AJP - Heart Journal of Applied Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 289: H1729-H1735, 2005. First published May 27, 2005; doi:10.1152/ajpheart.01129.2004
0363-6135/05 $8.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
289/4/H1729    most recent
01129.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (3)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Motte, S.
Right arrow Articles by Entee, K. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Motte, S.
Right arrow Articles by Entee, K. M.

Respiratory-related heart rate variability in progressive experimental heart failure

Sophie Motte,1 Myrielle Mathieu,1 Serge Brimioulle,2 Anne Pensis,1 Lynn Ray,1 Jean-Marie Ketelslegers,3 Nicola Montano,4 Robert Naeije,1 Philippe van de Borne,5 and Kathleen Mc Entee1

1Laboratory of Physiology, Faculty of Medicine, Free University of Brussels, Brussels, Belgium; 2Department of Intensive Care, Erasmus Hospital, Brussels, Belgium; 3Unit of Diabetes and Nutrition, Catholic University of Louvain, Brussels, Belgium; 4Department of Clinical Sciences, Ospedale, L Sacco, University of Milan, Milan, Italy; and 5Department of Cardiology, Erasmus Hospital, Brussels, Belgium

Submitted 8 November 2004 ; accepted in final form 16 May 2005


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Heart failure is associated with autonomic imbalance, and this can be evaluated by a spectral analysis of heart rate variability. However, the time course of low-frequency (LF) and high-frequency (HF) heart rate variability changes, and their functional correlates during progression of the disease are not exactly known. Progressive heart failure was induced in 16 beagle dogs over a 7-wk period by rapid ventricular pacing. Spectral analysis of heart rate variability and respiration, echocardiography, hemodynamic measurements, plasma atrial natriuretic factor, and norepinephrine was obtained at baseline and every week, 30 min after pacing interruption. Progressive heart failure increased heart rate (from 91 ± 4 to 136 ± 5 beats/min; P < 0.001) and decreased absolute and normalized (percentage of total power) HF variability from week 1 and 2, respectively (P < 0.01). Absolute LF variability did not change during the study until it disappeared in two dogs at week 7 (P < 0.05). Normalized LF variability increased in moderate heart failure (P < 0.01), leading to an increased LF-to-HF ratio (P < 0.05), but decreased in severe heart failure (P < 0.044; week 7 vs. week 5). Stepwise regression analysis revealed that among heart rate variables, absolute HF variability was closely associated with wedge pressure, right atrial and pulmonary arterial pressure, left ventricular ejection fraction and volume, ratio of maximal velocity of early (E) and atrial (A) mitral flow waves, left atrial diameter, plasma norepinephrine, and atrial natriuretic peptide (0.45 < r < 0.65, all P < 0.001). In tachycardia-induced heart failure, absolute HF heart rate variability is a more reliable indicator of cardiac dysfunction and neurohumoral activation than LF heart rate variability.

autonomic nervous system; tachycardiomyopathy

HEART FAILURE is associated with an autonomic imbalance consisting of an increase in sympathetic drive (25) and a reduction of parasympathetic activity (5). In these patients, efferent sympathetic nerve traffic has been shown to be increased in proportion to functional impairment (16), norepinephrine plasma levels are associated with an increased risk of death (7), and {beta}-blocker therapy improves survival (8). Thus autonomic imbalance with prominent sympathetic activation plays an important role in heart failure pathophysiology.

Cardiac autonomic imbalance can be evaluated by the spectral analysis of R-R interval (RRI) variability (35). In normal humans and in dogs, RRI variability occurs predominantly at low frequency (LF, between 0.04 and 0.15 Hz) and at high frequency (HF, between 0.15 and 1.0 Hz) (29). LF oscillations are present in both sympathetic and vagal outflows (24, 30). However, within physiological conditions, sympathetic activation is associated with an increase in LF when expressed in normalized units (24, 26). HF oscillations occur with breathing and are known as respiratory sinus arrhythmia. Their quantification characterizes the response of the sinus node to fluctuations in vagal activity at the respiratory frequency and may correlate with the underlying mean level of that activity (11).

