Respiratory sinus arrhythmia in freely moving and anesthetized rats.

Heart rate increases during inspiration and slows during postinspiration; this respiratory sinus arrhythmia helps match pulmonary blood flow to lung inflation and maintain an appropriate diffusion gradient of oxygen in the lungs. This cardiorespiratory pattern is found in neonatal and adult humans, baboons, dogs, rabbits, and seals. Respiratory sinus arrhythmia occurs mainly due to inhibition of cardioinhibitory parasympathetic cardiac vagal neurons during inspiration. Surprisingly, however, a recent study in anesthetized rats paradoxically found an enhancement of cardiac vagal activity during inspiration, suggesting that rats have an inverted respiratory sinus arrhythmia (Rentero N, Cividjian A, Trevaks D, Pequignot JM, Quintin L, and McAllen RM. Am J Physiol Regul Integr Comp Physiol 283: R1327-R1334, 2002). To address this controversy, this study examined respiratory sinus arrhythmia in conscious freely moving rats and tested whether the commonly used experimental anesthetics urethane, pentobarbital sodium, or ketamine-xylazine alter respiratory sinus arrhythmia. Heart rate significantly increased 21 beats/min during inspiration in conscious rats, a pattern similar to the respiratory sinus arrhythmia that occurs in other species. However, anesthetics altered normal respiratory sinus arrhythmia. Ketamine-xylazine (87 mg/kg and 13 mg/kg) depressed and pentobarbital sodium (60 mg/kg) abolished normal respiratory sinus arrhythmia. Urethane (1 g/kg) inverted the cardiorespiratory pattern so that heart rate significantly decreased during inspiration. Our study demonstrates that heart rate normally increases during inspiration in conscious, freely moving rats, similar to the respiratory sinus arrhythmia pattern that occurs in other species but that this pattern is disrupted in the presence of general anesthetics, including inversion in the case of urethane. The presence and consequences of anesthetics need to be considered in studying the parasympathetic control of heart rate.     

Sympathetic restraint of respiratory sinus arrhythmia: implications for vagal-cardiac tone assessment in humans

Clinicians and experimentalists routinely estimate vagal-cardiac nerve traffic from respiratory sinus arrhythmia. However, evidence suggests that sympathetic mechanisms may also modulate respiratory sinus arrhythmia. Our study examined modulation of respiratory sinus arrhythmia by sympathetic outflow. We measured R-R interval spectral power in 10 volunteers that breathed sequentially at 13 frequencies, from 15 to 3 breaths/min, before and after beta-adrenergic blockade. We fitted changes of respiratory frequency R-R interval spectral power with a damped oscillator model: frequency-dependent oscillations with a resonant frequency, generated by driving forces and modified by damping influences. beta-Adrenergic blockade enhanced respiratory sinus arrhythmia at all frequencies (at some, fourfold). The damped oscillator model fit experimental data well (39 of 40 ramps; r = 0.86 +/- 0.02). beta-Adrenergic blockade increased respiratory sinus arrhythmia by amplifying respiration-related driving forces (P < 0.05), without altering resonant frequency or damping influences. Both spectral power data and the damped oscillator model indicate that cardiac sympathetic outflow markedly reduces heart period oscillations at all frequencies. This challenges the notion that respiratory sinus arrhythmia is mediated simply by vagal-cardiac nerve activity. These results have important implications for clinical and experimental estimation of human vagal cardiac tone.     

Effect of anxiety on the function of the cardiorespiratory system

The effects of anxiety on the external respiration system and respiratory sinus arrhythmia (RSA) were studied in healthy subjects in real-life conditions. Changes in external respiration parameters and heart rate variability (HRV) in students going to take their end-of-term exams were assessed relative to a midterm period, and the cardiorespiratory system was monitored in a longitudinal study for 50 days. The function of the cardiorespiratory system was characterized by measuring external respiration parameters and calculating HRV parameters. State anxiety (SA) was assessed using Spielberger’s scale. An increase in SA before an exam was accompanied by a higher breathing rate, a higher tidal volume, and lower HRV indices, especially those related to respiratory sinus arrhythmia (HF and HF _norm). The changes in the parameters depended on the increase in SA. A negative correlation was observed between midterm HF and pre-exam SA. The longitudinal study revealed a distinct negative correlation between respiratory sinus arrhythmia parameters and peak expiratory flow (PEF) and a positive correlation between SA and PEF in the majority of subjects. Changes in cardiorespiratory parameters depended on the changes in SA in the longitudinal study. An increase in SA was accompanied by substantial changes in respiratory sinus arrhythmia (RAS) and external respiration parameters, and their correlation was assumed to indicate that modification of parasympathetic activity plays a leading role in increasing PEF.     

