| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, Osaka 565-8565; 2 Japan Space Forum, Tokyo 105-0013; and 3 Organization for Pharmaceutical Safety and Research, Tokyo 100-0013, Japan
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
|
|---|
To better understand the
pathophysiological significance of high plasma norepinephrine (NE)
concentration in regulating heart rate (HR), we examined the
interactions between high plasma NE and dynamic vagal control of HR. In
anesthetized rabbits with sinoaortic denervation and vagotomy, using a
binary white noise sequence (0-10 Hz) for 10 min, we stimulated
the right vagus and estimated the transfer function from vagal
stimulation to HR response. The transfer function approximated a
first-order low-pass filter with pure delay. Infusion of NE (100 µg · kg
1 · h1 iv)
attenuated the dynamic gain from 6.2 ± 0.8 to 3.9 ± 1.2 beats · min1 · Hz1
(n = 7, P < 0.05) without affecting
the corner frequency or pure delay. Simultaneous intravenous
administration of phentolamine (1 mg · kg1 · h1) and NE (100 µg · kg1 · h1) abolished
the inhibitory effect of NE on the dynamic gain (6.3 ± 0.8 vs.
6.4 ± 1.3 beats · min1 · Hz1, not
significant, n = 7). The inhibitory effect of NE at
infusion rates of 10, 50, and 100 µg · kg1 · h1 on dynamic
vagal control of HR was dose-dependent (n = 5). In conclusion, high plasma NE attenuated the dynamic HR response to vagal
stimulation, probably via activation of 
-adrenergic receptors on the
preganglionic and/or postganglionic cardiac vagal nerve terminals.
systems analysis; transfer function; -adrenergic receptors; heart rate variability; rabbit
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
|
|---|
HEART RATE (HR) is mainly regulated by the sympathetic and parasympathetic nervous systems. Sympathetic activation and/or vagal withdrawal increases HR, whereas sympathetic withdrawal and/or vagal activation decreases HR. Accordingly, information on the mean level of HR alone does not allow a separate estimate of efferent activities of the two divisions of the autonomic nervous system. In contrast, information on the dynamic HR response has been considered useful in assessing vagal efferent nerve activity separately from sympathetic efferent nerve activity, because dynamic HR regulation is much faster via the vagal system than via the sympathetic system (3, 12). Accordingly, the high-frequency (HF) component (>0.15 Hz in humans) of HR variability (HRV) might reflect the cardiac vagal efferent nerve activity (2, 23). However, this notion is simplistic, in that it disregards interactions between the sympathetic and vagal systems.
Complex sympathovagal interactions are known to occur in regulation of
HR. An increase in the background sympathetic tone augmented the HR
response to vagal nerve activity (16, 17). Levy
(17) termed this phenomenon an accentuated antagonism of the vagal control of HR. Accumulation of cAMP in the sinus nodal cells
via activation of the postjunctional 
-adrenergic receptors contributed to the accentuated antagonism (20). On the
other hand, activation of the prejunctional -adrenergic receptors
influenced acetylcholine (ACh) release from the cardiac vagal nerve
terminals (25). Local norepinephrine (NE) administration
in the in vivo feline heart attenuated the myocardial interstitial ACh
release during electrical stimulation of the vagi via the
-adrenergic mechanism (1). Cholinergic transmission in
the parasympathetic ganglia was also attenuated by NE via the
-adrenergic mechanism (24). Taken together, the HR
response to vagal stimulation can be enhanced or attenuated by the
concomitant sympathetic activity, depending on which of these
adrenergic receptors relating to cardiac regulation is the most
selectively activated.
