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Am J Physiol Heart Circ Physiol
279: H1201–H1207, 2000.
Inotropic, chronotropic, and dromotropic effects mediated
via parasympathetic ganglia in the dog heart
MASATO TSUBOI, YASUYUKI FURUKAWA, KOICHI NAKAJIMA,
FUMIO KUROGOUCHI, AND SHIGETOSHI CHIBA
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
Received 11 November 1999; accepted in final form 8 March 2000
parasympathetic ganglionic cells; atrial contractility; sinus
rate; atrioventricular conduction; trimethaphan
tissue overlying the right pulmonary veins of the human hearts (3). However, clustered parasympathetic
ganglionic cells controlling atrial contractile force have
not been identified yet in the mammalian heart, although stimulation of the parasympathetic neural elements at the SA fat pad increases spontaneous sinus
cycle length (SCL) and partly decreases the atrial contractile force in the dog heart (9). Recently, Chiou et al.
(4) have reported that there are ganglionic cells in the
fat pad located between the medial superior vena cava
and aortic root (SVC-Ao fat pad) and that radiofrequency catheter ablation to the SVC-Ao fat pad led to
complete vagal denervation or attenuation of vagally
induced effective refractory period (ERP) shortening of
the right and left atria of the dog. However, many
autonomic nerve fibers pass through and around the
SVC-Ao fat pad in the dog (17, 21, 22). In the present
study, therefore, we examined whether the parasympathetic ganglionic cells in the SVC-Ao fat pad selectively and totally control the right atrial contractile
and electrical responses to the activation of the vagus
nerves in the anesthetized dog. To accomplish this
purpose, we studied the effects of the topical injection
of a ganglionic nicotinic receptor blocker, trimethaphan, and a sodium channel blocker, lidocaine, into the
SVC-Ao fat pad on the first derivative of the right atrial
pressure (RA dP/dt), SCL, and AV conduction time
(AVCT) in response to parasympathetic nerve stimulation. We electrically stimulated both sides of cervical
vagus nerves, sinus rate-related parasympathetic neural elements in the SA fat pad, or AV conductionrelated parasympathetic neural elements in the AV fat
pad separately (8, 9).
METHODS
control the heart via ganglionic cells in the walls of the heart. Almost all parasympathetic ganglionic cells for sinus nodal pacemaker
activity exist in the fatty tissue overlying the right
pulmonary veins (SA fat pad), and those for atrioventricular (AV) conduction exist in the fatty tissue at the
junction of the inferior vena cava and left atrium (AV
fat pad) (1, 7–9, 19, 20). The parasympathetic neural
elements controlling sinus rate also exist in the fatty
EFFERENT VAGAL NERVE FIBERS
Address for reprint requests and correspondence: S. Chiba, Department of Pharmacology, Shinshu University School of Medicine,
Matsumoto 390-8621, Japan.
http://www.ajpheart.org
Preparation. Our animal experiments were approved by
the Shinshu University School of Medicine Animal Studies
Committee. Thirty-one mongrel dogs, weighing 10–23 kg,
were anesthetized with pentobarbital sodium (30 mg/kg iv),
and supplemental doses were given to maintain stable anesthesia. A tracheal cannula was inserted, and intermittent
positive-pressure ventilation was started. The chest was
opened transversely at the fourth intercostal space. To block
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0363-6135/00 $5.00 Copyright © 2000 the American Physiological Society
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Tsuboi, Masato, Yasuyuki Furukawa, Koichi Nakajima, Fumio Kurogouchi, and Shigetoshi Chiba. Inotropic, chronotropic, and dromotropic effects mediated via parasympathetic ganglia in the dog heart. Am J Physiol Heart
Circ Physiol 279: H1201–H1207, 2000.—Some parasympathetic ganglionic cells are located in the epicardial fat pad
between the medial superior vena cava and the aortic root
(SVC-Ao fat pad) of the dog. We investigated whether the
ganglionic cells in the SVC-Ao fat pad control the right atrial
contractile force, sinus cycle length (SCL), and atrioventricular (AV) conduction in the autonomically decentralized
heart of the anesthetized dog. Stimulation of both sides of the
cervical vagal complexes (CVS) decreased right atrial contractile force, increased SCL, and prolonged AV interval.
