Docsity
Docsity

Prepare for your exams
Prepare for your exams

Study with the several resources on Docsity


Earn points to download
Earn points to download

Earn points by helping other students or get them with a premium plan


Guidelines and tips
Guidelines and tips

Effects of Dopamine on Pulmonary and Systemic Vascular Resistance and Stroke Volume, Exams of Cardiology

An experimental study investigating the effects of dopamine infusions on pulmonary and systemic vascular resistance, mean pulmonary and aortic pressures, stroke volume, and heart rate. The study found significant changes in mean pulmonary and aortic pressures, left atrial pressure, mean aortic flow, and stroke volume at various dopamine doses.

What you will learn

  • What is the relationship between dopamine dosage and stroke volume?
  • What are the effects of dopamine on pulmonary and systemic vascular resistance?
  • How does dopamine influence mean pulmonary and aortic pressures?

Typology: Exams

2021/2022

Uploaded on 09/27/2022

elmut
elmut 🇺🇸

4.6

(16)

285 documents

1 / 9

Toggle sidebar

This page cannot be seen from the preview

Don't miss anything!

bg1
Br.
J.
Pharmac.
(1969),
37,
618-626.
The
pulmonary
and
systemic
circulatory
response
to
dopamine
infusion
D.
C.
HARRISON,
SUELLEN
PIRAGES,
SHERILYN
C.
ROBISON
AND
B.
U.
WINTROUB
Cardiology
Division,
Stanford
Uniiversity
School
of
Medicine,
Palo
Alto,
California
94305
1.
The
pulmonary
and
systemic
circulatory
responses
to
dopamine
infused
at
8,
15,
25
and
30
,g/kg
per
min
were
studied
in
eight
mongrel
dogs.
2.
Mean
pulmonary
artery
pressure,
mean
left
atrial
pressure,
mean
aortic
pressure,
mean
aortic
flow
and
the
electrocardiogram
were
monitored
in
open-
chest
preparations.
Pulmonary
vascular
resistance,
systemic
vascular
resistance
and
stroke
volume
were
calculated.
3.
Significant
increases
in
mean
pulmonary
and
aortic
pressures
were
noted
at
dopamine
infusions
of
25
and
30
,ug/kg
per
min.
The
left
atrial
pressure
fell
significantly
at
15
pg/kg
per
min
and
rose
significantly
at
30
,g/kg
per
min.
Mean
aortic
flow
increased
at
all
four
doses,
while
heart
rate
showed
no
change.
Pulmonary
vascular
resistance
did
not
change
significantly
at
any
dose
level,
but
systemic
vascular
resistance
fell
slightly
at
8
and
15
jug/kg
per
min
and
rose
significantly
at
30
pg/kg
per
min.
Stroke
volume
was
significantly
elevated
at
infusions
of
25
and
30
jig/kg
per
min.
4.
The
systemic
circulatory
response
to
dopamine
is
similar
to
that
described
by
previous
investigators.
5.
The
increased
pulmonary
pressures
without
change
in
resistance
suggest
a
dopamine-induced
increase
in
smooth
muscle
tension
in
the
pulmonary
vasculature.
Dopamine
(3,4
dihydroxyphenylethylamine)
is
a
naturally
occurring
catecholamine
and
is
the
direct
biochemical
precursor
to
norepinephrine
(Blaschko,
1957).
Investi-
gators
have
recently
described
the
cardiovascular
response
to
this
agent
in
animals
and
in
man
(McDonald
&
Goldberg,
1963;
Black
&
Rolett,
1966,
1968).
Vasocon-
striction
has
been
noted
in
the
femoral
vascular
bed
(McDonald
&
Goldiberg,
1963).
At
low
doses,
however,
a
slight
but
significant
drop
in
systemic
vascular
resistance
has
been
reported
without
significant
change
in
heart
rate
or
arterial
pressure
(McDonald
&
Goldberg,
1963;
Black
&
Rolett,
1966,
1968).
In
addition,
animal
studies
demonstrate
direct
cardiac
stimulation
through
a
beta-adrenoceptor
mechanism
(Black
&
Rolett,
1966).
Studies
in
both
dogs
and
man
offer
evidence
that
dopamine
is
a
selective
renal
and
mesenteric
vasodilator
(McNay,
McDonald
&
Goldberg,
1965;
McDonald,
Goldberg,
McNay
&
Tuttle,
1964
;
Goldberg,
McDonald
&
Zimmerman,
1963).
These
properties
make
dopamine
an
attractive
agent
for
the
pf3
pf4
pf5
pf8
pf9