Physiological and pathophysiological activation of the systemic sympathetic nerves accompanies an increase in plasma NE concentration (7). Although previous studies from our laboratory demonstrated that concomitant electrical stimulation of the cardiac sympathetic nerve augmented the dynamic HR response to electrical stimulation of the vagus (12-14), plasma NE concentration did not increase perceivably, because sympathetic nerves other than the cardiac sympathetic nerve were not stimulated (15). Accordingly, it remains to be elucidated how changes in plasma NE concentration modulate the dynamic HR response to vagal stimulation. We hypothesized that high plasma NE without direct activation of the cardiac sympathetic nerve affected dynamic vagal control of HR. Inasmuch as plasma NE concentration correlates positively with the severity of cardiovascular diseases such as heart failure (9), elucidating the effects of high plasma NE on dynamic vagal control of HR is essential for a better understanding of the pathophysiological significance of sympathovagal interactions in regulating HR. The purpose of the present study was to examine the effects of high plasma NE on dynamic HR regulation by the vagal system. The results indicated that high plasma NE attenuated the dynamic HR response to electrical stimulation of the vagus.
| |
MATERIALS AND METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
|
|---|
Surgical Preparations
Animals were cared for in accordance with guidelines approved by the Physiological Society of Japan. Nineteen Japanese white rabbits weighing 2.4-3.2 kg were anesthetized by intravenous injection (2 ml/kg) of a mixture of urethane (250 mg/ml) and-chloralose (40 mg/ml) and mechanically ventilated with oxygen-enriched room air.
Supplemental doses of these anesthetics were given as necessary via the
marginal ear vein. Aortic pressure (AP) was monitored by a
micromanometer catheter (Millar Instruments, Houston, TX) inserted via
the right femoral artery. A double-lumen catheter was inserted into the
right femoral vein for the later administration of pharmacological
agents. Sinoaortic denervation was performed bilaterally to minimize
changes in sympathetic efferent nerve activity via the arterial
baroreflexes. Briefly, the external and internal carotid arteries were
identified under a dissecting microscope. The connective tissues
between the two arteries were carefully detached from the arterial
walls. The connective tissues, including the carotid sinus nerves, were
then sectioned between two ligatures placed around the tissues. The
aortic depressor nerves, which run separately from the vagi in rabbits,
were sectioned at the neck. The vagi were also sectioned at the neck,
where a pair of bipolar platinum electrodes were attached to the
cardiac end of the sectioned right vagus. To prevent drying and to
provide insulation, the stimulation electrodes and the nerve were
immersed in a mixture of white petroleum jelly (Vaseline) and liquid
paraffin. The right cardiac sympathetic nerve was exposed through a
midline thoracotomy and sectioned, resulting in a decrease in HR of 40 beats/min on average. The right cardiac sympathetic nerve is considered more effective than the left cardiac sympathetic nerve in regulating HR
(19, 22). Finally, a pair of bipolar stainless steel wire electrodes were attached to the right atrium to record the
electrocardiogram for measuring HR. Body temperature was maintained at
38°C with a heating pad throughout the experiment.
Protocols
The pulse duration of electrical stimulation of the vagus was set at 2 ms. The amplitude of stimulation (3-6 V) was adjusted in each animal to yield a decrease in HR of ~50 beats/min at 5 Hz. To estimate the transfer function from vagal stimulation to the HR response, we stimulated the vagus using a frequency-modulated pulse train. The stimulation frequency was switched every second at 0 or 10 Hz according to a binary white noise signal. The power spectrum of the stimulation signal was reasonably constant up to 0.5 Hz, decreased gradually to 1/10 at ~0.8 Hz, and was attenuated sharply as the frequency increased to 1 Hz. We estimated the transfer function only up to 0.8 Hz, because the lack of input power above that frequency reduced the reliability of estimation. The frequency range spanned the physiological range of interest sufficiently with respect to the dynamic vagal control of HR in rabbits (12, 13, 20, 21).Protocol 1 (n = 7).
We examined the effects of intravenous infusion of NE on the transfer
function from vagal stimulation to the HR response. We first recorded
the dynamic HR response to vagal stimulation for 10 min under control
conditions. We then initiated intravenous administration of NE at 100 µg · kg1 · h1 and waited
until the new steady states of HR and AP were reached. After 15 min, we
repeated the vagal stimulation. The dose of NE was chosen near the
maximum dose used in previous studies (6, 11).