Stimulation of the rate-related parasympathetic nerves to
the sinoatrial (SA) node (SAPS) increased SCL and decreased
atrial contractile force. Stimulation of the AV conductionrelated parasympathetic nerves to the AV node prolonged AV
interval. Trimethaphan, a ganglionic nicotinic receptor
blocker, injected into the SVC-Ao fat pad attenuated the
negative inotropic, chronotropic, and dromotropic responses
to CVS by 33⬃37%. On the other hand, lidocaine, a sodium
channel blocker, injected into the SVC-Ao fat pad almost
totally inhibited the inotropic and chronotropic responses to
CVS and partly inhibited the dromotropic one. Lidocaine or
trimethaphan injected into the SAPS locus abolished the
inotropic responses to SAPS, but it partly attenuated those to
CVS, although these treatments abolished the chronotropic
responses to SAPS or CVS. These results suggest that parasympathetic ganglionic cells in the SVC-Ao fat pad, differing
from those in SA and AV fat pads, nonselectively control the
atrial contractile force, SCL, and AV conduction partially in
the dog heart.
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trimethaphan into the SAPS locus on the inotropic and chronotropic responses to CVS or SAPS in four anesthetized
animals. Each stimulation was separated by intervals of 1
min or more to allow a sufficient recovery time.
Drugs. Drugs used in the experiments were trimethaphan
camsylate (Nippon Rosch, Tokyo, Japan) and lidocaine hydrochloride (Fujisawa, Osaka, Japan).
Statistical analysis. All data are means ⫾ SE. ANOVA
with the Bonferroni test was used for the statistical analysis
of multiple comparisons of the data. Student’s t-test for
paried data was used for comparison between the two groups.
P values less than 0.05 were considered statistically significant.
RESULTS
Effects of trimethaphan or lidocaine injected into the
SVC-Ao fat pad. Before treatment with trimethaphan
or lidocaine into the SVC-Ao fat pad, we determined
the atrial contractile force, the spontaneous SCL, and
AVCT in responses to stimulation of both sides of CVS,
stimulation of the rate-related parasympathetic neural
elements to the SA nodal region at the SA fat pad
(SAPS), or stimulation of the AV conduction-related
parasympathetic neural elements to the AV nodal region at the AV fat pad (AVPS) as shown in Fig. 1. CVS
decreased right atrial pressure and RA dP/dt, increased SCL, and prolonged AVCT (Fig. 1A). We used
the RA dP/dt as an indicator of the atrial contractile
force. On the other hand, SAPS increased the SCL with
a decrease in atrial pressure responses but did not
prolong the AVCT (Fig. 1B), and AVPS prolonged the
AVCT without changes in SCL and atrial pressure
responses (Fig. 1C). Summarized data are shown in
Table 1.
To determine how the parasympathetic ganglionic
cells in the SVC-Ao fat pad control the cardiac responses, we then studied the effects of trimethaphan
injected into the SVC-Ao fat pad on the changes in
right atrial contractile force, SCL, and AV conduction
in response to CVS. Three minutes after topical injection of trimethaphan into the SVC-Ao fat pad, basal
heart rate and arterial blood pressure of the anesthetized dog did not change significantly from the predrug
control levels.
Topical injection of trimethaphan at a dose of 0.3 mg
in a volume of 0.2 ml saline into the SVC-Ao fat pad
similarly attenuated decreases in RA dP/dt, increases
in SCL, and the prolongation of AVCT in response to
CVS by 37.4 ⫾ 4.7%, 34.3 ⫾ 5.4%, and 33.1 ⫾ 6.5%
from the respective control level (100%) in eight experiments (Fig. 2). The 0.2 ml of saline injected into the
SVC-Ao fat pad did not affect the cardiac responses and
arterial blood pressure.