Partial preview of the text

Download Effects of Dopamine on Pulmonary and Systemic Vascular Resistance and Stroke Volume and more Exams Cardiology in PDF only on Docsity!

Br. J. Pharmac. (1969), 37, 618-626.

The pulmonary and systemic circulatory

response to dopamine infusion

D. C. HARRISON, SUELLEN PIRAGES, SHERILYN C. ROBISON AND

B. U. WINTROUB

Cardiology Division, Stanford Uniiversity School of Medicine, Palo Alto, (^) California 94305

  1. The pulmonary and systemic circulatory responses to dopamine infused at 8, 15, 25 and 30 ,g/kg per (^) min were (^) studied in (^) eight mongrel dogs.
  2. Mean pulmonary artery pressure, mean left atrial (^) pressure, mean (^) aortic pressure, mean aortic flow and the electrocardiogram were monitored in open- chest preparations. Pulmonary vascular resistance, systemic vascular resistance and stroke volume were calculated.
  3. (^) Significant increases in mean pulmonary and aortic pressures were noted at

dopamine infusions of 25 and 30 ,ug/kg per min. The left atrial pressure fell

significantly at 15 pg/kg per min and rose significantly at 30 ,g/kg per min.

Mean aortic flow increased at all four doses, while (^) heart rate showed no change.

Pulmonary vascular resistance did not change significantly at any dose level,

but systemic vascular resistance fell slightly at 8 and 15 jug/kg per min and

rose significantly at 30 pg/kg per min. Stroke volume was significantly elevated

at infusions of 25 and (^30) jig/kg per min.

  1. The systemic circulatory response to dopamine is similar to that described by previous investigators.
  2. The increased (^) pulmonary pressures without change in resistance suggest a dopamine-induced (^) increase in smooth muscle tension in the pulmonary vasculature.

Dopamine (3,4 dihydroxyphenylethylamine) is a naturally occurring catecholamine and is the direct biochemical precursor to norepinephrine (^) (Blaschko, 1957). Investi- gators have recently described the cardiovascular response to this agent in animals and in man (^) (McDonald & Goldberg, 1963; Black & Rolett, 1966, 1968). Vasocon- striction has been (^) noted in the femoral vascular bed (McDonald & Goldiberg, 1963). At low doses, however, a slight but significant drop in systemic vascular (^) resistance has been reported without significant change in heart rate or arterial pressure

(McDonald & Goldberg, 1963; Black & Rolett, 1966, 1968). In addition, animal

studies demonstrate direct cardiac stimulation through (^) a beta-adrenoceptor mechanism (Black & Rolett, 1966). Studies in (^) both dogs and man offer evidence that dopamine is a selective renal and mesenteric vasodilator (McNay, McDonald &

Goldberg, 1965; McDonald, Goldberg, McNay & Tuttle, 1964 ; Goldberg, McDonald

& (^) Zimmerman, 1963). These properties make dopamine an attractive agent for the

Dopamine on pulmonary circulation

treatment of patients with acute cardiovascular failure and shock. Two (^) reports

describing the response to dopamine treatment of patients in congestive heart failure

(Goldberg et al., 1963) and shock (MacConnell, McNay, Meyer & Goldberg, 1966)

have been published. Although dopamine has been considered for clinical use in

patients with^ circulatory failure, no^ studies^ have^ reported the effect^ of^ dopamine on

the altered pulmonary vascular responsiveness and hypoxia which often accompany

this failure. It is the purpose of this report to describe the haemodynamic response

of the pulmonary circulation to dopamine infusion at four different doses and, at the

same time, to compare the pulmonary vascular response to changes induced in the

systemic circulation.

