This Article Extract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Eckberg, D. L. Search for Related Content PubMed PubMed Citation Articles by Eckberg, D. L.

(Circulation. 1997;96:3224-3232.)
© 1997 American Heart Association, Inc.

Articles

Sympathovagal Balance

A Critical Appraisal

Dwain L. Eckberg, MD

From the Departments of Medicine and Physiology, Hunter Holmes McGuire Department of Veterans Affairs Medical Center and Medical College of Virginia, Virginia Commonwealth University, Richmond.

Correspondence to Dwain L. Eckberg, MD, Hunter Holmes McGuire Department of Veterans Affairs Medical Center, 1201 Broad Rock Blvd, Richmond, VA 23249. E-mail deckberg{at}aol.com

Key Words: nervous system, autonomic • electrocardiography • physiology

	Introduction

Top Introduction The Method and Its... Discussion References

 
Given the importance of the autonomic nervous system to cardiovascular health, it is not surprising that there is and has been great interest in measurements of human sympathetic and vagus nerve traffic as tools that might inform physiological and pathophysiological mechanisms. Pagani and coworkers¹ advanced the provocative notion that the instantaneous balance between sympathetic and vagal nerve activities can be captured by a single number, obtained by dividing RR-interval spectral power centered at 0.1 Hz by spectral power centered at higher, primarily respiratory frequencies. This ratio, or sympathovagal balance, has been embraced with great enthusiasm² because it offers new possibilities for understanding dynamic, critically important autonomic interrelations in humans by the use of totally noninvasive, unobtrusive means.³

The broad bases for this mathematical treatment are as follows: (1) 0.1-Hz RR intervals are importantly mediated by fluctuations of sympathetic nerve activity; (2) higher-frequency RR-interval rhythms are mediated almost exclusively by fluctuations of vagal-cardiac nerve activity; and (3) physiological interventions tend to provoke reciprocal changes of sympathetic and vagal neural outflows. Sympathovagal balance, the ratio of these periodicities, is taken to reflect the balance between the opposing neural mechanisms. This review examines the physiological foundations of sympathovagal balance.

	The Method and Its Mathematics

Top Introduction The Method and Its... Discussion References

 
The ECG is recorded with the subject in a steady state (when rhythms are stationary) for a period sufficiently long to define events occurring over frequencies of interest. RR-interval spectral power is calculated from this series of intervals with an autoregressive algorithm, which yields center frequencies and absolute power of component fluctuations, based on a model whose order (the number of parameters) is selected automatically to minimize Akaike's information criterion statistic.⁴ (The statistical uncertainty and consequences of the automatic selection of the autoregressive model have not been defined fully; however, it is clear that the model order importantly determines both center frequency and magnitude of spectral peaks.⁵)

Autoregressive analyses of short (5 minutes) RR-interval time series typically yield three peaks in very low (0 to 0.04 Hz; VLF), low (0.04 to 0.15 Hz; LF), and respiratory or high (0.15 to 0.40 Hz; HF) frequency ranges.⁶ Published examples (Fig 1 in Reference 1¹ and Figs 5c and 5d in Reference 6⁶ ) suggest that in such short-term recordings, these three frequencies account for almost all spectral power (in the examples, 94.6%, 96.1%, and 98.5%). Therefore, in practice, power in normalized (also called relative or fractional) units (nu) is power centered at the frequency of interest (LF or HF) divided by total power less power at VLFs. Thus, LF nu=LF/(LF+HF) and HF nu=HF/(LF+HF). Sympathovagal balance is the ratio between LF and respiratory-frequency powers. Sympathovagal balance (in dimensionless units) is simply the ratio of absolute LF to absolute HF power, or LF/HF.

View larger version (31K): [in this window] [in a new window]   Figure 1. Direct multifiber vagal-cardiac (VND) and sympathetic-cardiac (SND) nerve recordings from one anesthetized, decerebrate cat. Reproduced with permission.3 imp. indicates impulse; PSD, power spectral density.

View larger version (14K): [in this window] [in a new window]   Figure 5. Average maximum peroneal muscle sympathetic nerve and RR-interval responses of nine healthy supine subjects in response to 5-second periods of graded neck suction and pressure. Baseline levels are indicated by the circles. Adapted with permission.36

Several consequences issue from the mathematics of sympathovagal balance. First, a change of either the numerator or the denominator must change the fraction. Thus, a reduction of LF with no change of HF will reduce the fraction, and a reduction of HF with no change of LF will increase the fraction. According to published precedents,^1,3 the former change would be interpreted as a shift of sympathovagal balance toward vagal predominance and the latter as a shift of sympathovagal balance toward sympathetic predominance. Second, because calculations of normalized LF and HF powers involve merely rearrangement of the same LF and HF terms, a change of normalized LF power must necessarily be associated with a change of normalized HF power. For the same reason, relations among the different calculated values can be predicted simply on the basis of mathematics. For example, if LF and HF are distributed nearly normally, sympathovagal balance, plotted as a function of normalized LF power, will be almost exponential.

The remaining discussion touches on some of the physiological and pathophysiological processes that contribute to sympathovagal balance. The discussion is organized as a series of postulates that I believe tacitly or explicitly underlie the concept.

The Numerator
Human cardiovascular rhythms occurring at 0.1 Hz are of great interest because they convey information regarding activity of the sympathetic nervous system. Healthy humans may have strong fluctuations of muscle sympathetic nerve activity about every 10 seconds,⁷ a period that is sufficiently long for vascular smooth muscle and sinoatrial node effectors to respond to released norepinephrine and to modulate arterial pressure and heart rate.⁸

LF RR-Interval Rhythms Reflect Sympathetic Nerve Traffic to the Heart
Malliani and coworkers³ published what may be the only power spectral analyses of sympathetic and vagus nerve traffic assumed but not proven to be destined for the heart. Fig 1 shows preganglionic thoracic sympathetic and vagus nerve discharges measured from one artificially ventilated decerebrate cat. My integration of the two LF spectral powers in this figure suggests that sympathetic spectral power is 15% greater than vagal spectral power.

Kingwell and colleagues⁹ studied healthy supine subjects and found no significant correlation between myocardial norepinephrine spillover and absolute or relative 0.1-Hz RR-interval spectral power. Saul and coworkers¹⁰ also studied healthy supine subjects and found no significant correlation between baseline peroneal sympathetic nerve activity expressed as bursts/min (or antecubital vein plasma norepinephrine levels) and absolute or normalized LF heart rate spectral power.

Hopf et al¹¹ and Introna et al¹² measured RR-interval spectral power before and after high spinal anesthesia. Sympathetic blockade in the supine position (but see responses to tilt below) did not alter absolute or relative 0.1-Hz RR-interval spectral power significantly.

Pagani et al¹ reported that propranolol 0.2 mg/kg IV does not reduce normalized 0.1-Hz RR-interval spectral power significantly. Moreover, Jokkel et al¹³ reported that short-term ß-adrenergic blockade actually increases 0.1-Hz frequency RR-interval spectral power. Long-term ß-adrenergic blockade reduces normalized 0.1-Hz RR-interval spectral power.¹

Low-dose cholinergic blocking drugs, such as atropine and scopolamine, paradoxically increase average RR intervals¹⁴ and LF RR-interval spectral power.¹⁵ Increased LF spectral power is unlikely to be due to increased sympathetic nerve traffic because atropine does not alter (muscle) sympathetic nerve activity or plasma norepinephrine levels.¹⁶ Conversely, large-dose atropine abolishes nearly all RR-interval spectral power in LF as well as HF ranges.^17,18 The simplest interpretation of the effects of large-dose atropine is that it blocks sinoatrial responses to acetylcholine released by vagus nerve traffic; atropine does not alter heart rate in the absence of vagus nerve activity.¹⁹

Thus, vagal contributions to baseline LF RR-interval fluctuations are great, and evidence that baseline LF RR-interval spectral power is related quantitatively to sympathetic-cardiac nerve traffic is nonexistent.

Changes of 0.1-Hz RR-Interval Spectral Power Reflect Changes of Sympathetic-Cardiac Nerve Traffic
Two groups have sought correlations between muscle sympathetic nerve traffic and heart rate or RR-interval spectral power over a range of arterial pressures provoked by graded infusions of nitroprusside and phenylephrine. Saul and coworkers¹⁰ found significant correlations between sympathetic nerve activity, expressed as bursts/min, and normalized LF heart rate spectral power, but only in 4 of 10 subjects studied. Pagani and associates²⁰ found no significant correlation between sympathetic nerve activity, expressed as bursts/min, and normalized LF RR-interval spectral power. However, Pagani did find a highly significant but probably weak correlation between sympathetic nerve activity, expressed as burst area per second, and normalized LF RR-interval spectral power.

The studies by Saul et al¹⁰ and Pagani et al²⁰ differ in several respects. First, Saul normalized sympathetic bursts; Pagani did not. Normalization is necessary because burst heights differ among individuals; if sympathetic activity is not normalized, subjects with large sympathetic bursts will dominate average results. Second, subjects in the study by Saul et al controlled their breathing frequencies; those in the study by Pagani et al did not. As discussed below, breathing frequency profoundly influences spectral power measurements. Third, Saul reported individual regressions; Pagani did not. (It cannot be determined from the article by Pagani et al if there is a significant correlation between muscle sympathetic burst area per second and normalized LF RR-interval spectral power.) Rather, Pagani used a nonparametric regression analysis (Theil²¹) of all his data, both within and across subjects. This may have been inappropriate, because the Theil method requires that data be stochastically independent. Repeated measures (seven in each subject) violate this condition.