Protocol 2 (n = 7).
We examined the combined effects of simultaneous intravenous infusion
of the -adrenergic antagonist phentolamine (1 mg · kg1 · h1) and NE (100 µg · kg1 · h1) on the
transfer function from vagal stimulation to the HR response. Estimation
of the transfer function was repeated before and during the
pharmacological interventions with an intervening interval of 15 min.
Protocol 3 (n = 5).
We examined the dose dependence of the effects of intravenous NE
infusion on the transfer function from vagal stimulation to the HR
response. The intravenous infusion rate of NE was varied among 0, 10, 50, and 100 µg · kg1 · h1
in increasing order. Each infusion rate continued for 30 min. Data for
the transfer function analysis were recorded from 15 min after the
transition of the infusion rate.
Data Analysis
We resampled the input-output data pairs of the vagal stimulation frequency and HR at 10 Hz and then segmented them into eight 50%-overlapping segments of 1,024 data points each. For each segment, the linear trend was subtracted and a Hanning window was applied. We then performed fast Fourier transformation to obtain the frequency spectrum of vagal stimulation [N(f)] and that of HR [HR(f)] (5). We ensemble averaged, over the eight segments, the power of the vagal stimulation [SN.N(f)] and HR [SHR.HR(f)] and the cross power between vagal stimulation and HR [SN.HR(f)]. Finally, we obtained the transfer function [H(f)] from vagal stimulation to the HR response using the following equation (18)
|
|
1 · Hz1),
fC is the corner frequency (in Hz), L
is the pure delay (in s), and f and j represent
frequency and imaginary unit, respectively. The negative sign in the
numerator indicates the negative HR response to vagal stimulation. The
parameters were estimated by means of iterative nonlinear least-squares
regression. Errors in the fitting procedure were calculated from the
gain and phase differences averaged in the frequencies from 0.01 to 0.8 Hz (see APPENDIX).
To quantify the linear dependence of HR response on vagal stimulation,
we estimated the magnitude-squared coherence function [Coh(f)] by the following equation (18)
|
Statistics
Values are means ± SE. In protocols 1 and 2, differences in mean levels of HR and AP and fitted parameters of the transfer function before and during pharmacological interventions were examined using a paired t-test (10). The differences were considered significant at P < 0.05. In protocol 3, the percent change in dynamic gain from control was calculated at each infusion rate of NE. A linear regression analysis was performed on the pooled data of percent gain vs. the common logarithm of the infusion rate as follows
|
1 · h1) and
a and b are the intercept and slope of the linear
regression, respectively. The test for the regression slope at
P < 0.05 was performed to examine the dose dependence
in the effects of intravenous NE on dynamic vagal control of HR.
| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
|
|---|
Figure 1 shows typical recordings of
vagal stimulation and HR response in the absence and presence of the
intravenous NE infusion. Random vagal stimulation decreased HR
intermittently. Intravenous NE infusion increased the mean level of AP
but did not affect the mean level of HR before and during vagal
stimulation (Table 1). The amplitude of
the HR variation was smaller in the presence than in the absence of
intravenous NE. The speed of the HR response to vagal stimulation
appeared to be unchanged by intravenous NE.
|
|
Figure 2 shows the transfer functions
from vagal stimulation to the HR response averaged from all animals in
protocol 1. The gain plots, phase plots, and coherence
functions are shown. The transfer gain was relatively constant below
0.03 Hz and decreased above the frequency up to 0.8 Hz in the absence
and presence of exogenous NE. The phase approached 
radians at the
lowest frequency and lagged with increasing frequency. Coherence was
near unity at frequency <0.3 Hz under control conditions. Coherence
was >0.8 at frequency <0.3 Hz in the presence of exogenous NE. The
fitted parameters of the transfer functions and errors in the
fitting procedure are summarized in Table
2. Intravenous NE infusion decreased the
dynamic gain without affecting the corner frequency or pure delay.