Mild or moderate heart failure has been reported to be associated with reduced HF and increased LF RRI variabilities (5, 10, 20). LF variability has also been shown to decrease or even to disappear in advanced congestive heart failure (5, 18, 19, 33, 36). Despite the fact that LF RRI variability increases in heart failure, but eventually decreases in the most advanced stages of the disease, quantification of LF RRI variability has been shown to have prognostic implications, such as prediction of increased risk of arrhythmic events or mortality in stable or decompensated heart failure and after myocardial infarction (2, 4, 18, 22, 31). However, how RRI variability, and in particular the HF variability, correlates to cardiac function during the progressive aggravation of heart failure is not exactly known.

Our laboratory (27) therefore investigated the RRI variability and cardiac function changes over a period of 7 wk in an overpacing-induced canine heart failure model that was adapted in our laboratory to allow for the observation of all stages of disease severity. The results suggest that HF RRI oscillations are better related to an alteration in cardiac function than LF RRI oscillations.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Animal Preparation

The investigation was approved by the Institutional Animal Care and Use Committee of the Free University of Brussels and was conducted in accordance with the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health (NIH Publication No. 85-23, Revised 1996).

Sixteen male beagle dogs were included in the study. After administration of cefazolin (20 mg/kg iv and 20 mg/kg sc) and premedication with midazolam (0.1 mg/kg iv) and methadone (0.3 mg/kg iv), the animals were anesthetized with intravenous propofol, 5 mg/kg followed by 5 mg·kg–1·h–1. During anesthesia, the dogs were intubated and ventilated with Elema B servo-ventilator (Siemens, Erlangen, Germany), the fraction of inspired oxygen being 0.4, the respiratory rate at 12 breaths/min, and the tidal volume at 15 ml/kg. A bipolar pacemaker lead (Fineline II, model 4471, Guidant Brussels, Belgium) was surgically inserted in the right jugular vein and implanted in the right ventricular apex under fluoroscopic control. A multiprogrammable pulse generator (Insignia, Guidant) was inserted in the subcutaneous tissues of the cervical region and connected to the pacemaker lead.

Experimental Protocol

The experiment was a longitudinal repeated-measures study. The dogs underwent a modified pacing protocol with a stepwise increase of stimulation frequencies. The pacing was initiated after a 2-wk recovery period by activating the multiprogrammable pulse generator at 180 beats/min and continued during the first week, followed by 200 beats/min during a second week, 220 beats/min during a third week, and finally 240 beats/min during the final fourth week. The investigations were carried out at baseline (week 0) and once weekly throughout the pacing period (i.e., from week 1 to week 7) with exactly the same methods. Investigations were performed after a pacing interruption of at least 30 min and included blood sampling, hemodynamic and echocardiographic evaluation, as well as spectral analysis of RRI and respiration.

To exclude a possible impact of surgical intervention or the presence of inactivated pacemaker on cardiac function, preliminary experiments were performed on three sham-operated dogs. In these animals, clinical state, heart rate, and echocardiographic variables remained stable during 7 wk. It was therefore decided not to include a sham-operated control group in the present study.

Measurements and Analytic Methods

Clinical examination. The clinical examination included cardiac and lung auscultation, measurements of body weight, rectal temperature, and blood pressure. Systolic blood pressure was measured by Doppler sphygmomanometry (model 811-BTS, Parks Medical Electronics, Aloka, OR) on the forelimb of dogs placed in sternal recumbency and calculated as the mean of three consecutive measurements.

Doppler echocardiography. Doppler echocardiography (Pandion, Pie Medical Benelux, Zaventem, Belgium) was performed under continuous ECG monitoring using a 3.5- to 5-MHz mechanical sector probe, as previously described (27). Briefly, all the measurements were done in triplicate. A right parasternal window was used to evaluate systolic cardiac function and systolic and diastolic volume indexes. Left ventricular internal end-diastolic (LVIDd) and -systolic (LVIDs) diameters were determined in a right short-axis M-mode projection of the heart in a plane just below the mitral valves. From these data, left ventricular end-diastolic volume (EDV) and left ventricular ejection fraction (LVEF) were calculated by using the following formulas:


with body surface area (BSA; m2) = body weight (kg)2/3, and

A left apical long-axis view of the left ventricle was used to obtain images of the aortic flow and of the biphasic miral inflow (E and A wave) by pulsed-wave Doppler. Velocity spectra of aortic flow were used to measure the preejection period and left ventricular ejection time, whereas those of the mitral inflow were used to calculate the ratio of early-to-late diastolic flow velocities (E/A). Left ventricular isovolumic relaxation time (IVRT) was measured as the time period from the Doppler signal of aortic valve closure to the start of early diastolic flow.