Koh and coworkers¹⁸ also measured RR-interval spectral power during infusions of nitroprusside and phenylephrine. Fig 2 shows RR-interval spectral power of healthy subjects and patients with complete high cervical spinal cord injuries during saline infusion and two or three levels of nitroprusside and phenylephrine. Arterial pressures (not shown) are highest toward the back and left and lowest toward the front and right of both graphs. Changes of spectral power in the 0.05- to 0.15-Hz range (enlarged in the insets) were different in the two groups. Healthy subjects (right) did not alter their LF RR-interval spectral power systematically. Tetraplegic patients, on the other hand, altered their LF RR-interval spectral power systematically but in direct, not inverse, proportion to arterial pressure changes.

View larger version (39K): [in this window] [in a new window]   Figure 2. Mean data from 8 tetraplegic and 10 healthy supine subjects, breathing at 0.25 Hz, at different levels of arterial pressure provoked by graded phenylephrine (pe) and nitroprusside (NP) infusions. The insets are enlargements of 0.05- to 0.15-Hz spectral power. Reproduced with permission.18 c indicates control.

Koh et al¹⁸ concluded that vagal mechanisms contribute importantly to baroreflex-mediated 0.1-Hz RR-interval spectral power in both healthy subjects and tetraplegic patients. In healthy subjects, LF spectral power does not change systematically, because arterial pressure changes provoke reciprocal changes of sympathetic and vagal nerve fluctuations, which cancel one another. Conversely, in tetraplegic patients, who lack the ability to modulate sympathetic nerve activity according to changes of baroreceptor input, LF RR-interval spectral power changes in proportion to arterial pressure. Koh's conclusion that baseline 0.1-Hz RR-interval rhythms importantly reflect fluctuations of vagus nerve traffic was supported by responses of both healthy subjects and tetraplegic patients to large-dose atropine, which nearly abolished LF RR-interval spectral power.

Thus, most evidence refutes the notion that LF RR-interval spectral power tracks baroreflex-mediated changes of sympathetic nerve activity; the published documentation of a weak association²⁰ may have resulted from use of inappropriate statistical methods.

The Denominator
Respiratory-Frequency RR-Interval Fluctuations Reflect Vagus Nerve Traffic to the Heart
The denominator in the sympathovagal balance equation comprises higher, primarily respiratory-frequency RR-interval spectral power. HF RR-interval fluctuations are thought to be mediated by fluctuations of vagal activity because in anesthetized but spontaneously breathing dogs, they are proportional to vagus nerve traffic,²² and in humans, they are nearly abolished by large-dose atropine.^14,17,23 Eckberg,²⁴ Fouad et al,²³ and Hayano et al²⁵ promoted respiratory-frequency RR-interval fluctuations as noninvasive indexes of vagal-cardiac nerve traffic in humans. Kollai and Mizsei²⁶ qualified this recommendation. They compared respiratory peak minus valley RR-interval changes with RR-interval shortening provoked by large-dose atropine after ß-adrenergic blockade. Although their study supported the use of respiratory RR-interval fluctuations as indexes of vagal-cardiac nerve traffic, it showed that this measure is not a perfect index.

Thus, baseline respiratory-frequency RR-interval fluctuations are related significantly but imperfectly to the level of human vagal-cardiac nerve traffic.

Changes of HF RR-Interval Fluctuations Reflect Changes of Vagus Nerve Traffic to the Heart
Studies by Eckberg et al²⁷ and Goldberger et al²⁸ in humans extended observations made much earlier by Anrep et al in dogs,²⁹ which challenged the notion that respiratory-frequency RR-interval fluctuations are proportional to vagal-cardiac nerve activity during changes of arterial pressure. Fig 3, adapted from the study by Eckberg et al,²⁷ shows average diastolic arterial pressure (range, 70 to 86 mm Hg), RR intervals, and peak minus valley RR-interval changes during graded infusions of nitroprusside and phenylephrine in healthy supine subjects breathing at a fixed frequency of 0.2 Hz. Over this arterial pressure range, RR intervals but not peak minus valley RR-interval changes were proportional to diastolic arterial pressure. (In the studies by both Eckberg et al and Anrep et al, however, larger arterial pressure reductions provoked parallel reductions of RR intervals and peak minus valley RR-interval changes.)

View larger version (34K): [in this window] [in a new window]   Figure 3. Average relation between diastolic pressure and RR intervals during graded infusions of nitroprusside (five levels, 0.2 to 3.2 µg · kg-1 · min-1) and phenylephrine (three levels, 0.2 to 0.8 µg · kg-1 · min-1) measured in 10 healthy supine subjects. Respiratory, peak minus valley RR-interval differences are plotted at each arterial pressure level and smoothed with a spline fit. Least-squares linear regression correlation coefficient for average data was 0.96. Adapted with permission.27

There are also circumstances in which changes of HF RR-interval fluctuations may not reflect changes in vagal-cardiac nerve traffic at all. Brown and coworkers² measured RR-interval spectral power in healthy supine subjects who breathed to a constant depth at frequencies between 0.4 and 0.1 Hz (24 to 6 breaths/min). Fig 4 indicates that maximum spectral power was 10-fold greater at the slowest breathing frequency (to the left and back) than at the fastest breathing frequency (to the right and front). Notwithstanding the huge differences in spectral power at different breathing frequencies, mean RR intervals (right) were nearly constant across all breathing frequencies. In that study, the constancy of RR intervals was taken as inferential evidence for the constancy of vagal-cardiac nerve traffic.³⁰

View larger version (35K): [in this window] [in a new window]   Figure 4. Average RR-interval spectral power and RR intervals from 10 healthy supine subjects breathing to a nominal tidal volume of 1000 mL, at seven breathing rates. Adapted with permission.2

Brown's data document a pivotal, largely ignored² role for respiration as a determinant of HF RR-interval spectral power. Grossman et al³¹ studied the usefulness of respiratory-frequency RR-interval fluctuations as indexes of tonic vagal-cardiac neural outflow, as reflected by mean RR intervals, in healthy subjects after ß-adrenergic blockade. They documented a reasonable correspondence between the two measures during interventions that raised or lowered tonic vagal-cardiac outflow, but only when respiration was controlled (and therefore accounted for). When respiration was not controlled, respiratory-frequency RR-interval fluctuations bore no significant relation to tonic vagal-cardiac nerve activity.

Saul and coworkers³² made a convincing case that there is no need to postulate changes of vagal-cardiac nerve traffic to explain the RR-interval variability shown in Fig 4 (left); such variability can be explained simply on the basis of the kinetics of sinoatrial node responses to acetylcholine. During slow breathing, responses to acetylcholine are expressed more fully than during rapid breathing, when responses to one mainly expiratory bolus of acetylcholine merge with responses to the next, and fluctuations of RR intervals are minimized. Data shown in Fig 4 (left) may apply to the numerator as well as the denominator of the sympathovagal equation; during periods of slow breathing (which healthy people have³³), LF and respiratory-frequency center frequencies may be the same.

Thus, moderate changes of arterial pressure, which alter vagal-cardiac nerve activity, do not change HF RR-interval fluctuations, and changes of breathing frequency and depth, which profoundly alter HF RR-interval fluctuations, may not change vagal-cardiac nerve activity at all.

The Quotient
The foregoing discussion treats the numerator and denominator of the sympathovagal fraction separately, with the unstated belief that these measures should correspond with actual levels of nerve traffic. I now discuss the quotient itself.

Sympathetic and Vagal Nerve Activities Change Reciprocally
Immersion of the face in cold water, a "diving reflex," provokes simultaneous increases of muscle sympathetic nerve activity³⁴ and bradycardia,³⁵ which can be prevented by large-dose atropine. Reductions of carbon dioxide chemoreceptor stimulation appear to lead to parallel reductions of sympathetic and vagal nerve activities (D.L.E., MD, et al, unpublished data, 1997).

There may be no physiological intervention more likely to change sympathetic and vagal outflows reciprocally than the arterial baroreflex. However, examination of baroreflex physiology exposes layers of complexity that qualify the notion that changes of baroreceptor activity trigger simple reciprocal changes of sympathetic and vagal nerve outflow.

All evidence points to the fact that humans lie above threshold on their arterial pressure-sympathetic and -vagal response relations. Fig 5 shows average changes of muscle sympathetic nerve and RR-interval (vagal) responses to abrupt increases and decreases of carotid baroreceptor input provoked by changes of external neck pressure.³⁶ The resting position of the subjects studied on their arterial pressure–sympathetic response relations was eccentric, being close to threshold. The consequence of this is that although small increases of arterial pressure provoked reciprocal changes of sympathetic and vagal neural outflows, larger increases of pressure provoked exclusively increases of vagal-cardiac nerve activity. Fig 5 (right) indicates that these subjects lie in the middle their vagally mediated arterial pressure–RR-interval response relations. However, other studies indicate that some healthy subjects lie in the threshold³⁷ or saturation³⁸ regions of this relation.

Thus, some physiological interventions provoke parallel, not reciprocal, changes of vagal and sympathetic nerve activity, and other interventions, such as baroreceptor stimulation, provoke reciprocal changes, but only over a very limited range of arterial pressure.

