An Analysis of Phase Relationships between Oscillatory Processes in the Human Cardiovascular System

Biophysics - Abstract—The phase relationships between heart rate variability, respiration, forearm skin blood flow oscillations (according to laser Doppler flowmetry), and finger-pad tissue...     

Blood flow oscillations at a frequency of about 0.1 Hz in skin microvessels do not reflect the sympathetic regulation of their tone

Wavelet analysis of blood flow oscillations recorded with laser Doppler flowmetry in finger glabrous skin microvessels was carried out in 82 subjects with different variations in the syndromes of hand and foot sympathectomy and denervation. As distinct from the 0.02–0.046-Hz (about 0.03–0.04 Hz) blood flow oscillations in skin microvessels of sympathetic thermoregulatory origin, no relationship was found between the presence of 0.07–0.015 Hz (about 0.1 Hz) vasomotions in the wavelet spectrum and intactness of sympathetic innervation in the tissue region. The use of the myogenic band oscillation parameters, in particular, the amplitudes of vasomotions, for assessing the state of sympathetic thermoregulatory innervation determining the neurogenic tone of skin microvessels is not physiologically correct. The influence of local environmental factors on the vasomotion parameters confirms their local origin. The local perfusion pressure value significantly influenced the amplitude but not the frequency of vasomotions. The amplitude dominance of vasomotions was observed upon a decrease in perfusion pressure, whereas a marked increase in perfusion pressure or venous congestion resulted in a sharp depression of their amplitudes. Under the sympathectomy conditions, the oscillatory dynamic component of the arteriolar myogenic tone in the glabrous skin of the extremity acral zones is involved in the blood flow’s autoregulation. The presence of fine sensory fibers is necessary to carry out the dynamic autoregulation of the blood flow. Sensory nonmyelinated fibers and the trophic neuropeptides secreted by them not only initiate independent oscillations in the low-frequency (0.047–0.069 Hz) myogenic band, but also contribute to the normalized amplitudes of vasomotions being increased. At the same time, no appreciable influence of the sympathetic vasomotor activity and the corresponding influence of catecholamines on the amplitude and frequency of vasomotions was observed.     

The influence of the sympathetic innervation on the skin microvascular tone and blood flow oscillations

The influence of the sympathetic innervation on the tone of resistive vessels and blood flow oscillations was studied using laser Doppler flowmetry and skin thermography in 18 healthy subjects (before and after reflex cold and heat tests and local thermal testing), 42 patients with denervation syndromes caused by median nerve damage, and 10 patients with an acute stage of aseptic inflammation after radius fracture. The blood flow oscillations in the range of neurogenic sympathetic influences (0.02–0.052 Hz) supported by low-frequency sympathetic rhythms are an essential component of neurovascular interrelations. The importance of these oscillations is determined by their contribution to an increase in tissue perfusion owing to a decrease in the peripheral resistance and also by the leveling of drastic changes in blood flow and stabilization of microhemodynamics upon pronounced changes in the stationary tone. The high-and low-frequency (tonic and oscillatory, respectively) sympathetic rhythmic activities are expressed in two ways: (1) a synchronous increase or decrease in their amplitudes and (2) frequency dominance. The reactivity of the vessel smooth muscles is an important factor in maintaining the blood flow oscillations. Denervation decreases the oscillation amplitude in the neurogenic range. Under the conditions of local “inflammatory sympatholysis,” reflex tonic effects, rather than oscillatory ones, of the sympathetic impulses are mainly suppressed. An isolated evaluation of the blood flow oscillations in the neurogenic sympathetic range cannot be a measure of sympathetic activity. In studies on its functional state and evaluation of the neurogenic tone (NT) of resistive vessels, it is necessary to take into account the parameters of both stationary and oscillatory components of the NT.     