To inhibit the action of the nerve fibers passing
through the SVC-Ao fat pad as well as the ganglionic
nicotinic receptor mediated action, we studied the effects of lidocaine injected into the SVC-Ao fat pad on
the cardiac responses to CVS. Topical injection of lidocaine at a dose of 3.0 mg depressed decreases in RA
dP/dt, increases in SCL, and the prolongation of AVCT
in response to CVS by 83.1 ⫾ 2.4%, 89.0 ⫾ 2.2%, and
53.2 ⫾ 13.1% from the respective control level (100%)
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neural conduction, both cervical vagus nerves were ligated
tightly and crushed at the neck, and both stellate ganglia
were crushed with a tight ligature at their junctions with the
ansa subclaviae. These maneuvers remove almost all tonic
neural activity to the heart (10).
To record the electrical activity of the right atrium and
ventricle, two bipolar electrodes were placed on the base of
the epicardial surface of the right atrial appendage and on
the epicardial surface of the right ventricle, respectively. The
spontaneous SCL and AVCT were measured and displayed
on a thermowriting rectigraph (model WT 685T; Nihon Kohden, Tokyo, Japan). The right atrial pressure was measured
by a catheter-tip pressure transducer (model TCP2, Nihon
Kohden) that was inserted into the middle of the right atrial
cavity via the right jugular vein. Right atrial pressure and
RAdP/dt were recorded on the rectigraph. Systemic arterial
pressure was also measured via the right femoral artery.
Two bipolar silver electrodes, at a 2-mm interelectrode
distance, were used to stimulate the intracardiac parasympathetic neural elements. One was placed on the fatty tissue
overlying the right atrial side of the juncture of the right
pulmonary veins (8, 19); we refer to this electrical stimulation of the intracardiac parasympathetic neural elements to
the SA nodal region as SAPS. Another was placed on the
fatty tissue at the juncture of the inferior vena cava and left
atrium; we refer to this electrical stimulation of the intracardiac neural elements to the AV nodal region as AVPS. Both
electrodes were connected an electrical stimulator (model
SEN 7103, Nihon Kohden). Stimulation was subthreshold for
activation of pacemaker cells and cardiac muscle cells when
a quite narrow stimulation pulse duration (0.01–0.06 ms) for
parasympathetic nerve stimulation was used (8). To stimulate extracardiac parasympathetic efferent nerves to the
heart, two fine copper needle electrodes were inserted into
each cervical vagus nerve at the neck; we refer to such
electrical stimulation as the cervical vagal complex (CVS).
Before the experiment, we arbitrarily determined the pulse
duration and a frequency of the stimulation (SAPS and
AVPS, 0.01–0.06 ms and 10–30 Hz; CVS, 0.01–0.04 ms and
5–20 Hz) to increase the SCL by 300 ms and prolong the
AVCT by 30 ms. The voltage amplitude of the stimulation
was 10 V.
Protocols. We conducted two series of experiments. In the
first series, to determine the role of the parasympathetic
ganglionic cells in the SVC-Ao fat pad on the cardiac responses, we investigated the effects of topical injection of
trimethaphan (n ⫽ 8), a nicotinic ganglionic receptor antagonist, or lidocaine (n ⫽ 6), a sodium channel blocker, into the
SVC-Ao fat pad on the inotropic, chronotropic, and dromotropic responses to CVS in the anesthetized dogs. Trimethaphan was injected at a dose of 0.3 mg in a volume of 0.2
ml saline, and lidocaine was injected at a dose of 3.0 mg in a
volume of 0.2 ml saline. Used doses of trimethaphan or
lidocaine did not significantly influence the SCL, the AVCT,
and atrial contractility. Direct cardiac effects of a blocker
were determined 3 min after the drug administration, and
then the drug effects on the cardiac responses to CVS were
determined at the end of a 30-s stimulation.