Measurements of Sympathovagal Balance Are Applicable to Patients as Well as Healthy Subjects
There are at least two problems with the use of sympathovagal balance in patients with heart failure. First, responses of heart failure patients to baroreflex forcings may be qualitatively different from those of healthy people. Heart failure patients may not increase their plasma norepinephrine levels during upright tilt,³⁹ and they may reduce rather than increase their plasma norepinephrine levels³⁹ and muscle sympathetic nerve traffic⁴⁰ during pharmacological arterial pressure reductions. Second, although heart failure patients may have extraordinarily high levels of muscle sympathetic nerve activity,^16,41 plasma norepinephrine,⁴² and cardiac norepinephrine spillover^43,44 and low RR-interval SDs (Fig 6),¹⁶ their calculated sympathovagal balance is extremely low.^3,45

View larger version (18K): [in this window] [in a new window]   Figure 6. Average antecubital vein plasma norepinephrine concentrations and RR-interval SDs from 18 patients with heart failure and 34 age-matched healthy subjects obtained during 5 minutes of uncontrolled breathing. Adapted with permission.16

There are other patients in whom the concept of sympathovagal balance may not apply. Although hypertensive patients may have average breathing rates comparable to those of normotensive people, they are much more likely to have episodic slow breathing and even apnea.⁴⁶ Tetraplegic patients breathe more rapidly than healthy people.⁴⁷ In such patient groups, profound differences in sympathovagal balance may arise simply on the basis of systematic differences in breathing.

Thus, measures of sympathovagal balance are not valid in heart failure patients and may not be valid in hypertensive or sleep apnea patients.

Changes of Sympathovagal Balance Reflect Changes of the Ratio of Sympathetic to Vagus Nerve Traffic to the Heart
The intervention that makes the most compelling case for sympathovagal balance is upright tilt. Iwase and colleagues⁴⁸ showed that muscle sympathetic nerve activity increases linearly with the sine of the angle during passive head-up tilt. Hopf and coworkers¹¹ reported that epidural anesthesia reduces sympathovagal balance in the upright tilt position. Montano and coworkers⁴⁹ and Mukai and Hayano⁵⁰ extended this observation by showing that sympathovagal balance increases linearly with the angle of tilt. However, both groups showed that this increase results from progressive reductions of HF RR-interval spectral power without progressive reciprocal increases of LF RR-interval spectral power.

Burke and coworkers⁵¹ showed clearly that in some individuals, 0.1-Hz fluctuations of muscle sympathetic nerve activity increase in the upright position. However, they also showed that some subjects reduce their muscle sympathetic nerve traffic in the upright position. Wallin and coworkers⁵² showed that although upright tilt increases myocardial norepinephrine spillover (and presumably sympathetic-cardiac nerve activity), it does not increase 0.1-Hz RR-interval spectral power.

Exercise is another physiological perturbation that affects autonomic neural outflow profoundly. During exercise, muscle sympathetic nerve activity⁵³ and myocardial norepinephrine spillover⁴³ increase and vagal-cardiac nerve activity (as reflected by instantaneous RR-interval shortening) decreases.⁵⁴ Sympathovagal balance, however, decreases during intense exercise⁵⁵ in proportion to the intensity of exercise.⁵⁶ Calculations of sympathovagal balance may give specious results during light exercise as well; two groups^57,58 showed that the RR-interval shortening that occurs during the transition from rest to light exercise is due almost exclusively to vagal withdrawal. Therefore, the apparent shift from vagal to sympathetic predominance at the beginning of exercise⁵⁵ probably reflects vagal withdrawal without concurrent sympathetic excitation.

Thus, neither upright tilt (arguably the flagship of sympathovagal balance) nor light or heavy exercise provokes the reciprocal changes of sympathetic and vagal nerve traffic predicted by calculations of sympathovagal balance.

	Discussion

Top Introduction The Method and Its... Discussion References

 
This review, which examines the physiological foundations for the concept of sympathovagal balance, was undertaken because of concern that this new measure has entered the mainstream of cardiovascular research without having been critically vetted. My review in no way disputes the value of heart rate variability in stratifying risk in patients with cardiovascular diseases^59–61 or in better understanding autonomic mechanisms.⁶² Rather, it focuses on the manipulation of heart rate variability to quantify the putative balance that exists between sympathetic and vagal cardiovascular neural outflows.

The concept of sympathovagal balance has been promoted in part on philosophical grounds. For example, sympathovagal balance has been compared with the action of the arm. Fine control of arm movements is made possible by simultaneous reciprocal changes of tension in flexor and extensor muscle groups.³ Although my review is of physiology, I also have philosophical problems with the concept. I am aware of no compelling physiological requirement that the levels of sympathetic and vagal nerve fluctuations be balanced. I am aware of no physiological evidence that fluctuations of sympathetic and vagus nerve activities "constantly interact."⁶ To be sure, oscillators influence one another in complex ways, and the two branches of the autonomic nervous system are "controlled and balanced." However, such control probably reflects the fact that sympathetic and vagal motoneurons respond to interrelated neural influences. My sense is that the construct of sympathovagal balance imposes attributes on physiological regulatory mechanisms that they do not possess.

I also have major concerns regarding the language used to support the concept of sympathovagal balance. Qualifiers such as "mainly"¹ and "mostly,"⁶³ as in "0.1 Hz RR-interval rhythms are mainly sympathetic," imply >50%. Is sympathovagal balance a robust tool if sympathetic contributions to 0.1-Hz spectral power are only marginally greater than vagal contributions, as Fig 1 indicates? The qualifiers "marker"³ and "quantitative markers,"⁶⁴ as in ">0.1-Hz RR-interval spectral power is a marker of sympathetic traffic," are vague. Can there be any doubt that sympathetic neural mechanisms contribute to LF rhythms? Such contributions could arise simply on the basis that sympathetically mediated⁶⁵ fluctuations of arterial pressure provoke vagally mediated fluctuations of RR intervals.⁶⁶ Does the fact that there is a sympathetic contribution mean that LF rhythms are quantitative probes for sympathetic traffic?

The word "drive," as in "..normalized LF [low-frequency], an indicator of sympathetic drive,"⁶⁴ and "..maneuvers enhancing vagal and sympathetic drive,"³ connotes nerve traffic rather than variability of nerve traffic. Similarly, the word "activity," as in "maneuvers enhancing sympathetic and vagal activities," connotes nerve traffic rather than variability of nerve traffic. The word "predominance," as in "vagal predominance,"¹ is vague; in such a context, does predominance mean that vagal fluctuations are larger than sympathetic fluctuations or that absolute levels of vagus nerve traffic are larger than absolute levels of sympathetic nerve traffic? The recurring^3,67 assertion that "..a reciprocal relation exists between these two rhythms [0.1 Hz and respiratory] that is similar to that characterizing the sympathovagal balance" is tautological. The word "modulation," as in "enhance the vagal modulation of the heart rate,"³ is binary, not graded; it is something that is present or not. These concerns about language reflect a larger concern that because the words are so familiar that the concepts engendered by these words may also be regarded as familiar. As this review suggests, I find many of the concepts foreign. In the end, however, it is not philosophy or language that must justify sympathovagal balance; it is physiology, which I have reviewed here.

The Numerator
It is inarguable that fluctuations of vagus nerve traffic contribute to 0.1-Hz RR-interval spectral power; Fig 1 documents a major vagal contribution. (It is curious that the near disappearance of respiratory-frequency RR-interval spectral power after large-dose atropine is taken as evidence that this component is vagally mediated,¹ but the near disappearance of 0.1-Hz RR-interval spectral power is ascribed to different mechanisms.)

Myocardial norepinephrine spillover is the current gold standard for sympathetic traffic to the human heart; this measure correlates well with muscle sympathetic nerve traffic and plasma norepinephrine levels, at rest and during isometric exercise and mental arithmetic.^9,52 Normalized 0.1-Hz RR-interval spectral power bears no significant relation to baseline levels or to baroreflex-mediated changes of myocardial norepinephrine spillover,⁹ muscle sympathetic nerve activity,¹⁰ or antecubital vein plasma norepinephrine concentrations.¹⁰

The Denominator
RR-interval shortening after large-dose atropine is given to ß-adrenergically blocked subjects is the current gold standard for vagal traffic to the human heart. Normalized respiratory-frequency RR-interval spectral power at rest bears no significant relation to RR-interval shortening after large-dose atropine.²⁵

Although there is a quantitative relation between respiratory-frequency RR-interval spectral power and vagal-cardiac nerve activity,^22,26 moderate changes of vagal-cardiac nerve activity from baseline, such as those that accompany increases or decreases of arterial pressure, do not alter respiratory-frequency RR-interval spectral power (Fig 3). Conversely, huge changes of HF RR-interval spectral power provoked by changes of breathing (which in most sympathovagal balance research is neither controlled nor measured²) may not reflect changes of vagal-cardiac nerve traffic at all. It is unclear how sympathovagal balance should be calculated or interpreted when systematic changes of breathing frequency occur during the period of measurement, such as those reported in patients with sleep apnea.⁶⁸

These considerations betray what I consider a fundamental misconception of what RR-interval rhythms represent. At arterial pressures moderately above and below baseline levels, HF RR-interval rhythms reflect primarily respiratory gating of vagal-cardiac motoneuron responsiveness to baroreceptor and other sensory receptor stimulation.⁶⁹ At baseline arterial pressures, variations of RR-interval fluctuations associated with variations of breathing frequency or depth reflect primarily the kinetics of sinoatrial node responses to acetylcholine.³² Neither mechanism requires the fine-tuning of rhythmicity that is invoked to explain sympathovagal balance.

