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Transcript
Systemic Blood Pressure Response to Changes
in Right Ventricular Function
By Alan L. Pinkerson, M.D., and Peter A. Kot, M.D.
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• Previous investigations have described
areas in the circulation which, when appropriately stimulated, induce changes in total peripheral vascular resistance.1"3 Such receptor
areas have been demonstrated in vessels of the
lesser and greater circulation and three of the
heart chambers. Whether similar vascular
reflexes can originate in the right ventricle
has been questioned.4 Although increasing
pressure in the vascularly isolated left ventricle results in a decrease in total peripheral
vascular resistance,4'" a similar response is
not elicited from the isolated right ventricle.4
A reflex increase in pulmonary blood flow
without changes in systemic vascular resistance has been demonstrated following elevation of the systolic pressure in the intact right
ventricle.0
The present report describes a pressor
reflex which originates in the intact functioning right ventricle. An increase in systemic
blood pressure and vascular resistance is
shown after a rise in right ventricular systolic
pressure.
Experiments were performed in open-chest
anesthetized dogs. The systemic vascular
response was measured 1) with the circulation
intact, 2) during total perfusion of the systemic circulation with a mechanical pump,
3) after the administration of atropine, and
4) following bilateral cervical vagotomy.
positive pressure ventilation maintained with a
Starling Ideal pump. A cotton tie was passed
around the main pulmonary artery. Intravascular
pressures were measured in the inferior vena cava,
right atrium, right ventricle, pulmonary artery,
and abdominal aorta via polyethylene catheters
and recorded on a direct-writing, multichannel
oscillograph.
Right ventricular systolic pressure was increased by gradual constriction of the main pulmonary artery at its bifurcation or at the level
of the pulmonic valve by gradual tightening of
the cotton ligature.
After initial studies in dogs with an intact circulation, a mechanical pump, which could be preset to deliver a constant stroke volume at a fixed
rate, was connected between the left atrium and
descending thoracic aorta7 (fig. 1). When blood
draining from the left atrium into the reservoir
was pumped through the T tube into the aorta,
aortic diastolic pressure remained higher than left
ventricular systolic pressure. The aortic valves
therefore remained closed and the systemic cir-
Methods
Fifteen mongrel dogs weighing 10 to 20 kg
were anesthetized with sodium pentobarbital (25
mg/kg). A left thoracotomy was performed under
FIGURE 1
From the Departments of Physiology and Medicine,
Georgetown University School of Medicine, Washington, D. C.
Supported in part by Grant H-1904 from the National Heart Institute, U. S. Public Health Service.
Received for publication November 4, 1963.
Circulation Research, Volume XIV, May 1964
Schematic diagram of the technique used to bypass
the left ventricle. Tygon tube is tied into the left
atrium and the pulmonary venous return drained out
of the atrium into the open reservoir. Blood is pumped
into the aorta through the T tube. Arrows show the
direction of blood flow.
461
PINKERSON, KOT
462
culation, including the coronary arteries, was perfused only by blood from the pump. Complete
diversion of blood from the left atrium to the
pump reservoir was determined by inspection of
the aortic pulse contour as previously described.7
The effect of gradual and total occlusion of
the main pulmonary artery was then recorded
with the vagi intact, following the administration
of atropine (0.4 mg/kg) and after bilateral cervical vagotomy.
Results
In each instance as the main pulmonary
artery was gradually constricted, right ventricular systolic pressure progessively increased
above base line values. Right ventricular end
diastolic, right atrial, and venous pressures
remained constant until the main pulmonary
artery was markedly constricted (figs. 2 and
3). Mean pulmonary artery pressure showed
no consistent changes during the early stages
of stenosis. When right ventricular end diastolic pressure began to rise, pulmonary
artery pressure and the pump reservoir level
40
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20
PA
0
40
20
RA
0
40
20
Vtn
0
80
RV
wmM
40
—.200
100
Ao
3
mm Hg
FIGURE 2
Effects of increasing degrees of main pulmonary artery constriction in dogs with an intact circulation. PPA = pulmonary artery pressure. PRi = right atrial pressure. P r E V = venous pressure.
