Vol. 280, Issue 4, H1602-H1607, April 2001
Dynamic sympathetic control of atrioventricular conduction
time and heart period
Toru
Kawada,
Shi-Liang
Chen,
Masashi
Inagaki,
Toshiaki
Shishido,
Takayuki
Sato,
Teiji
Tatewaki,
Masaru
Sugimachi, and
Kenji
Sunagawa
Department of Cardiovascular Dynamics, National Cardiovascular
Center Research Institute, Suita, Osaka 565-8565, Japan
 |
ABSTRACT |
Although power spectra of R-R and P-R
intervals in response to random respiration show similar frequency
distributions, the way in which dynamic sympathetic regulation
contributes to such similarity remains unknown. We estimated the
transfer function from sympathetic stimulation to the atrioventricular
interval (AV conduction time; TAV) with and
without constant atrial pacing in seven anesthetized cats. The transfer
function from sympathetic stimulation to TAV,
except for absolute gain values, approximated a low-pass filter similar
to that from sympathetic stimulation to the A-A interval (heart period;
TAA). The 90%-rise times did not differ between
the TAA and TAV step
responses (32.3 ± 1.8 vs. 29.6 ± 3.2 s). Constant
pacing augmented the TAV step response (
0.58 ± 0.10 vs. 0.86 ± 0.12 ms/Hz, P < 0.05) without affecting the 90%-rise time. These findings suggest
that the dynamic characteristics of sympathetic control are similar
between TAA and TAV
despite the different electrophysiological mechanisms determining
TAA and TAV. A numerical
simulation indicated that if the dynamic characteristics of the
sympathetic control do not match between TAA and
TAV, a critical condition for initiation of
reentrant tachycardia would be encountered.
systems analysis; Gaussian white noise; sympathetic stimulation; transfer function; atrioventricular node
| |
INTRODUCTION |
THE HEART PERIOD
(A-A interval) reflects a rhythmicity or an automaticity of the sinus
nodal cells (5), whereas the atrioventricular conduction
time (A-V interval) reflects a conduction delay through the
atrioventricular nodal cells (14). The different
electrophysiological mechanisms responsible for the generation of the
A-A and A-V intervals result in the significant difference in absolute
length between the A-A and A-V intervals, i.e., the former is much
longer than the latter. However, Leffler et al. (9)
demonstrated similar distributions of R-R and P-R interval power
spectra in response to random respiration, suggesting similar frequency
responses of R-R and P-R intervals to autonomic perturbation. To
elucidate the physiological mechanisms underlying such similar
frequency responses to autonomic perturbation between R-R and P-R
intervals, identification of the dynamic transfer characteristics from
autonomic nerve stimulation to the A-A and A-V intervals is essential.
As for the vagal system, we have shown that dynamic transfer
characteristics from vagal stimulation to the A-V interval are similar
to those from vagal stimulation to the A-A interval (3).
In the present study, we aimed to identify the dynamic transfer
characteristics from sympathetic stimulation to the A-A and A-V
intervals. Our previous study (Nakahara et al., Ref. 18)
indicated that dynamic transfer characteristics from sympathetic
stimulation to heart rate approximate low-pass filter and that
norepinephrine removal from the neuroeffector junction is one of the
determinants responsible for the low-pass characteristics. If this
paradigm is also true for the A-V interval response to sympathetic
stimulation, dynamic transfer characteristics from sympathetic
stimulation to the A-A and A-V intervals would reveal similar low-pass
characteristics, regardless of the difference in electrophysiological
mechanisms governing the A-A and A-V intervals. We tested this
hypothesis in anesthetized cats by use of a white noise technique
(1, 3, 6-8, 13, 16-19).
| |
MATERIALS AND METHODS |
Animal preparation.