|
|
Figure 3 shows typical recordings of
vagal stimulation and the associated changes in HR in the absence and
presence of intravenous phentolamine and NE infusion. Vagal stimulation
randomly decreased HR. Simultaneous administration of phentolamine and
NE decreased the mean levels of AP but did not affect the mean levels
of HR (Table 1). The amplitude of the HRV was similar in the presence and absence of the pharmacological interventions.
|
Figure 4 shows the transfer functions
from vagal stimulation to the HR response averaged from all animals in
protocol 2. The transfer gain was relatively constant at
<0.03 Hz and decreased between 0.03 and 0.8 Hz in the absence and
presence of pharmacological interventions. The phase approached
radians at the lowest frequency and lagged with increasing frequency.
Coherence was near unity at frequency <0.4 Hz in the presence and
absence of pharmacological interventions. The fitted parameters of the
transfer functions and errors in the fitting procedure are summarized
in Table 2. The dynamic gain, corner frequency, and pure delay were not
changed by the pharmacological interventions.
|
Figure 5 depicts the dose dependence in
the effects of intravenous NE on the dynamic gain of the transfer
function from vagal stimulation to the HR response obtained from
protocol 3. NE infusion decreased the dynamic gain to
83.0 ± 8.4, 68.9 ± 13.2, and 62.4 ± 17.9%
(means ± SD) at infusion rates of 10, 50, and 100 µg · kg1 · h1,
respectively. The slope of the regression was significant, indicating that the inhibitory effect of NE on the dynamic gain was dose dependent.
|
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
|
|---|
We have shown that intravenous NE infusion decreased dynamic gain
of the transfer function from vagal stimulation to the HR response.
Simultaneous administration of phentolamine with NE prevented the
inhibitory effects of intravenous NE on the dynamic gain of the HR
response to vagal stimulation, suggesting that the attenuation was
attributable to activation of the -adrenergic receptors on the
preganglionic and/or postganglionic vagal nerve terminals.
Effects of Intravenous NE Infusion on Dynamic Vagal Control of HR
Myocardial interstitial NE may be classified into NE of neuronal origin (NE released from the cardiac sympathetic nerve terminals) and NE of plasma origin (NE taken up from the coronary arteries into the myocardial interstitial space). In previous studies, concomitant electrical stimulation of the cardiac sympathetic nerve increased the dynamic gain of the transfer function from vagal stimulation to the HR response (12, 13). Selective stimulation of the cardiac sympathetic nerve alone does not increase plasma NE concentration perceivably (8, 15, 26). Thus the augmentation of the dynamic vagal control of HR observed in previous studies is mainly attributable to NE of neuronal origin. NE of neuronal origin would activate the postjunctional-adrenergic receptors on the sinus nodal
cells more selectively than the prejunctional -adrenergic receptors
on the cardiac vagal nerve terminals. The preferential activation of
the postjunctional -receptors accumulates cAMP in the sinus nodal
cells, leading to augmentation of the dynamic HR response to vagal
stimulation (20).
Stimulation of the cardiac sympathetic nerve and intravenous infusion
of NE increased left ventricular contractility to a similar extent,
providing the resulting myocardial interstitial NE levels are
comparable (15). In other words, there appeared to be no
qualitative difference between NE of neuronal origin and NE of plasma
origin with respect to sympathetic regulation of the heart. However,
intravenous NE infusion attenuated the dynamic HR response to vagal
stimulation (Figs. 2 and 5, Table 2), in marked contrast to the effects
of cardiac sympathetic nerve stimulation (12, 13). Changes
in the corner frequency and pure delay of the transfer function from
vagal stimulation to the HR response reflect changes in the degradation
process of ACh (21). Neither the corner frequency nor pure
delay was affected by intravenous NE infusion, suggesting that the
degradation process of ACh was not responsible for attenuation of the
vagal control of HR. One possible mechanism for attenuation of the
vagal control of HR by intravenous NE infusion is activation of
-adrenergic receptors on the cardiac vagal nerve terminals. This
interpretation is supported by the fact that simultaneous
administration of phentolamine with NE prevented attenuation of the
dynamic HR response to vagal stimulation (Fig. 4, Table 2). High plasma
NE inhibits cholinergic transmission in parasympathetic ganglia
(24) and the neuroeffector junction (1, 25)
via activation of the -adrenergic receptors. The possible
augmentation of dynamic vagal control of HR via activation of the
-adrenergic receptors on the sinus nodal cells was not observable
during intravenous NE infusion.