In the second series, to determine the different roles between the parasympathetic ganglionic cells in the SVC-Ao fat
pad and those in the SAPS locus, we studied the effects of
topical injection of trimethaphan at a dose of 0.3 mg (n ⫽ 8)
or lidocaine at a dose of 3.0 mg (n ⫽ 5) in a volume of 0.2 ml
saline into the SAPS locus on the inotropic, chronotropic, and
dromotropic responses to CVS, SAPS, or AVPS. Additionally,
we also studied the effects of topical injection of trimethaphan into the SVC-Ao fat pad followed by injection of
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Fig. 1. Representative functional responses to stimulation of both
sides of cervical vagus complex (CVS) at a frequency of 20 Hz with
0.01-ms pulse duration and 10 V ( A) stimulation of the rate-related
parasympathetic nerves to the SA node (SAPS) at a frequency of 30
Hz with 0.03-ms pulse duration and 10 V (B), and stimulation of
atrioventricular conduction-related parasympathetic nerves to the
AV node (AVPS) at a frequency of 30 Hz with 0.05-ms pulse duration
and 10 V (C), 30 s after the beginning of stimulation in an autonomically decentralized heart of the open-chest anesthetized dog. SCL,
sinus cycle length; AVCT, atrioventricular conduction time dP/dt,
change in pressure over time.
in six experiments (Fig. 3). Three minutes after lidocaine treatment, basal heart rate and arterial blood
pressure did not change significantly from the predrug
control levels.
Effects of trimethaphan or lidocaine injected into the
SAPS locus. To investigate the relationship between
the functional role of the parasympathetic ganglionic
cells in the SVC-Ao fat pad and those of the SAPS
locus, we studied the effects of trimethaphan injected
into the SAPS locus on the changes in right atrial
contractile force, SCL, and AVCT in response to CVS,
SAPS, or AVPS. Topical injection of trimethaphan into
the SAPS locus suppressed the negative chronotropic
and inotropic responses to SAPS by 98.0 ⫾ 1.0% and
95.8 ⫾ 2.3% from the respective control level (100%),
respectively, and it also suppressed the negative chronotropic response to CVS by 86.0 ⫾ 3.5% (Fig. 4).
However, trimethaphan injected into the SAPS locus
attenuated the negative inotropic response to CVS
partially by 42.4 ⫾ 3.5%. Dromotropic responses to
Table 1. Inotropic, chronotropic, and dromotropic responses to stimulation of both sides of the cervical vagus
nerves, stimulation of SAPS, and stimulation of AVPS in anesthetized dog hearts
CVS
Control
Stimulation
SAPS
Control
Stimulation
AVPS
Control
Stimulation
n
RAP, mmHg
RA dP/dt, mmHg/s
SCL, ms
AVCT, ms
12
12
5.3 ⫾ 0.2
2.8 ⫾ 0.3**
40.7 ⫾ 2.1
12.4 ⫾ 1.7***
451 ⫾ 13
778 ⫾ 41***
133 ⫾ 6
176 ⫾ 8***
12
12
5.3 ⫾ 0.2
4.0 ⫾ 0.3*
40.6 ⫾ 1.7
24.6 ⫾ 1.8**
451 ⫾ 14
782 ⫾ 50***
133 ⫾ 6
123 ⫾ 6
11
11
5.1 ⫾ 0.2
5.1 ⫾ 0.2
38.2 ⫾ 1.3
39.6 ⫾ 1.7
454 ⫾ 13
459 ⫾ 12
133 ⫾ 6
165 ⫾ 8**
Data are shown as means ⫾ SE; n, number of hearts. RAP, right atrial a wave pressure; RA dP/dt, first derivative of the RAP; SCL, sinus
cycle length; AVCT, atrioventricular conduction time; CVS, cervical vagus complex; SAPS, parasympathetic nerves to the sinoatrial node;
AVPS, parasympathetic nerves to the atrioventricular node. * P ⬍ 0.05, ** P ⬍ 0.01, and *** P ⬍ 0.001 vs. control.
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Fig. 2. Effects of trimethaphan at a dose of 0.3 mg injected into the
superior vena cava and aortic root (SVC-Ao) fat pad, decreases in
right atrial first pressure derivative (RA dP/dt, A), increases in SCL
(B), and prolongation of AVCT (C) in response to stimulation of both
sides of CVS in 8 anesthetized dogs. Changes of basal state: decreases in RA dP/dt by CVS from 40.4 ⫾ 2.3 to 10.6 ⫾ 1.6 mmHg
(73.7%), increases in SCL by CVS from 459 ⫾ 18 to 806 ⫾ 64 ms
(74.4%), and prolongations of AVCT by CVS from 122 ⫾ 5 to 172 ⫾
9 ms (41.6%). Open and solid columns present responses to CVS
before and after trimethaphan treatment, respectively. * P ⬍ 0.001
vs. control.