Cardiac autonomic function in Blacks with congestive heart failure: vagomimetic action, alteration in sympathovagal balance, and the effect of ACE inhibition on central and peripheral vagal tone.

Cardiac autonomic dysfunction is common in heart disease with or without congestive heart failure, and can cause sudden cardiac death. However, cardiac autonomic abnormalities in non-ischemic (hypertensive) heart failure, which is prevalent in Black Africans is poorly documented. We conducted a cross-sectional study of 32 patients with congestive heart failure, mostly secondary to hypertension (aged 52 +/- 15 years, with ejection fraction of 0.38 +/- 11) and 30 age- and sex-matched healthy volunteers (aged 51 +/- 11 years, 14 males/16 females). Cardiac autonomic function was assessed by the Valsalva's maneuver, respiratory sinus arrhythmia (for cardiac vagal tone) and the pressor and chronotropic changes following forearm isometric handgrip exercise and the assumption of upright posture (tests of sympathetic function). The exercise tolerance of the cardiac patients was assessed by the distance covered during 6 min of walking. The Valsalva ratio was significantly lower in chronic heart failure, 1.10 +/- 0.08 compared to the healthy controls 1.47 +/- 0.20 (p<0.001). Specifically, the phase IV bradycardia in heart failure, was significantly attenuated to 650 +/- 121 msec compared to the value of 935 +/- 101 msec in healthy controls (p<0.001). The phase 11 Valsalva tachycardia did not differ between the patients and controls. The respiratory sinus arrhythmia was also significantly reduced in chronic heart failure (p<0.05) compared to controls. Treatment of the heart failure patients with enalapril-digoxin and diuretics by 4 weeks, resulted in a reversal of the autonomic abnormalities. The phase IV bradycardia increased significantly to 798 +/- 164 msec (p<0.01) and the Valsalva ratio to 1.35 +/- 0.25 (p<0.01) and the respiratory sinus arrhythmia increased toward normal. There was close positive correlation between the Valsalva's ratio and the 6 min self paced distance covered (r = 0.44, p = 0.03 ANOVA), and a weak inverse correlation to cardiac size and cardiothoracic ratio (r = -0.31, p = 0.09). This study demonstrates cardiac autonomic dysfunction (especially reduced vagal tone) in Black Nigerians with mainly non-ischemic congestive heart failure. The parasympathetic dysfunction significantly correlates with severity of heart failure. Current treatment reverses autonomic dysfunction to values seen in healthy age matched controls, mainly through augmentation of cardiac parasympathetic activity.     

Cardiorespiratory interactions during resistive load breathing

The addition to the respiratory system of a resistive load results in breathing pattern changes and in negative intrathoracic pressure increases. The aim of this study was to use resistive load breathing as a stimulus to the cardiorespiratory interaction and to examine the extent of the changes in heart rate variability (HRV) and respiratory sinus arrhythmia (RSA) in relation to the breathing pattern changes. HRV and RSA were studied in seven healthy subjects where four resistive loads were applied in a random order during the breath and 8-min recording made in each condition. The HRV spectral power components were computed from the R-R interval sequences, and the RSA amplitude and phase were computed from the sinusoid fitting the instantaneous heart rate within each breath. Adding resistive loads resulted in 1) increasing respiratory period, 2) unchanging heart rate, and 3) increasing HRV and changing RSA characteristics. HRV and RSA characteristics are linearly correlated to the respiratory period. These modifications appear to be linked to load-induced changes in the respiratory period in each individual, because HRV and RSA characteristics are similar at a respiratory period obtained either by loading or by imposed frequency breathing. The present results are discussed with regard to the importance of the breathing cycle duration in these cardiorespiratory interactions, suggesting that these interactions may depend on the time necessary for activation and dissipation of neurotransmitters involved in RSA.     

