Sudden large and periodic changes in heart rate in healthy young men after short periods of exercise.

The instantaneous heart rate and respiratory pattern were recorded immediately after brief periods of exercise in 41 healthy male students. Recordings were taken with the subjects both supine and standing. More than half of these subjects showed oscillatory heart changes when recovering supine but not when standing. During these oscillations the heart rate slowed suddenly by more than 30 beats/min; the oscillations had a period of 4 to 8 seconds, and they continued for half to two minutes. The P waves of the electrocardiogram were decreased during the slowing, consistent with increased vagal activity. When these oscillations occurred they each followed the start of an inspiration with the same latency as in respiratory sinus arrhythmia; unlike respiratory sinus arrhythmia, however, they did not occur after every inspiration but varied from 1:1 to 1:3 oscillations:breaths. They were not usually stopped by breath holding but were reduced or abolished by procedures which reduced venous return. This pattern of oscillations--"vagushalt"--seems to be different from respiratory sinus arrhythmias, and central venous pressure may contribute to the phenomenon. Although it is not widely recognised, vagushalt is probably very common and possibly its occurrence may change in disease.     

Synaptic and intrinsic activation of GABAergic neurons in the cardiorespiratory brainstem network

GABAergic pathways in the brainstem play an essential role in respiratory rhythmogenesis and interactions between the respiratory and cardiovascular neuronal control networks. However, little is known about the identity and function of these GABAergic inhibitory neurons and what determines their activity. In this study we have identified a population of GABAergic neurons in the ventrolateral medulla that receive increased excitatory post-synaptic potentials during inspiration, but also have spontaneous firing in the absence of synaptic input. Using transgenic mice that express GFP under the control of the Gad1 (GAD67) gene promoter, we determined that this population of GABAergic neurons is in close apposition to cardioinhibitory parasympathetic cardiac neurons in the nucleus ambiguus (NA). These neurons fire in synchronization with inspiratory activity. Although they receive excitatory glutamatergic synaptic inputs during inspiration, this excitatory neurotransmission was not altered by blocking nicotinic receptors, and many of these GABAergic neurons continue to fire after synaptic blockade. The spontaneous firing in these GABAergic neurons was not altered by the voltage-gated calcium channel blocker cadmium chloride that blocks both neurotransmission to these neurons and voltage-gated Ca(2+) currents, but spontaneous firing was diminished by riluzole, demonstrating a role of persistent sodium channels in the spontaneous firing in these cardiorespiratory GABAergic neurons that possess a pacemaker phenotype. The spontaneously firing GABAergic neurons identified in this study that increase their activity during inspiration would support respiratory rhythm generation if they acted primarily to inhibit post-inspiratory neurons and thereby release inspiration neurons to increase their activity. This population of inspiratory-modulated GABAergic neurons could also play a role in inhibiting neurons that are most active during expiration and provide a framework for respiratory sinus arrhythmia as there is an increase in heart rate during inspiration that occurs via inhibition of premotor parasympathetic cardioinhibitory neurons in the NA during inspiration.     

Respiratory and cardiovascular effects of thyrotropin-releasing hormone as modified by isoflurane, enflurane, pentobarbital and ketamine

Thyrotropin-releasing hormone (TRH) possesses significant arousing and cardio-respiratory stimulant actions. The effects of a 2 mg/kg i.v. bolus dose of TRH on respiration and systemic hemodynamics were compared in conscious, freely-moving rats and during anesthesia with 4 different anesthetics. Fifty-four male Sprague-Dawley rats weighing 285 +/- 4 g (mean +/- S.E.M.) were divided into 5 groups: conscious, enflurane (2%), isoflurane (1.4%), pentobarbital (8 mg/kg/h i.v.), and ketamine (60 mg/kg/h i.v.). Anesthetized rats were intubated and breathed oxygen or anesthetic/oxygen spontaneously. Aortic blood pressure, heart rate, cardiac output, respiratory rate, arterial blood pH, blood gases, lactate and glucose were measured, and data were collected over a 20 min baseline period and for 130 min post-TRH. TRH increased respiratory rate in all groups; concomitant changes in arterial PCO2 indicated increased minute ventilation in the inhalation agent groups but not in the i.v. anesthetic groups or in the awake group. Significant respiratory depression in the enflurane group was rapidly reversed by TRH. The respiratory stimulant and arousing effects of TRH were smallest with ketamine anesthesia. The hemodynamic responses to TRH were consistent with a pattern of sympathoadrenalmedullary activation and were relatively uniform across groups despite anesthetic-induced alterations in baseline values. TRH or its analogues may prove useful as an analeptic in clinical anesthesia.     