Animals were cared for in strict accordance with the Guiding Principles
for the Care and Use of Animals in the Field of Physiological Sciences
approved by the Physiological Society of Japan. Seven adult cats of
either sex weighing 2.4-3.5 kg were anesthetized with
pentobarbital sodium (30-35 mg/kg ip). Supplemental doses of
pentobarbital sodium were injected (2 mg/kg iv) as necessary to
maintain an appropriate depth of anesthesia. The animals were intubated
and mechanically ventilated with room air mixed with oxygen. Body
temperature was maintained at ~37°C with a heating pad and a heat lamp.
The bilateral vagal nerves were sectioned through a midline cervical
incision to eliminate vagal innervation to the heart. The chest was
opened transversely at the second intercostal space. The bilateral
stellate ganglia were exposed, and their upper and lower poles as well
as their spinal cord branches were cut. A pair of bipolar platinum
electrodes was attached to the cardiac sympathetic nerves arising from
each stellate ganglion for electrical stimulation. To prevent drying
and to provide insulation, the stimulation electrodes and nerves were
soaked in a mixture of white petrolatum (Vaseline) and liquid paraffin.
A pair of bipolar stainless steel wire electrodes was sutured to the
right atrial appendage through the right fifth intercostal space to
allow pacing. The right femoral artery was cannulated for the
monitoring of arterial pressure. The right femoral vein was cannulated
for administration of anesthetics and for maintenance of fluid balance.
A 5-Fr bipolar electrode catheter was introduced in a retrograde manner
via the right common carotid artery to the noncoronary cusp of the
aortic valve to record activity from the His bundle (3,
12). The His bundle electrogram was band-pass filtered in the
frequency range of 50-1,000 Hz.
Stimulation protocols.
The study consisted of the following two protocols. In protocol
1, we dynamically stimulated the cardiac sympathetic nerves for 10 min according to a Gaussian white noise signal (3 ± 1.5 Hz,
mean ± SD). The stimulation frequency was switched every 2 s. The pulse duration was set at 2 ms. The baseline heart rate was 165 ± 13 beats/min (mean ± SD). The stimulation amplitude was
adjusted in each animal to produce a heart rate increase of ~30
beats/min at a 5-Hz tonic sympathetic stimulation. After the adjustments, the stimulation amplitude ranged from 2.5 to 5.0 V. The
efficacy of sympathetic stimulation on the heart rate response did not
change more than 10% throughout the experiment. In protocol 2, dynamic sympathetic stimulation was performed under conditions of constant atrial pacing to abolish the influence of changes in the
A-A interval on the A-V interval. The pacing rate (200 ± 18 beats/min) was set just above the maximal heart rate achieved by the
5-Hz tonic sympathetic stimulation.
We used different sequences of Gaussian white noise for different
animals. The order of the experimental protocols was randomized to
reduce the likelihood of bias or of systematic error in our identification approach. The stimulation command signal and the His
bundle electrogram were digitized at 2,000 Hz through a 12-bit analog-to-digital converter and stored on the hard disk of a dedicated laboratory computer system (NEC PC-9801FA, Tokyo, Japan).
Data analysis.
Atrioventricular conduction time was assessed from the His bundle
electrogram as follows. The A-H interval was defined as the time from
the earliest deflection of the atrial wave to the peak of the His
potential. The H-V interval was defined as the time from the His
potential to the earliest deflection of the ventricular wave. We
manually selected the templates for A, H, and V waves and subsequently
detected matched signals through an adaptive template-matching
algorithm. Discrete time series data were then obtained from the
measured A-A, A-V, A-H, and H-V intervals so as to follow the principle
of causality. Finally, we linearly interpolated the respective discrete
time series data to a frequency of 8 Hz. We represented the
atrioventricular conduction time by the A-V interval rather than the
A-H interval in the present study because the H-V interval did not
change perceivably in either protocol.
The transfer functions representing dynamic system characteristics were
calculated as follows. We segmented the 8-Hz resampled input-output
data pairs into six 50%-overlapping bins of 1,024 points each. For
each bin, a linear trend was removed and a Hanning window was applied.
