AORTIC CHEMORECEPTORS AND THE HEART/Karim et al.
Bellamy RF (1978) Diastolic coronary artery pressure-flow relations in the dog. Circ Res 43: 92-101
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Fixler, DE (1971) Some sources of error in measuring regional
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598-604
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Downey JM, Kirk ES (1975) Inhibition of coronary blood flow
by a vascular waterfall mechanism. Circ Res 36: 753-760
Haddy FJ, Gilbert RP (1956) The relation of a venous-arteriolar
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systemic vessels. Circ Res 4: 25-32
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5-15
Heymann MA, Payne BD, Hoffman JIE, Rudolph AM (1977)
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Prog Cardiovasc Dis 20: 55-79
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Hoffman JIE, Buckberg GD (1978) The myocardial supply:demand ratio—a critical review. Am J Card 41: 327-332
Johnson PC (1959) Myogenic nature of increase in intestinal
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7: 992-999
Kjekshus JK (1973) Mechanism for flow distribution in normal
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Roberts DL, Nakazawa HK, Nordlicht SM, Sekovski B, Mageli
J, Oliveros RA, Orlick AE, Klocke FJ (1979) Evaluation of
regional myocardial perfusion and ischemia from coronary
venous blood. Am J Physiol 236: H385-H390
Rudolph AM, Heymann MA (1967) The circulation of the fetus
in utero. Circ Res 21: 163-184
Snedecor GW, Cochran WG (1967) Statistical Methods. Ames,
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shell. Am Heart J 75: 649-662
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Responses of the Heart to Stimulation of
Aortic Body Chemoreceptors in Dogs
F. KARIM, R. HAINSWORTH, O.A. SOFOLA, AND L.M. WOOD
SUMMARY We stimulated the aortic chemoreceptors in dogs that were anesthetized with chloralose
and artificially ventilated by perfusing the isolated aortic arch with venous blood. Inotropic responses
were determined by measuring the maximum rate of change of left ventricular pressure (dP/dt max)
with aortic pressure and heart rate held constant. Stimulation of the aortic chemoreceptors resulted in
an average increase in heart rate of 14 ± 2.0 beats/min (mean ± SE) from 166 ± 7.7 beats/min and an
increase in dP/dt max of 501 ± 85 mm Hg/sec from 3508 ± 154 mm Hg/sec. These changes were
statistically significant (P < 0.001). The afferent pathway of the reflex was shown to be in the vagus
nerves and the efferent pathway in the cardiac sympathetic nerves. In some of the dogs, the carotid
chemoreceptors were also stimulated. This resulted in decreases in heart rate and dP/dt max of 48 ±
24 beats/min and 795 ± 142 mm Hg/sec. Thus we have shown that stimulation of aortic chemoreceptors
evokes chronotropic and inotropic responses opposite to those evoked from stimulation of carotid
chemoreceptors. Circ Res 46: 77-83, 1980
STIMULATION of the carotid body chemoreceptors, with ventilation held constant, results in reflex
bradycardia (Daly and Scott, 1958) and negative
inotropic responses (Hainsworth et al., 1979). However, there has been no adequate study of the effect
of physiological stimulation of the aortic body chemoreceptors on the inotropic and chronotropic
state of the heart. Several groups of investigators
have attempted to stimulate these receptors by
injection of drugs such as nicotine into the open
aortic arch, but the results are inconclusive largely
because of inadequate localization of the stimulus
From the Departments of Cardiovascular Studies and Physiology.
University of Leeds, Leeds, England.
This work was supported in part by a grant from the Medical Research
Council. Dr. O.A. Sofola was a Commonwealth Scholar, and his present
address is: Department of Physiology, College of Medicine, University of
Lagos, Nigeria. Mr. L.M. Wood is a Medical Research Council Scholar.
Received May 2, 1979; accepted for publication September 4, 1979.
to the chemoreceptors and control of pressure to
the baroreceptors (Comroe and Mortimer, 1964;
Stern and Rapaport, 1967; Biro et al., 1973; Stern et
al., 1964).