Hemodynamic evaluation. Dogs were anesthetized and ventilated with the same anesthetic protocol as described in Animal Preparation and equipped with a fluid-filled systemic catheter and a 5-Fr Swan-Ganz catheter inserted in the left jugular vein. Heart rate, mean pulmonary arterial pressure (Ppa), occluded Ppa, and right auricular blood pressure were measured

Spectral analysis. Ten-minute recordings of RRI period and respiration were made with dogs laying on a table in a conscious state. ECG electrodes were attached to forelimbs and hindlimbs while respiration was recorded with inductive plethysmography (spirotrace digital 100, Medical Electronic Construction, Brussels, Belgium) using a chest belt sensitive to both frequency and amplitude.

Analog-to-digital conversion was performed in real time at a rate of 200 Hz/channel with a six-channel recorder (model 2600S, Gould). The principles of the software for spectral analysis have been described elsewhere (29). In brief, a derivative-threshold algorithm provided the continuous series of RRI (tachogram) and the respirogram, derived from the ECG and the inductive plethysmography, respectively. All interpolated values were visually checked. Stationary segments devoid of arrhythmias were analyzed with autoregressive parametric spectral algorithms. This allowed a determination of total heart rate power (or variance), the power of the LF and HF oscillatory components in absolute units (ms2), and their center frequencies. In addition, the LF-to-HF ratio and LF and HF in normalized units were determinated. Normalized units were obtained by dividing the power of each component by the total variance, from which the very LF (VLF) component had been substracted, and this value was multiplied by 100. The respirogram underwent a similar analysis. The VLF component, which requires specific algorithms and longer data series, was not addressed in this study.

Atrial natriuretic peptide. Venous blood was drawn after each physical examination and collected into prechilled tubes containing EDTA (3 mM) and benzamidine (9 mM) for measurement of plasma atrial natriuretic peptide (NH2-terminal portion). After centrifugation within 1 h, plasma was stored at –80°C until use. Atrial natriuretic peptide was measured on extracts by radioimmunoassay, as previously described (9), using commercially available specific antibodies and synthetic peptides from Peninsula (Belmont, CA), as well as tracers iodinated and HPLC purified in our laboratory.

Plasma norepinephrine. Venous blood was collected into heparinate lithium tubes containing 200 µl of a solution of glutathion peroxidase (0.2 M) to avoid catecholamines degradation. Norepinephrine was measured by HPLC with intraassay and interassay coefficients of variation of 5% and 12.3%, respectively.

Statistical Analysis

All values are means ± SE. Echocardiographic and hemodynamic variables displayed a normal distribution. However, the distribution of the majority of the frequency domain heart rate variability variables was extremely skewed. Thus a log transformation of these measurements was applied to improve normality before the statistical analysis was performed. These measurements were back-transformed for presentation in the tables and figures. A repeated measures one-way ANOVA was first performed to calculate the P value for the trend of each variable over the time. When the F ratio of ANOVA reached a critical value of P < 0.05, modified t-tests, i.e., t-tests computed by using the residual mean square given by the ANOVA, were performed to compare specific situations (37). A forward stepwise regression analysis was used to investigate the correlation among echocardiographic, hemodynamic variables, and heart rate variability measurements (28).


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 GRANTS
 REFERENCES
 
The clinical examination showed a decrease in blood pressure and an increase in heart rate starting at the first week (Table 1). Mitral or tricuspid regurgitant murmurs were detected in 2, 9, 12, and 14 dogs from week 4, 5, 6, and 7, respectively. At week 5, 6, and 7, respectively, 3, 5, and 11 dogs presented with ascites.


View this table:
[in this window]
[in a new window]
  		Table 1. Changes in hemodynamic variables, plasma atrial natriuretic peptide, and norepinephrine levels during progression of tachycardia-induced heart failure in dogs

 
Circulating atrial natriuretic peptide and norepinephrine were increased from week 2 and remained elevated until the end of the study (Table 1).

Mean Ppa increased from the fourth week, whereas occluded Ppa and right atrial blood pressure increased from the third week (Table 1).