The Quotient
The intuitively attractive notion that changes of sympathetic and vagal nerve activities occur reciprocally does not occur with all interventions, including immersion of the face in iced water^34,35 and carbon dioxide chemoreceptor stimulation (D.L.E., MD, et al, unpublished data, 1997). During these interventions, both neural outflows appear to change in parallel. More importantly, changes of sympathetic and vagal neural outflows do not necessarily occur reciprocally with moderate changes of baroreceptor input; increases of arterial pressure that are more than modest increase vagal-cardiac nerve traffic but do not alter (muscle) sympathetic nerve traffic. A highly significant inverse relation between muscle sympathetic nerve activity and indirectly measured vagal-cardiac nerve activity exists in heart failure patients.¹⁶ However, calculations of sympathovagal balance in heart failure patients yield extremely low values,^3,45 not the high values that would have been predicted. Because of this, sympathovagal balance is qualified as being useful only in patients with "less advanced"³ stages of heart failure. This qualification provides small comfort. How are patients whose heart failure is severe enough to invalidate sympathovagal balance to be identified? Does this noninvasive measure require corroboration by invasive measurements of sympathetic nerve activity?

My review challenges both the notion that the linear increase of sympathovagal balance that occurs during upright tilt reflects a shift of autonomic predominance from vagal to sympathetic mechanisms and the extrapolation from this narrowly restricted circumstance to other very different circumstances.

The sympathovagal-balance literature is replete with disclaimers that spectral power reflects fluctuations, not absolute levels of autonomic nerve traffic (Akselrod's discussion is particularly thoughtful and probing⁷⁰). My reading, however, suggests that the great majority of articles that use sympathovagal balance as a tool are based on the de facto notion that this number reflects the ratio of sympathetic to vagus nerve activities. This notion may even be stated explicitly. For example, Pagani and coworkers propose that "..the increased HF component of RR variability would indicate that during metronome breathing there is enhanced vagal tone."¹

Grossman and Kollai⁷¹ liken RR-interval fluctuations to ripples on a sea of varying depths. I am aware of no arguments in the sympathovagal literature that support the view that it is the fluctuations of nerve traffic (the ripples on the surface of the sea) rather than the absolute levels (the depth of the sea) that are important. Such justification is necessary. What evidence indicates that during moderate changes of arterial pressure, such as those shown in Fig 4, the physiologically relevant variable is the nearly constant fluctuations of vagus nerve traffic rather than the varying absolute levels of vagus nerve traffic that are proportional to arterial pressure?

In summary, if mathematical manipulation of RR-interval spectral power is to inspire confidence as a robust, reliable metric, it must be grounded solidly on physiological principles. It must stand on its own. This review calls attention to major problems with the construct of sympathovagal balance. It can be argued with some justification that my review raises objections to sympathovagal balance that have been stipulated. If the manifold problems this review documents are indeed, universally accepted, the review may still be useful in calling attention to what I consider the implication of these problems: calculations of sympathovagal balance may obscure rather than illuminate human physiology and pathophysiology.

	Acknowledgments

 
This work was supported by grants and contracts from the Veterans Administration, the National Institutes of Health (HL-22296 and UO1 HL-53204), and the National Aeronautics and Space Administration (NAG 2–408 and NAS-17720). I especially thank Paul Grossman for his critical review of the manuscript and helpful suggestions.

	Footnotes

 

	References

Top Introduction The Method and Its... Discussion References

 
1. Pagani M, Lombardi F, Guzzetti S, Rimoldi O, Furlan R, Pizzinelli P, Sandrone G, Malfatto G, Dell'Orto S, Piccaluga E, Turiel M, Baselli G, Cerutti S, Malliani A. Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog. Circ Res. 1986;59:178–193.[Abstract/Free Full Text]

2. Brown TE, Beightol LA, Koh J, Eckberg DL. Important influence of respiration on human RR interval power spectra is largely ignored. J Appl Physiol. 1993;75:2310–2317.[Abstract/Free Full Text]

3. Malliani A, Pagani M, Lombardi F, Cerutti S. Cardiovascular neural regulation explored in the frequency domain. Circulation. 1991;84:482–492.[Abstract/Free Full Text]

4. Akaike H. Statistical predictor identification. Ann Inst Stat Math. 1970;22:203–217.

5. Christini DJ, Kulkarni A, Rao S, Stutman ER, Bennett FM, Hausdorff JM, Oriol N, Lutchen KR. Influence of autoregressive model parameter uncertainty on spectral estimates of heart rate dynamics. Ann Biomed Eng. 1995;23:127–134.[Medline] [Order article via Infotrieve]

6. 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. 1996;93:1043–1065.[Free Full Text]

7. Eckberg DL, Nerhed C, Wallin BG. Respiratory modulation of muscle sympathetic and vagal cardiac outflow in man. J Physiol (Lond). 1985;365:181–196.[Abstract/Free Full Text]

8. Wallin BG, Nerhed C. Relationship between spontaneous variations of muscle sympathetic activity and succeeding changes of blood pressure in man. J Auton Nerv Syst. 1982;6:293–302.[Medline] [Order article via Infotrieve]

9. Kingwell BA, Thompson JM, Kaye DM, McPherson GA, Jennings GL, Esler MD. Heart rate spectral analysis, cardiac norepinephrine spillover, and muscle sympathetic nerve activity during human sympathetic nervous activation and failure. Circulation. 1994;90:234–240.[Abstract/Free Full Text]

10. Saul JP, Rea RF, Eckberg DL, Berger RD, Cohen RJ. Heart rate and muscle sympathetic nerve variability during reflex changes of autonomic activity. Am J Physiol. 1990;258:H713–H721.[Abstract/Free Full Text]

11. Hopf H-B, Skyschally A, Heusch G, Peters J. Low-frequency spectral power of heart rate variability is not a specific marker of cardiac sympathetic modulation. Anesthesiology. 1995;82:609–619.[Medline] [Order article via Infotrieve]

12. Introna R, Yodlowski E, Pruett J, Montano N, Porta A, Crumrine R. Sympathovagal effects of spinal anesthesia assessed by heart rate variability analysis. Anesth Analg. 1995;80:315–321.[Abstract]

13. Jokkel G, Bonyhay I, Kollai M. Heart rate variability after complete autonomic blockade in man. J Auton Nerv Syst. 1995;51:85–89.[Medline] [Order article via Infotrieve]

14. Raczkowska M, Eckberg DL, Ebert TJ. Muscarinic cholinergic receptors modulate vagal cardiac responses in man. J Auton Nerv Syst. 1983;7:271–278.[Medline] [Order article via Infotrieve]

15. Vybiral T, Bryg RJ, Maddens ME, Bhasin SS, Cronin S, Boden WE, Lehmann MH. Effects of transdermal scopolamine on heart rate variability in normal subjects. Am J Cardiol. 1990;65:604–608.[Medline] [Order article via Infotrieve]

16. Porter TR, Eckberg DL, Fritsch JM, Rea RF, Beightol LA, Schmedtje JF Jr, Mohanty PK. Autonomic pathophysiology in heart failure patients: sympathetic-cholinergic interrelations. J Clin Invest. 1990;85:1362–1371.

17. Pomeranz B, Macaulay RJB, Caudill MA, Kutz I, Adam D, Gordon D, Kilborn KM, Barger AC, Shannon DC, Cohen RJ, Benson H. Assessment of autonomic function in humans by heart rate spectral analysis. Am J Physiol. 1985;248:H151–H153.[Abstract/Free Full Text]

18. Koh J, Brown TE, Beightol LA, Ha CY, Eckberg DL. Human autonomic rhythms: vagal cardiac mechanisms in tetraplegic subjects. J Physiol (Lond). 1994;474:483–495.[Abstract/Free Full Text]

19. Epstein AE, Hirschowitz BI, Kirklin JK, Kirk KA, Kay GN, Plumb VJ. Evidence for a central site of action to explain the negative chronotropic effect of atropine: studies on the human transplanted heart. J Am Coll Cardiol. 1990;15:1610–1617.[Abstract]

20. Pagani M, Montano N, Porta A, Malliani A, Abboud FM, Birkett C, Somers VK. Relationship between spectral components of cardiovascular variabilities and direct measures of muscle sympathetic nerve activity in humans. Circulation. 1997;95:1441–1448.[Abstract/Free Full Text]

21. Theil H. A rank-invariant method of linear and polynomial regression analysis. Koninkl Ned Akad Wetenschap Proc. 1950;53:386,521,1397–392,525,1412.

22. Katona PG, Jih F. Respiratory sinus arrhythmia: noninvasive measure of parasympathetic cardiac control. J Appl Physiol. 1975;39:801–805.[Abstract/Free Full Text]

23. Fouad FM, Tarazi RC, Ferrario CM, Fighaly S, Alicandri C. Assessment of parasympathetic control of heart rate by a noninvasive method. Am J Physiol. 1984;246:H838–H842.

24. Eckberg DL. Human sinus arrhythmia as an index of vagal cardiac outflow. J Appl Physiol. 1983;54:961–966.[Abstract/Free Full Text]

25. Hayano J, Sakakibara Y, Yamada A, Yamada M, Mukai S, Fujinami T, Yokoyama K, Watanabe Y, Takata K. Accuracy of assessment of cardiac vagal tone by heart rate variability in normal subjects. Am J Cardiol. 1991;67:199–204.[Medline] [Order article via Infotrieve]

26. Kollai M, Mizsei G. Respiratory sinus arrhythmia is a limited measure of cardiac parasympathetic control in man. J Physiol (Lond). 1990;424:329–342.[Abstract/Free Full Text]

27. Eckberg DL, Rea RF, Andersson OK, Hedner T, Pernow J, Lundberg JM, Wallin BG. Baroreflex modulation of sympathetic activity and sympathetic neurotransmitters in humans. Acta Physiol Scand. 1988;133:221–231.[Medline] [Order article via Infotrieve]

28. Goldberger JJ, Ahmed MW, Parker MA, Kadish AH. Dissociation of heart rate variability from parasympathetic tone. Am J Physiol. 1994;266:H2152–H2157.[Abstract/Free Full Text]

29. Anrep GV, Pascual W, Rössler R. Respiratory variations of the heart rate, I: the reflex mechanism of the respiratory arrhythmia. Proc R Soc Lond B. 1936;119B:191–217.