Respiratory sinus arrhythmia from two coupled pacemakers.

We reproduce global features of respiratory sinus arrhythmia (RSA), a prominent source of heart rate variability, from two signals coupled in alternate fashion so dominance periodically switches back and forth between them. We consider two different possibilities for this coupling and illustrate our method with numerical simulations that we contrast with the corresponding results from real data. We interpret our findings within the context of the two-pacemaker model of the heartbeat, an alternative to the single-pacemaker mechanism of pulse generation in the orthodox conduction model.     

Changes in R–R variability before and after endurance training measured by power spectral analysis and by the effect of isometric muscle contraction

 The long-term conditioning effects of physical training on cardiorespiratory interaction in 11 young healthy males were studied. Significant increases in maximum oxygen uptake (V˙O_2max)(P<0.05) and decreases in heart rate (P<0.05) were achieved in all subjects following a 6-week training programme consisting of cycling for 25min each day at a work level that increased heart rate to 85% of maximum. Heart rate variability, measured as the differences between the maximum and minimum R–R interval in a respiratory cycle, increased in nine of the subjects and decreased in two. The respiratory-cycle-related high-frequency peak in the power spectral plot of R–R variability also showed significant increases in the same nine subjects and decreases in two. The latter result was similar after normalisation of the data for changes in heart rate by calculating the common coefficient of variance (CCV=HFR–R×<∮∮), where HF is the high-frequency component of the power spectral plots, using a further measure of vagal tone it was shown that, for all subjects, the R–R interval change in response to isometric contractions of the arm flexors in one respiratory cycle were significantly greater after training. These data suggest that cardiac vagal tone is increased by aerobic training for all subjects and that this is accompanied by a respiratory sinus arrhythmia (RSA) in most, but may be associated with a decrease in RSA in subjects with a very low (< 50 beats⋅min^-1 heart rate. Accepted: 23 April 1996     

Respiratory sinus arrhythmia in the denervated human heart

We performed this study to test whether the denervated human heart has the ability to manifest respiratory sinus arrhythmia (RSA). With the use of a highly sensitive spectral analysis technique (cross correlation) to define beat-to-beat coupling between respiratory frequency and heart rate period (R-R) and hence RSA, we compared the effects of patterned breathing at defined respiratory frequency and tidal volumes (VT), Valsalva and Mueller maneuvers, single deep breaths, and unpatterned spontaneous breathing on RSA in 12 normal volunteers and 8 cardiac allograft transplant recipients. In normal subjects R-R changes closely followed changes in respiratory frequency (P less than 0.001) but were little affected by changes in VT. On the R-R spectrum, an oscillation peak synchronous with respiration was found in heart transplant patients. However, the average magnitude of the respiration-related oscillations was 1.7-7.9% that seen in normal subjects and was proportionally more influenced by changes in VT. Changes in R-R induced by Valsalva and Mueller maneuvers were 3.8 and 4.9% of those seen in normal subjects, respectively, whereas changes in R-R induced by single deep breaths were 14.3% of those seen in normal subjects. The magnitude of RSA was not related to time since the heart transplantation, neither was it related to patient age or sex. Thus the heart has the intrinsic ability to vary heart rate in synchrony with ventilation, consistent with the hypothesis that changes, or rate of changes, in myocardial wall stretch might alter intrinsic heart rate independent of autonomic tone.     