Using an experimental setting similar to the present study, Nakahara et
al. (20) demonstrated that intravenous administration of
the -adrenergic agonist isoproterenol increased the dynamic gain of
the transfer function from vagal stimulation to the HR response. We had
expected that simultaneous administration of phentolamine with NE
stimulated the -adrenergic receptors selectively, resulting in
augmentation of the dynamic HR response to vagal stimulation, similar
to that caused by administration of isoproterenol. However, dynamic
gain was not increased by simultaneous administration of phentolamine
with NE in the present study (Fig. 4, Table 2). Although the dose of
phentolamine was set at 10 times higher than the dose of NE
(1), it might have been insufficient to completely block
the -adrenergic action of NE on the vagal nerve terminals. Further
increasing the dose of phentolamine relative to NE could result in an
increase in dynamic gain. However, because administration of
phentolamine decreased AP and the conditions of the animals deteriorated, even in the presence of simultaneous NE infusion (Table
1), we could not increase the dose of phentolamine further.
Impact of Sympathovagal Interactions on Interpretation of the HF Component of HRV
The sympathetic and vagal systems showed low-pass filter characteristics in regulating HR (3). Sympathetic control of HR approximated a second-order low-pass filter; vagal control of HR approximated a first-order low-pass filter (12). Because the natural frequency of the second-order low-pass filter relating to sympathetic control and the corner frequency of the first-order low-pass filter relating to vagal control have similar values, dynamic gain of the HR response in the high-frequency range is much smaller in sympathetic than in vagal control. As a result, the HF component of HRV cannot carry information on sympathetic efferent nerve activity in the corresponding frequency range. In contrast, the HF component can transmit information on vagal efferent nerve activity in the corresponding frequency range. By taking advantage of the differential dynamic characteristics of HR regulation between the sympathetic and vagal systems, the HF component of HRV has served as an index of vagal efferent nerve activity (2, 23). The interpretation regarding the HF component, however, disregards the interactions between the sympathetic and vagal systems.As demonstrated in previous studies and the present study, concomitant sympathetic activation modulated the dynamic HR response to vagal stimulation (12, 13). Thus the HF component of HRV does not necessarily parallel vagal efferent nerve activity when sympathetic activation coexists. The HF component can be modulated by sympathetic activity, even when the vagal efferent nerve activity that generates the HF component remains unchanged. Making the interpretation of the HF component more complicated is the possibility that sympathetic nerve activation and high plasma NE might exert opposite influences on the dynamic HR response to vagal stimulation. When the dynamic HR response to vagal stimulation is augmented by concomitant sympathetic nerve activity, the HF component might overestimate the vagal efferent nerve activity. When the dynamic HR response to vagal stimulation is attenuated by high plasma NE, the HF component might underestimate vagal efferent nerve activity. Although the significance of high plasma NE relative to sympathetic nerve activity during physiological activation of the sympathetic system was unclear in the present study, high plasma NE associated with exercise or cardiovascular diseases such as heart failure could potentially modulate the dynamic HR response to vagal stimulation. As an example, a decrease in HRV during exercise and during additional infusion of NE demonstrated by Breuer et al. (4) may be in part attributable to the inhibitory effects of high plasma NE on dynamic vagal control of HR.