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PARASYMPATHETIC GANGLIA AND CARDIAC FUNCTION
negative cardiac responses to CVS or SAPS were not
additive to the inhibition by trimethaphan treatment
alone.
DISCUSSION
CVS and AVPS were not affected by trimethaphan
injected into the SAPS locus.
We also studied the effects of lidocaine injected into
the SAPS locus on the cardiac responses to CVS, SAPS,
or AVPS (Fig. 5). Topical injection of lidocaine at a dose
of 3.0 mg in a volume of 0.2 ml saline into the SAPS
locus abolished the negative chronotropic responses to
SAPS and CVS and the negative inotropic response to
SAPS. Lidocaine attenuated the negative inotropic response to CVS partly by 56.0 ⫾ 6.7% from the respective control level (100%). These effects of lidocaine on
the cardiac responses to CVS and SAPS were similar to
those effects of trimethaphan injected into the SAPS
locus (Figs. 4 and 5). Lidocaine did not affect the
dromotropic responses to each parasympathetic stimulation.
Additionally, we investigated the effects of trimethaphan on the cardiac responses to CVS or SAPS
when trimethaphan was injected into the SVC-Ao fat
pad followed by injection into the SAPS locus in four
anesthetized dogs (Fig. 6). Topical injection of trimethaphan into the SVC-Ao fat pad attenuated the
negative inotropic (Fig. 6A) and chronotropic (Fig. 6B)
responses to CVS by 29.9 ⫾ 6.4% and 35.6 ⫾ 9.3% from
the control level (100%), respectively. The injection of
trimethaphan into the SAPS locus following the trimethaphan injection into the SVC-Ao fat pad then
further attenuated the negative inotropic response to
CVS by 49.9 ⫾ 2.4% from the predrug control level and
suppressed the residual negative chronotropic response to CVS by 91.8 ⫾ 2.0%. The negative inotropic
(Fig. 6C) and chronotropic (Fig. 6D) responses to SAPS
were slightly but not significantly attenuated by the
injection of trimethaphan into the SVC-Ao fat pad and
suppressed by the following injection of trimethaphan
into the SAPS locus. The inhibitions by trimethaphan
injected into the SVC-Ao fat pad and SAPS locus of the
Fig. 4. Effects of trimethaphan at a dose of 0.3 mg injected into the
SAPS locus on decreases in RA dP/dt ( A), increases in SCL (B), and
prolongation of AVCT (C) in response to both sides of CVS, the
rate-related SAPS, and AVPS in 8 anesthetized dogs. Changes of
basal state: decreases in RA dP/dt by CVS and SAPS from 37.0 ⫾ 2.4
to 11.4 ⫾ 2.0 mmHg (68.5%) and from 36.5 ⫾ 2.6 to 20.2 ⫾ 1.7 mmHg
(43.5%), respectively; increases in SCL by CVS and SAPS from 500 ⫾
24 to 824 ⫾ 23 ms (66.9%) and from 503 ⫾ 24 to 824 ⫾ 42 ms (64.4%),
respectively; and prolongations of AVCT by CVS and AVPS from
127 ⫾ 8 to 178 ⫾ 11 ms (42.0%) and from 126 ⫾ 9 to 166 ⫾ 15 ms
(31.1%), respectively. Open and solid columns present responses to
each stimulation before and after trimethaphan treatment, respectively. * P ⬍ 0.001 vs. control.
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Fig. 3. Effects of lidocaine at a dose of 3.0 mg injected into the
SVC-Ao fat pad on decreases in RA dP/dt ( A), increases in SCL (B),
and prolongation of AVCT (C) in response to both sides of CVS in 6
anesthetized dogs. Changes of basal state: decreases in RAdP/dt by
CVS from 37.0 ⫾ 2.4 to 9.8 ⫾ 3.1 mmHg (74.5%), increases in SCL by
CVS from 455 ⫾ 16 to 773 ⫾ 46 ms (70.3%), and prolongations of
AVCT by CVS from 140 ⫾ 7 to 192 ⫾ 4 ms (38.9%). Open and solid
columns present responses to each stimulation before and after
lidocaine treatment, respectively. * P ⬍ 0.001 vs. control.