Methods

Eight mongrel dogs (15-22 kg) were anaesthetized with a mixture of alpha-

chloralose and urethane, 65 mg/kg, and 400 mg/kg, respectively. Supplemental

anaesthetic was administered when corneal reflexes were noted. The chest was

opened in the mid-line and the animals (^) were prepared to record changes in the

circulatory system. Pulmonary artery pressure was monitored through a No. 7

Birdseye catheter positioned in the main pulmonary artery via the right external

jugular vein. Left atrial pressures were measured by a flange-tipped PE 260

catheter positioned through a stab wound in the left atrial appendage and secured

with a purse-string suture. Central aortic pressure was monitored through a PE 260 fluid-filled catheter placed in the ascending aorta via the right femoral artery. The

right femoral vein was cannulated with a PE 260 catheter for drug infusion. All

fluid-filled catheters were flushed frequently, and/or kept patent by means of a

heparinized (4 U.S.P. units/ml.) saline (^) drip. All pressures were measured with Statham P23Db pressure transducers. Mean (^) pressures were electrically determined by integration of the phasic pressure tracings.

Mean aortic blood flow was measured with a gated sine wave electromagnetic

flow (^) meter (Biotronex, Silver Spring, Md.) placed around the ascending aorta distal to the (^) coronary arteries. Each aortic flow probe was calibrated ,by comparison

with multiple cardiac outputs determined by standard indicator dilution techniques.

Aortic flow was used as (^) cardiac output for all of these studies, and aortic flow was assumed to equal pulmonary (^) blood flow. (^) The electrocardiogram was followed by means of subcutaneous electrodes placed in the (^) appropriate extremity. All record- ings were made on a multi-channel Beckman Model R (^) direct-writing oscillograph. The animals were intubated with a cuffed endotracheal tube and ventilated with a (^) Harvard respirator. Arterial blood samples were analysed frequently utilizing a

Model AME-1 Astrup micro-apparatus. The pH and PO2 were measured S min

before any intervention and before killing each (^) animal. In order to determine pulmonary and systemic responses to dopamine, the drug was infused (^) for 10 min periods at doses of 8, 15, 25 and 30 pLg/kg per min. These doses were (^) administered in randomized fashion from animal to animal, and all infusions were delivered with a variable-speed (^) Harvard apparatus infusion pump. After control measurements, each infusion was begun and data recorded (^) throughout the 10 min infusion period. Because the animals reached steady state within (^5) min,

5 min data were chosen as peak response data. At least 15 min were allowed

between infusions for each animal (^) to return to control.

Dopamine on pulmonary circulation

Left atrial pressure

Mean left atrial (^) pressure fell (^) slightly but (^) significantly in (^) response to (^) dopamine infused at 15 jig/kg per min and rose (^) significantly when infused at (^30) ,g/kg per

min, but no significant change occurred at 8 or 25 ptg/kg per min (Talble 1). The

15 pg/kg per min response differed significantly from the 30 ,g/kg per min response

(P<O-05).

TABLE 1. Haemodynamic response to dopamine Dose: (^8) jiglkg per min

PA mean pressure mmHg LA mean pressure mmHg Ao mean pressure mmHg PVR (^) mmHg/l. per min SVR mmHgf1. per min Flow ./mmin SV ml./beat Heart rate

PA (^) mean pressure mmHg LA mean pressure mmHg Ao mean pressure mmHg PVR mmHg/l. per min SVR mmHg/l. per min Flow b.!min SV (^) m]./beat Heart rate

PA mean pressure mmHg LA mean pressure mmHg Ao mean pressure mmHg PVR mmHg/l. per min SVR mmHg/1. per min Flow (^) l,bmin SV ml./beat Heart rate