30. Parker P, Celler BG, Potter EK, McCloskey DI. Vagal stimulation and cardiac slowing. J Auton Nerv Syst. 1984;11:226–231.[Medline] [Order article via Infotrieve]

31. Grossman P, Karemaker J, Wieling W. Prediction of tonic parasympathetic cardiac control using respiratory sinus arrhythmia: the need for respiratory control. Psychophysiol. 1991;28:201–216.[Medline] [Order article via Infotrieve]

32. Saul JP, Berger RD, Albrecht P, Stein SP, Chen MH, Cohen RJ. Transfer function analysis of the circulation: unique insights into cardiovascular regulation. Am J Physiol. 1991;261:H1231–H1245.[Abstract/Free Full Text]

33. Priban IP. An analysis of some short-term patterns of breathing in man at rest. J Physiol (Lond). 1963;166:425–434.

34. Fagius J, Sundlöf G. The diving response in man: effects on sympathetic activity in muscle and skin nerve fascicles. J Physiol (Lond). 1986;377:429–443.[Abstract/Free Full Text]

35. Eckberg DL, Mohanty SK, Raczkowska M. Trigeminal-baroreceptor reflex interactions modulate human cardiac vagal efferent activity. J Physiol (Lond). 1984;347:75–83.[Abstract/Free Full Text]

36. Rea RF, Eckberg DL. Carotid baroreceptor-muscle sympathetic relation in humans. Am J Physiol. 1987;253:R929–R934.[Abstract/Free Full Text]

37. Eckberg DL. Nonlinearities of the human carotid baroreceptor-cardiac reflex. Circ Res. 1980;47:208–216.[Abstract/Free Full Text]

38. Levine BD, Buckey JC, Fritsch JM, Yancy CW Jr, Watenpaugh DE, Snell PG, Lane LD, Eckberg DL, Blomqvist CG. Physical fitness and cardiovascular regulation: mechanisms of orthostatic intolerance. J Appl Physiol. 1991;70:112–122.[Abstract/Free Full Text]

39. Olivari MT, Levine TB, Cohn JN. Abnormal neurohumoral response to nitroprusside infusion in congestive heart failure. J Am Coll Cardiol. 1983;2:411–417.[Abstract]

40. Ferguson DW, Berg WJ, Roach PJ, Oren RM, Mark AL. Effects of heart failure on baroreflex control of sympathetic neural activity. Am J Cardiol. 1992;69:523–531.[Medline] [Order article via Infotrieve]

41. Leimbach WN Jr, Wallin BG, Victor RG, Aylward PE, Sundlöf G, Mark AL. Direct evidence from intraneural recordings for increased central sympathetic outflow in patients with heart failure. Circulation. 1986;73:913–919.[Abstract/Free Full Text]

42. Cohn JN, Levine TB, Olivari MT, Garberg V, Lura D, Francis GS, Simon AB, Rector T. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med. 1984;311:819–823.[Abstract]

43. Hasking GJ, Esler MD, Jennings GL, Burton D, Johns JA, Korner PI. Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity. Circulation. 1986;73:615–621.[Abstract/Free Full Text]

44. Meredith IT, Eisenhofer G, Lambert GW, Dewar EM, Jennings GL, Esler MD. Cardiac sympathetic nervous activity in congestive heart failure: evidence for increased neuronal norepinephrine release and preserved neuronal uptake. Circulation. 1993;88:136–145.[Abstract/Free Full Text]

45. Saul JP, Arai Y, Berger RD, Lilly LS, Colucci WS, Cohen RJ. Assessment of autonomic regulation in chronic congestive heart failure by heart rate spectral analysis. Am J Cardiol. 1988;61:1292–1299.[Medline] [Order article via Infotrieve]

46. Novak V, Novak P, de Champlain J, Nadeau R. Altered cardiorespiratory transfer in hypertension. Hypertension. 1994;23:104–113.[Abstract/Free Full Text]

47. Loveridge BM, Dubo HI. Breathing pattern in chronic quadriplegia. Arch Phys Med Rehabil. 1990;71:495–499.[Medline] [Order article via Infotrieve]

48. Iwase S, Mano T, Saito M. Effects of graded head-up tilting on muscle sympathetic activities in man. Physiologist. 1987;30(suppl):S-62-S-65.

49. Montano N, Gnecchi Ruscone T, Porta A, Lombardi F, Pagani M, Malliani A. Power spectrum analysis of heart rate variability to assess the changes in sympathovagal balance during graded orthostatic tilt. Circulation. 1994;90:1826–1831.[Abstract/Free Full Text]

50. Mukai S, Hayano J. Heart rate and blood pressure variabilities during graded head-up tilt. J Appl Physiol. 1995;78:212–216.[Abstract/Free Full Text]

51. Burke D, Sundlöf G, Wallin BG. Postural effects on muscle nerve sympathetic activity in man. J Physiol (Lond). 1977;272:399–414.[Abstract/Free Full Text]

52. Wallin BG, Esler M, Dorward P, Eisenhofer G, Ferrier C, Westerman R, Jennings G. Simultaneous measurements of cardiac noradrenaline spillover and sympathetic outflow to skeletal muscle in humans. J Physiol (Lond). 1992;453:45–58.[Abstract/Free Full Text]

53. Mark AL, Victor RG, Nerhed C, Wallin BG. Microneurographic studies of the mechanisms of sympathetic nerve responses to static exercise in humans. Circ Res. 1985;57:461–469.[Abstract/Free Full Text]

54. Freyschuss U. Cardiovascular adjustment to somatomotor activation. Acta Physiol Scand. 1970;suppl 342:1–63.

55. Arai Y, Saul JP, Albrecht P, Hartley LH, Lilly LS, Cohen RJ, Colucci WS. Modulation of cardiac autonomic activity during and immediately after exercise. Am J Physiol. 1989;256:H132–H141.[Abstract/Free Full Text]

56. Perini R, Orizio C, Baselli G, Cerutti S, Veicsteinas A. The influence of exercise intensity on the power spectrum of heart rate variability. Eur J Appl Physiol. 1990;61:143–148.

57. Robinson BF, Epstein SE, Beiser GD, Braunwald E. Control of heart rate by the autonomic nervous system: studies in man on the interrelation between baroreceptor mechanisms and exercise. Circ Res. 1966;19:400–411.[Abstract/Free Full Text]

58. Fagraeus L, Linnarsson D. Autonomic origin of heart rate fluctuations at the onset of muscular exercise. J Appl Physiol. 1976;40:679–682.[Abstract/Free Full Text]

59. Kleiger RE, Miller JP, Bigger JT Jr, Moss AJ, for the Multicenter Post-Infarction Research Group. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol. 1987;59:256–262.[Medline] [Order article via Infotrieve]

60. Bigger JT Jr, Kleiger RE, Fleiss JL, Rolnitzky LM, Steinman RC, Miller JP, for the Multicenter Post-Infarction Research Group. Components of heart rate variability measured during healing of acute myocardial infarction. Am J Cardiol. 1988;61:208–215.[Medline] [Order article via Infotrieve]

61. Farrell TG, Paul V, Cripps TR, Malik M, Bennett ED, Ward D, Camm AJ. Baroreflex sensitivity and electrophysiological correlates in patients after acute myocardial infarction. Circulation. 1991;83:945–952.[Abstract/Free Full Text]

62. Appel ML, Berger RD, Saul JP, Smith JM, Cohen RJ. Beat to beat variability in cardiovascular variables: noise or music? J Am Coll Cardiol. 1989;14:1139–1148.[Abstract]

63. Guzzetti S, Cogliati C, Broggi C, Carozzi C, Caldiroli D, Lombardi F, Malliani A. Influences of neural mechanisms on heart period and arterial pressure variabilities in quadriplegic patients. Am J Physiol. 1994;266:H1112–H1120.[Abstract/Free Full Text]

64. Guzzetti S, Dassi S, Balsamà M, Ponti GB, Pagani M, Malliani A. Altered dynamics of the circadian relationship between systemic arterial pressure and cardiac sympathetic drive early on in mild hypertension. Clin Sci. 1994;86:209–215.[Medline] [Order article via Infotrieve]

65. Preiss G, Polosa C. Patterns of sympathetic neuron activity associated with Mayer waves. Am J Physiol. 1974;226:724–730.

66. Airaksinen KEJ, Tahvanainen KUO, Kuusela TA, Huikuri HV, Niemelä MJ, Karjalainen P, Eckberg DL. Cross spectral analysis in assessment of baroreflex gain in patients with coronary artery disease. Ann Noninvas Electrocardiol. 1997;2:229-235.[Medline] [Order article via Infotrieve]

67. Malliani A. Association of heart rate variability components with physiological regulatory mechanisms. In: Malik M, Camm AJ, eds. Heart Rate Variability. Armonk, NY: Futura; 1995:173–188.

