Vol. 279, Issue 3, H1201-H1207, September 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
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ABSTRACT |
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 conduction-related 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.
parasympathetic ganglionic cells; atrial contractility; sinus rate; atrioventricular conduction; trimethaphan
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INTRODUCTION |
EFFERENT VAGAL NERVE
FIBERS 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 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 conduction-related
parasympathetic neural elements in the AV fat pad separately (8,
9).
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METHODS |
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 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 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.
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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.
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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.
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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
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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.
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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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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%) 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.
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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.
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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 CVS
and AVPS were not affected by trimethaphan injected into the SAPS
locus.
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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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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.
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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.
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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 negative cardiac
responses to CVS or SAPS were not additive to the inhibition by
trimethaphan treatment alone.
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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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DISCUSSION |
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 epicardial
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. 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 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 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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FOOTNOTES |
Address for reprint requests and correspondence: S. Chiba,
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 11 November 1999; accepted in final form 8 March 2000.
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