We then performed fast Fourier transformation to obtain frequency
spectra of the input, X(f), and output,
Y(f) (2). We then ensemble averaged,
over the six bins, the power of the input,
SXX(f), power of the output,
SYY(f), and crosspower between the
input and output, SYX(f). Finally, we
estimated the transfer function, H(f), with the
use of the following equation (13)
To quantify the linear dependence between the input and
output signals in the frequency domain, we calculated a
magnitude-squared coherence function, Coh(f), with the use
of the following equation (13)
The coherence value ranges from zero to unity. A unity coherence
indicates a perfect linear dependence between the input and output
signals, whereas zero coherence indicates total independence between
the two signals.
In protocol 1, we estimated the transfer function from
sympathetic stimulation to the A-A interval
(HS-AA) and that from sympathetic stimulation to
the A-V interval under no pacing conditions
(HS-AV,N). Because changes in the A-A interval
affect the A-V interval through an electrophysiological mechanism,
HS-AV,N includes both a direct sympathetic
effect on the A-V interval and an indirect sympathetic effect through
changes in the A-A interval. In protocol 2, we estimated the
transfer function from sympathetic stimulation to the A-V interval
under constant pacing conditions (HS-AV,P).
HS-AV,P represents the direct sympathetic effect
on the A-V interval without including the indirect effect. As the
sympathetic stimulation frequency was changed every 2 s, the input
power spectrum was fairly constant up to 0.25 Hz. Therefore, we
presented transfer functions in the frequencies below 0.25 Hz.
To facilitate intuitive understanding of HS-AA,
HS-AV,N, and HS-AV,P, we
calculated a step response corresponding to each transfer function. To
derive the step response, we obtained the impulse response from the
inverse Fourier transformation of the transfer function. We then
calculated a time integral of the impulse response up to 60 s. To
quantify the step response, the maximum negative response was obtained
by averaging the last 10-s data of the calculated step response. The
50- and 90%-rise times, at which times 50 and 90% of the maximum
negative response were attained, respectively, were also calculated. We
tested the differences in the parameters of the step responses by the
Friedman's test for repeated measures nonparametric multiple
comparisons. If there was a significant difference (P < 0.05) among three groups, we applied the Student-Newman-Keuls test
on the basis of ranks to identify the difference between any two of the
three groups (4).
| |
RESULTS |
Figure 1A shows
representative time series data obtained from protocol 1.
The top panel shows the stimulation frequency of the cardiac
sympathetic nerves according to a Gaussian white noise signal. The
middle panel shows the associated A-A interval response. Increasing sympathetic stimulation frequency shortened the A-A interval, whereas decreasing it prolonged the A-A interval. The A-A
interval did not respond to rapid changes in the sympathetic stimulation frequency. The bottom panel shows the A-V
interval response. Although the A-V interval showed proportional
changes to the A-A interval response, the magnitude of the A-V interval response was much smaller than the A-A interval response.
View larger version (23K):
[in this window]
[in a new window]
|
Fig. 1.
Representative time series data showing the sympathetic stimulation
protocols with no pacing (A) and constant pacing
(B) in 1 animal. STIM, sympathetic stimulation frequency
according to the Gaussian white noise command signal; A-A, the A-A
interval response to sympathetic stimulation; A-V, the A-V interval
response to sympathetic stimulation. Both the A-A and A-V intervals
were shortened by sympathetic stimulation. The constant pacing enhanced
the A-V interval response to sympathetic stimulation.
|
|
Figure 1B shows time series data obtained from
protocol 2 in the same animal. The sympathetic stimulation
frequency (top), the A-A interval (middle), and
the A-V interval response (bottom) are shown. The A-A
interval was fixed at a constant pacing interval. The constant pacing
increased the mean level of the A-V interval and enhanced the dynamic
A-V interval response to sympathetic stimulation when compared with
Fig. 1A. Because we used the same command signal for
sympathetic stimulation between protocols 1 and
2, the A-V interval response under constant pacing
conditions was similar to the A-A interval response under no pacing
conditions except for the difference in the magnitude of response.