Limitations
There are several limitations to the present study. First, we obtained data from anesthetized animals. If data had been obtained from conscious animals, the results might have been different. However, we disabled the arterial baroreflexes and cut the autonomic efferent pathways; thus the anesthetics should have had little effect on our results. Second, we could not dissect out the effects of high plasma NE on the preganglionic vagal nerve fibers from the effects on the postganglionic vagal nerve fibers. Although separation of preganglionic and postganglionic mechanisms is of interest, it is beyond the scope of the present study, which focused on interactions between high plasma NE and dynamic vagal control of HR. Finally, high plasma NE may affect autonomic regulation of HR chronically. Further studies focused on the effects of chronic elevation of plasma NE on autonomic regulation of HR are clearly required to elucidate the pathophysiological significance of elevated NE.In conclusion, high plasma NE without direct activation of the cardiac
sympathetic nerve attenuated the dynamic HR response to vagal
stimulation. The attenuation was prevented by simultaneous administration of phentolamine with NE. These results indicate that
high plasma NE activates the -adrenergic receptors on the preganglionic and/or postganglionic cardiac vagal nerve terminals, leading to a reduced ACh release in response to preganglionic vagal
stimulation. Owing to the complex interactions between the sympathetic
and vagal systems, the HF component of HRV alone may not correctly
represent cardiac vagal nerve activity.
| |
APPENDIX |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
|
|---|
Errors in the fitting procedure of the transfer function.
Errors in the fitting procedure were calculated by the gain and phase
differences averaged at frequencies of 0.01-0.8 Hz. Gain
[G(f)] and phase [
(f)] values of the
transfer function were calculated from the following equations
|
|
|
error; in radians) were calculated between the
estimated (est) and fitted (fit) transfer functions using the following
equations
|
|
| |
ACKNOWLEDGEMENTS |
|---|
This study was supported by Ministry of Health and Welfare of Japan Research Grants for Cardiovascular Diseases 11C-3 and 11C-7; a Health Sciences Research Grant for Advanced Medical Technology from the Ministry of Health and Welfare of Japan; a Ground-Based Research Grant for Space Utilization promoted by National Space Development Agency of Japan and the Japan Space Forum; Ministry of Education, Science, Sports, and Culture of Japan Grants-in-Aid for Scientific Research B-11694337, C-11680862, and C-11670730 and Grant-in-Aid for Encouragement of Young Scientists 13770378; Japan Science and Technology Research and Development for Applying Advanced Computational Science and Technology; and the Organization for Pharmaceutical Safety and Research Program for Promotion of Fundamental Studies in Health Science.
| |
FOOTNOTES |
|---|
Address for reprint requests and other correspondence: T. Miyamoto, Dept. of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan (E-mail: miyamoto{at}res.ncvc.go.jp).
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.
First published February 21, 2003;10.1152/ajpheart.00660.2002
Received 31 July 2002; accepted in final form 11 February 2003.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
APPENDIX
REFERENCES
|
|---|
1.
Akiyama, T,
and
Yamazaki T.
Adrenergic inhibition of endogenous acetylcholine release on postganglionic cardiac vagal nerve terminals.
Cardiovasc Res
46:
531-538,
2000
2.
Akselrod, S,
Gordon D,
Ubel FA,
Shannon DC,
Berger AC,
and
Cohen RJ.
Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control.
Science
213:
220-222,
1981
3.
Berger, RD,
Saul JP,
and
Cohen RJ.
Transfer function analysis of autonomic regulation. I. Canine atrial rate response.
Am J Physiol Heart Circ Physiol
256:
H142-H152,
1989
4.
Breuer, HW,
Skyschally A,
Schulz R,
Martin C,
Wehr M,
and
Heusch G.
Heart rate variability and circulating catecholamine concentrations during steady-state exercise in healthy volunteers.
Br Heart J
70:
144-149,
1993
5.
Brigham, EO.
