively steady state of anesthesia as judged by
absence of comeal reflexes. Respiration was maintained by a Harvard pump and cuffed endotracheal tube.
The femoral veins were cannulated with polyethylene tubing for intravenous administration of
drugs. Retrograde catheterization of the left ventricle and central aorta was performed through
one femoral and one carotid artery leaving the
other carotid artery intact. The pressure signals
were obtained through 50-cm 7F woven dacron
catheters connected to Statham P23Db transducers by means of 80-cm lengths of polyethylene
280 tubing. The catheters were filled with heparinized isotonic saline; the polyethylene tubing
and transducers were filled with mineral oil. The
amplitude-frequency response of each catheter
system was linear (±5%) to 25 to 30 cycles/
sec as determined by periodic testing with a sine
wave pressure generator. Peak velocity of left
ventricular pressure rise (dp/dt) was obtained
by electronic differentiation of the left ventricular pressure signal using a Philbrick P2
differential operational amplifier and external circuit linear to 28 cycles/sec. Calibration was accomplished by differentiating a sine wave from
a waveform generator.12 Cardiac output (CO)
was determined in duplicate by indicator dilution (left ventricular injection of indocyanine
BLACK, ROLETT
green*) and ventricular volumes by thermodilution (10 dogs).18 Mean aortic pressure (AOm)
was obtained by electronic integration of the
aortic pressure signal, and the left ventricular
end diastolic pressure (LVed) was evaluated
from high gain tracings of left ventricular pressure. Lead n of the electrocardiogram was constantly monitored. All signals were recorded on a
Sanborn 550M photographic recorder either directly or after initial recording on a model 700
TMC magnetic tape recorder.
One to two hours after the induction of anesthesia, control observations were obtained. Dopamine,** diluted with isotonic saline, was then infused intravenously at rates of 1, 2, 3, 4, 5, 8, or
10 /ng/kg/min for 30 minutes utilizing a peristaltic roller pump (Holter, model RDO34). Ah1
hemodynamic measurements were repeated during the last fve minutes of each infusion period.
Once initiated, the rate of dopamine infusion was
increased from one level to the next without interruption. Each dog was studied at one to five
of the selected levels of dopamine infusion. During dopamine stimulation (4 yug/kg/min) one dog
was given, intravenously, 10 mg (0.4 mg/kg) of
propranolol.t a known beta adrenergic blocking
agent, and hemodynamic measurements were repeated within fifteen minutes.
CALCULATIONS
For each period of observation mean values for
heart rate (HR), stroke volume (SV), systolic
ejection period (SEP, seconds/beat), and systolic
ejection rate (SER, SV/SEP) were calculated.
Peripheral vascular resistance (PR, dynes'sec*
cm-5) was estimated by: P R = ( A O m / C O ) x
79.92. Mean left ventricular end diastolic volume
(EDV) was computed from the thermodilution curves by:
EDV =
SV
where t n + 1 and tn represent deflections of the
thermodilution curves from base line on sequential strokes. A mean t n + 1 /t n value was obtained
from 20 to 45 determinations during each period
of observation. Mean left ventricular end systolic
volume (ESV) was calculated by: ESV = EDV
— SV. The ejection fraction (EF, SV/EDV) was
obtained from the thermodilution curves as 1 —
( t n + 1 / t n ) . The left ventricle was assumed to be
spherical in shape, and its mean circumferential
shortening rate (CSR, cm/sec) was calculated
*Cardio-Green; Hynson, Westcott and Dunning,
Inc.
"3-hydroxytyramine • HC1, California Corporation
for Biochemical Research.
tlnderal, Ayerst Laboratories.
Gradation Reseucfa, VoL XIX, July 1966
73
DOPAMINE AND VENTRICULAR PERFORMANCE
from the equation: CSR= 2TT{T1 — r 2 )/SEP,
where i1 and r2 are the respective left ventricular
end diastolic and end systolic radii.