Figure 2A shows the averaged
HS-AA (left),
HS-AV,N (center), and
HS-AV,P (right). The top
and middle panels are the gain and phase plots of
the transfer functions, respectively. The gain decreases as the
frequency increases in all three transfer functions. The decreasing
slopes in the higher frequency range (0.04-0.08 Hz) were
11.5 ± 0.6, 10.8 ± 1.4, and 12.3 ± 1.0 dB/octave in HS-AA,
HS-AV,N, and HS-AV,P,
respectively. These values approximated the decreasing slope of a
second-order low-pass filter (12 dB/octave). There were no
significant differences in the decreasing slope among the three
transfer functions. The phase difference approaches 
radians in
the lowest frequency in all three transfer functions, reflecting the
fact that sympathetic stimulation shortens both the A-A and the A-V
intervals. The phase difference increases as the frequency increases.
The phase difference is dispersed in the frequencies above 0.1 Hz in
HS-AV,N and HS-AV,P,
possibly because of a low signal-to-noise ratio in these frequencies.
The coherence shows a moderate linearity in the frequencies below 0.1 Hz in HS-AA and HS-AV,P.
The coherence seems to be lower in HS-AV,N than
in HS-AV,P.
View larger version (38K):
[in this window]
[in a new window]
|
Fig. 2.
Transfer functions (A) and step responses (B)
associated with dynamic sympathetic stimulation averaged from all
animals. HS-AA, transfer function from
sympathetic stimulation to the A-A interval;
HS-AV,N, transfer function from sympathetic
stimulation to the A-V interval estimated under no pacing conditions;
HS-AV,P, transfer function from sympathetic
stimulation to the A-V interval estimated under constant pacing
conditions; Coh, coherence function; Step Res, step response
corresponding to each transfer function; rad, radians. Vertical axis of
the step response for the A-V interval is scaled at only 1/5 of that
for the A-A interval. Solid and dashed lines indicate mean and
mean + SE values, respectively.
|
|
Figure 2B shows the calculated step responses derived from
HS-AA, HS-AV,N, and
HS-AV,P. There were significant differences in
the maximum negative response for all pairwise comparisons among the
three step responses (Table 1). The
constant pacing increased the maximum negative response of the A-V
interval by 87.7 ± 47.0%. There were no significant differences in
the 50- or 90%-rise time among the three step responses (Table 1).
| |
DISCUSSION |
Transfer characteristics.
The transfer function representing the sympathetic control of the A-A
interval approximated a second-order low-pass filter (Fig. 2,
left). Taking into account the reciprocal relationship between the A-A interval and heart rate, these characteristics are
comparable with the transfer function from sympathetic stimulation to
heart rate estimated in dogs (1, 16) and rabbits
(6-8, 18). The 90%-rise time of the A-A interval
step response was, however, longer than that estimated in rabbits,
suggesting species differences in the positive chronotropic effect of
sympathetic stimulation.
The transfer function representing the sympathetic control of the A-V
interval also approximated a second-order low-pass filter (Fig. 2,
middle and right). These low-pass filter
characteristics resemble the frequency responses of vascular resistance
(20) and ventricular contractility (16) to
sympathetic stimulation. As Berger et al. (1) pointed out,
these findings suggest that low-pass filter characteristics of
sympathetic regulation reflect the kinetics of the adrenergic receptors
or of the intracellular signaling processes coupled to the
receptors and are not necessarily intrinsic to effector organs.
According to our previous study (18), norepinephrine
removal from the neuroeffector junction would play an important role in
determining the low-pass filter characteristics of sympathetic regulation.