In the present study, by vascularly isolating the
aortic arch, we were able to stimulate the chemoreceptors with venous blood. The inotropic responses were assessed by measuring the maximum
rate of change of left ventricular pressure (dP/dt
max) with heart rate and aortic pressure held constant (Furnival et al., 1970). In four of the experiments, we also examined the cardiac responses to
stimulation of the carotid body chemoreceptors.
Methods
Dogs weighing 20-29 kg were anesthetized with
chloralose (0.1 g/kg body weight, Cambrian Chemicals Ltd.) infused through a catheter inserted into
78
CIRCULATION RESEARCH
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the inferior vena cava through a saphenous vein.
Additional doses of chloralose (about 10 mg/kg
every 15 minutes) were given to maintain a state of
light surgical anesthesia. The neck was opened in
the midline, the trachea was cannulated, and the
dog was ventilated with positive pressure by means
of a Starling "Ideal" pump using 40% oxygen in
nitrogen humidified at room temperature. The rate
of the pump was 18 strokes/min, and the stroke
volume was approximately 17 ml/kg. When the
pleura was opened, a resistance to expiration was
inserted, equivalent to 3 cm H2O.
The regions of both common carotid bifurcations
were vascularly isolated and perfused at constant
pressure, as previously described (Hainsworth and
Karim, 1973, 1976). In four experiments in which
we stimulated the carotid chemoreceptors, the
blood was drained, through the catheters in the
lingual arteries, into an external jugular vein. In the
remaining experiments, blood was allowed to flow
through the internal carotid arteries.
The technique for isolating the aortic arch region
was similar to that described previously (Hainsworth et al., 1970; Hainsworth and Karim, 1972;
Hainsworth et al., 1975; Karim et al., 1978). Briefly,
the left 2nd to 5th ribs were removed to expose the
aortic arch. The pericardium was opened, and
strings were placed around the ascending aorta and
the origins of the left subclavian and brachiocephalic arteries in preparation for aortic cannulation.
The descending aorta was mobilized by cutting the
upper four pairs of intercostal arteries between ties.
Two silver-ring electrodes were sewn onto the
right atrial appendage for pacing. In all but two
dogs, a miniature pressure transducer (model P13,
Konningsberg Instrument Inc.) was introduced into
the left ventricle through the left atrial appendage
and secured in place by a tie around the base of the
appendage. In the remaining two dogs, a short
stainless steel cannula with side holes (length = 5
cm, bore = 1.2 mm) was inserted into the left
ventricle through the apical dimple, tied in place by
means of a purse-string suture, and firmly clamped
in position. The dogs were given heparin (Pularin,
Evans Medical Ltd., 500 IU/kg followed by 50 IU/
kg every 30 minutes), and the circuit (Fig. 1) was
filled with dextran solution (Dextraven 150, Fisons
Pharmaceuticals Ltd.) or a mixture of dextran and
blood obtained from another dog. Temporary bypasses were connected between the proximal ends
of the left subclavian and a femoral artery to allow
some circulation to the caudal part of the body
during cannulation procedure.
The perfusion circuit (Fig. 1) was connected to
the dog as follows. A curved stainless steel cannula
was inserted into the aortic arch, and the arch was
isolated by tightening the snare around the ascending aorta and clamping the bypass. The aortic blood
passed through the aortic cannula and was distributed to the descending aorta and the aortic reser-
VOL. 46, No. 1, JANUARY
1980
To Vein
FIGURE 1 Diagram of the experimental preparation.
Blood leaving the left ventricle passed via the aortic
cannula into a reservoir maintained at constant pressure and into the descending aorta. Blood from the
aortic reservoir or inferior vena cava (IVC) was pumped
(pump I) at constant pressure through the left subclavian
artery into the aortic arch, and from there it passed via
a cannula in the brachiocephalic artery into an external
jugular vein. Arterial blood from the reservoir was
pumped (pump 2), at constant flow, into the left subclavian and brachiocephalic arteries to perfuse the brain
and, at constant pressures (pump 3), into both carotid
bifurcations. CCA = common carotid artery; BcA =
brachiocephalic artery; LSA = left subclavian artery;
Ao = aorta, CP = constant pressure; SG = strain gauge;
CTT = catheter tip pressure transducer; Cann = metal
aortic cannula; HE = heat exchanger; P = roller pump;
Sh S-, = clips.
voir, from which blood was distributed to the isolated carotid sinuses, the isolated aortic arch, and
the head of the dog through cannulas inserted into
the distal end of the left subclavian artery and the
proximal end of the left common carotid artery.