Heart rate control and mechanical cardiopulmonary coupling to assess central volume: a systems analysis

Small negative changes of central volume reduce cardiac output without significant alterations of arterial blood pressure (ABP), suggesting an adequate regulatory response. Furthermore, evidence has arisen supporting a Bainbridge reflex (tachycardia with hypervolemia) in humans. To investigate these phenomena, multivariate autoregressive techniques were used to evaluate the beat-to-beat interactions between respiration, R-R interval, and ABP at six levels of decreased and increased central volume. With reductions of central volume below control, baroreflex and respiratory sinus arrhythmia gains were reduced, while with increases of volume above control, gains increased for the first two levels but decreased again at the highest volume level, suggesting the presence of a Bainbridge reflex in healthy human subjects. The mechanical influence of respiration on central venous pressure (CVP) had an unexpected shift in phase at the point of mild central hypervolemia, with the expected negative relation at lower volumes (inspiration lowers CVP) but a positive relation at higher volumes (inspiration raises CVP). We conclude that multivariate techniques can quantify the relations between a variety of respiratory and hemodynamic parameters, allowing for the in vivo assessment of complex cardiorespiratory interactions during manipulations of central volume. The results identify the presence of a Bainbridge reflex in humans and suggest that short-term cardiovascular control is optimized at mild hypervolemia.     

Does respiratory sinus arrhythmia occur in fishes?

The hypothesis that respiratory modulation of heart rate variability (HRV) or respiratory sinus arrhythmia (RSA) is restricted to mammals was tested on four Antarctic and four sub-Antarctic species of fish, that shared close genotypic or ecotypic similarities but, due to their different environmental temperatures, faced vastly different selection pressures related to oxygen supply. The intrinsic heart rate (fH) for all the fish species studied was approximately 25% greater than respiration rate (fV), but vagal activity successively delayed heart beats, producing a resting fH that was synchronized with fV in a progressive manner. Power spectral statistics showed that these episodes of relative bradycardia occurred in a cyclical manner every 2-4 heart beats in temperate species but at >4 heart beats in Antarctic species, indicating a more relaxed selection pressure for cardio-respiratory coupling. This evidence that vagally mediated control of fH operates around the ventilatory cycle in fish demonstrates that influences similar to those controlling RSA in mammals operate in non-mammalian vertebrates.     

Phase-averaged characterization of respiratory sinus arrhythmia pattern

A method for the accurate time-domain characterization of respiratory sinus arrhythmia (RSA) pattern is presented and applied to two groups of healthy subjects to lay the baseline of RSA patterns and to underlay their features: response to standing, stability in successive recordings, and individuality of the shape of RSA pattern. RSA pattern is evaluated by selective averaging of heart rate (HR) changes from multiple respiratory cycles over the respiratory phase and represents the complete modulating function of HR by respiration. The RSA pattern is evaluated with free respiration and even in cases of severe arrhythmia. Estimation error is 6-8% in magnitude, phase resolution is 0.2 rad, and sensitivity margin for respiratory-related HR variability (HRV) components is 1%. RSA magnitude, phase lag, and expiration-to-inspiration time ratio are derived in addition to the entire pattern. In a group of 10 healthy young adults, a phase lag difference of 11.4 +/- 8.5% (mean +/- SD, P < 0.004) was observed between supine and standing postures, possibly ascribed to breathing mechanics. A second group of 15 healthy young adults at supine rest showed stability of the RSA pattern in successive recordings (several weeks apart) as well as individuality among subjects. This may suggest a nonscalar individual long-term index for cardiorespiratory coupling. The method is complementary to the existing statistical and spectral methods. It allows the complete characterization of the primary RSA components and may provide new insight into the effects of vagal activity and changes in clinical conditions.     

The effect of the tidal volume on the sinus arrhythmia of the heart]

The sinus arrhythmia of the human heart was investigated in its relation to the tidal volume under resting conditions in the course of the day, in voluntarily changed tidal volume, under atropine medication and during physical work. In resting conditions it was found that nearly 40% of the sinus arrhythmia is of respiratory origin, and that no respiratory influence is demonstrable any longer at sufficient doses of atropine. Under physical load, the sinus arrhythmia is diminished in spite of the enlarged tidal volume. In this case, an additional smoothing influence to the sinus arrhythmia has to be assumed.     