PRV = right ventricular pressure. P40 = aortic pressure. Straight lines before the instantaneous
pressure recordings indicate mean pressures. Panel C represents the immediate preconstriction
control. Panels 1, 2, and 3 show responses to graded increases in main pulmonary artery constriction. Fine lines represent 1-sec intervals.
Circulation Research, Volume XIV, May 1964
463
PRESSOR REFLEX FROM RIGHT VENTRICLE
POST VAGOTOMY
PRE VAGOTOMY
so
P RV
40
-i 200
«••
r
100
P AO
H
0
L
mm Hg
I
c
I
FIGURE 3
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Effects of increasing degrees of main pulmonary artery stenosis in dogs with left ventricle bypassed by an extracorporeal pump. On the left are the recordings before division of the cervical vagi; on the right, after vagotomy. Symbols and time lines are the same as in figure 1.
declined rapidly. Similar pressure responses
following main pulmonary artery stenosis have
been reported previously.0' 8
Prior to vagotomy, both before and after
left ventricular bypass, aortic pressure consistently increased with the elevation of
right ventricular systolic pressure (figs. 2 and
3). The graphs in figure 4 show this relationship in ten dogs before there was any rise in
right ventricular end diastolic pressure. In
table 1, under "Vagi intact," are listed the
maximum aortic pressure responses to partial
pulmonary artery occlusion in eight dogs with
controlled perfusion of the systemic circulation. As also shown in table 1, the increases in
TABLE 1
Maximum Increase in Mean Aortic Blood Pressure
Following Gradual Partial Constriction of the Main
Pulmonary Artery in Dogs with Bypass of the Left
Ventricle
Dog no.
1
2
3
4
5
6
7
8
Vagi intact
mm Hg
20
30
22
24
15
15
20
20
Atropine
(0.4 mg/kg) Bilateral vagotomy
mm Hg
mm Hg
0
6
•Q
0
7
0
.15
20
20
Q
0
0
Circulation Research, Volume XIV, May 1964
aortic pressure in four dogs were similar after
the administration of atropine.
Following bilateral cervical vagotomy,
aortic blood pressure showed no increase
although right ventricular systolic pressure
still increased and the ventricular end diastolic
pressure remained unchanged (fig. 3 and
table 1).
With the left ventricle bypassed, sudden
complete occlusion of the main pulmonary
artery with total interruption of pulmonary
blood flow was associated with an increase
in mean aortic pressure of 14 ± 9 mm Hg in
seven of nine animals (fig. 5). Following
release of the occlusion there was a sudden
further rise in aortic pressure. The aortic and
right ventricular systolic pressures then returned gradually to base line levels. After
division of both cervical vagi, the systemic
responses associated with total main pulmonary artery block were markedly diminished
or absent (fig. 5).
Discussion
The experimental results show that appropriate stimulation of receptors in the right
ventricle influences peripheral vasomotor
activity through autonomic nervous pathways.
This interaction between the heart and systemic circulation was demonstrated by gradually increasing right ventricular systolic pres-
464
PINKERSON, KOT
Downloaded from http://circres.ahajournals.org/ by guest on April 30, 2017
sure. The systemic vascular responses were
dependent on the presence of intact vagal
fibers.
Similar increases in aortic pressure following partial occlusion of the main pulmonary
artery have been previously noted in animals
with intact circulation.9 The possible explanations for the systemic pressure rise include
increased blood flow, increased activity of
the left ventricle, or increased total systemic
resistance. In the present experiments, with
use of a mechanical left ventricle, flow to the
systemic circulation was controlled. The increased aortic pressure while venous and right
atrial pressure remained constant represented
an increase in total systemic vascular resistance. An increased vascular resistance in the
isolated dog hind limb has been described
after occlusion of the main pulmonary artery.10 However in these experiments, total
systemic perfusion was not controlled and
the increased resistance was attributed to decreased carotid sinus pressure.