Oscillatory processes in lymph microcirculation in the human skin

This study was the first to use laser Doppler flowmetry followed by wavelet analysis in order to estimate oscillations in lymph microcirculation in 30 subjects with (n = 13) or without (n = 17) edema of the distal part of the upper limb. Lymph flow in the human skin exhibited clear dominance of pacemaker phase oscillations in the frequency ranges of 0.021–0.042 and 0.016–0.035 Hz in the skin of the palm surface of the finger nail bone and in the skin of the forearm, respectively. Edema was associated with an increase in the peak frequencies and normalized maximum amplitudes (Al/Ml, where Al is the mean value of the maximum amplitude of phase oscillations, and Ml is the value of the averaged lymph flow expressed in perfusion units). Low-amplitude oscillations were recorded rarer in the myogenic, endothelial, and respiratory ranges. We did not find any cardiac pulse rhythm in the wavelet spectrum of the lymph flow. We did not find any interaction between the Al/Ml value and the skin temperature. In the group of subjects without edema, under physiological conditions only, we found a negative correlation between the Al/Ml value and the amplitudes of myogenous proper blood flow oscillations, which reflected the number of functional capillaries and activity of oxidative metabolism in the tissue. In the group with edema, we did not find any correlations between the indices of lymph flow and blood flow. The values of normalized amplitude and frequency of phase oscillations may be used as efficient diagnostic tools in the studies on lymph microcirculation.     

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.     

Dynamic oscillatory circuit of regulation of capillary hemodynamics

We used laser Doppler flowmetry with wavelet analysis of blood flow oscillations, computer capillaroscopy, and thermometry of the nail bed in 30 subjects to show an important role of the oscillatory circuit in the regulation of capillary hemodynamics, number of functioning capillaries, and linear and volumetric velocity of blood flow. The number of functioning capillaries is regulated by oscillations of myogenic and sensory peptidergic origin. The appearance of sensory oscillations, especially high-amplitude oscillations, is an adaptive neurotrophic mechanism that significantly increases the number of functioning capillaries and intensity of blood flow from arterioles to capillaries. The linear velocity of blood flow depends on both the tone of microvessels and changes in the dynamic component of blood pressure. Under conditions of skin hypoperfusion, the mean linear velocity of capillary blood flow may be inversely related to the extracapillary perfusion, including the amplitude of heart rate (A _h) and oscillations of the tone of precapillary sphincters, whereas under conditions of vasodilation and increased skin perfusion, it may be inversely related to the amplitude of arteriolar oscillations of endothelial or neurogenic sympathetic origin (A _maxe + n) and the shunting index. The A _h affects the linear velocity of blood flow in the arterial part of capillaries, whereas the A _maxe + n influences the same factor in the venous part. The contribution of oscillations to the regulation of the linear velocity varies depending on the perfusion and skin temperature. The resultant tone of distributing microvessels is determined by the competition between the stationary and oscillatory components. In addition to changes in the amplitude, the frequency of vasomotions may also be important. The regulatory importance of the oscillatory circuit is increased with a decrease in the skin blood flow.     

Clinical correlates of frequency analyses of cardiovascular control after spinal cord injury

Spinal cord injury (SCI) has profound effects on cardiovascular autonomic function due to injury to descending autonomic pathways, and cardiovascular diseases are the leading causes of morbidity and mortality after SCI. Evaluation of cardiovascular autonomic dysfunction after SCI and appraisal of simple noninvasive autonomic assessments that are clinically meaningful would be useful to SCI clinicians and researchers. We aimed to assess supine and upright cardiovascular autonomic function from frequency analyses of heart rate and blood pressure variability (HRV and BPV) after SCI. We studied 26 subjects with chronic cervical or thoracic SCI and 17 able-bodied controls. We continuously recorded R-R interval (RRI, by ECG) and beat-to-beat blood pressure (by Finometer) in supine and seated positions. Cardiovascular control was assessed from spectral analysis of RRI and blood pressure time series. Cardiac baroreflex control was assessed from cross-spectral analyses of low-frequency spectra. Supine and upright low-frequency HRV and BPV were reduced in cervical SCI subjects, as were total BPV and HRV. Supine high-frequency HRV was reduced in thoracic SCI subjects. Cardiac baroreflex delay was increased in cervical SCI subjects. Supine frequency domain indexes were correlated with sympathetic skin responses, orthostatic cardiovascular responses, and plasma catecholamine levels. SCI results in reduced sympathetic drive to the heart and vasculature and increased baroreflex delay in cervical SCI subjects and reduced cardiac vagal tone in thoracic SCI subjects. Frequency analyses of autonomic function are related to clinical measures of autonomic control after SCI and provide useful noninvasive clinical tools with which to assess autonomic completeness of injury following SCI.     