PA mean pressure mmHg LA mean pressure mmHg Ao (^) mean pressure mmHg PVR mmHg1l. per min SVR (^) mmHg!l. per min

Flow b, min

SV (^) ml.bbeat Heart rate

Control 17-2± 1- 7-54± 109-6±7- 6-7±0- 70-7±6- 1-6±0- 9-3±1- 172-4±6- Dose: 17-64±0- 7-1 1 0 108-5±4- 6-5±0- 66-9±7- 1-8±0- 9.6±1^1 180.9±5- Dose: 17.3±0- 7-4±1- 105-4±5- 6-5±0- 70-0±8- 1.7+0. 9-5± 1- 174-3±7. Dose: 16-9±0- 8-2±0- 98-6±6- 5-8±0- 63-4±5- 1-6±0- 9-5±0- 165-8±9-

Absolute change Significance 0-740-4 NS -0-4±0-4 NS -5-5±3-1 NS -0-4±0-2 NS -9-1±3-1 <0- 0-23±0-07 < 0- 0-4±0-5 NS 13-8±7-2 NS

15 pggkg per min

0-5±04 NS -1-0±0-3 <^ 0- 2-7±7-3 NS -0-3±0-3 NS -6-9±3-1 NS 0-28±0-07 < 0- 0-8±0-5 NS 12-8±6-0 NS (^25) ,gg'kg per min 2-6±1-0 <0- -0-0±0-7 NS 22-6±8-1 < 0- -0-5±0-3 (^) NS -3-3±10-0 NS 0-51±0-12 < 0- 2-4±0-7 <0- 9-5±8-9 NS (^30) jig/kg per min 3-1±0-7 <0- 1-8±0-8 <0- 47-0±9-8 < 0- -0-2±0-2 NS 27-3±11-2 <0- 0-23±0-10 < 0- 3-7±1-4 <0- -5-8±6-5 (^) NS

O% change^ Significance

5-0±2-7 NS -3.4±6-6 NS 4-2±2-9 NS -5-6±3-0 NS -12-6±4-0 <^ 0- 15-8±6-1 < 0- 6-6±6-2 NS 9-2±5-6 NS

2-3±2-1 NS -14.714-2 < (^0 ) 3-1±6.7 NS 4-0±4-6 NS -12-0±4-8 < 0- 17.8±4-4 < 0- 11-2±6-1 NS 7-4±3-5 NS

14-3±5-1 < 0- 2-0±10-4 NS 21.8±8-3 <0- 9-4±5-0 NS 2-0±11-5 NS 36-7+11-7 (^) <0- 28-1±9-5 <0- 6-3±5-0 NS

17-8±3- 21-5±9- 48-7± 12- -4-5±4- 41-4±16- 12-0±5- 42-4±18- -2-9±3-

<0- NS <0- NS <0- <0- NS NS Responses to dopamine at 5 min for all infusions. PA mean, Mean pulmonary artery pressure: LA (^) mean, mean left atrial (^) pressure; Ao (^) mean, mean aortic pressure; PVR, pulmonary vascular (^) resistance; SVR, systemic vascular (^) resistance; AoF, mean aortic flow; SV, stroke volume; HR, heart rate.

621

D. C. Harrison (^) and others

Aortic pressure

Aortic pressure did not change significantly with infusion of the two low (^) doses;

however, a significant pressor response was induced with infusion of 25 and 30 gg/

kg per min (Fig. 2, Table 1). It was impossilble to separate the responses to 8 and 15 ,g/kg per min. Pressor responses induced by (^) the high doses (25 and (^30) jag/kg

per min) were significantly greater than the low dose response. In addition, the

increase in pressure at 30 ,ug/kg per min was significantly greater than the increase

at 25 ug/kg per min (P<001).

Mean aortic flow

Significant increases in cardiac output were demonstrated at all doses (Talble 1).

No significant difference was demonstrated between the four doses of dopamine

administered.