Although the increases in right ventricular
systolic pressure were similar, the rise in
INTACT
0
5
aortic pressure was blocked only by vagotomy
and not by the administration of atropine.
This difference in systemic response clearly
shows that the changes in vascular resistance
were dependent on impulses transmitted
through vagal afferent fibers from the heart.
In addition, the increase in aortic pressure
prior to vagotomy could not have been due to
release of vasoactive elements directly from
the right ventricle into the general circulation
or incomplete bypass of the left ventricle.
The possibility that occlusion of the main
pulmonary artery could stimulate other receptors on the right side of the circulation in
addition to those in the right ventricle has
been discussed previously." Since central
venous, right atrial, and right ventricular end
diastolic pressures showed no change, and
pulmonary artery pressure responses were
variable, the important stimulus must have
been in the right ventricle. A slight decrease
in pulmonary artery pressure distal to the site
of occlusion has been suggested as a stimulus
for the increased aortic pressure.9 In many
instances in the present study, however,
CIRCULATION
10
15
LEFT VENTRICULAR
20
29
0
Rt. Vent Systolic Pressure Change
(mm Hg)
5
10
B
BYPASS
20
25
30
Rt.Vent. Systolic Pressure Change
(mm Hg)
FIGURE 4
Relationship between the increase in right ventricular systolic and mean aortic pressure during
various degrees of occlusion of the main pulmonary artery. Graplxs on the left are from animals
with an intact circulation and on the right, the same animals but with fixed perfusion of the
systemic circulation. Each line represents one animal, and the points, the recorded pressure
changes. Points on both graphs were calculated before any change occurred in right ventricular
end diastolic, right atrial or venous pressure.
Circulation Research, Volume XIV, May 1964
PRESSOR REFLEX FROM RIGHT VENTRICLE
465
PRE VAGOTOMY
POST VAGOTOMY
P
^^ ^^
•
v
f~*
^^ ^^
v
^^
rvi
40
PPA
20
0
PR V
200
PAO
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100
_J 0 I—
mm Hg
^rl
TOTAL OCCLUSION
M.P.A.
TOTAL OCCLUSION
M.P.A.
FIGURE 5
Effects of sudden complete occlusion of the main pulmonary artery in dogs with controlled
perfusion of the systemic circulation. Tracings on the left are before, and on the right, after
bilateral cervical vagotomy. Brackets at the bottom of each panel show the total time from
onset to release of the occlusion. Symbols and time lines are the same as in figure 1.
pulmonary artery pressure increased with the
rise in systemic pressure.
An increase in systemic vascular resistance
has also been described following acute overdistention of the main pulmonary artery.3 The
pressures used to distend the pulmonary artery
were from 80 to 200 mm Hg. In the present
experiments the changes in systemic pressure
were obtained while main pulmonary artery
pressures were lower. Stenosis near the
pulmonic valve or distally near the bifurcation
also did not alter the systemic response.
During acute total occlusion of the main
pulmonary artery, there was still a direct
relationship noted between the elevation in
right ventricular systolic and aortic pressures
in the pump dog. Under these extreme circumstances there was an associated elevation of
right ventricular end diastolic, right atrial,
and venous pressures which also probably
influenced the systemic response. 4 ' n The
further increase in pressure which was seen
immediately following release of the main
pulmonary artery constriction in the pump
dog was interpreted as release of vasoinhibiCirculation Research, Volume XIV, May 1964
tory impulses probably originating in the
right atrium 4 while vasoconstrictor impulses
from the right ventricle and possibly the
veins n were still active. Incomplete drainage
of the sudden increased blood volume in the
left atrium could also have contributed to the
post release rise in aortic pressure. This latter
possibility, however, would not explain the
marked decrease in response noted after
vagotomy.