ANALYSIS OF DATA
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Experimental observations at any dose level of
dopamine were compared with the appropriate
control observations. Because of the nonhomogenous animal population the signed rank method
was used to determine statistically significant
(P<0.05) changes from control observations.14
Regression equations relating mean differences
between control and experimental observations
to dopamine infusion rates were calculated by
the method of least squares. Correlation coefficients for dose-response relationships and standard errors of individual mean observations were
calculated from standard formulae of statistical
analysis.
dogs, closely approximate basal values reported for the unanesthetized dog.17 All dogs
had either regular sinus rhythm (10 dogs)
or sinus arrhythmia (4 dogs).
DOPAMINE INFUSIONS
Cardiac Output and H«art Rat*
The directional changes in the mean cardiac output and heart rate values are illustrated in figure 1. All dogs except one
responded to dopamine administration with
increases of systemic blood flow which were
significant at infusion rates of 5, 8, and 10
/Ltg/kg/min. Furthermore, five of eight and
six of seven dogs had elevated cardiac outputs at 3 and 4 /xg/kg/min respectively. The
Results
CONTROL OBSERVATIONS
r-0.233
y-O.I86X+O.I77
p>0.60
"5—I
•-
10
Mean values for control observations of all
dogs are listed in table 1. Minor discrep-
5 6
<^
0
< S -I0J
TABLE 1
1.6
Mean (±SE) Values of Control Observations
Cardiac output (L/min)
Heart rate (beats/min)
Stroke volume (ml)
Ejection fraction
LV end diastolic volume (ml)
LV end systolic volume (ml)
Systolic ejection period
(sec/beat)
Systolic ejection period
(ml/sec)
Circumferential shortening
rate (cm/sec)
LV dp/dt (mm Hg/sec)
Aortic systolic pressure (mm Hg)
Aortic diastolic pressure (mm Hg)
Aortic mean pressure (mm Hg)
LV diastolic pressure (mm Hg)
Peripheral resistance
(dynes • sec • cm- 8 )
2.59 ± 0.34
74 ± 6
34±3
0.35 ± 0.02
96 ± 6
63±4
1.2
I
0.205 ± 0.004
0.975
yO.l55X-0.053
(XO.OOOI
o 0.8
168 ± 1 4
1
12.0
3549
165
100
131
7.9
± 0.8
±340
±6
±4
±5
± 0.4
4826 ± 550
ancies among these figures are accounted for
by the four dogs which did not have ventricular volume determinations. The values for
stroke volume and end diastolic volume are
approximately 503? greater than those values
initially reported for chloralose-anesthetized
dogs but are essentially the same as more
recent values obtained from dogs of comparable size.15'16 The heart rates, although lower than those found usually in anesthetized
Grcularion Reieirch, Vol. XIX, July 1966
1.4
O6
S °4
0.2
MM
1 2
3 4 3
8
DOPAMINE, ;ig/kg/mln
10
FIGURE 1
Mean changes, dopamine over control values, in
cardiac output and heart rate at different levels of
dopamine stimulation. Each point represents the
average of observations made in six to nine dogs. The
calculated least squares regression equations ate
drawn, and r is the coefficient of correlation between
the observed mean values and corresponding dopamine infusion rates. Although no significant change
(P > 0.6) in heart rate was observed, the cardiac output shows a highly significant (P < 0.0001) doserelated rise.
74
BLACK, ROLETT
TABLE 2
Effects of Dopamine on Cardiovascular Pressures and Peripheral Resistance; Mean (±SE) Changes from Control Values
Dopunine, /ig/kg/min —>
l
Aortic systolic
pressure, mm Hg
<
2
3
4
j
8
10
±2.5
<1
±3.9
1.4
±4.5
<1
±3.3
-5.4
±3.4
17
±17.3
28.5
±12.9
Aortic diastolic
pressure, nun Hg
4.4
±3.0
<1
±2.0
0
±3.1
-2.7
±1.8
-6.3
±2.7
-2.8
±6.1
4.8
±9.0
Aortic mean
pressure, mm Hg
-3.6
±1.7
—3.0
±3.3
-1.0
±2.2
-3.6
±3.9
-6.0
±3.6
3.0
±6.0
15
±9.0
LV end diastolic
pressure, nun Hg
<1
<1
<1
<1
<1
<1
<1
Peripheral resistance,
dynes • sec • cm-*
-204
±362
-355
±445
-359
±129
-962
±430
-871
±226
-924
±343
-1281
±240
Downloaded from http://circres.ahajournals.org/ by guest on June 14, 2017
*LV: left ventricular.