The echo-Doppler examination of the heart showed a progressive decrease in LVEF and an increase in aortic ratio of preejection period to ejection time, starting at week 1, together with progressive increases in left ventricular volume and in left atrial diameter, which started at week 2 and 4, respectively (Table 2). Indexes of diastolic function, E/A and IVRT, showed a biphasic evolution with a decreased relaxation starting at week 1, a pseudonormal mitral inflow at the fourth week, a restrictive pattern with elevated E/A at the fifth week, and a trend toward a shortened IVRT (Table 2).


View this table:
[in this window]
[in a new window]
  		Table 2. Echocardiographic changes during progression of tachycardia-induced heart failure in dogs

 
The spectral analysis showed an early and drastic reduction of total and HF RRI power (from week 1; Table 3 and Fig. 1). Reductions in total RRI power were tightly correlated to absolute HF RRI variability changes (r = 0.96; P < 0.001). Absolute LF RRI variability decreased in week 7 (Fig. 1). During the progression of the disease, no significant differences were noted in the center frequency of the LF component of RRI variability, whereas the center frequency of the HF component, synchronous with the respiration, progressively increased from week 2 (Table 3). The percentage of HF in the spectral analysis of the respiratory signal was constant over the entire duration of the pacing protocol (Table 3).


View this table:
[in this window]
[in a new window]
  		Table 3. Changes in center frequency of the LF and HF component of heart rate variability, variance of R-R interval, and percentage of HF in the respiratory power spectrum density during progression of tachycardia-induced heart failure in dogs

 


View larger version (14K):
[in this window]
[in a new window]
  		Fig. 1. Box plots showing high- (HF) and low-frequency (LF) components of R-R interval in absolute units (ms2) during tachycardia-induced heart failure in dogs. The box, which is placed around the median (50%), represents centile 25–75%, and vertical lines outside of the box represent range 10–90%. *P < 0.001 vs. baseline week; {dagger}P < 0.01 vs. baseline week; {ddagger}P < 0.05 vs. baseline week.

 
The normalized HF RRI variability displayed a reduction from week 2 to 7 compared with the baseline week, but this reduction remained stable from week 5 to 7. As the normalized LF RRI increased (week 1), this led to an increased LF-to-HF ratio (week 2; Fig. 2). However, the normalized LF RRI decreased between week 5 and 7. The absolute and normalized LF component even disappeared in two dogs at week 7.



View larger version (13K):
[in this window]
[in a new window]
  		Fig. 2. Box plots showing HF and LF components of R-R interval in normalized units (nu) and their ratio (LF/HF) during tachycardia-induced heart failure in dogs. The box, which is placed around the median (50%), represents centile 25–75%, and vertical lines outside of the box represent range 10–90%. *P < 0.001 vs. baseline week; {dagger}P < 0.01 vs. baseline week; §P < 0.05 vs. week 5.

 
Mean Ppa, occluded Ppa, and right atrial blood pressure were inversely correlated to the absolute HF RRI (Table 4). Markers of left ventricular systolic dysfunction (LVEF, aortic ratio of preejection period to ejection time) and diastolic dysfunction (E/A), as well as left ventricular volume, left atrial diameter, plasma norepinephrine, and atrial natriuretic peptide, were correlated to the absolute HF RRI (Table 4). Stepwise regression analysis among heart rate and four parameters of RRI (total power of RRI, absolute LF and HF RRI variability, as well as the normalized HF RRI variability) revealed that absolute HF RRI oscillations best predicted hemodynamics, plasma norepinephrine, and atrial natriuretic peptide changes (Table 4). Identical results were obtained when stepwise regression analysis among RRI, total power of RRI, absolute LF and HF RRI variability, as well as the normalized LF RRI variability, was performed. In addition, when the analysis was performed with only the normalized values and the LF-to-HF ratio, we observed consistently that normalized HF RRI was still the most significant variable, except for E/A and plasma atrial natriuretic factor that were more closely related to LF-to-HF ratio.