Oscillations of heart rate and respiration synchronize during poetry recitation

The objective of this study was to investigate the synchronization between low-frequency breathing patterns and respiratory sinus arrhythmia (RSA) of heart rate during guided recitation of poetry, i.e., recitation of hexameter verse from ancient Greek literature performed in a therapeutic setting. Twenty healthy volunteers performed three different types of exercises with respect to a cross-sectional comparison: 1). recitation of hexameter verse, 2). controlled breathing, and 3). spontaneous breathing. Each exercise was divided into three successive measurements: a 15-min baseline measurement (S1), 20 min of exercise, and a 15-min effect measurement (S2). Breathing patterns and RSA were derived from respiratory traces and electrocardiograms, respectively, which were recorded simultaneously using an ambulatory device. The synchronization was then quantified by the index gamma, which has been adopted from the analysis of weakly coupled chaotic oscillators. During recitation of hexameter verse, gamma was high, indicating prominent cardiorespiratory synchronization. The controlled breathing exercise showed cardiorespiratory synchronization to a lesser extent and all resting periods (S1 and S2) had even fewer cardiorespiratory synchronization. During spontaneous breathing, cardiorespiratory synchronization was minimal and hardly observable. The results were largely determined by the extent of a low-frequency component in the breathing oscillations that emerged from the design of hexameter recitation. In conclusion, recitation of hexameter verse exerts a strong influence on RSA by a prominent low-frequency component in the breathing pattern, generating a strong cardiorespiratory synchronization.     

Atrial Pacing to Control Heart Rate and Rhythm in Acute Cardiac Conditions

Increasing the heart rate by a bedside atrial pacing technique was successfully utilized to treat serious cardiac arrhythmia or failure in 13 patients. Nine of these had ventricular arrhythmia refractory to drugs. Seven had evidence of sinus node depression or disease since their sinus pacemaker was below 70 beats per minute under decompensated conditions. In five, coronary artery disease was associated with the bradycardia and in two, digitalis toxicity was related to depression of the intrinsic pacemaker rate. Two patients in the coronary group required implantation of a permanent demand ventricular pacemaker. Hemodynamic studies were performed in seven patients. Only one patient had no increase in cardiac output with pacing rates above his resting rate. The other six patients showed an increase in cardiac output from 22 to 81% at paced rates between 70 and 125/minute. The duration of pacing ranged from one hour to 14 days and averaged five days.     

Self-regulation of respiratory sinus arrhythmia.

Respiratory sinus arrhythmia (RSA)--the peak-to-peak variations in heart rate caused by respiration--can be used as a noninvasive measure of parasympathetic cardiac control. In the present study four strategies to increase RSA amplitude are investigated: (1) biofeedback of RSA amplitude, (2) biofeedback of RSA amplitude plus respiratory instructions, (3) respiratory biofeedback, and (4) respiratory instructions only. All four procedures produce a significant increase of RSA amplitude from the first physiological control trial compared to baseline. This increase is faster for the groups that received respiratory biofeedback and respiratory instructions only than for the two groups that received biofeedback of RSA amplitude, the increases being equivalent for the four groups in the third session. All subjects of the group that received biofeedback of RSA amplitude only reported respiratory strategies in order to achieve the increase in RSA. Possible clinical implications of these results for parasympathetic cardiac control and cardiovascular disorders are discussed.     

Heart Rate Variability Biofeedback Improves Cardiorespiratory Resting Function During Sleep

The present study was designed to examine the effect of heart rate variability (HRV) biofeedback on the cardiorespiratory resting function during sleep in daily life. Forty-five healthy young adults were randomly assigned to one of three groups: HRV biofeedback, Autogenic Training (AT), and no-treatment control. Participants in the HRV biofeedback were instructed to use a handheld HRV biofeedback device before their habitual bedtime, those in the AT were asked to listen to an audiotaped instruction before bedtime, and those in the control were asked to engage in their habitual activity before bedtime. Pulse wave signal during sleep at their own residences was measured continuously with a wristwatch-type transdermal photoelectric sensor for three time points. Baseline data were collected on the first night of measurements, followed by two successive nights for HRV biofeedback, AT, or control. Cardiorespiratory resting function was assessed quantitatively as the amplitude of high-frequency (HF) component of pulse rate variability, a surrogate measure of respiratory sinus arrhythmia. HF component increased during sleep in the HRV biofeedback group, although it remained unchanged in the AT and control groups. These results suggest that HRV biofeedback before sleep may improve cardiorespiratory resting function during sleep.     