68. Vanninen E, Tuunainen A, Kansanen M, Uusitupa M, Lansimies E. Cardiac sympathovagal balance during sleep apnea episodes. Clin Physiol. 1996;16:209–216.[Medline] [Order article via Infotrieve]

69. Eckberg DL, Kifle YT, Roberts VL. Phase relationship between normal human respiration and baroreflex responsiveness. J Physiol (Lond). 1980;304:489–502.[Abstract/Free Full Text]

70. Akselrod S. Components of heart rate variability: basic studies. In: Malik M, Camm AJ, eds. Heart Rate Variability. Armonk, NY: Futura; 1995:147–163.

71. Grossman P, Kollai M. Respiratory sinus arrhythmia, cardiac vagal tone, and respiration: within- and between-individual relations. Psychophysiol. 1993;30:486–495.[Medline] [Order article via Infotrieve]

This article has been cited by other articles:

				V. Manzi, C. Castagna, E. Padua, M. Lombardo, S. D'Ottavio, M. Massaro, M. Volterrani, and F. Iellamo Dose-response relationship of autonomic nervous system responses to individualized training impulse in marathon runners Am J Physiol Heart Circ Physiol, June 1, 2009; 296(6): H1733 - H1740. [Abstract] [Full Text] [PDF]

				A. E Aubert, S. Vandeput, F. Beckers, J. Liu, B. Verheyden, and S. Van Huffel Complexity of cardiovascular regulation in small animals Phil Trans R Soc A, April 13, 2009; 367(1892): 1239 - 1250. [Abstract] [Full Text] [PDF]

				J. Cruz, J. Sousa, A. G. Oliveira, and L. Silva-Carvalho Effects of endoscopic thoracic sympathectomy for primary hyperhidrosis on cardiac autonomic nervous activity. J. Thorac. Cardiovasc. Surg., March 1, 2009; 137(3): 664 - 669. [Abstract] [Full Text] [PDF]

				A. Porta, F. Aletti, F. Vallais, and G. Baselli Multimodal signal processing for the analysis of cardiovascular variability Phil Trans R Soc A, January 28, 2009; 367(1887): 391 - 409. [Abstract] [Full Text] [PDF]

				M. Pagani and D. Lucini Cardiovascular physiology, emotions, and clinical applications: are we ready for prime time? Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H1 - H3. [Full Text] [PDF]

				T. Ishizawa, K. Yoshiuchi, Y. Takimoto, Y. Yamamoto, and A. Akabayashi Heart Rate and Blood Pressure Variability and Baroreflex Sensitivity in Patients With Anorexia Nervosa Psychosom Med, July 1, 2008; 70(6): 695 - 700. [Abstract] [Full Text] [PDF]

				V. Vaccarino, R. Lampert, J. D. Bremner, F. Lee, S. Su, C. Maisano, N. V. Murrah, L. Jones, F. Jawed, N. Afzal, et al. Depressive Symptoms and Heart Rate Variability: Evidence for a Shared Genetic Substrate in a Study of Twins Psychosom Med, July 1, 2008; 70(6): 628 - 636. [Abstract] [Full Text] [PDF]

				R. Howden, E. Liu, L. Miller-DeGraff, H. L. Keener, C. Walker, J. A. Clark, P. H. Myers, D. C. Rouse, T. Wiltshire, and S. R. Kleeberger The genetic contribution to heart rate and heart rate variability in quiescent mice Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H59 - H68. [Abstract] [Full Text] [PDF]

				M. K. Lahiri, P. J. Kannankeril, and J. J. Goldberger Assessment of Autonomic Function in Cardiovascular Disease: Physiological Basis and Prognostic Implications J. Am. Coll. Cardiol., May 6, 2008; 51(18): 1725 - 1733. [Abstract] [Full Text] [PDF]

				A. Porta, T. Gnecchi-Ruscone, E. Tobaldini, S. Guzzetti, R. Furlan, and N. Montano Progressive decrease of heart period variability entropy-based complexity during graded head-up tilt J Appl Physiol, October 1, 2007; 103(4): 1143 - 1149. [Abstract] [Full Text] [PDF]

				R. M. Baevsky, V. M. Baranov, I. I. Funtova, A. Diedrich, A. V. Pashenko, A. G. Chernikova, J. Drescher, J. Jordan, and J. Tank Autonomic cardiovascular and respiratory control during prolonged spaceflights aboard the International Space Station J Appl Physiol, July 1, 2007; 103(1): 156 - 161. [Abstract] [Full Text] [PDF]

				A. Porta, E. Tobaldini, S. Guzzetti, R. Furlan, N. Montano, and T. Gnecchi-Ruscone Assessment of cardiac autonomic modulation during graded head-up tilt by symbolic analysis of heart rate variability Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H702 - H708. [Abstract] [Full Text] [PDF]

				M. Ichinose, S. Koga, N. Fujii, N. Kondo, and T. Nishiyasu Modulation of the spontaneous beat-to-beat fluctuations in peripheral vascular resistance during activation of muscle metaboreflex Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H416 - H424. [Abstract] [Full Text] [PDF]

				B. E. Westerhof, J. Gisolf, J. M. Karemaker, K. H. Wesseling, N. H. Secher, and J. J. van Lieshout Time course analysis of baroreflex sensitivity during postural stress Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2864 - H2874. [Abstract] [Full Text] [PDF]

				Y. Zhong, K.-M. Jan, K. H. Ju, and K. H. Chon Quantifying cardiac sympathetic and parasympathetic nervous activities using principal dynamic modes analysis of heart rate variability Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1475 - H1483. [Abstract] [Full Text] [PDF]

				A. Malliani, C. Julien, G. E. Billman, S. Cerutti, M. F. Piepoli, L. Bernardi, P. Sleight, M. A. Cohen, C. O. Tan, D. Laude, et al. Cardiovascular variability is/is not an index of autonomic control of circulation J Appl Physiol, August 1, 2006; 101(2): 684 - 688. [Full Text] [PDF]

				A. Weissman, L. Lowenstein, A. Peleg, I. Thaler, and E. Z. Zimmer Power Spectral Analysis of Heart Rate Variability During the 100-g Oral Glucose Tolerance Test in Pregnant Women. Diabetes Care, March 1, 2006; 29(3): 571 - 574. [Abstract] [Full Text] [PDF]

				M. E. Alvarenga, J. C. Richards, G. Lambert, and M. D. Esler Psychophysiological Mechanisms in Panic Disorder: A Correlative Analysis of Noradrenaline Spillover, Neuronal Noradrenaline Reuptake, Power Spectral Analysis of Heart Rate Variability, and Psychological Variables Psychosom Med, January 1, 2006; 68(1): 8 - 16. [Abstract] [Full Text] [PDF]

				S. Andreas, S. D. Anker, P. D. Scanlon, and V. K. Somers Neurohumoral Activation as a Link to Systemic Manifestations of Chronic Lung Disease Chest, November 1, 2005; 128(5): 3618 - 3624. [Abstract] [Full Text] [PDF]

				J. R. Padley, D. H. Overstreet, P. M. Pilowsky, and A. K. Goodchild Impaired cardiac and sympathetic autonomic control in rats differing in acetylcholine receptor sensitivity Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H1985 - H1992. [Abstract] [Full Text] [PDF]

				E Ronkainen, H Ansakorpi, H V Huikuri, V V Myllyla, J I T Isojarvi, and J T Korpelainen Suppressed circadian heart rate dynamics in temporal lobe epilepsy J. Neurol. Neurosurg. Psychiatry, October 1, 2005; 76(10): 1382 - 1386. [Abstract] [Full Text] [PDF]

				P. P. J. van der Veek, C. A. Swenne, H. v. d. Vooren, A. L. Schoneveld, R. Maestri, and A. A. M. Masclee Viscerosensory-cardiovascular reflexes: altered baroreflex sensitivity in irritable bowel syndrome Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2005; 289(4): R970 - R976. [Abstract] [Full Text] [PDF]

				P. Taggart, P. Sutton, C. Redfern, V. N. Batchvarov, K. Hnatkova, M. Malik, U. James, and A. Joseph The Effect of Mental Stress on the Non-Dipolar Components of the T Wave: Modulation by Hypnosis Psychosom Med, May 1, 2005; 67(3): 376 - 383. [Abstract] [Full Text] [PDF]

				R. Winker, A. Barth, D. Bidmon, I. Ponocny, M. Weber, O. Mayr, D. Robertson, A. Diedrich, R. Maier, A. Pilger, et al. Endurance Exercise Training in Orthostatic Intolerance: A Randomized, Controlled Trial Hypertension, March 1, 2005; 45(3): 391 - 398. [Abstract] [Full Text] [PDF]

				M. Buchheit, C. Simon, F. Piquard, J. Ehrhart, and G. Brandenberger Effects of increased training load on vagal-related indexes of heart rate variability: a novel sleep approach Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2813 - H2818. [Abstract] [Full Text] [PDF]

				G. Grassi, A. Vincenti, R. Brambilla, F. Q. Trevano, R. Dell'Oro, A. Ciro, G. Trocino, A. Vincenzi, and G. Mancia Sustained Sympathoinhibitory Effects of Cardiac Resynchronization Therapy in Severe Heart Failure Hypertension, November 1, 2004; 44(5): 727 - 731. [Abstract] [Full Text] [PDF]

				S. Wakabayashi and Y. Aso Adiponectin Concentrations in Sera From Patients With Type 2 Diabetes Are Negatively Associated With Sympathovagal Balance as Evaluated by Power Spectral Analysis of Heart Rate Variation Diabetes Care, October 1, 2004; 27(10): 2392 - 2397. [Abstract] [Full Text] [PDF]