View this table:
[in this window]
[in a new window]
  		Table 4. Associations between heart rate variability parameters and hemodynamic or neurohumoral dysfunction assessed by forward stepwise linear regression in a dog model of tachycardiomyopathy

 
Because LF variability could have been a predictor of some of the dependent variables up to the 5-wk point but failed to provide over all predictability because of a large fall at the end of the study, we repeated the multiple regression analysis after exclusion of the sixth- and seventh-week measurements. This did not change the significance of the results (data not shown). In addition, we calculated post hoc a simple linear correlation between the change in LVEF ({Delta}LVEF) and the changes in LF and HF variabilities ({Delta}LF and {Delta}HF, respectively) from baseline to week 7. The correlation between {Delta}LVEF and {Delta}LF was not significant (r = 0.11, P is not significant), whereas the correlation between {Delta}LVEF and {Delta}LHF was significant (r = 0.30, P < 0.01). The results were exactly the same for calculated correlations between changes in LVEF and changes in LF and HF variabilities at week 5 (data not shown).


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
In the present model of progressive heart failure, spectral analysis of heart rate variability disclosed a biphasic evolution of LF variability, with initial increase followed by late decrease, whereas absolute HF variability showed a continuous decrease along with progressive alteration in systolic and diastolic indexes of ventricular function. This result suggests that absolute HF RRI variability may be superior to LF RRI variability as an indicator of heart failure severity.

The overpacing-induced congestive heart failure model is characterized by the rapid development (a few weeks) of a dilated cardiomyopathy with impaired systemic and regional hemodynamics, broad neurohumoral activation, and avid sodium and fluid retention (34). The model has been previously used to investigate the time course of sympathovagal imbalance in progressive congestive heart failure (10, 20). However, in these studies, severe stages of the disease were induced in 1 or 2 wk with aggressive HF pacing (~250 beats/min), resulting in a subacute condition that might not be a sufficiently realistic reproduction of a chronic dilated cardiomyopathy clinical course. In the present study, the model was adapted with more progressive pacing, over a 7-wk observation period of time, allowing for heart rate variability analysis along with detailed echocardiographic and hemodynamic measurements at all stages of congestive heart failure severity (27).

In the present experiments, the baseline power density spectrum of heart rate was characterized by a predominance of the HF parasympathetically mediated region. This is in keeping with the known predominant resting vagal tone in resting dogs (32). With the onset of mild left ventricular systolic and diastolic dysfunction, there were major decreases of total RRI power and HF RRI variability, suggesting a significant contribution of decreased parasympathetic nervous system modulation in early heart failure pathophysiology. Rapid changes in RRI that occur at the start of muscular exercise, when standing up or lying down, are known to be parasympathetically mediated (3, 13, 14). A decrease in parasympathetic modulation is an integral component of cardiac autonomic imbalance (5) and, as such, is potentially implicated in ventricular arrhythmias and sudden cardiac death.

The HF spectral component of RRI variability continued to decrease during the progression of heart failure, whereas the LF component and the LF-to-HF ratio increased gradually. This result is consistent with previous RRI variability studies (5, 10, 20) in patients or animals with moderate heart failure. There were also progressive increases in heart rate and in plasma norepinephrine, which is in keeping with previous reports (7, 36) on patients with advanced heart failure. The most obvious explanation for concomitant increases in LF RRI variability, resting heart rate, and plasma norepinephrine is a sympathetic nervous system activation.

However, in the present study, whereas the most advanced heart failure was, as expected, associated with tachycardia and increased plasma norepinephrine, a paradoxical decrease in the normalized LF component of RRI variability was observed, and this component in fact even disappeared in two of the animals. This biphasic evolution of the LF component of RRI variability was not observed in previous studies (10, 20) on the same canine overpacing heart failure model, probably because of too rapid evolution related to very aggressive pacing protocol.

An augmented LF oscillation of heart rate as a reflection of increased sympathetic drive is observed in healthy subjects during passive upright tilt (17, 26, 29), standing, mental stress, and moderate physical exercise or during moderate hypotension (24). Previous studies (1, 20, 21) of heart failure have also shown that the LF area of RRI spectrum is closely linked to the degree of sympathoexcitation. Indeed, a relationship between LF and microneurographic recordings of sympathetic activity (1, 21) or plasma norepinephrine (20, 21) has been demonstrated. However, in advanced stages of the disease the opposite is true (5, 18, 19, 33, 36) because the LF component present in RRI variability disappears in the presence of a markedly elevated sympathetic drive. The disappearance of this LF variability has distinct negative pronostic implications. La Rovere et al. (22) as well as Galinier et al. (18) have recently demonstrated that among the spectral measures of RRI variability, reduced power within the LF band was an independent predictor of sudden death in patients with stable congestive heart failure.