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.     

Dynamic autoregulation of cutaneous circulation: differential control in glabrous versus nonglabrous skin

The purpose of this project was to test the hypothesis that, independent of neural control, glabrous and nonglabrous cutaneous vasculature is capable of autoregulating blood flow. In 10 subjects, spectral and transfer function analyses of arterial pressure and skin blood flow (laser-Doppler flowmetry) from glabrous (palm) and nonglabrous (forearm) regions were performed under three conditions: baseline, ganglionic blockade via intravenous trimethaphan administration, and trimethaphan plus oscillatory lower body negative pressure (LBNP; -5 to -10 mmHg) from 0.05 to 0.07 Hz. Oscillatory LBNP was applied to regenerate mean arterial pressure variability that was abolished by ganglionic blockade. Ganglionic blockade was verified by an absence of a heart rate response to a Valsalva maneuver. Spectral power and transfer function gain between blood pressure and skin blood flow were calculated in this oscillatory frequency range (0.05-0.07 Hz). Within this frequency range, ganglionic blockade significantly decreased spectral power of blood flow in both the forearm and palm, whereas regeneration of arterial blood pressure oscillations significantly increased spectral power of forearm blood flow but not palm blood flow. During oscillatory LBNP, transfer function gain between blood pressure and skin blood flow was significantly elevated at the forearm (0.28 +/- 0.03 to 0.53 +/- 0.02 flux units/mmHg; P < 0.05) but was reduced at the palm (4.7 +/- 0.5 to 1.2 +/- 0.1 flux units/mmHg; P < 0.05). These data show that independent of neural control of blood flow, glabrous skin has the ability to buffer blood pressure oscillations and demonstrates a degree of dynamic autoregulation. Conversely, these data suggest that nonglabrous skin has diminished dynamic autoregulatory capabilities.     

Gender differences in autonomic cardiovascular regulation: spectral, hormonal, and hemodynamic indexes.

The autonomic nervous system drives variability in heart rate, vascular tone, cardiac ejection, and arterial pressure, but gender differences in autonomic regulation of the latter three parameters are not well documented. In addition to mean values, we used spectral analysis to calculate variability in arterial pressure, heart rate (R-R interval, RRI), stroke volume, and total peripheral resistance (TPR) and measured circulating levels of catecholamines and pancreatic polypeptide in two groups of 25 +/- 1.2-yr-old, healthy men and healthy follicular-phase women (40 total subjects, 10 men and 10 women per group). Group 1 subjects were studied supine, before and after beta- and muscarinic autonomic blockades, administered singly and together on separate days of study. Group 2 subjects were studied supine and drug free with the additional measurement of skin perfusion. In the unblocked state, we found that circulating levels of epinephrine and total spectral power of stroke volume, TPR, and skin perfusion ranged from two to six times greater in men than in women. The difference (men > women) in spectral power of TPR was maintained after beta- and muscarinic blockades, suggesting that the greater oscillations of vascular resistance in men may be alpha-adrenergically mediated. Men exhibited muscarinic buffering of mean TPR whereas women exhibited beta-adrenergic buffering of mean TPR as well as TPR and heart rate oscillations. Women had a greater distribution of RRI power in the breathing frequency range and a less negative slope of ln RRI power vs. ln frequency, both indicators that parasympathetic stimuli were the dominant influence on women's heart rate variability. The results of our study suggest a predominance of sympathetic vascular regulation in men compared with a dominant parasympathetic influence on heart rate regulation in women.     