The pressure of blood in the aortic cannula was
maintained by the aortic reservoir in which the
pressure of the air above the blood was controlled.
The aortic arch was perfused at constant pressure
with blood taken either from the aortic reservoir or
from a cannula in the inferior vena cava. The temperature of the perfusate was maintained at 3738°C by use of a heat exchanger. A cotton mesh
filter (pore size about 220 jum) was also placed in
the perfusion line between the roller pump and the
aortic arch. The blood from the aortic arch drained
from a cannula (bore = 2 mm) tied in the brachi-
AORTIC CHEMORECEPTORS AND THE HEART/Karim et al.
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ocephalic artery and was returned to an external
jugular vein. Samples of blood were withdrawn from
the outflow cannula to measure the P02, Pco2, and
pH of blood perfusing the arch using a blood gas
electrode system (Corning, model 165). In some
experiments, the blood passed through an oxygen
electrode system (Electronic Instruments Ltd.) before draining into an external jugular vein.
Pressures were recorded using Statham (P23 Gb)
transducers connected to cannulas (bore = 4 mm)
in the central end of the left subclavian artery
(aortic arch pressure), aortic cannula (systemic arterial blood pressure), common carotid arteries, and
the left ventricle. After amplification by carrier
amplifiers (S.E. Laboratories Ltd.), the pressures
were recorded on photographic paper by a directwriting ultraviolet light recorder (S.E. Laboratories
Ltd.). The output from the amplifier for the left
ventricular pressure transducer was distributed in
four ways: (1) directly to a galvanometer to record
left ventricular end-diastolic pressure at a high sensitivity (7.5 mm Hg = 10-mm paper); (2) through a
variable series resistance to a galvanometer to measure left ventricular pressure at lower sensitivity (20
mm Hg = 10-mm paper); (3) to an analogue differentiator to provide a signal of dP/dt which was
amplified and recorded; and (4) to a digital cardiotachometer (Gilford Instruments Inc.) to record
ventricular rate. The differentiator was calibrated
according to the method of Neal et al. (1960). We
determined the frequency response of the cannula
and transducer system to be flat (±5%) to better
than 80 Hz in the case of the apical cannula and
better than 200 Hz for the catheter tip transducer.
During determinations of inotropic responses,
the heart was paced by a Grass stimulator (model
S4). A thermistor probe (Yellow Springs Instruments Inc.) recorded esophageal temperature which
was maintained at 37-39° C by means of electric
heaters under the operating table. Arterial Po2,
Pco2, and pH were determined frequently during
the experiments using a blood gas analyzer (Corning, model 165). Arterial Pco2 and pH were maintained within the ranges of 32-40 mm Hg and 7.307.40 units, respectively, by adjusting the stroke of
the respiration pump and by intravenous infusions
of molar sodium bicarbonate. Since the dogs
breathed air enriched with oxygen, arterial Po 2 was
greater than 113 mm Hg.
The effectiveness of the vascular isolation of the
aortic arch was assessed in all experiments by stopping the inflow and noting the pressure, which fell
to between 0 and 10 mm Hg. The regions perfused
through the aortic arch were visualized at the ends
of the experiments by injections, in four dogs, of
Evans blue dye, and, in two dogs, of Indian ink into
the perfusion tubing at pressures similar to those
which perfused the isolated arch during the tests.
In all six dogs, no dye or ink was seen either in the
aorta, proximal or distal to the isolated segment of
79
the aortic arch, or in the coronary or pulmonary
circulations, but dye or ink was found in the region
between the aortic arch and pulmonary trunk.
Experimental Procedure
About half an hour after the circuit had been
connected, the following procedures were carried
out.