The constant pacing significantly increased the gain of the transfer
function and augmented the A-V interval step response without affecting
the 50- or 90%-rise time (Table 1). Shortening of the A-A interval
prolongs the A-V interval through the electrophysiological mechanism,
and vice versa, in the absence of autonomic innervation (10). The electrophysiological effect of changes in the
A-A interval on the A-V interval is almost instantaneous in the
frequency range of 0.01-0.1 Hz (3). As a result,
changes in the A-A interval during sympathetic stimulation dynamically
attenuated the direct effect of sympathetic stimulation on the A-V interval.
Simulation study.
Once the dynamic characteristics of HS-AA and
HS-AV,P are identified, we can manipulate the
parameters of the transfer function to examine what would happen if the
parameters were deviated from their normal physiological values. We
examined, with the use of a mathematical model (see
APPENDIX), the influences of the frequency bandwidth and
dynamic gain of HS-AV,P on the A-V interval step response to sympathetic stimulation (Fig.
3, A and B). The
simulation results indicate that if the parameters of
HS-AV,P are deviated from their baseline
physiological values, sympathetic stimulation can prolong the A-V
interval while shortening the A-A interval. Such imbalance between the
A-A and A-V interval controls would occur when the sympathetic
innervation on the atrioventricular node, but not on the sinus node, is
impaired by regional ischemia and so forth.
View larger version (16K):
[in this window]
[in a new window]
|
Fig. 3.
Simulated A-V interval step response to 1-Hz sympathetic
stimulation under sinus rhythm. A: the natural frequency for
the A-V interval response was varied from 4 times (×4) to one-fourth
(×1/4) of the baseline value (equal to the natural frequency for the
A-A interval response). The A-V interval can be transiently prolonged
in response to sympathetic stimulation when the natural frequencies for
the A-A and A-V intervals do not match. B: the dynamic gain
of the A-V interval response was reduced to one-half (×1/2) of the
baseline value or set at zero (×0). When dynamic gain of the A-V
interval response is zero, sympathetic stimulation prolongs the A-V
interval while shortening the A-A interval.  AV: changes in the A-V
interval. See APPENDIX for detailed simulation settings.
|
|
Shortening of the A-A interval during sympathetic stimulation increases
the tendency of anterograde conduction block in the accessory pathway
between the atria and ventricles. If the A-V interval is prolonged at
the same time because of the impaired sympathetic innervation on the
atrioventricular node, the accessory pathway would recover excitability
for the retrograde conduction, thereby initiating atrioventricular
reentrant tachycardia (15). This mechanism would
contribute to the initiation of some type of reentrant tachycardia that
lacks a preceding premature extrasystole.
Limitations.
Several variables that can potentially affect the A-V interval have not
been considered in the present study. First, we obtained all data from
animals under anesthesia. If data had been obtained from conscious
animals, the results might have been different.
Second, there was a difference in the operating range of the A-A
interval during the estimation of HS-AV,N and
HS-AV,P. Because the effect of sympathetic
stimulation on the A-V interval is sensitive to the A-A interval range
(22), the difference in the operating range of the A-A
interval would have affected the absolute gain values of
HS-AV,N and HS-AV,P.
Third, the A-V conduction is regulated by both the sympathetic and
vagal systems. Although previous studies have demonstrated minimal
(11, 22) or small interactions (21) between
the sympathetic and vagal controls in the steady-state A-V interval response, further studies are clearly needed to characterize the dynamic interactions between the sympathetic and vagal systems.
Finally, sympathetic stimulation according to the Gaussian white noise
is different from the physiological discharge pattern in sympathetic
nerve activity. Furthermore, because we stimulated the bilateral
cardiac sympathetic nerves simultaneously, laterality in the
sympathetic innervation on the atrioventricular node was not assessed.
To elucidate the sympathetic control of the A-V interval by the
physiological sympathetic discharge, experiments such as those using
sympathetic activation through arterial baroreflex might be required.