Phase synchronization of skin blood flow oscillations in humans under asymmetric local heating

The hypothesis is proposed that an external local stimulus may cause a change in the phase relationships of oscillations in the peripheral skin blood flow of contralateral extremities. To test this assumption, the wavelet phase coherence of skin blood flow oscillations of the left and right forearms of 18 healthy volunteers of both sexes at rest and in response to unilateral local heating was investigated. An area of the skin of the left forearm was exposed to heat and the native blood perfusion in an area of the skin of the right forearm was recorded simultaneously. It was shown that an asymmetric local change of skin perfusion led to a significant change in the phase relationships of the blood flow oscillations in all the analyzed frequency ranges. A significant reduction of phase synchronization of oscillations of skin blood flow in the range of endothelial, neurogenic, and myogenic activity, as well as in the range of respiratory rhythm was revealed. In contrast, in the range of the cardiac rhythm, a significant increase in phase synchronization of the oscillations of the blood flow of contralateral skin areas of the forearm was detected.     

Incoherent oscillations of respiratory sinus arrhythmia during acute mental stress in humans

Respiratory sinus arrhythmia (RSA) has been widely used as a measure of the cardiac vagal control in response to stress. However, RSA seems not to be a generalized indicator because of its dependency on respiratory parameter and individual variations of RSA amplitude (A(RSA)). We hypothesized that phase-lag variations between RSA and respiration may serve as a normalized index of the degree of mental stress. Twenty healthy volunteers performed mental arithmetic task (ART) after 5 min of resting control followed by 5 min of recovery. Breathing pattern, beat-to-beat R-R intervals, and blood pressure (BP) were determined using inductance plethysmography, electrocardiography, and a Finapres device, respectively. The analytic signals of breathing and RSA were obtained by Hilbert transform and the degree of phase synchronization (λ) was quantified. With the use of spectral analysis, heart rate variability (HRV) was estimated for the low-frequency (LF) and high-frequency (HF) bands. A steady-state 3-min resting period (REST), the first 3 min (ART1), and the last 3 min (ART2) of the ART period (ranged from 6- to 19 min) and the last 3 min of the recovery period (RCV) were analyzed separately. Heart rate, systolic BP, and breathing frequency (f(R)) increased and λ, A(RSA), and HF power decreased from REST to ART (P < 0.01). The λ was correlated with normalized A(RSA) and the HF power. The decrease in λ could not be explained solely by the increase in f(R). We conclude that mental stress exerts an influence on RSA oscillations, inducing incoherent phase lag with respect to breathing, in addition to a decrease in RSA.     

Microcirculation characteristics in apparently healthy subjects during acute hypoxia and intermittent hypoxic training

The characteristics of the microcirculation in the forearm skin of 29 apparently healthy male volunteers were studied in acute hypoxia and during intermittent hypoxic training (IHT) using computer laser Doppler flowmetry. It was shown that short-term exposure of apparently healthy subjects to simulated acute hypoxia optimized the microcirculation owing to sympathetic innervation and concomitant rearrangement of microvascular tone regulation (activation of skin perfusion and reduction of blood flow through arteriovenular shunts when the neurogenic tone component increases). A second (placebo-controlled) series of experiments showed that long-term hypoxic preconditioning (20 IHT sessions) facilitated fixing of the adaptive dynamic rearrangements aimed at microcirculation improvement. The microvasculature response during acute hypoxia and a course of IHT depends on the initial sensitivity of subjects to simulated hypoxia. Significant perfusion enhancement in the tissues studied and microvascular tone normalization were observed in the subjects that were initially sensitive to hypoxia.     