The isolated aortic arch was perfused with arterial blood at a constant pressure of 151 ± 9.0 mm
Hg (mean ± SE, n = 11). The pressure of the blood
in the aortic cannula was set to 111 ± 4.5 mm Hg
and that in the carotid bifurcations to 124 ± 7.5 mm
Hg. The heart was paced at a rate higher than that
expected during chemoreceptor stimulation. When
all measured variables were steady, records were
taken. The pacing of the heart then was stopped to
record free heart rate. The aortic chemoreceptors
were stimulated by perfusing the isolated aortic
arch with blood from the inferior vena cava. Records were taken continuously for about 2-4 minutes
while pressures in the aortic arch, aortic cannula,
and carotid arteries were held constant. The heart
again was paced at the same rate as during the
arterial perfusion, and a further record was obtained. Pacing then was stopped, the aortic perfusate was changed back to arterial blood, and further
records were obtained without and with pacing.
The values of free heart rate and of dP/dt max
during pacing, which were obtained during venous
perfusion of the chemoreceptors, were compared
with the average values obtained during the two
periods of arterial perfusion.
In four of the dogs, we also determined the responses to perfusion of the carotid bodies with
venous blood with the carotid and aortic pressures
held constant.
The values reported are means ± SE of the mean.
Significance was determined by paired t-test.
Results
Po 2 , Pco 2 , and pH of Perfusate
The values of Po2, Pco2, and pH of the arterial
perfusate were 105 ± 3.0 mm Hg, 39 ± 0.22 mm Hg,
and 7.37 ± 0.001 units, respectively. The corresponding values for the venous perfusate were 31
± 1.0 mm Hg, 54 ± 1.0 mm Hg, and 7.28 ± 0.004
units.
Responses to Perfusion of the Aortic Arch
with Venous Blood
During arterial perfusion, in 19 tests in 11 dogs,
the values of the variables measured were as follows: aortic arch perfusion pressure, 151 ± 9.0 mm
Hg; carotid sinus pressure, 124 ± 7.5 mm Hg; systemic arterial pressure, 111 ± 4.5 mm Hg; heart rate
(when not paced), 166 ± 7.7 beats/min (results from
10 dogs only); left ventricular end-diastolic pressure
(in four dogs measured), 5.8 ± 1.13 mm Hg; left
CIRCULATION RESEARCH
TABLE 1 Heart Rate and Left Ventricular Inotropic
Responses to Venous Perfusion of the Isolated Aortic
Arch
HR (unpaced) (beats/min)
Mean
SB
% Change
% Change
Dog no.
1
2
3
4
5
6
7
8
9
10
11
dP/dt max (mm Hg/sec)
VOL. 46, No. 1, JANUARY 1980
A. HEART UNPACEO
J; 6000
•53000
1E 3000°
dP/ dl
225
140
150
175
162
115
186
186
180
190
179
156
168
189
174
119
194
201
192
200
206
166.3 179.5
7.7
8.7
P < 0.001
+ 11.4
+ 12.0
+8.0
+7.4
+3.5
+4.3
+8.1
+6.7
+5.3
+ 15.1
+8.2
1.2
3360 3600
3638 4515
3390 3765
2648 2993
3555 3998
4238 5160
4260 4523
3788 4275
3758 4740
2985 3270
2970 3263
+7.1
+24.1
+ 11.1
+ 13.0
+ 12.4
+21.8
+6.2
+ 12.9
+26.1
+9.5
+9.8
3508 4009
154 209
P < 0.001
+ 14.0
2.1
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Values listed are the averages obtained from each dog during perfusion
of aortic arch with arterial (A) and venous (V) blood with constant
pressures in the aortic arch, carotid sinuses, and aortic cannula (systemic).
Heart rate (HR) was held constant by electrical pacing of the heart when
inotropic responses were determined.
ventricular systolic pressure, 154 ± 5.2 mm Hg; and
left ventricular dP/dt max, 3508 ± 154 mm Hg/sec.
With the heart not paced, perfusion of the aortic
arch with venous blood resulted in an increase in
heart rate of 13.6 ± 2.0 beats/min (8.2 ± 1.2%). This
response was statistically significant (P < 0.001).
The average values of heart rate from each dog,
during perfusion of the aortic arch with arterial and
venous blood, are listed in Table 1. Figure 2A shows
an example of the responses obtained.