P<0-0I 60

50 -

40 -

..I 1-^ 0- , 30.

c^

° 20 c 660 X

10

-*

P<0.

NS

NS

I I I 8 15 25

Dopamine (1&g/kg per min)

30

FIG. 2. Mean (^) change (%A) and standard errors of the (^) change in aortic (^) pressure produced by various concentrations of (^) dopamine are shown. No (^) significant changes were noted at 8 and (^15) ,ug/kg per min, whereas (^) significant increases were noted at 25 and 30 (^) jg/kg per min dopamine infusion. The increase^ at^30 pg/kg per min was (^) significantly greater than that at 25 p,g/kg per min.

D. C. Harrison and others

Systemic vascular resistance

A significant fall in systemic vascular resistance at the two low doses^ was^ noted

(Fig. 3). There was no significant change at 25 ug/kg per min, but peripheral

resistance rose significantly by 4144+16.2% at 30 ,ug/kg per min (Talble 1). The

responses at 8, 15 and 25 ug/kg per min could not be separated statistically; how-

ever, the increase in resistance demonstrated at 30 (^) ,ug/kg per min was significantly

greater than the response observed during the first three doses (P<0-01).

Stroke volume

Low dose infusion of dopamine (8 and 15^ jug/kg^ per^ min) failed^ to^ increase^ the

stroke volume significantly; however,^ infusions^ at 25 and 30^ ,ug/kg^ per^ min pro- duced statistically^ significant^ increases (Table^ 1).^ The response at higher^ doses^ was significantly greater than the response at low doses (P<005), but again it was

impossible to separate the changes at 8 ,g/kg per min from 15 jg/kg per min or

(^25) Ag/kg per min from 30 (^) ,ug/kg per min.

Blood gases

Average blood gases before dopamine infusion were pH=7.42 and p02=98.

At the end of the experiments, average blood gases were pH =^ 7.39^ and^ P02^ =^ 95.

These values did not differ significantly.

Discussion

The pulmonary and systemic circulatory responses to dopamine infusion were

studied in this investigation. The pulmonary artery pressure rose with all four of

the dopamine doses administered. Only at the higher doses (25 and 30 (^) ,gg/kg per

min), however, was evidence of a statistically significant pressor response noted;

the pressor responses at 25 and 30 ,g/kg per min were of comparable magnitudes.

At no time were the increased pulmonary pressures accompanied by significant

changes in pulmonary vascular resistance (Table 1).^ Therefore,^ since^ vessel caliibre

remained unchanged while^ pressure^ rose,^ dopamine^ must act^ by^ increasing^ the^ level

of smooth muscle^ tension^ in^ the^ blood^ vessels of^ the^ lung.^ The^ very^ slight^ tendency

toward decreased pulmonary vascular resistance which occurred suggests that the

action of dopamine on vessel calibre in the pulmonary vascular^ beds during increased

cardiac output is that of slight dilatation only. This would^ be^ comparable with^ its

effect on the peripheral circulation, where a^ small^ reduction^ in^ systemic resistance

generally occurs.

Increase in aortic pressure in response to larger doses^ of^ dopamine-25 and^30 jig/kg per min^ (Table^1 and^ Fig.^ 2)-are^ in^ accord with^ findings^ of^ other^ investi-

gators (McDonald &^ Goldberg, 1963).

Heart rate^ did^ not^ change significantly^ at^ any^ level of^ dopamine^ infusion.^ How-

ever, the^ tendency toward^ an^ increase^ at^ the three low doses and^ a^ decrease^ at

(^30) pg/kg per min was noted. This decrease in heart rate^ at^ the^ highest administered dose was (^) probably due to the activation of baroreceptors and other pressor receptor mechanisms by the increase in^ peripheral pressure. The systemic vascular^ response to^ dopamine was^ dose-dependent; a^ slight^ but significant decrease in^ resistance^ occurred^ at^ the^ two^ low doses^ (8^ and 15^ jig/kg

Dopamine on pulmonary circulation

per min) and^ a^ very large, significant vasoconstriction^ at^ the^ high,^ ,ug/kg^30 per^ min.