FFT transform applications.
In: The Fast Fourier Transform and Its Applications. Englewood Cliffs, NJ: Prentice-Hall, 1988, p. 167-203.
6.
Casals-Stenzel, J,
Tree M,
Brown JJ,
Fraser R,
Lever AF,
Millar JA,
Morton JJ,
Robertson JI,
Reid JL,
and
Hamilton C.
Effects of prolonged and brief infusions of noradrenaline on arterial pressure and on the plasma concentrations of active renin, angiotensin II, aldosterone and potassium.
J Hypertens
1:
27-35,
1983[Medline].
7.
Cryer, PE.
Physiology and pathology of the human sympathoadrenal neuroendocrine system.
N Engl J Med
303:
436-444,
1980[Web of Science][Medline].
8.
Ellingsen, O,
Vengen OA,
Kjeldsen SE,
Eide I,
and
Ilebekk A.
Myocardial potassium uptake and catecholamine release during cardiac sympathetic nerve stimulation.
Cardiovasc Res
21:
892-901,
1987[Web of Science][Medline].
9.
Esler, M,
Kaye D,
Lambert G,
Esler D,
and
Jennings G.
Adrenergic nervous system in heart failure.
Am J Cardiol
80:
7L-14L,
1997[Medline].
10.
Glantz, SA.
Primer of Biostatistics (5th ed). New York: McGraw-Hill, 2002.
11.
Huang, YG,
Wong KC,
Yip WH,
McJames SW,
and
Pace NL.
Cardiovascular responses to graded doses of three catecholamines during lactic and hydrochloric acidosis in dogs.
Br J Anaesth
74:
583-590,
1995
12.
Kawada, T,
Ikeda Y,
Sugimachi M,
Shishido T,
Kawaguchi O,
Yamazaki T,
Alexander J, Jr,
and
Sunagawa K.
Bidirectional augmentation of heart rate regulation by autonomic nervous system in rabbits.
Am J Physiol Heart Circ Physiol
271:
H288-H295,
1996
13.
Kawada, T,
Sugimachi M,
Shishido T,
Miyano H,
Ikeda Y,
Yoshimura R,
Sato T,
Takaki H,
Alexander J, Jr,
and
Sunagawa K.
Dynamic vagosympathetic interaction augments heart rate response irrespective of stimulation patterns.
Am J Physiol Heart Circ Physiol
272:
H2180-H2187,
1997
14.
Kawada, T,
Sugimachi M,
Shishido T,
Miyano H,
Sato T,
Yoshimura R,
Miyashita H,
Nakahara T,
Alexander J, Jr,
and
Sunagawa K.
Simultaneous identification of static and dynamic vagosympathetic interactions in regulating heart rate.
Am J Physiol Regul Integr Comp Physiol
276:
R782-R789,
1999
15.
Kawada, T,
Yamazaki T,
Akiyama T,
Shishido T,
Miyano H,
Sato T,
Sugimachi M,
Alexander J, Jr,
and
Sunagawa K.
Interstitial norepinephrine level by cardiac microdialysis correlates with ventricular contractility.
Am J Physiol Heart Circ Physiol
273:
H1107-H1112,
1997
16.
Levy, MN.
Autonomic interactions in cardiac control.
Ann NY Acad Sci
601:
209-221,
1990[Web of Science][Medline].
17.
Levy, MN.
Sympathetic-parasympathetic interactions in the heart.
Circ Res
29:
437-445,
1971
18.
Marmarelis, PZ,
and
Marmarelis VZ.
The white noise method in system identification.
In: Analysis of Physiological Systems. New York: Plenum, 1978, p. 131-221.
19.
Miyano, H,
Nakayama Y,
Shishido T,
Inagaki M,
Kawada T,
Sato T,
Miyashita H,
Sugimachi M,
Alexander J, Jr,
and
Sunagawa K.
Dynamic sympathetic regulation of left ventricular contractility studied in the isolated canine heart.