With the heart paced at 200 ± 4 beats/min,
perfusion of the aortic arch with venous blood resulted in an increase in dP/dt max of 501 ± 85 mm
Hg/sec (14.0 ± 2.1%; P < 0.001). Left ventricular
systolic pressure increased by 3.4 ± 1.7 mm Hg (P
> 0.05), and left ventricular end-diastolic pressure
decreased by 1.03 ± 0.6 mm Hg (P > 0.05). The
average values of dP/dt max obtained from each
dog during pacing are given in Table 1, and an
example of experimental records is shown in Figure
2B.
Responses to Perfusion of the Aortic Arch
with Venous Blood at Pressures below
Threshold for Baroreceptors
In five dogs, we increased aortic pressure in steps
of about 20 mm Hg to determine the lowest pressure
that resulted in reflex changes in heart rate and
dP/dt max. Values between 120 and 140 mm Hg
were obtained as the threshold for baroreceptors.
These values are similar to those reported previously (Hainsworth et al., 1970; Hainsworth and
Karim, 1972). The effects then were determined of
perfusing the aortic arch with venous blood with
the perfusion pressure held below this level. Heart
rate, measured in two of the dogs, increased by 12
9. '50
x
I 75
0
L
10s
B. HEART PACED
rr'VtV'
225
150
75
FIGURE 2 Heart rate and inotropic responses to perfusion of the aortic arch with venous blood, (A) with
heart rate paced and (B) at a faster paper speed with
heart paced at 186 beats/min. Second and third panels
were taken approximately 90 seconds after changing the
perfusate when all variables were steady. During perfusion with venous blood, there were increases in heart
rate (A) and dP/dt max (B), which returned toward their
previous values on reestablishing arterial perfusion. dP/
dt = rate of change of ventricular pressure; L VP — left
ventricular pressure; AoAP = aortic arch pressure; CSP
= carotid sinus pressure; AoCP = aortic cannula (systemic arterial) pressure; HR = heart rate (beats/min).
and 27 beats/min from 180 and 179 beats/min; dP/
dt max, in all five dogs when the heart was paced,
increased by 383 ± 79 mm Hg from 3637 ± 195 mm
Hg (+10.5 ± 1.8%). These responses were not significantly different from those obtained at higher
aortic arch perfusion pressures.
Effect of Section or Cold Blockade of the
Vagus Nerves
In one dog both cervical vagosympathetic trunks
were cut, and in another they were cooled to a
surface temperature of 8°C by a thermoelectric
module (De La Rue Frigistor Ltd.). Before the
nerves were cut, perfusion of the aortic arch with
venous blood resulted in an increase in dP/dt max
(heart paced) of 375 mm Hg/sec from 3435 mm Hg/
sec. No response was obtained after the nerves were
cut. In the other dog before the nerves were cooled,
AORTIC CHEMORECEPTORS AND THE HEART/Karim et al.
dP/dt max increased by 323 mm Hg/sec from 2910
mm Hg/sec. When the nerves were cooled, venous
perfusion of the aortic arch increased dP/dt max by
only 52 mm Hg/sec from 2490 mm Hg/sec.
Effect of Crushing or Blocking Efferent
Sympathetic Nerves
In one dog both ansae subclaviae were crushed,
and in another the efferent sympathetic nerves to
the heart were blocked by intravenous propranolol
(0.5 mg/kg). The responses of heart rate and dP/dt
max to venous perfusion of the aortic arch before
crushing the ansae were +6 beats/min and +600
mm Hg/sec and before giving propranolol +20
beats/min and +293 mm Hg/sec. After crushing
the ansae or giving propranolol, no responses of
either heart rate of dP/dt max were obtained.
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Comparison of the Cardiac Responses to
Venous Perfusion of the Aortic Arch and
Carotid Bifurcations in the Same Dog
In four dogs, perfusion of the isolated carotid
bifurcations with venous blood resulted in a decrease in heart rate of 48 ± 24 beats/min from 147
± 20 beats/min (-31.3 ± 13.7%) and a decrease in
dP/dt max of 795 ± 144 mm Hg/sec from 3824 ±
295 mm Hg/sec (-20.6 ± 3.3%). In the same preparations, perfusion of the aortic arch with venous
blood resulted in an increase in heart rate of 11 ±
3.1 beats/min from 157 ± 16 beats/min (+7.0 ±
2.0%) and an increase in dP/dt max of 476 ± 151
mm Hg/sec from 3630 ± 382 mm Hg/sec (+13.0 ±
3.0%). An example of the opposite inotropic responses to stimulation of the aortic and carotid
chemoreceptors in the same dog is shown in Figure
3, and the averages of the values obtained from all
four dogs during venous perfusion of the carotid
bifurcations are listed in Table 2.