Heart rate variability parameters are affected not only by cardiac responsiveness to stimuli but also by variation and modulation in autonomic tone. Malik et al. (23) suggested that sympathetic activation that approaches maximal stimulation may be accompanied by a pattern of reduced LF variability. This could be explained by a progressive downregulation of myocardial {beta}-adrenergic receptors (6), a reduction in myocardial catecholamine stores (12), a baroreflex impairment (15), and by an alteration in central autonomic drive (36).

We excluded the possibility that the RRI oscillations were influenced by concurrent respiratory changes, which could not be recorded in previous studies (10, 20) using the same experimental model. Respiration is a powerful modulator of RRI variability (19). Changes in breathing frequency can confound the respective predominance of LF and HF oscillations in RRI variability. Recordings of respiratory activity that allowed us to rule out that reductions in HF oscillations in RRI were a result of irregular or slow breathing.

In the present study, the absolute HF component of RRI variability was better than the LF component related to echocardiographic and hemodynamic severity of heart failure and also to atrial natriuretic factor and norepinephrine concentrations. This could have been in part explained by a biphasic course with initial increase, followed by a decrease after the fifth week of evolution of the LF component of RRI variability. However, in this study, limiting the statistical analysis to the first 5 wk of evolution still did not disclose any significant correlation between LF RRI variability and severity of heart failure. Ishise et al. (20) reported that a parasympathetic withdrawal paralleled the decline in left ventricular contractility but did not describe the link between these variables. Our results showed that the total power of RRI variability is closely correlated to the absolute HF area of RRI variability and therefore suggest that the overall RRI variability is mainly influenced by cardiac vagal activity in dogs.

A limitation of the present study is that the variability of RRI was not investigated after the seventh week of evolution and until the death of the animals. Accordingly, heart rate variability analysis could not be related to cardiac events or to mortality. Another limitation is that RRI variability was analyzed on short-term recordings only. The analysis was impossible during HF pacing, and longer periods of interruption of overpacing could have affected the evolution of heart failure. Thus, despite the fact that the duration of the recordings appeared sufficient for meaningful readings, we cannot exclude that longer periods of recordings would have produced different variability profiles.

In conclusion, parasympathetic nervous system-related HF RRI oscillations appear to be more reliable than sympathetic nervous system-related LF heart rate oscillations as a measurement of congestive heart failure severity. We suggest that spectrum analysis of RRI variability in the evaluation of patients with heart failure takes into account the whole frequency spectrum with focus on the HF component.


   GRANTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
REFERENCES
 
This study was supported by Grant 3.4516.02 from the National Funds for Scientific Medical Research, Belgium, by the Foundation for Cardiac Surgery, Belgium, and by a grant from the Intervet International and from CEVA Santé Animale. S. Motte is a research fellow "aspirant" of the National Funds for Scientific Research (FNRS), and M. Mathieu is a research fellow from the Foundation of Cardiac Surgery.


   ACKNOWLEDGMENTS
 
We thank Dr. Christian Mélot, Professor of Biostatistics at the Free University of Brussels, for excellent statistical advice.


   FOOTNOTES
 

Address for reprint requests and other correspondence: K. Mc Entee, Free Univ. of Brussels, Laboratory of Physiology, CPI 604, Lennik Road 808, B-1070 Brussels, Belgium (e-mail: kmcentee{at}ulb.ac.be)

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.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 