It would appear that in the normal animal
as well as during certain pathological states
the vasomotor centers in the central nervous
system are influenced by nerve impulses
transmitted through vagal afferent fibers from
the right ventricle. Nervous end organs have
been described in histologic preparations of
the right ventricle in the endocardium, myocardium, and epicardium.12 The various
nerve endings which were seen are similar to
sensory receptors in other areas of the body.
Electroneurograms of the vagus nerves also
have shown bursts of impulse activity with
each ventricular systole.2'13
466
PINKERSON, KOT
Summary
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The relationship between right ventricular
and aortic pressure was studied in open-chest
anesthetized dogs. A simultaneous increase in
both pressures was observed in animals with
an intact circulation and animals with the systemic circulation perfused at a constant rate
and stroke volume by an extracorporeal pump.
With gradual partial constriction of the main
pulmonary artery, the increase in right ventricular systolic and aortic pressures occurred
without consistent change in other measured
parameters. Bilateral cervical vagotomy abolished the systemic vascular response.
These observations are consistent with a
pressor reflex which is mediated over vagal
afferent fibers from the right ventricle. It is
suggested that in animals under varying physiologic stimuli an increase in right ventricular
pressure is associated with a reflex increase in
systemic vascular resistance. In abnormal circumstances with increased resistance to right
ventricular emptying, the increased total peripheral vascular resistance would be important in maintaining systemic blood pressure
and blood flow.
References
1. AVIADO, D. M., JR., AND SCHMIDT, C. F.:
Re-
flexes from stretch receptors in blood vessels,
heart and lungs. Physiol. Rev. 35: 247, 1955.
2. HEYMANS, C , AND NEIL, E.: Reflexogenic Areas
of the Cardiovascular System. London, J. and
A. Churchill Ltd., 1958.
3.
LEWIN, R. J., CROSS, C. E., RIEBIN. P. A., AND
SALISBURY, P. F.: Stretch reflexes from the
main pulmonary artery to the systemic circulation. Circulation Res. 9: 585, 1961.
4.
AVIADO, D. M., JR., L I , T. H., KALOW, W., PES-
KIN, E. W., TURNBUL, G. L., AND HESS, M. E.:
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SALISBURY, P. F., CROSS, C. E., AND RIEBEN,
P. A.: Reflex effects of left ventricular distention. Circulation Res. 8: 530, 1960.
6. TAQUINI, A. C , AND AVIADO, D. M., JR.: Reflex
stimulation of heart induced by partial occlusion of pulmonary artery. Am. J. Physiol. 200:
647, 1961.
7.
ROSE, J. C , BROIDA, H. P., HUFNAGEL, C. A.,
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E. D.: Method for the study of the circulation in the dog using a mechanical left ventricle. J. Appl. Physiol. 7: 580, 1955.
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GUYTON, A. C , LlNDSEY, A. W., AND GlLLULY,
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AVIADO, D. M., JR., AND SCHMIDT, C. F.:
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diovascular and respiratory reflexes from the
left side of the heart. Am. J. Physiol. 196:
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11.
HADDY, F. J., AND GILBERT, R. P.: Relation of a
venous arteriolar reflex to transmural pressure
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12. KING, A. B.: Nerve endings in the cardiac muscle
of the rat. Bull. Johns Hopkins Hosp. 65: 489,
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13. PAINTAL, A. S.: A study of ventricular pressure
receptors and their role in the Bezold reflex.
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Circulation Research, Volume XIV, May 1964
Systemic Blood Pressure Response to Changes in Right Ventricular Function
ALAN L. PINKERSON and PETER A. KOT
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Circ Res. 1964;14:461-466
doi: 10.1161/01.RES.14.5.461
Circulation Research is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1964 American Heart Association, Inc. All rights reserved.
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