Discussion
Our experiments have shown that perfusion of
the aortic arch with venous blood, in dogs anesthetized with chloralose, consistently results in increases in the rate and the inotropic state of the
heart. The responses were abolished by cutting or
cooling the vagus nerves in the neck or by crushing
the cardiac sympathetic nerves or blocking their
effect with propranolol. This shows that the afferent
pathway for the reflex was in the vagus nerves and
the efferent pathway in the cardiac sympathetic
nerves. The key question to be answered is whether
we can assume that the effects produced by perfusing the aortic arch with venous blood are due to
stimulation of aortic chemoreceptors.
The region of the aorta that was isolated vascularly from the rest of the circulation contains most
of the arteries to the chemoreceptors (Comroe,
1939; Coleridge et al., 1970). We confirmed the
effectiveness of the isolation procedure in all dogs
81
AORTIC BODIES
*• 6000
2-3000
•— dP/ dt
1
I 75
i i5O r
^
75
iw w
ii
*—Ao AP
—CSP
•— LVP
— Ao CP
1
1
it
J
B.
! ,!.!
J J \i
CAROTID BODIES
ill
-•"•M-4H
0L
FIGURE 3 Inotropic responses to perfusion of the aortic
(A) and carotid (B) chemoreceptors in the same dog. The
heart was paced at 180 beats/min, and pressures in the
aortic arch, aortic cannula, and carotid sinuses were
held constant throughout. The records show that stimulation of the aortic chemoreceptors resulted in a positive inotropic response, whereas stimulation of the carotid chemoreceptors resulted in a negative inotropic
response. Abbreviations as in Figure 2.
by stopping the perfusion and noting that the pressure in the isolated aortic arch fell to near venous
levels. Furthermore, in four of the dogs, we determined the region perfused through the aortic segment by injection of Evans blue dye or Indian ink
into the isolated arch at normal perfusion pressures
and observed staining only in the region between
the aorta and the pulmonary artery. No staining
was seen in the coronary arteries, in the aorta
proximal or distal to the isolated segment, or in the
pulmonary circulation. The venous blood, therefore, would not have changed the activity of the
afferent nerves in the pulmonary or coronary regions.
The only other mechanism to exclude is whether
the responses may have been due to reduced activity of aortic baroreceptors during perfusion of the
aortic arch with venous blood. This is unlikely
because the responses to perfusion with venous
blood were not different when the perfusion pressure was held below the threshold for the aortic
baroreceptor reflexes (Hainsworth et al., 1970;
Hainsworth and Karim, 1972). Also A.U. Kadiri,
CM. Malpus, and C. Kidd (personal communication) showed that baroreceptors, at least those at
82
CIRCULATION RESEARCH
2 Heart Rate and Left Ventricular Inotropic
Responses to Venous Perfusion of the Isolated Carotid
Bifurcations
TABLE
HR (unpaced) (beats/min)
dP/dt max (mm Hg/sec)
Dog no.
A
V
% Change
A
V
% Change
3
114
4
168
113
192
84
48
96
168
-26.3
-71.4
-15.0
-12.5
2993
3840
4343
4118
2490
2693
3443
3488
-16.8
-29.8
-20.7
-15.3
147
20
99
25
-31.3
13.7
3824
295
3029
256
-20.6
3.3
6
7
Mean
SE
Values listed are averages obtained from each dog during perfusion of
carotid bifurcations with arterial (A) and venous (V) blood at constant
aortic arch pressure (169 ± 17 mm Hg), carotid sinus pressure (129 ± 13
mm Hg), aortic cannula pressure (111 ± 9 mm Hg). Heart rate also was
held constant at 198 ± 1.5 beats/min when inotropic responses were
determined.