  1. Adamopoulos S, Piepoli M, McCance A, Bernardi L, Rocadaelli A, Ormerod O, Forfar C, Sleight P, and Coats AJ. Comparison of different methods for assessing sympathovagal balance in chronic congestive heart failure secondary to coronary artery disease. Am J Cardiol 70: 1576–1582, 1992.
  2. Aronson D, Mittleman MA, and Burger AJ. Measures of heart period variability as predictors of mortality in hospitalized patients with decompensated congestive heart failure. Am J Cardiol 93: 59–63, 2004.
  3. Bellavere F and Ewing DJ. Autonomic control of the immediate heart rate response to lying down. Clin Sci (Lond) 62: 57–64, 1982.
  4. Bigger JT, Fleiss JL, Rolnitzsky LM, and Steinman RC. The ability of several short-term measures of RR variability to predict mortality after myocardial infarction. Circulation 88: 927–934, 1993.
  5. Binkley PF, Nunziata E, Haas GJ, Nelson SD, and Cody RJ. Parasympathetic withdrawal is an integral component of autonomic imbalance in congestive heart failure: demonstration in human subjects and verification in a paced canine model of ventricular failure. J Am Coll Cardiol 18: 464–472, 1991.
  6. Bristow MR, Ginsburg R, Minobe W, Cubicciotti RS, Sageman WS, Lurie K, Billingham ME, Harrison DC, and Stinson EB. Decreased catecholamine sensitivity and beta-adrenergic-receptor density in failing human hearts. N Engl J Med 307: 205–211, 1982.
  7. Cohn JN, Levine TB, Olivari MT, Garberg V, Lura D, Francis GS, Simon AB, and Rector T. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 311: 819–823, 1984.
  8. Domanski MJ, Krause-Steinrauf H, Massie BM, Deedwania P, Follmann D, Kovar D, Murray D, Oren R, Rosenberg Y, Young J, Zile M, and Eichhorn E, for the BEST Investigators. A comparative analysis of the results from 4 trials of {beta}-blocker therapy for heart failure: BEST, CIBIS-II, MERIT-HF, and COPERNICUS. J Card Fail 9: 354–363, 2003.
  9. Donckier J, Hanet C, Berbinschi A, Galanti L, Robert A, Van Mechelen H, Pouleur H, and Ketelslegers JM. Cardiovascular and endocrine effects of endothelin-1 at pathophysiological and pharmacological plasma concentrations in conscious dogs. Circulation 84: 2476–2484, 1991.
  10. Eaton GM, Cody RJ, Nunziata E, and Binkley PF. Early left ventricular dysfunction elicits activation of sympathetic drive and attenuation of parasympathetic tone in the paced canine model of congestive heart failure. Circulation 92: 555–561, 1995.
  11. Eckberg DL. Human sinus arrhythmia as an index of vagal cardiac outflow. J Appl Physiol 54: 961–966, 1983.
  12. Eisenhofer G, Friberg P, Rundqvist B, Quyyumi AA, Lambert G, Kaye DM, Kopin IJ, Goldstein DS, and Esler MD. Cardiac sympathetic nerve function in congestive heart failure. Circulation 93: 1667–1676, 1996.
  13. Ewing DJ, Hume L, Campbell IW, Murray A, Neilson JM, and Clarke BF. Autonomic mechanisms in the initial heart rate response to standing. J Appl Physiol 49: 809–814, 1980.
  14. Fagraeus L and Linnarsson D. Autonomic origin of heart rate fluctuations at the onset of muscular exercise. J Appl Physiol 40: 679–682, 1976.
  15. Ferguson DW, Abboud FM, and Mark AL. Selective impairment of baroreflex-mediated vasoconstrictor responses in patients with ventricular dysfunction. Circulation 69: 451–460, 1984.
  16. Ferguson DW, Berg WJ, and Sanders JS. Clinical and hemodynamic correlates of sympathetic nerve activity in normal humans and patients with heart failure: evidence from direct microneurographic recordings. J Am Coll Cardiol 16: 1125–1134, 1990.
  17. Furlan R, Porta A, Costa F, Tank J, Baker L, Schiavi R, Robertson D, Malliani A, and Mosqueda-Garcia R. Oscillatory patterns in sympathetic neural discharge and cardiovascular variables during orthostatic stimulus. Circulation 101: 886–892, 2000.
  18. Galinier M, Pathak A, Fourcade J, Androdias C, Curnier D, Varnous S, Boveda S, Massabuau P, Fauvel M, Senard JM, and Bounhoure JP. Depressed low frequency power of heart rate variability as an independent predictor of sudden death in chronic heart failure. Eur Heart J 21: 475–482, 2000.
  19. Guzzetti S, Cogliati C, Turiel M, Crema C, Lombardi F, and Malliani A. Sympathetic predominance followed by functional denervation in the progression of chronic heart failure. Eur Heart J 16: 1100–1107, 1995.