				D. Rubinger, N. Revis, A. Pollak, M. H. Luria, and D. Sapoznikov Predictors of haemodynamic instability and heart rate variability during haemodialysis Nephrol. Dial. Transplant., August 1, 2004; 19(8): 2053 - 2060. [Abstract] [Full Text] [PDF]

				W. H. Cooke, J. R. Carter, and T. A. Kuusela Human cerebrovascular and autonomic rhythms during vestibular activation Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2004; 286(5): R838 - R843. [Abstract] [Full Text] [PDF]

				A. Blasi, J. Jo, E. Valladares, B. J. Morgan, J. B. Skatrud, and M. C. K. Khoo Cardiovascular variability after arousal from sleep: time-varying spectral analysis J Appl Physiol, October 1, 2003; 95(4): 1394 - 1404. [Abstract] [Full Text] [PDF]

				H. D. Critchley, C. J. Mathias, O. Josephs, J. O'Doherty, S. Zanini, B.-K. Dewar, L. Cipolotti, T. Shallice, and R. J. Dolan Human cingulate cortex and autonomic control: converging neuroimaging and clinical evidence Brain, October 1, 2003; 126(10): 2139 - 2152. [Abstract] [Full Text] [PDF]

				P-F. Migeotte, G. K. Prisk, and M. Paiva Microgravity alters respiratory sinus arrhythmia and short-term heart rate variability in humans Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H1995 - H2006. [Abstract] [Full Text] [PDF]

				T. S. Campbell, B. Ditto, J. R. Seguin, S. Sinray, and R. E. Tremblay Adolescent Pain Sensitivity Is Associated With Cardiac Autonomic Function and Blood Pressure Over 8 Years Hypertension, June 1, 2003; 41(6): 1228 - 1233. [Abstract] [Full Text] [PDF]

				L. Spicuzza, L. Bernardi, A. Calciati, and G. U. Di Maria Autonomic Modulation of Heart Rate during Obstructive versus Central Apneas in Patients with Sleep-disordered Breathing Am. J. Respir. Crit. Care Med., March 15, 2003; 167(6): 902 - 910. [Abstract] [Full Text] [PDF]

				D. E. Burgess, D. C. Randall, R. O. Speakman, and D. R. Brown Coupling of sympathetic nerve traffic and BP at very low frequencies is mediated by large-amplitude events Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2003; 284(3): R802 - R810. [Abstract] [Full Text] [PDF]

				J. A. Jo, A. Blasi, E. Valladares, R. Juarez, A. Baydur, and M. C. K. Khoo Model-based Assessment of Autonomic Control in Obstructive Sleep Apnea Syndrome during Sleep Am. J. Respir. Crit. Care Med., January 15, 2003; 167(2): 128 - 136. [Abstract] [Full Text] [PDF]

				T. Gori, J. S. Floras, and J. D. Parker Effects of nitroglycerin treatment on baroreflex sensitivity andshort-term heart rate variability in humans J. Am. Coll. Cardiol., December 4, 2002; 40(11): 2000 - 2005. [Abstract] [Full Text] [PDF]

				L. Poulsen Blood pressure and cardiac autonomic function in relation to risk factors and treatment perspectives in Type 1 diabetes Journal of Renin-Angiotensin-Aldosterone System, December 1, 2002; 3(4): 222 - 242. [Abstract] [PDF]

				P. Abraham, J. Berthelot, J. Victor, J.-L. Saumet, J. Picquet, and B. Enon Holter changes resulting from right-sided and bilateral infrastellate upper thoracic sympathectomy Ann. Thorac. Surg., December 1, 2002; 74(6): 2076 - 2081. [Abstract] [Full Text] [PDF]

				J Andrich, T Schmitz, C Saft, T Postert, P Kraus, J T Epplen, H Przuntek, and M W Agelink Autonomic nervous system function in Huntington's disease J. Neurol. Neurosurg. Psychiatry, June 1, 2002; 72(6): 726 - 731. [Abstract] [Full Text] [PDF]

				R Egg, B Hogl, S Glatzl, R Beer, and T Berger Autonomic instability, as measured by pupillary unrest, is not associated with multiple sclerosis fatigue severity Multiple Sclerosis, June 1, 2002; 8(3): 256 - 260. [Abstract] [PDF]

				N. Hirshoren, I. Tzoran, I. Makrienko, Y. Edoute, M. M. Plawner, J. Itskovitz-Eldor, and G. Jacob Menstrual Cycle Effects on the Neurohumoral and Autonomic Nervous Systems Regulating the Cardiovascular System J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1569 - 1575. [Abstract] [Full Text] [PDF]

				T. A. Kuusela, T. T. Jartti, K. U. O. Tahvanainen, and T. J. Kaila Nonlinear methods of biosignal analysis in assessing terbutaline-induced heart rate and blood pressure changes Am J Physiol Heart Circ Physiol, February 1, 2002; 282(2): H773 - H781. [Abstract] [Full Text] [PDF]

				D. L. Jardine, C. J. Charles, I. C. Melton, C. N. May, M. D. Forrester, C. M. Frampton, S. I. Bennett, and H. Ikram Continual recordings of cardiac sympathetic nerve activity in conscious sheep Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H93 - H99. [Abstract] [Full Text] [PDF]

				P. P. Jones, L. F. Shapiro, G. A. Keisling, J. Jordan, J. R. Shannon, R. A. Quaife, and D. R. Seals Altered Autonomic Support of Arterial Blood Pressure With Age in Healthy Men Circulation, November 13, 2001; 104(20): 2424 - 2429. [Abstract] [Full Text] [PDF]

				W. J. Kop, R. J. Verdino, J. S. Gottdiener, S. T. O'Leary, C. N. Bairey Merz, and D. S. Krantz Changes in heart rate and heart rate variability before ambulatory ischemic events J. Am. Coll. Cardiol., September 1, 2001; 38(3): 742 - 749. [Abstract] [Full Text] [PDF]

				S. M.M.S. Bezerra, C. M. dos Santos, E. D. Moreira, E. M. Krieger, and L. C. Michelini Chronic AT1 Receptor Blockade Alters Autonomic Balance and Sympathetic Responses in Hypertension Hypertension, September 1, 2001; 38(3): 569 - 575. [Abstract] [Full Text] [PDF]

				J. S. Floras, G. C. Butler, S.-I. Ando, S. C. Brooks, M. J. Pollard, and P. Picton Differential sympathetic nerve and heart rate spectral effects of nonhypotensive lower body negative pressure Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2001; 281(2): R468 - R475. [Abstract] [Full Text] [PDF]

				C. Keyl, A. Schneider, M. Dambacher, and L. Bernardi Time delay of vagally mediated cardiac baroreflex response varies with autonomic cardiovascular control J Appl Physiol, July 1, 2001; 91(1): 283 - 289. [Abstract] [Full Text] [PDF]

				F. Franchi, C. Lazzeri, G. Barletta, L. Ianni, and M. Mannelli Centrally Mediated Effects of Bromocriptine on Cardiac Sympathovagal Balance Hypertension, July 1, 2001; 38(1): 123 - 129. [Abstract] [Full Text] [PDF]

				M.F. Hilton, M.J. Chappell, W.A. Bartlett, A. Malhotra, J.M. Beattie, and R.M. Cayton The sleep apnoea/hypopnoea syndrome depresses waking vagal tone independent of sympathetic activation Eur. Respir. J., June 1, 2001; 17(6): 1258 - 1266. [Abstract] [Full Text] [PDF]

				Y. Akehi, H. Yoshimatsu, M. Kurokawa, T. Sakata, H. Eto, S. Ito, and J. Ono VLCD-Induced Weight Loss Improves Heart Rate Variability in Moderately Obese Japanese Experimental Biology and Medicine, May 1, 2001; 226(5): 440 - 445. [Abstract] [Full Text]

				J. J. Goldberger, S. Challapalli, R. Tung, M. A. Parker, and A. H. Kadish Relationship of Heart Rate Variability to Parasympathetic Effect Circulation, April 17, 2001; 103(15): 1977 - 1983. [Abstract] [Full Text] [PDF]

				T H Haapaniemi, V Pursiainen, J T Korpelainen, H V Huikuri, K A Sotaniemi, and V V Myllyla Ambulatory ECG and analysis of heart rate variability in Parkinson's disease J. Neurol. Neurosurg. Psychiatry, March 1, 2001; 70(3): 305 - 310. [Abstract] [Full Text] [PDF]

				D. M. Bloomfield, A. Magnano, J. T. Bigger Jr., H. Rivadeneira, M. Parides, and R. C. Steinman Comparison of spontaneous vs. metronome-guided breathing on assessment of vagal modulation using RR variability Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H1145 - H1150. [Abstract] [Full Text] [PDF]

				J. A. Shaw, J. P. F. Chin-Dusting, B. A. Kingwell, and A. M. Dart Diurnal Variation in Endothelium-Dependent Vasodilatation Is Not Apparent in Coronary Artery Disease Circulation, February 13, 2001; 103(6): 806 - 812. [Abstract] [Full Text] [PDF]

				P. Van De Borne, N. Montano, K. Narkiewicz, J. P. Degaute, A. Malliani, M. Pagani, and V. K. Somers Importance of ventilation in modulating interaction between sympathetic drive and cardiovascular variability Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H722 - H729. [Abstract] [Full Text] [PDF]