Influence of external periodic stimuli on heart rate variability in healthy subjects and in coronary heart disease patients

Frequency estimates of the heart rate variability (HRV) spectrum influenced by external periodic stimuli were studied in healthy subjects and patients with coronary heart disease (CHD). Sensory stimulation by periodic eye opening at a rate of 15, 10, 8, 6, or 5 times per minute, as well as spontaneous and controlled breathing at a rate of 15, 10, 8, 6, or 5 times per minute, was used. It was found that the spectral response to external periodic oscillations was determined by a frequency-dependent phenomenon, the maximal amplitude of heart rate variations being observed in the case of external stimuli at a frequency of 0.1 Hz. A resonance frequency in the 0.1-Hz range may be suggested to exist in the cardiovascular controls. Significant differences in the HRV frequency characteristics between CHD patients and healthy subjects were shown. CHD patients had a characteristic decline in HRV responses to external oscillations; the power of these responses did not depend on the frequency of external stimuli.     

The problem of information value in microvascular networks

A novel methodology of quantitative estimation of the information value in microvascular networks is proposed. The methodology has been developed on the basis of the results of wavelet analysis of skin blood flow oscillations measured by means of laser Doppler flowmetry (LDF) in 30 healthy subjects and 56 patients with hand diseases or consequences of hand injuries. The method is based on the calculation of the relative indices of information preservation, dominance of the preserved information, and information effectiveness. The deviation from the multistable information regimen is the largest in the case of resonance oscillations: the total information quantity is significantly decreased; however, the preservation of dominant information and its effectiveness are improved. The preservation of trophic myogenic information predominates upon reduction of sympathetic influences. An increase in the number of information channels increases only the information quantity, whereas the degree of its preservation varies. Sensory peptidergic nerve fibers are activated in response to local heating of the dorsal forearm skin to 34°C. This information is the most effective at the beginning of the heating, when the blood flow increases to a plateau. The blood flow oscillations represented in the wavelet spectrum of microcirculatory oscillations serve as operators based on effective information. These oscillations not only play the hemodynamic role, but also carry information in microvascular networks.     

Age-related differences in the dynamics of the skin blood flow oscillations during postocclusive reactive hyperemia

Age-related changes in peripheral microcirculation were studied using laser Doppler flowmetry in 60 apparently healthy subjects. The response of microcirculation to short-term ischemia was studied using the occlusion test. Changes in the amplitude of the peripheral blood flow oscillations were determined using time-amplitude analysis based on continuous adaptive wavelet filtration. The oscillation amplitude in the frequency range of the heart rate was found to reach the maximum with a delay after the removal of the occlusion, whereas in the range of the respiratory rhythm, no delay was observed. The hyperemic response to short-term ischemia is assumed to develop under the predominant influence of the arterial-arteriolar component, whereas the dynamics of amplitude oscillations in the range of the respiratory rhythm is a result of the devastation of the venular component after removal of occlusion. In response to short-term ischemia, the maximum oscillation amplitudes of myogenic, neurogenic, and endothelial rhythms decreased with age, which demonstrates the restriction of the regulatory control of the peripheral blood flow by the corresponding systems.     

Influence of sensory peptidergic innervation on human skin blood flow oscillations in the range 0.047–0.069 Hz

Thirty-six healthy subjects and 65 patients with neurogenic inflammation (complex regional pain syndrome of the hand) or denervation syndromes (after median and ulnar nerve injuries or transplantation of denervated vascularized musculocutaneous autografts), as well as after thoracoscopic sympathectomy, underwent laser Doppler flowmetry with spectral wavelet analysis of the blood flow oscillations in cutaneous microvessels and thermography. It was shown that, along with maintenance of the blood flow oscillations of endothelial genesis, peptidergic sensory nerve fibers (SPFs) are involved in activating independent, including high-amplitude, oscillations in the myogenic range 0.047–0.069 Hz (an average of three to four oscillations per minute). The above-mentioned oscillations were recorded against the background of neurogenic inflammation and nociceptive activation of C afferents after nerve injuries, as well as in the course of functional tests in healthy subjects (the forearm skin electrostimulation test, capsaicin application). Sympathectomy and hyposympathicotonia contributed to their manifestation; they were not detected under the conditions of severe sensory-trophic skin denervation. The appearance of high-amplitude blood flow oscillations in human skin microvessels at a frequency of 0.047–0.069 Hz may serve as an objective criterion of SPF activation.     