Am J Physiol Heart Circ Physiol
275:
H400-H408,
1998
20.
Nakahara, T,
Kawada T,
Sugimachi M,
Miyano H,
Sato T,
Shishido T,
Yoshimura R,
Miyashita H,
Inagaki M,
Alexander J, Jr,
and
Sunagawa K.
Accumulation of cAMP augments dynamic vagal control of heart rate.
Am J Physiol Heart Circ Physiol
275:
H562-H567,
1998
21.
Nakahara, T,
Kawada T,
Sugimachi M,
Miyano H,
Sato T,
Shishido T,
Yoshimura R,
Miyashita H,
and
Sunagawa K.
Cholinesterase affects dynamic transduction properties from vagal stimulation to heart rate.
Am J Physiol Regul Integr Comp Physiol
275:
R541-R547,
1998
22.
Nakayama, Y,
Miyano H,
Shishido T,
Inagaki M,
Kawada T,
Sugimachi M,
and
Sunagawa K.
Laterality in direct and indirect inotropic effects of sympathetic stimulation in isolated canine heart.
Jpn J Physiol
51:
365-370,
2001[Web of Science][Medline].
23.
Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology.
Heart rate variability: standards of measurement, physiological interpretation and clinical use.
Circulation
93:
1043-1065,
1996
24.
Vizi, ES.
Interaction between adrenergic and cholinergic systems: presynaptic inhibitory effect of noradrenaline on acetylcholine release.
J Neural Transm Suppl
11:
61-78,
1974.
25.
Wetzel, GT,
Goldstein D,
and
Brown JH.
Acetylcholine release from rat atria can be regulated through an 1-adrenergic receptor.
Circ Res
56:
763-766,
1985
26.
Yamaguchi, N,
de Champlain J,
and
Nadeau R.
Correlation between the response of the heart to sympathetic stimulation and the release of endogenous catecholamines into the coronary sinus of the dog.
Circ Res
36:
662-668,
1975
This article has been cited by other articles:
|
|
 |
|
  M. Buchheit, H. Al Haddad, P. B. Laursen, and S. Ahmaidi Effect of body posture on postexercise parasympathetic reactivation in men Exp Physiol, July 1, 2009; 94(7): 795 - 804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kawada, M. Mizuno, S. Shimizu, K. Uemura, A. Kamiya, and M. Sugimachi Angiotensin II disproportionally attenuates dynamic vagal and sympathetic heart rate controls Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1666 - H1674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Buchheit, J. J. Peiffer, C. R. Abbiss, and P. B. Laursen Effect of cold water immersion on postexercise parasympathetic reactivation Am J Physiol Heart Circ Physiol, February 1, 2009; 296(2): H421 - H427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mizuno, A. Kamiya, T. Kawada, T. Miyamoto, S. Shimizu, and M. Sugimachi Muscarinic potassium channels augment dynamic and static heart rate responses to vagal stimulation Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1564 - H1570. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Buchheit, P. B. Laursen, and S. Ahmaidi Parasympathetic reactivation after repeated sprint exercise Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H133 - H141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Sala-Mercado, M. Ichinose, R. L. Hammond, T. Ichinose, M. Pallante, L. W. Stephenson, D. S. O'Leary, and F. Iellamo Muscle metaboreflex attenuates spontaneous heart rate baroreflex sensitivity during dynamic exercise Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2867 - H2873. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ogoh, J. P Fisher, E. A Dawson, M. J White, N. H Secher, and P. B Raven Autonomic nervous system influence on arterial baroreflex control of heart rate during exercise in humans J. Physiol., July 15, 2005; 566(2): 599 - 611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Miyamoto, T. Kawada, Y. Yanagiya, M. Inagaki, H. Takaki, M. Sugimachi, and K. Sunagawa Cardiac sympathetic nerve stimulation does not attenuate dynamic vagal control of heart rate via {alpha}-adrenergic mechanism Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H860 - H865. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