Parasympathetic ganglionic cells in the SAPS locus
and AVPS locus selectively control the atrial pacemaker activity and AV conduction, respectively, in the
dog heart (5, 7). Since the SAPS caused a negative
chronotropic and inotropic effect and was blocked by
treatment with hexamethomium (7) or with trimethaphan in this study, ganglionic cells might not be
activated directly by the stimulus but rather the
preganglionic fibers were. Miyazaki et al. (13) demonstrated that 1) vagal neuronal transmission in the
heart was readily inhibited by either hexamethonium,
a ganglionic blocker, or tetrodotoxin, an axonal
blocker, and 2) sympathetic neurotransmission was
blocked by tetrodotoxin but not by hexamethonium. In
the present study, we showed that trimethaphan, a
ganglionic blocker, readily blocked SAPS-induced negative chronotropic and inotropic effects, confirming the
results demonstrated by Miyazaki et al. (13). To inhibit
the shortening of the atrial refractory period by parasympathetic activation, Chiou et al. (4) applied epicar-
PARASYMPATHETIC GANGLIA AND CARDIAC FUNCTION
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Fig. 5. Effects of lidocaine at a dose of 3.0 mg injected into the SAPS
locus on decreases in RA dP/dt ( A), increases in SCL (B), and
prolongation of AVCT (C) in response to both sides of CVS, the
rate-related SAPS, and AVPS in 5 anesthetized dogs. Changes of
basal state: decreases in RA dP/dt by CVS and SAPS from 38.4 ⫾ 3.0
to 11.6 ⫾ 2.8 mmHg (69.6%) and from 37.4 ⫾ 3.2 to 17.4 ⫾ 3.5 mmHg
(54.3%), respectively; increases in SCL by CVS and SAPS from 494 ⫾
32 to 822 ⫾ 79 ms (69.6%) and from 490 ⫾ 29 to 840 ⫾ 104 ms
(69.0%), respectively; and prolongations of AVCT by CVS and AVPS
from 130 ⫾ 7 to 185 ⫾ 9 ms (44.0%) and from 130 ⫾ 9 to 166 ⫾ 8 ms
(29.4%), respectively. Open and solid columns present responses to
each stimulation before and after lidocaine treatment, respectively.
* P ⬍ 0.001 vs. control.
dial radiofrequency catheter ablation to the SVC-Ao fat
pad in the dog heart. From their results, they thought
that the parasympathetic neural elements in the
SVC-Ao fat pad were the head station of vagal fibers to
both atria and to the sinus and AV nodes in the dog.
They investigated changes in atrial refractory period in
the fat pads, but they did not study other cardiac
responses, although there are parasympathetic ganglionic cells in the SVC-Ao fat pad of the dog. In 1992,
Mick et al. (12) reported that another fat pad controlling the sinus function exists at the posterior atrial site
(PAFP, posterior atrial fat pad) neighbor to the SVC-Ao
fat pad in the dog heart. However, the PAFP is not
identical with SVC-Ao fat pad that Chiou et al. (4)
reported, in anatomical location, because the SVC-Ao
fat pad is located between the medial SVC and aortic
root, superior to the right pulmonary artery, and the
PAFP is located the posterior atrial site. In the present
study we demonstrated first that parasympathetic
ganglionic cells in the SVC-Ao fat pad control the right
atrial contractile force, sinus node activity, and AV
conduction partially and nonselectively in the dog
heart. These results suggest that the parasympathetic
ganglionic cells in the SVC-Ao fat pad are functionally
different from those in the SAPS locus and AVPS locus.