Characteristics of Resonance in Heart Rate Variability Stimulated by Biofeedback

As we previously reported, resonant frequency heart rate variability biofeedback increases baroreflex gain and peak expiratory flow in healthy individuals and has positive effects in treatment of asthma patients. Biofeedback readily produces large oscillations in heart rate, blood pressure, vascular tone, and pulse amplitude via paced breathing at the specific natural resonant frequency of the cardiovascular system for each individual. This paper describes how resonance properties of the cardiovascular system mediate the effects of heart rate variability biofeedback. There is evidence that resonant oscillations can train autonomic reflexes to provide therapeutic effect. The paper is based on studies described in previous papers. Here, we discuss the origin of the resonance phenomenon, describe our procedure for determining an individual's resonant frequency, and report data from 32 adult asthma patients and 24 healthy adult subjects, showing a negative relationship between resonant frequency and height, and a lower resonant frequency in men than women, but no relationship between resonant frequency and age, weight, or presence of asthma. Resonant frequency remains constant across 10 sessions of biofeedback training. It appears to be related to blood volume.     

Rapid blunting of sympathetic vasoconstriction in the human forearm at the onset of exercise.

The purpose of this study was to test the hypothesis that sympathetic vasoconstriction is rapidly blunted at the onset of forearm exercise. Nine healthy subjects performed 5 min of moderate dynamic forearm handgrip exercise during -60 mmHg lower body negative pressure (LBNP) vs. without (control). Beat-by-beat forearm blood flow (Doppler ultrasound), arterial blood pressure (finger photoplethysmograph), and heart rate were collected. LBNP elevated resting heart rate by approximately 45%. Mean arterial blood pressure was not significantly changed (P = 0.196), but diastolic blood pressure was elevated by approximately 10% and pulse pressure was reduced by approximately 20%. At rest, there was a 30% reduction in forearm vascular conductance (FVC) during LBNP (P = 0.004). The initial rapid increase in FVC with exercise onset reached a plateau between 10 and 20 s of 126.6 +/- 4.1 ml. min(-1). 100 mmHg(-1) in control vs. only 101.6 +/- 4.1 ml. min(-1). 100 mmHg(-1) in LBNP (main effect of condition, P = 0.003). This difference was quickly abolished during the second, slower phase of adaptation in forearm vascular tone to steady state. These data are consistent with a rapid onset of functional sympatholysis, in which local substances released with the onset of muscle contractions impair sympathetic neural vasoconstrictor effectiveness.     

Microgravity alters respiratory sinus arrhythmia and short-term heart rate variability in humans

We studied heart rate (HR), heart rate variability (HRV), and respiratory sinus arrhythmia (RSA) in four male subjects before, during, and after 16 days of spaceflight. The electrocardiogram and respiration were recorded during two periods of 4 min controlled breathing at 7.5 and 15 breaths/min in standing and supine postures on the ground and in microgravity. Low (LF)- and high (HF)-frequency components of the short-term HRV (< or =3 min) were computed through Fourier spectral analysis of the R-R intervals. Early in microgravity, HR was decreased compared with both standing and supine positions and had returned to the supine value by the end of the flight. In microgravity, overall variability, the LF-to-HF ratio, and RSA amplitude and phase were similar to preflight supine values. Immediately postflight, HR increased by approximately 15% and remained elevated 15 days after landing. LF/HF was increased, suggesting an increased sympathetic control of HR standing. The overall variability and RSA amplitude in supine decreased postflight, suggesting that vagal tone decreased, which coupled with the decrease in RSA phase shift suggests that this was the result of an adaptation of autonomic control of HR to microgravity. In addition, these alterations persisted for at least 15 days after return to normal gravity (1G).