  20. Ishise H, Asanoi H, Ishizaka S, Joho S, Kameyama T, Umeno K, and Inoue H. Time course of sympathovagal imbalance and left ventricular dysfunction in conscious dogs with heart failure. J Appl Physiol 84: 1234–1241, 1998.
  21. Kienzle MG, Ferguson DW, Birkett CL, Myers GA, Berg WJ, and Mariano DJ. Clinical, hemodynamic and sympathetic neural correlates of heart rate variability in congestive heart failure. Am J Cardiol 69: 761–767, 1992.
  22. La Rovere MT, Pinna GD, Maestri R, Mortara A, Capomolla S, Febo O, Ferrari R, Franchini M, Gnemmi M, Opasich C, Riccardi PG, Traversi E, and Cobelli F. Short-term heart rate variability strongly predicts sudden cardiac death in chronic heart failure patients. Circulation 107: 565–570, 2003.
  23. Malik M and Camm AJ. Components of heart rate variability—what they really mean and what we really measure. Am J Cardiol 72: 821–822, 1993.
  24. Malliani A, Pagani M, Lombardi F, and Cerutti S. Cardiovascular neural regulation explored in the frequency domain. Circulation 84: 482–492, 1991.
  25. Mancia G. Sympathetic activation in congestive heart failure. Eur Heart J 11, Suppl A: 3–11, 1990.
  26. Montano N, Ruscone TG, Porta A, Lombardi F, Pagani M, and Malliani A. Power spectrum analysis of heart rate variability to assess the changes in sympathovagal balance during graded orthostatic tilt. Circulation 90: 1826–1831, 1994.
  27. Motte S, van Beneden R, Mottet J, Rondelet B, Mathieu M, Havaux X, Lause P, Clercx C, Ketelslegers JM, Naeije R, and Mc Entee K. Early activation of cardiac and renal endothelin systems in experimental heart failure. Am J Physiol Heart Circ Physiol 285: H2482–H2491, 2003.
  28. Neter J, Kutner MH, Nachtsheim CJ, and Wasserman W. Applied Linear Statistical Models (4th ed.). Boston, MA: WCB/McGraw-Hill, 1996.
  29. Pagani M, Lombardi F, Guzzetti S, Rimoldi O, Furlan R, Pizzinelli P, Sandrone G, Malfatto G, Dell'Orto S, and Piccaluga E. Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog. Circ Res 59: 178–193, 1986.
  30. Pagani M, Montano N, Porta A, Malliani A, Abboud FM, Birkett C, and Somers VK. Relationship between spectral components of cardiovascular variabilities and direct measures of muscle sympathetic nerve activity in humans. Circulation 95: 1441–1448, 1997.
  31. Ponikowski P, Anker SD, Chua TP, Szelemej R, Piepoli M, Adamopoulos S, Webb-Peploe K, Harrington D, Banasiak W, Wrabec K, and Coats AJ. Depressed heart rate variability as an independent predictor of death in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 79: 1645–1650, 1997.
  32. Rimoldi O, Pagani MR, Piazza S, Pagani M, and Malliani A. Restraining effects of captopril on sympathetic excitatory responses in dogs: a spectral analysis approach. Am J Physiol Heart Circ Physiol 267: H1608–H1618, 1994.
  33. Saul JP, Arai Y, Berger RD, Lilly LS, Colucci WS, and Cohen RJ. Assessment of autonomic regulation in chronic congestive heart failure by heart rate spectral analysis. Am J Cardiol 61: 1292–1299, 1988.
  34. Stevens TL, Borgeson DD, Luchner A, Wennberg PW, Redfield MM, and Burnett JC Jr. Pathophysiology of Tachycardia-Induced Heart Failure, edited by Spinale FG. Armonk, NY: Futura, 1996.
  35. 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. Eur Heart J 17: 354–381, 1996.
  36. Van de Borne P, Montano N, Pagani M, Oren R, and Somers VK. Absence of low-frequency variability of sympathetic nerve activity in severe heart failure. Circulation 95: 1449–1454, 1997.
  37. Winer BJ, Brown DR, and Michels KM. Statistical Principles in Experimental Design (3rd ed.). New York: McGraw-Hill, 1991, p. 220–283.



This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
E. A. Jankowska, P. Ponikowski, M. F. Piepoli, W. Banasiak, S. D. Anker, and P. A. Poole-Wilson
Autonomic imbalance and immune activation in chronic heart failure - Pathophysiological links
Cardiovasc Res, June 1, 2006; 70(3): 434 - 445.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
289/4/H1729    most recent
01129.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (3)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Motte, S.
Right arrow Articles by Entee, K. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Motte, S.
Right arrow Articles by Entee, K. M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2005 by the American Physiological Society.