In conclusion, the transfer function representing the direct
sympathetic effect on the A-V interval approximated a second-order low-pass filter similar to that representing the direct
sympathetic effect on the A-A interval despite the different
electrophysiological mechanisms governing the A-A and A-V
intervals. The similarity in the dynamic sympathetic regulations of the
A-A and A-V intervals, together with the similarity in the dynamic
vagal regulations of the A-A and A-V intervals (3), yields
similar frequency distributions between R-R and P-R interval power
spectra observed in a human study (9). A numerical
simulation indicates that if the dynamic characteristics of the A-A and
A-V interval regulations by the sympathetic system do not match, it
would provide a critical condition for initiating reentrant tachycardia.
| |
APPENDIX |
Simulation of the A-V Interval Response to Sympathetic
Stimulation
On the basis of the estimated transfer functions (Fig. 2), we
simulated the A-A and A-V interval responses by a mathematical model of
the second-order low-pass filter. The transfer function of the
second-order low-pass filter is described as follows
where K is the dynamic gain,
fn is the natural frequency (in Hz), and 
is
the damping coefficient; f and j denote the
frequency (in Hz) and the imaginary unit, respectively. The upper
frequency bandwidth of the system is determined by
fn. When fn increases, the system response becomes quicker. The coefficient determines the
damping behavior of the system. Depending on the value of , the
system behaves as underdamped (0 < < 1), as critically damped
( = 1), or as overdamped ( > 1).
To mimic the estimated transfer functions, we set dynamic gains for the
simulated HS-AA and
HS-AV,P to 3.6 and 0.86, respectively (Table
1). The damping ratio and the natural frequency were set at 1.1 and
0.03 Hz, respectively, for both the simulated
HS-AA and HS-AV,P. The
electrophysiological effect of changes in the A-A interval on the A-V
interval was modeled as a simple all-pass filter with a gain of 0.1
(3). Hence the overall transfer function from sympathetic
stimulation to the A-V interval, including both the direct and
indirect sympathetic effects, was simulated as
follows: [HS-AV,P 0.1 × HS-AA]. The A-V interval impulse response was
then derived from the inverse Fourier transform of the overall transfer
function. The A-V interval step response was calculated from a time
integral of the impulse response. Figure 3, A and
B, illustrates the influences of changes in
fn and K on the A-V interval step
response, respectively.
| |
ACKNOWLEDGEMENTS |
This study was supported by Ministry of Health and Welfare of Japan
Grants for Cardiovascular Diseases (9C-1, 11C-3, and 11C-7) and a
Health Sciences Research Grant for Advanced Medical Technology, by
Science and Technology Agency of Japan Special Funds for Encourage System of Center of Excellence, by a Ground-Based Research Grant for
Space Utilization promoted by National Space Development Agency of
Japan and the Japan Space Forum, by a Science and Technology Agency of
Japan Bilateral International Joint Research Grant, by a grant-in-aid
for Scientific Research (B: 11694337, C: 11680862, and 11670730), from
the Ministry of Education, Science, Sports, and Culture of Japan, by a
grant-in-aid for Encouragement of Young Scientists (11770390 and
11770391), and by a grant provided by the Ichiro Kanehara Foundation.
| |
FOOTNOTES |
Address for reprint requests and other correspondence: T. Kawada, Dept. of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan (E-mail: torukawa{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.
Received 8 June 2000; accepted in final form 8 November 2000.
| |
REFERENCES |
1.
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[Abstract/Free Full Text].
2.
Brigham, EO.
FFT transform applications.
In: The Fast Fourier Transform and Its Applications. Englewood Cliffs, NJ: Prentice-Hall, 1988, p. 167-203.
3.
Chen, S,
Kawada T,
Inagaki M,
Shishido T,
Miyano H,
Sato T,
Sugimachi M,
Takaki H,
and
Sunagawa K.