Self-regulation of respiratory sinus arrhythmia

Respiratory sinus arrhythmia (RSA) — the peak-to-peak variations in heart rate caused by respiration — can be used as a noninvasive measure of parasympathetic cardiac control. In the present study four strategies to increase RSA amplitude are investigated: (1) biofeedback of RSA amplitude, (2) biofeedback of RSA amplitude plus respiratory instructions, (3) respiratory biofeedback, and (4) respiratory instructions only. All four procedures produce a significant increase of RSA amplitude from the first physiological control trial compared to baseline. This increase is faster for the groups that received respiratory biofeedback and respiratory instructions only than for the two groups that received biofeedback of RSA amplitude, the increases being equivalent for the four groups in the third session. All subjects of the group that received biofeedback of RSA amplitude only reported respiratory strategies in order to achieve the increase in RSA. Possible clinical implications of these results for parasympathetic cardiac control and cardiovascular disorders are discussed.This research was supported by a grant to the first author from the University of Granada (Spain).     

Static magnetic field influence on rat brain function detected by heart rate monitoring

The aim of the present study was to identify the effects of a static magnetic field (SMF) on rat brain structures that control autonomic functions, specifically heart rate and heart rhythmicity. The experiments were carried out on 44 male Wistar rats under ketamine-xylazine anesthesia. SMF was induced using samarium-cobalt fused magnets (20 x 20 x 10 mm in size) placed bitemporally. Magnetic induction intensity was 100 mT on the surface of the head. Duration of magnetic field application was 15 min. An electrocardiogram was recorded from limb lead II, and both heart rate (average duration of cardiac cycles) and heart rhythmicity were analyzed before and after SMF application. SMF evoked changes in both heart rate and rhythm in 80% of the animals; the predominant effects were bradycardia and disappearance of respiratory sinus arrhythmia. However, the effectiveness of SMF in large measure depends on both functional peculiarities and functional activities of brain autonomic centers.     

CO2-dependent components of sinus arrhythmia from the start of breath holding in humans

A substantial portion of sinus arrhythmia in conscious humans appears to be caused by the CO2-dependent central respiratory rhythm. Under some circumstances, therefore, sinus arrhythmia might indicate the presence of the central respiratory rhythm. Humans can voluntarily modify their central respiratory rhythm (e.g., by pacing breathing or by delaying or advancing breaths), but it is not clear what happens to it from the start of breath holding. In this study, we show that sinus arrhythmia persists from the start of breath holds prolonged by preoxygenation. We also show that some of the frequency components of sinus arrhythmia start within each subject's eupneic frequency range and change when end-tidal Pco2 is lowered or raised, as we would expect if the central respiratory rhythm continues from the start of breath holding. We discuss whether sinus arrhythmia can indicate if the central respiratory rhythm continues from the start of breath holding.     

Contribution of the respiratory rhythm to sinus arrhythmia in normal unanesthetized subjects during positive-pressure mechanical hyperventilation

The precise contribution of the CO2-dependent respiratory rhythm to sinus arrhythmia in eupnea is unclear. The respiratory rhythm and sinus arrhythmia were measured in 12 normal, unanesthetized subjects in normocapnia and hypocapnia during mechanical hyperventilation with positive pressure. In normocapnia (41 +/- 1 mmHg), the respiratory rhythm was always detectable from airway pressure and inspiratory electromyogram activity. The amplitude of sinus arrhythmia (138 +/- 21 ms) during mechanical hyperventilation with positive pressure was not significantly different from that in eupnea. During the same mechanical hyperventilation pattern but in hypocapnia (24 +/- 1 mmHg), the respiratory rhythm was undetectable and the amplitude of sinus arrhythmia was significantly reduced (to 40 +/- 5 ms). These results show a greater contribution to sinus arrhythmia from the respiratory rhythm during hypocapnia caused by mechanical hyperventilation than previously indicated in normal subjects during hypocapnia caused by voluntary hyperventilation. We discuss whether the respiratory rhythm provides the principal contribution to sinus arrhythmia in eupnea.