				C. F. Notarius and J. S. Floras Limitations of the use of spectral analysis of heart rate variability for the estimation of cardiac sympathetic activity in heart failure Europace, January 1, 2001; 3(1): 29 - 38. [Abstract] [PDF]

				K.-I. Iwasaki, R. Zhang, J. H. Zuckerman, J. A. Pawelczyk, and B. D. Levine Effect of head-down-tilt bed rest and hypovolemia on dynamic regulation of heart rate and blood pressure Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2000; 279(6): R2189 - R2199. [Abstract] [Full Text] [PDF]

				C. G. Crandall, R. Zhang, and B. D. Levine Effects of whole body heating on dynamic baroreflex regulation of heart rate in humans Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2486 - H2492. [Abstract] [Full Text] [PDF]

				C. Keyl, A. Schneider, M. Dambacher, U. Wegenhorst, M. Ingenlath, M. Gruber, and L. Bernardi Dynamic Cardiocirculatory Control During Propofol Anesthesia in Mechanically Ventilated Patients Anesth. Analg., October 1, 2000; 91(5): 1188 - 1195. [Abstract] [Full Text] [PDF]

				G. Paolisso, D. Manzella, M. R. Rizzo, E. Ragno, M. Barbieri, G. Varricchio, and M. Varricchio Elevated plasma fatty acid concentrations stimulate the cardiac autonomic nervous system in healthy subjects Am. J. Clinical Nutrition, September 1, 2000; 72(3): 723 - 730. [Abstract] [Full Text] [PDF]

				S. Chowdhary, J. C. Vaile, J. Fletcher, H. F. Ross, J. H. Coote, and J. N. Townend Nitric Oxide and Cardiac Autonomic Control in Humans Hypertension, August 1, 2000; 36(2): 264 - 269. [Abstract] [Full Text] [PDF]

				M. Petretta, L. Spinelli, F. Marciano, C. Apicella, M. L. E. Vicario, G. Testa, M. Volpe, and D. Bonaduce Effects of losartan treatment on cardiac autonomic control during volume loading in patients with DCM Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H86 - H92. [Abstract] [Full Text] [PDF]

				D. Cysarz, H. Bettermann, and P. van Leeuwen Entropies of short binary sequences in heart period dynamics Am J Physiol Heart Circ Physiol, June 1, 2000; 278(6): H2163 - H2172. [Abstract] [Full Text] [PDF]

				D. Lucini, R. V. Milani, H. O. Ventura, M. R. Mehra, F. Messerli, and M. Pagani Study of Arterial and Autonomic Effects of Cyclosporine in Humans Hypertension, June 1, 2000; 35(6): 1258 - 1263. [Abstract] [Full Text] [PDF]

				G. Paolisso, D. Manzella, N. Montano, A. Gambardella, and M. Varricchio Plasma Leptin Concentrations and Cardiac Autonomic Nervous System in Healthy Subjects with Different Body Weights J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 1810 - 1814. [Abstract] [Full Text]

				J.M. Karemaker and K.I. Lie Heart rate variability: a telltale of health or disease Eur. Heart J., March 2, 2000; 21(6): 435 - 437. [PDF]

				B. Nafz, J. Stegemann, M. H. Bestle, N. Richter, E. Seeliger, I. Schimke, H. W. Reinhardt, and P. B. Persson Antihypertensive Effect of 0.1-Hz Blood Pressure Oscillations to the Kidney Circulation, February 8, 2000; 101(5): 553 - 557. [Abstract] [Full Text] [PDF]

				M. G. W. BARNAS, W. H. BOER, and H. A. KOOMANS Hemodynamic Patterns and Spectral Analysis of Heart Rate Variability during Dialysis Hypotension J. Am. Soc. Nephrol., December 1, 1999; 10(12): 2577 - 2584. [Abstract] [Full Text]

				A. Stahle, R. Nordlander, and L. Bergfeldt Aerobic group training improves exercise capacity and heart rate variability in elderly patients with a recent coronary event. A randomized controlled study Eur. Heart J., November 2, 1999; 20(22): 1638 - 1646. [Abstract] [PDF]

				J. A. Taylor, C. W. Myers, N. Montano, C. Cogliati, A. Porta, M. Pagani, A. Malliani, K. Narkiewicz, F. M. Abboud, and V. K. Somers Mathematical Treatment of Autonomic Oscillations - 2 • Response Circulation, October 12, 1999; 100 (15): e64 - e64. [Full Text] [PDF]

				C. A. Swenne, J. Frederiks, A. V.G. Bruschke, R. Furlan, S. Piazza, S. Dell'Orto, F. Barbic, A. Bianchi, L. Mainardi, S. Cerutti, et al. Cardiac Neural Changes Before Vasovagal Syncope • Response Circulation, October 12, 1999; 100 (15): e67 - e67. [Full Text] [PDF]

				L. Spinelli, M. Petretta, F. Marciano, G. Testa, M. A. E. Rao, M. Volpe, and D. Bonaduce Cardiac autonomic responses to volume overload in normal subjects and in patients with dilated cardiomyopathy Am J Physiol Heart Circ Physiol, October 1, 1999; 277(4): H1361 - H1368. [Abstract] [Full Text] [PDF]

				C Kouakam, D Lacroix, N Zghal, R Logier, D Klug, P Le Franc, M Jarwe, and S Kacet Inadequate sympathovagal balance in response to orthostatism in patients with unexplained syncope and a positive head up tilt test Heart, September 1, 1999; 82(3): 312 - 318. [Abstract] [Full Text] [PDF]

				A. Malliani The Pattern of Sympathovagal Balance Explored in the Frequency Domain Physiology, June 1, 1999; 14(3): 111 - 117. [Abstract] [Full Text] [PDF]

				J. J. Goldberger Sympathovagal balance: how should we measure it? Am J Physiol Heart Circ Physiol, April 1, 1999; 276(4): H1273 - H1280. [Abstract] [Full Text] [PDF]

				V. Pichot, J.-M. Gaspoz, S. Molliex, A. Antoniadis, T. Busso, F. Roche, F. Costes, L. Quintin, J.-R. Lacour, and J.-C. Barthelemy Wavelet transform to quantify heart rate variability and to assess its instantaneous changes J Appl Physiol, March 1, 1999; 86(3): 1081 - 1091. [Abstract] [Full Text] [PDF]

				J. Freitas, S. Pereira, P. Lago, O. Costa, M.J. Carvalho, and A. FalcaO de Freitas Impaired arterial baroreceptor sensitivity before tilt-induced syncope Europace, January 1, 1999; 1(4): 258 - 265. [Abstract] [PDF]

				P. Van De Borne, M. Hausberg, R. P. Hoffman, A. L. Mark, and E. A. Anderson Hyperinsulinemia produces cardiac vagal withdrawal and nonuniform sympathetic activation in normal subjects Am J Physiol Regulatory Integrative Comp Physiol, January 1, 1999; 276(1): R178 - R183. [Abstract] [Full Text] [PDF]

				M. S. Houle and G. E. Billman Low-frequency component of the heart rate variability spectrum: a poor marker of sympathetic activity Am J Physiol Heart Circ Physiol, January 1, 1999; 276(1): H215 - H223. [Abstract] [Full Text] [PDF]

				J. Minami, T. Ishimitsu, and H. Matsuoka Effects of Smoking Cessation on Blood Pressure and Heart Rate Variability in Habitual Smokers Hypertension, January 1, 1999; 33(1): 586 - 590. [Abstract] [Full Text] [PDF]

				P. Sleight and L. Bernardi Sympathovagal Balance Circulation, December 8, 1998; 98(23): 2640 - 2640. [Full Text] [PDF]

				M. Malik and D. L Eckberg Sympathovagal Balance: A Critical Appraisal • Response Circulation, December 8, 1998; 98(23): 2643 - 2644. [Full Text] [PDF]

				A. Malliani, M. Pagani, N. Montano, and G. S. Mela Sympathovagal Balance: A Reappraisal Circulation, December 8, 1998; 98 (23): 2640 - 2643. [Full Text] [PDF]

				V. Shusterman, B. Aysin, V. Gottipaty, R. Weiss, S. Brode, D. Schwartzman, K. P. Anderson, and for the ESVEM Investigators Autonomic nervous system activity and the spontaneous initiation of ventricular tachycardia J. Am. Coll. Cardiol., December 1, 1998; 32(7): 1891 - 1899. [Abstract] [Full Text] [PDF]

				C. D Wagner and P. B Persson Chaos in the cardiovascular system: an update Cardiovasc Res, November 1, 1998; 40(2): 257 - 264. [Abstract] [Full Text] [PDF]

				J. A. Taylor, D. L. Carr, C. W. Myers, and D. L. Eckberg Mechanisms Underlying Very-Low-Frequency RR-Interval Oscillations in Humans Circulation, August 11, 1998; 98(6): 547 - 555. [Abstract] [Full Text] [PDF]

				R Sinnreich, J D Kark, Y Friedlander, D Sapoznikov, and M H Luria Five minute recordings of heart rate variability for population studies: repeatability and age-sex characteristics Heart, August 1, 1998; 80(2): 156 - 162. [Abstract] [Full Text]

				J. A. Taylor, T. D. Williams, D. R. Seals, and K. P. Davy Low-frequency arterial pressure fluctuations do not reflect sympathetic outflow: gender and age differences Am J Physiol Heart Circ Physiol, April 1, 1998; 274(4): H1194 - H1201. [Abstract] [Full Text] [PDF]

This Article Extract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Eckberg, D. L. Search for Related Content PubMed PubMed Citation Articles by Eckberg, D. L.