Dynamic counterbalance between direct and indirect vagal controls of atrioventricular conduction in cats.
Am J Physiol Heart Circ Physiol
277:
H2129-H2135,
1999[Abstract/Free Full Text].
4.
Glantz, SA.
Primer of Biostatistics (4th ed.). New York: McGraw-Hill, 1997.
5.
Irisawa, H,
Brown HF,
and
Giles W.
Cardiac pacemaking in the sinoatrial node.
Physiol Rev
73:
197-227,
1993[Free Full Text].
6.
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[Abstract/Free Full Text].
7.
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[Abstract/Free Full Text].
8.
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 Regulatory Integrative Comp Physiol
276:
R782-R789,
1999[Abstract/Free Full Text].
9.
Leffler, CT,
Saul JP,
and
Cohen RJ.
Rate-related and autonomic effects on atrioventricular conduction assessed through beat-to-beat PR interval and cycle length variability.
J Cardiovasc Electrophysiol
5:
2-15,
1994[Web of Science][Medline].
10.
Levy, MN,
Martin PJ,
Iano T,
and
Zieske H.
Effects of single vagal stimuli on heart rate and atrioventricular conduction.
Am J Physiol
218:
1256-1262,
1970.
11.
Levy, MN,
and
Zieske H.
Autonomic control of cardiac pacemaker activity and atrioventricular transmission.
J Appl Physiol
27:
465-470,
1969[Free Full Text].
12.
Loeb, JM,
deTarnowsky JM,
Warner MR,
and
Whitson CC.
Dynamic interactions between heart rate and atrioventricular conduction.
Am J Physiol Heart Circ Physiol
249:
H505-H511,
1985.
13.
Marmarelis, PZ,
and
Marmarelis VZ.
The white noise method in system identification.
In: Analysis of Physiological System. New York: Plenum, 1978, p. 131-221.
14.
Meijler, FL,
and
Janse MJ.
Morphology and electrophysiology of the mammalian atrioventricular node.
Physiol Rev
68:
608-647,
1988[Abstract/Free Full Text].
15.
Miles, WM,
and
Zipes DP.
Atrioventricular reentry and variants: mechanisms, clinical features, and management.
In: Cardiac Electrophysiology: from Cell to Bedside (3rd ed.), edited by Zipes DP,
and Jalife J.. Philadelphia, PA: Saunders, 2000, p. 488-504.
16.
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[Abstract/Free Full Text].
17.
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[Abstract/Free Full Text].
18.
Nakahara, T,
Kawada T,
Sugimachi M,
Miyano H,
Sato T,
Shishido T,
Yoshimura R,
Miyashita H,
Inagaki M,
Alexander J, Jr,
and
Sunagawa K.
Neuronal uptake affects dynamic characteristics of heart rate response to sympathetic stimulation.
Am J Physiol Regulatory Integrative Comp Physiol
277:
R140-R146,
1999[Abstract/Free Full Text].
19.
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 Regulatory Integrative Comp Physiol
275:
R541-R547,
1998[Abstract/Free Full Text].
20.
Rosenbaum, M,
and
Race D.
Frequency-response characteristics of vascular resistance vessels.
Am J Physiol
215:
1397-1402,
1968.
21.
Urthaler, F,
Neely BH,
Hageman GR,
and
Smith LR.
Differential sympathetic-parasympathetic interactions in sinus node and AV junction.
Am J Physiol Heart Circ Physiol
250:
H43-H51,
1986.
22.
Wallick, DW,
Martin PJ,
Masuda Y,
and
Levy MN.
Effects of autonomic activity and changes in heart rate on atrioventricular conduction.
Am J Physiol Heart Circ Physiol
243:
H523-H527,
1982.
Am J Physiol Heart Circ Physiol 280(4):H1602-H1607
0363-6135/01 $5.00
Copyright © 2001 the American Physiological Society
TOP
ABSTRACT
INTRODUCTION