Similar dose-related responses of the systemic circulation have been reported

(McDonald &^ Goldberg,^ 1963;^ Black &^ Rolett,^ 1968).^ The^25 ,g/kg^ per^ min

response, an^ intermediate^ response, may represent a^ balanced stimulation^ of^ peri.

pheral alpha and^ beta-adrenoceptors. Thus,^ low^ doses of^ dopamine^ would appear

to stimulate the beta-adrenoceptor, thereby causing a^ fall in^ resistance.^ It^ is also

possible, however,^ that^ dopamine has^ a^ slight direct^ vasodilatory^ effect,^ independent

of beta-adrenoceptor stimulation.

Although mean^ aortic flow^ rose^ significantly with^ all levels of^ infusion,^ statistically

significant incremental increases^ in^ output with^ increasing^ doses^ of^ dopamine could

not be demonstrated. It appears that the output increases as the^ dose is raised

from 8 to 25 ,ug/kg per min and then increases to a lesser degree at^ the^30 ,pg/kg per

min level.^ The smaller increase in^ output^ at^30 ,g/kg^ per^ min^ is^ correlated^ with a

large increase in^ peripheral pressure and^ resistance;^ it^ may^ represent^ inadequate

response to^ increasing afterload^ secondary to^ direct^ peripheral^ vasoconstriction

caused by high doses of dopamine. However, it may also be due to the reflex

slowing of^ the^ heart^ rate, since^ the stroke volume did^ change^ significantly.^ The

latter explanation seems more likely.

The significant decrease in left atrial pressure when dopamine was infused at

15 g/kgg1 per min and slight increasein response to the 30 ,ug/kg per^ min^ dose did

not produce atrial pressures outside the normal physiological range.^ The fall at

15 j&g/kg per min is explained by an increase in cardiac output without a significant

change in^ afterload.^ These^ findings would^ imply an increase in^ cardiac^ contractility,

which has been observed tby others (Black & Rolett, 1966). A similar increase in

cardiac output, accompanied by increases in peripheral pressure and systemic

resistance, accounted for the rise at 30,ug/kg per min.

The increase in stroke volume was significant at only 25 and 30 jig/kg^ per^ min,

but at all doses the trend was toward increased stroke volume, the increases^ appear-

ing to^ be^ dose-related^ (Table 1). Since^ the cardiac^ output^ produced^ by 30jug/kg

per min was less than that^ produced by 25 ,ug/kg per min,^ the maintenance^ of stroke

volume may be explained by the decreased heart rate which occurred as^ a result^ of

the large pressor response.

The results of this study confirm previous reports on systemic response to dopa-

mine (McDonald &Goldberg, 1963 ; Black & Rolett, 1966, 1968), as well as demon-

strate that dopamine causes a pressor response in the pulmonary artery at high doses

but creates no significant change in pulmonary resistance. However, these results

do suggest that dopamine increases smooth muscle^ tension in^ the^ pulmonary^ vascu-

lature. Dopamine-induced increases^ in^ pulmonary pressures would^ then^ be

secondary to increased cardiac output and increased wall tension.

Despite the^ difficulties inherent in^ applying an^ open-chested,^ anaesthetized^ animal

model to the clinical situation, it seems that these findings may have^ clinical rele-

vance. The dopamine-induced elevation of^ pulmonary pressures in^ the^ clinical

setting of^ pulmonary hypertension may be^ detrimental^ to the^ patient^ with a com-

promised right heart.^ It^ is^ even^ possible that an^ increase^ in smooth^ muscle^ tension

without accompanying increase in cardiac output might result in undesirable^ vaso-

constriction in the patient with pulmonary hypertension or congestive^ heart^ failure.

These studies were (^) supported in (^) part by N.I.H. Grants Nos. HE-09058, HE-5709 and HE-05866, and a grant from the American Heart Association, No. 67-708.