Fig. 6. Inhibition by trimethaphan injected into the SVC-Ao fat pad
followed by that into the SAPS locus of the negative inotropic (RA
dP/dt) and chronotropic (SCL) responses to stimulation of both sides
of CVS and the rate-related SAPS in 4 anesthetized dogs. Changes of
basal state: decreases in RAdP/dt by CVS from 39.8 ⫾ 2.7 to 10.0 ⫾
1.2 mmHg (75.0%); increases in SCL by CVS from 493 ⫾ 12 to 938 ⫾
40 ms (91.0%); decreases in RA dP/dt by SAPS from 39.6 ⫾ 2.6 to
23.0 ⫾ 2.8 mmHg (42.4%); and increases in SCL by CVS from 492 ⫾
11 to 873 ⫾ 42 ms (78.7%). Open, hatched, and solid columns present
the cardiac responses to each stimulation before and after trimethaphan treatment into the SVC-Ao fat pad followed by treatment
with trimethaphan into the SAPS locus, respectively. * P ⬍ 0.001 vs.
control.
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The parasympathetic ganglionic cells in the SAPS locus and AVPS locus selectively control the chronotropic
and dromotropic activity, respectively. On the other
hand, those in the SVC-Ao fat pad affect to some degree
inotropic, chronotropic, and dromotropic activity, respectively.
Control of the sinus node pacemaker activity. Effect
of the application of lidocaine or trimethaphan into the
SAPS locus or the SVC-Ao fat pad (Figs. 2–5) suggests
that 1) almost all parasympathetic nerve fibers that
induce the negative chronotropic effect pass through
the SVC-Ao fat pad, 2) they change the ganglionic
neurotransmission at the parasympathetic ganglionic
cells in the dog heart, and 3) some of the cervical nerve
fibers change the synapses in the SVC-Ao fat pad
and/or the SAPS locus in the dog heart.
Control of atrial contractile force. We studied the a
wave pressure and its first derivative of the right
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PARASYMPATHETIC GANGLIA AND CARDIAC FUNCTION
only in part (9, 23). On the other hand, Chiou et al.
(4) thought that the parasympathetic neural elements including parasympathetic ganglia in the
SVC-Ao fat pad were the head station of the vagal
fibers to both atria and to the SA and AV nodes in the
dog. However, in the present study, we presented
that the parasympathetic ganglionic cells in the
SVC-Ao fat pad might not be the head station of
vagal fibers to the right atrium and to the sinus and
AV nodes in the dog. They might work as an overall
modulator of the atrial pacemaker activity, atrial
contractility, and AV conduction in the dog heart.
This modulator may balance pacemaker activity and
AV conductivity to complete heartbeat as previously
suggested (15).
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H1112–H1118, 1990.
9. Inoue Y, Furukawa Y, Nakano H, Sawaki S, Oguchi T, and
Chiba S. Parasympathetic control of right atrial pressure in
anesthetized dogs. Am J Physiol Heart Circ Physiol 266: H861–
H866, 1994.
10. Levy MN, Ng ML, and Zieske H. Functional distribution of the
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11. McGuirt AS, Schmacht DC, and Ardell JL. Autonomic interactions for control of atrial rate are maintained after SA nodal
parasympathectomy. Am J Physiol Heart Circ Physiol 272:
H2525–H2533, 1997.
12. Mick JD, Wurster RD, Duff M, Weber M, Randall WC, and
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11: 179–188, 1998.
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atrium as an indicator of the right atrial myocardial
contractility in the dog heart. The first derivative of the
a wave pressure reflects the sum of the contraction of
the right atrial muscles form the right intra-atrial
cavity, although the a wave pressure is influenced by
timing of the closure of the tricuspid valves and other
factors, e.g., the venous return as preload, and the
right ventricular pressure as afterload (16).
In the present study, we confirm that parasympathetic ganglionic cells in the SAPS locus from both
sides of CVS control the right atrial myocardial contractility partially in the dog heart (9). Furthermore,
lidocaine injected into the SVC-Ao fat pad suppressed
the negative inotropic response to CVS (Fig. 3), and
trimethaphan injected into the SVC-Ao fat pad alone
and into the SVC-Ao fat pad and the SAPS locus also
attenuated the inotropic response to CVS in part (Figs.