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the right subclavian angle, were not affected by
perfusion with venous blood for periods of up to 4
minutes. The responses to perfusion of the aortic
arch with venous blood were not mediated by the
receptors with afferents running in the sympathetic
nerves (Lioy et al., 1974; Malliani and Pagani, 1976)
because we showed that the reflex was dependent
on the integrity of the vagus nerves.
Some of the aortic bodies receive their blood
supply from the left coronary artery (Comroe, 1939;
Coleridge et al., 1970), and these would not have
been stimulated in the present experiments. Therefore, the responses obtained are not likely to have
been the maximum that the aortic chemoreceptors
are capable of producing. Furthermore, there was a
wide variation in both the inotropic and chronotropic responses obtained from the different dogs
(see Table 1). This variation may have been due to
variations in the levels of anesthesia; in the numbers
of aortic bodies perfused, which may vary from dog
to dog (Coleridge et al., 1970); and in the amounts
of damage caused to the chemoreceptors and their
nerves during the dissection. It is also possible that
the dissection may have caused variable degrees of
damage to some of the efferent cardiac nerves.
There have been previous investigations that
attempted to examine the cardiac responses from
aortic chemoreceptors. These have involved the
injection into the ascending aorta of substances
known to stimulate chemoreceptors. Dawes and
Comroe (1954) injected phenyldiguanide into the
aorta and noted a decrease in heart rate. Comroe
and Mortimer (1964) and Stern and Rapaport
(1967) inserted delay coils in the carotid arteries to
separate temporally the stimuli to aortic and carotid
chemoreceptors. Injections of nicotine resulted in
initial increases in heart rate in most experiments
(Comroe and Mortimer, 1964) and in the inotropic
state (Stern and Rapaport, 1967). The criticism of
the studies involving injections of drugs into the
nonisolated aorta is that the site of action cannot
be localized. Nicotine has a widespread action on
many nerve endings and ganglia (e.g., Coleridge and
VOL. 46, No. 1, JANUARY
1980
Coleridge, 1977). Also, when delay coils are used, it
is not possible to be certain that some of the drug
did not reach the carotid and cerebral circulations
earlier than expected via collateral vessels.
Angell-James and Daly (1969) vascularly isolated
the aortic arch and found, in two experiments, that
perfusion with venous blood slowed the rate of the
atria. However, in their preparation, the ventricles
were taped firmly to a cannula and the coronary
ostia were included with the aortic perfusion. It is
possible, therefore, that in the two experiments the
atrial bradycardia was due to perfusion of the sinoatrial node with venous blood (Chiba et al., 1976).
The present report is the first in which aortic
chemoreceptors have been isolated effectively and
stimulated physiologically. The finding, in the present experiments, that the cardiac responses from
aortic chemoreceptors were directionally opposite
to those that we recently had shown to be produced
from carotid chemoreceptors (Hainsworth et al.,
1979) was surprising. To confirm this difference, in
four of the dogs we determined responses from both
aortic and carotid chemoreceptors. We were able to
alternate repeatedly between stimulation of carotid
and aortic chemoreceptors and consistently produced opposite responses. What the significance of
the difference is, we find hard to say. Certainly the
responses from the carotid receptors were much
greater, and when both aortic and carotid chemoreceptors were stimulated simultaneously, the net
effect was bradycardia and negative inotropism.
However, we cannot be certain how much of this is
due to the fact that carotid chemoreceptors could
be isolated with relatively little dissection, whereas
the aortic receptors were more difficult. Because of
the methodological problems, we did not feel that
quantitative studies of the interaction would be
very informative. It is known that vascular resistance is increased by stimulation of either carotid or
aortic chemoreceptors (Daly and Scott, 1962; Daly
et al., 1965). This implies that it is the carotid rather
than the aortic chemoreceptors that give rise to the
differential pattern of responses. Stimulation of the
carotid chemoreceptors increases the activity in the
sympathetic nerves to peripheral vessels but decreases the activity in the cardiac sympathetic
nerves. Stimulation of the aortic chemoreceptors,
on the other hand, results in excitation of the sympathetic nerves to both regions.
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Circ Res. 1980;46:77-83
doi: 10.1161/01.RES.46.1.77
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