tdp/dt = peak velocity of LV pressure rise.
one dog that never responded with an increased blood flow received a maximum
dopamine dose of only 3 /Ag/kg/min. Mean
increments in cardiac output, despite being
statistically significant only at higher infusion rates, were nearly linear over the entire
dose range. Heart rate for most dogs remained relatively constant, and there was no
significant difference from control values at
any level of dopamine infusion.
Stroke and Left Ventricular Volumei
The increase in cardiac output without
change in heart rate represented a significant
elevation of stroke volume at 4, 5, 8, and 10
/^g/kg/min. In addition, stroke volume was
increased in seven of eight dogs at 3 fig/'kg/
min. The progressive rise in stroke volume
was a function of more complete ventricular
emptying from a constant end diastolic volume (fig. 2). The dopamine-induced increments in stroke volume and ventricular emptying resulted in a concomitant decline in
end systolic .volume. The change in stroke
volume as a function of the rise in ventricular
ejection fraction can be examined further in
figure 3. In 36 of 39 paired stroke volume
and ejection fraction determinations obtained
during dopamine infusion, both variables increased simultaneously over their respective
control observations. In only one instance was
the ejection fraction elevated from control
without a simultaneous rise in stroke volume.
Velocity Function! of Ventricular Performance
Figure 4 illustrates the induced changes in
three velocity functions of left ventricular
performance. The systolic ejection rate (fig.
4A) and circumferential shortening rate (fig.
4B) rose to maximum differences of 153
ml/sec and 11.5 cm/sec respectively. These
values represent an increase of almost 200%
of control. Both variables were elevated significantly from control observations by doses
of 4 to 10 /xg/kg/min. The systolic ejection
period, important in the calculation of systolic ejection rate and circumferential shortening rate, was shortened maximally from
control by a mean difference of 0.03 sec at
10 /Ag/kg/min. This was not statistically significant. The dp/dt (fig. 4C) proved to be
an easily monitored indicator of alterations
in left ventricular performance. During dopamine infusion at levels which changed cardiac
performance significantly, an observable rise
in the monitored dp/dt signal occurred within five minutes after initiating a given infusion dose. In 45 paired SV and dp/dt determinations the SV was increased. In 43 of
these, dp/dt increased simultaneously above
control values, regardless of changes of heart
rate, aortic pressure or end diastolic volume.
Mean dp/dt values were elevated significantCircuktion Rejeirdi, VoL XXX, July 1966
DOPAMINE AND VENTRICULAR PERFORMANCE
75
20
16
12
8
E
3°
>
z
<
-4
-8
2 -12
3
r» 0.953
y-l.49X-2.54
P *aooi
-16
-20
4
3
DOPAMINE,
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FIGURE 2
Mean changes in stroke volume and left ventricular volumes secondary to dopamine administration. The stroke volume figures are based on values from aU dogs and on the ventricular
volume figures from 10 of 14. The mean difference from control for end diastolic volume
varied no more than ±3 ml; however, the mean stroke volume change at 10 iig/kg/mhi
represented 156% of control observations.
30
28
26
24
r = 0.776
(wOOOOOl
22
20
18
-4-2
<"•*
0
2
4 6 8 10 12 14 16 18 20 22 24 26 28 30
A IN EFxOO
FIGURE 3
Individual changes in stroke volume (ml) plotted vs.
ejection fraction (%) for all animals. The relatively
high correlation coefficient (r) confirms conclusion that
changes in stroke volume were primarily a function
of changes in ejection fraction rather than in end
diastolic volume.
ly from control at a lower dose level, 3
/tg/kg/min, than any other variable measured.