2 and 6). These results, therefore, suggest that one-half
of the parasympathetic ganglionic cells controlling the
right atrial contractility exist in the SAPS locus and
SVC-Ao fat pad, and there may be no selective cluster
of the intracardiac parasympathetic ganglia for the
control of atrial contractile force in the dog heart.
There are many clusters of the ganglionic cells in the
dog heart (2, 24), but AVPS or stimulation of the
clusters of the ganglionic cells at the AV fat pad did not
affect the right atrial contractility in the anesthetized
dog (14). Cardiac responses to vagus stimulation are
also regulated by intracardiac and extracardiac neural
regulation in the dog heart (11). Thus, to control the
atrial contractile force at the parasympathetic ganglia,
we need further studies to define the residual parasympathetic ganglionic cells in the heart or extra-cardiac
sites.
In the present study, we have focused on the selective control of the parasympathetic ganglionic
cells in the SVC-Ao fat pad on the atrial contractile
force. Thus we did not investigate precisely the relationship between the parasympathetic ganglionic
cells in the SVC-Ao fat pad and those in the AVPS
locus. However, from present results and previous
reports (7, 18), we can speculate that control of the
dromotropic response to parasympathetic nerve activations similarly involves both the SVC-Ao fat pad
and the SAPS locus.
There are three functional parasympathetic ganglia groups in the dog heart: parasympathetic ganglionic cells in the SA fat pad for the pacemaker
activity and those in the AV fat pad for the AV
conduction (1, 8, 19), and parasympathetic ganglionic cells in the SVC-Ao fat pad for the pacemaker
activity, atrial contractility, and AV conduction
shown in the present study. The parasympathetic
ganglia in the SA fat pad work as a controller of the
atrial rate and those in the AV fat pad work as a
controller of the AV conduction. We have investigated whether those parasympathetic ganglia control respective cardiac functions at the presynaptic
site or at the heart (6–9, 14, 23). Some of the parasympathetic ganglionic cells in the SA fat pad regulate the atrial contractile force and refractory period
PARASYMPATHETIC GANGLIA AND CARDIAC FUNCTION
15. O’Toole MF, Ardell JL, and Randall WC. Functional interdependence of discrete vagal projections to SA and AV nodes.
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16. Parmley WW and Talbot L. Heart as a pump. In: Handbook of
Physiology. The Cardiovascular System. The Heart. Bethesda,
MD: Am. Physiol. Soc., 1979, sect. 2, vol. I, chapt. 11, p. 429–460.
17. Randall WC. Selective autonomic innervation of the heart. In:
Nervous Control of Cardiovascular Function, edited by Randall
WC. New York: Oxford Univ. Press, 1984, p. 46–67.
18. Randall WC. Changing perspectives concerning neural control
of the heart. In: Neurocardiology, edited by Armour JA and
Ardell JL. New York: Oxford Univ. Press, 1993, p. 3–17.
19. Randall WC and Ardell JL. Selective parasympathectomy of
automatic and conductile tissues of the canine heart. Am J
Physiol Heart Circ Physiol 248: H61–H68, 1985.
H1207
20. Randall WC, Ardell JL, Caldwood D, Milosavljevic M, and
Goyal SC. Parasympathetic ganglia innervating the canine atrioventricular nodal region. J Auton Nerv Syst 16: 311–323, 1986.
21. Randall WC, Kaye MP, Thomas JX, and Barber JM. Intrapericardial denervation of the heart. J Surg Res 29: 101–109, 1980.
22. Randall WC, Thomas JX, Barber JM, and Rinkema LE.
Selective denervation of the heart. Am J Physiol Heart Circ
Physiol 244: H607–H613, 1983.
23. Takei M, Furukawa Y, Narita M, Ren L, Karasawa Y,
Murakami M, and Chiba S. Synergistic nonuniform shortening of atrial refractory period induced by autonomic stimulation.
Am J Physiol Heart Circ Physiol 261: H1988–H1993, 1991.
24. Yuan BX, Ardell JL, Hopkins DA, Rosier AM, and Armour
JA. Gross and microscopic anatomy of the canine intrinsic cardiac nervous system. Anat Rec 239: 75–87, 1994.
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