Pressures and Peripheral .Resistance
Mean changes in pressure values and calGrcnlauoo Reseircb, Vol. XIX. July 1966
culated peripheral resistances are tabulated
in table 2. Only one of the -fourteen dogs
demonstrated a pressor response, and this
accounts for the elevated aortic systolic pressure at 8 /Ag/kg/min. Five of six dogs, however, had elevated aortic systolic pressures
at 10 /ig/kg/min; and of these five, three had
a simultaneous rise in aortic diastolic pressure. Aortic diastolic pressure tended to fall
at 4, 5, and 8 /ig/kg/min but was significantly
lowered from control at 5 /ig/kg/min only.
No significant change in mean aortic pressure or left ventricular end diastolic pressure
was found at any level of dopamine infusion.
Calculated peripheral resistance declined
progressively. Because the mean aortic pressure was never significantly different from
control, the changes in peripheral resistance
were inversely proportional to increases in
systemic blood flow.
Beta Adrenerglc Receptor Blockade
In the one dog given propranolol during
dopamine stimulation, the effect of dopamine
was abolished almost instantaneously as
judged by a prompt fall in the monitored
dp/dt signal. Measurements obtained within
fifteen minutes after propranolol administra-
76
BLACK, ROLETT
tion revealed a return to control values
(table 3).
dopamine-induced changes in left ventricular
performance have not been characterized
previously.18 The presently described cardiac
stimulatory properties and previously noted
peripheral vascular effects of dopamine suggest that it may be a useful agent in the
clinical management of congestive heart failure and nonhemorrhagic shock.1-6> 18 At-
Ditcuision
In the present study, dopamine has proved
to be a potent stimulant of the canine myocardium. Although clinical benefit has been
demonstrated in congestive heart failure,
175
3600
13
ISO
3900
14 B
r = 0.974
y=l5.9X-l3.7
p<O.OOOI
T
r>0.985
yl.23X-l .17
p<0.000l
12
II
1
1
3300
4
;
3000
/i
S 10
2700
]/
1/
S 9
IOO
I
UJ
/1
7
z
<
<
a
4
3
25
2
8
10
i
i
X
a.
2400
2100
1800
z
1500
V
1J
UJ
\
z
5
I
if
/
1 /
1 /
c
UJ
SO
/
T
1
1
to o
-4-1
in
E
E
_•
^
/
« e•
UJ
I
<n
+j 1200
EAI
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/ i
125
0 1 2 3 4 3
r = 0.997
y=383X-546
p<0.000l
A
• /!
"ft
2
900
600
300
/ l
0
0 12 3 4 5
8
10
0
12 3 4 5
8
10
DOPAMINE, pg/ kg/ min
FIGURE 4
Mean (±SE) differences from control in A: systolic ejection rate; B: circumferential shortening
rate; and C: dp/dt induced by dopamine. Although individual bars showing standard error
exhibit overlap, each of the three variables increase almost linearly with increasing dopamine
infusion rates over the range of 1 to 10 itg/kg/min. This dose-dependent relationship Is
characterized by a highly significant r value for each variable instance, although the individual
mean values were not significantly elevated at infusion rates below 3 to 4 ng/kg/min.
TABLE 3
Effects of Beta Adrenergic Blockade on Action of Dopamine
Stroke
vofrime
Ejection
fraction
ml
Hurt rate
beati/min
Control
25
67
0.31
Dopamine,
4 jig/kg/min
41
71
Propranolol,
0.4 mgAg
28
56
dp/dt*
nun Hg/iec
Syitolk Circumferential
ejoction
ihortening
rate
rate
cm/iec
ml/sec
3154
125
9.9
0.49
5182
210
17.5
0.35
2659
120
9.9
*dp/dt = peak velocity of LV pressure rise.
Circulation Research. Vol. XDC July 1966
DOPAMINE AND VENTRICULAR PERFORMANCE
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tempts to elucidate the adrenergic mechanisms by which dopamine produces its effects
have been complicated by a wide variation
in administered dopamine doses.4'7i 19 The
doses employed in the present study are
those which have been shown previously to
increase stroke volume without a major
change in heart rate or mean systemic blood
pressure in the dog and which cover the
range of dopamine infusion rates employed
in clinical studies.6'8 The pressor response
associated with larger doses of dopamine
could itself be a prominent factor in modifying left ventricular performance, and such
doses were therefore avoided.20'21
In addition to direct catecholamine stimulation, regulation of myocardial performance
can be achieved by changes in end diastolic
ventricular volume (Frank-Starling principle), heart rate (frequency-dependent modification of contractility), and resistance to
systolic ejection (afterload*) ,22 In the present study none of these mechanisms can be
implicated because end diastolic volume and
pressure (preload), heart rate, and aortic systolic pressure were relatively uniform over
the dose range examined. The rise in stroke
volume represents an increased fraction of
ventricular volume emptied rather than an
enlargement of end diastolic volume.
In these respects dopamine differs from
two of the most commonly used catecholamines: norepinephrine and isoproterenol. The
myocardial stimulatory properties of norepinephrine in the intact subject are countered by
a potent alpha adrenergic action which causes
a pronounced pressor response, thereby inducing a reflex bradycardia and afterloading
the ventricle. As a consequence the end diastolic volume tends to increase, and any
augmentation of stroke volume may be a reflection of this increase rather than of a
change in the ejection fraction.10 Isoproterenol, often considered the prototype of beta
adrenergic catecholamines, induces a tachy•Variabons in afterload, under the present experimental conditions, are detectable primarily by
changes in aortic pressure during systole.
Circulation RoMrch, VoL XIX, July 1966
77
cardia, reduces end diastolic volume, and
lowers the resistance to ventricular ejection
through active peripheral vasodilation. Although isoproterenol causes more complete
ventricular emptying, stroke volume increments are small and variable because of the
decreased end diastolic volume.10' n
The calculated ejection variables (stroke
volume, systolic ejection rate, and circumferential shortening distance and rate) are
functions of ventricular end diastolic volume
and myocardial fiber shortening distance and
rate. Since dopamine produced no significant
change in the end diastolic volume, the increases in these four variables of systolic
ejection reflect enhanced myocardial fiber
shortening distance and rate and can be explained by a direct myocardial action.
The peak velocity of left ventricular pressure rise occurs during isovolumic contraction
and may be altered by variations in heart
rate, aortic blood pressure, and ventricular
end diastolic pressure.28'24 Changes "in dp/
dt observed in the present study, however,
cannot be explained by alteration of any of
these variables. If the surface area of the
left ventricle is considered to be relatively
constant during isovolumic contraction, then
the peak velocity of left ventricular pressure rise is proportional to the peak velocity
of left ventricular force generation. Although
instantaneous force-velocity relationships and
maximal left ventricular force generation
could not be evaluated with this experimental
model, the peak isovolumic contraction force
(Fp) could be estimated from Fp =
AOdp • Aed, where AOdp is the aortic diastolic pressure and Aed is the end diastolic area
of the left ventricular chamber. Because the
end diastolic volume was never significantly
altered, the calculated end diastolic area can
be assumed to have been essentially constant.
The aortic diastolic pressure was ' feither
slightly decreased or unchanged, suggesting
a relatively constant Fp despite dopamine
administration. Nevertheless, the peak velocity of force generation (as judged from
dp/dt) during the same period was greatly
enhanced. This finding is essentially similar
BLACK, ROLETT
78
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to those catecholamine-induced alterations in
isolated papillary muscle and isometric ventricle preparations in which the velocity of
pressure rise divided by the integrated systolic isometric tension proved useful as an
index of myocardial contractility.25 Thus, the
dopamine-induced alterations in dp/dt appear to represent a catecholamine-mediated
increase in myocardial contractility which
was otherwise unmodified by changes in
heart rate, end diastolic volume, or aortic
blood pressure over the dose range employed.
The biochemical and pharmacological
mechanisms responsible for the observed
effects of dopamine have yet to be elucidated,
but fall potentially into three classes: direct
myocardial beta adrenergic stimulation, release of norepinephrine from adrenergic nerve
endings, or in vivo hydroxylation to norepinephrine. As illustrated by one animal of the
present study, a drug (propranolol) which
blocks beta adrenergic receptors completely
abolished dopamine-induced alterations in
cardiac performance. Furthermore, recent
evidence from this laboratory has demonstrated a complete lack of inotropic response
to dopamine infusions of 5, 8, and 10
/u.g/kg/min following propranolol-induced
beta adrenergic blockade.26 When these and
previous studies are considered together there
seems to be little question that these myocardial responses to dopamine were mediated
through beta adrenergic receptors.4 Very little is known about the relationship between
dopamine and norepinephrine release, and an
earlier investigation is difficult to interpret because extremely large doses were used.18 The
rapid onset of dopamine-induced changes
might be interpreted as evidence against the
in vivo conversion of dopamine to norepinephrine. Levitt et al., however, have recently
presented data indicating that hydroxylation
of dopamine can proceed very rapidly.27
Utilizing their data, one can estimate a local
norepinephrine production of 2 /u.g/min for a
100-g left ventricle under our experimental
conditions. The possibility that norepinephrine
is formed or released does not, however,
fully explain the lack of chronotropy in the
absence of important changes in systemic
pressure, the failure to elevate plasma nonesterified fatty acids,28 and the peripheral
hemodynamic effects found with dopamine.2"4
Studying rabbit atria, Lee and Yoo have obtained additional evidence that dopamine has
a direct myocardial stimulatory effect that is
independent of norepinephrine release.29
Acknowledgment
The authors acknowledge gratefully the technical
assistance of Mr. H. Dieter Ambos.
References
1.
MCNAY,
J. L.,
MCDONALD,
R. H., JR.,
AND
GOLDBERG, L. I.: Direct renal vasodilatation
produced by dopamine in the dog. Circulation
Res. 16: 510, 1965.
2. EBLE, J. N.: A proposed mechanism for the depressor effect of dopamine in the anesthetized
dog. J. Pharmacol. Exptl. Therap. 145: 64,
1964.^
3.
ALL WOOD, M. J., AND GINSBURC, J.: Peripheral
vascular and other effects of dopamine infusions in man. Clin. Sci. 27: 271, 1964.
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MCDONALD, R. H., JR., AND GOLDBERG, L. I.:
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Therap. 140: 60, 1963.
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MCNAY,
J.
L.,
MCDONALD,
R.
H., JR.,
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GOLDBERC, L. I.: Natriuretic effect of dopamine infusion in the dog. Federation Proc.
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6. MCDONALD, R. H., JR., GOLDBERG, L. I., MCNAY,
J. L., AND TUTTLE, E. P., JR.: Effects of
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excretion, glomerular filtration rate, and renal
plasma flow. J. Clin. Invest. 43: 1116, 1964.
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HOLMES, J. C ,
AND FOWLER,
N. O.:
Direct
cardiac effects of dopamine. Circulation Res.
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8. HORWTTZ, D., Fox, S. M., Ill, AND GOLDBERG,
L. I.: Effects of dopamine in man. Circulation Res. 10: 237, 1962.
9. AHLQUIST, R. P.: A study of the adrenotropic
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Dopamine-Induced Alterations in Left Ventricular Performance
WILLIAM L. BLACK and ELLIS L. ROLETT
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Circ Res. 1966;19:71-79
doi: 10.1161/01.RES.19.1.71
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