Cardiorespiratory effects of μ and δ opiate agonists following third or fourth ventricular injections

The cardiorespiratory effects of prototype μ (morphine and β-casomorphine 1–4) and δ (D-Ala²-D-Leu⁵Enkephalin—DADLE) opioid ligands were compared following microinjection into third and fourth ventricular spaces in conscious and anesthetized rats. The direction of change in arterial pressure produced by ventricular opioid injections varied according to ligand, site of administration, and state of consciousness of the animal. In general, pentobarbital anesthesia blocked or reversed the pressor response to these opiate agonists; depressor responses became magnified following pentobarbital. Qualitatively, the predominant effect of third ventricular DADLE in anesthetized rats was to produce a depression of arterial pressure and pulse pressure, suggesting an involvement of hypothalamic δ opioid receptors in decreasing sympathetic outflow. By contrast, morphine exerted pronounced bradycardic effects following fourth ventricular administration, suggesting an action at μ opioid receptors which influence vagal parasympathetic activity. Both ligands lowered respiratory rates upon fourth ventricular injection, indicating a possible involvement of either opioid receptor subtype in the depression of brainstem respiratory centers. These depressant effects of opioids upon cardiorespiratory function were readily reversed by naloxone. The qualitative similarity between the cardiovascular effects of third ventricular DADLE administration and various forms of circulatory shock may indicate that both phenomena involve delta opioid receptors at hypothalamic sites.     

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.     

The relationship between respiratory sinus arrhythmia and heart rate during anesthesia in rat.

During inspiration the heart rate (HR) increases and during expiration it decreases. Contribution of respiratory sinus arrhythmia (RSA) to spontaneous heart rate variability (HRV) can be measured as the high frequency (HF) component of variation in consecutive R-R intervals on ECG. In conscious rats, slowing of HR is associated with an increase in HF. The aim of this study was to investigate whether this relationship between HF and HR is preserved during anesthesia in rat. A 15 minutes long ECG signal was recorded from rats (N=15) under moderate chloral hydrate (CHL) anesthesia. Recordings were extended with 45 minutes to investigate the effect of atropine (N=3), against controls (N=3). Short term HRV was investigated in 30 seconds long epochs. HF was considered the frequency band between 0.8 and 1.6 Hz. RSA was quantified as the relative spectral power of the HF. Respiratory frequency (RF) was quantified as the mean spectral frequency within the HF band. One minute estimates of HR, RSA and HF were calculated by averaging 3 epochs of 30 seconds overlapped 50%. The average HR was 427 +/- 3 bpm. The magnitude of RSA was 45 +/- 1% at a RF of 71 +/- 1 rpm. We found that: (1) the decrease in HR that occurs during CHL anesthesia in rat correlates with an increase in RSA; (2) atropine reduces RSA and the time-dependent decrease in HR; (3) the time-dependent increase in RSA is preserved after atropine. We conclude that the correlation between RSA and HR reflects the cardio-pulmonary coupling under parasympathetic control.     

Development of acute tolerance to the cardiorespiratory effects of alfentanil after subsequent bolus injection in conscious rats

The cardiovascular and respiratory effects of alfentanil in conscious freely moving rats, were evaluated after initial and subsequent injections. Doses of alfentanil (50, 130, 260, and 500 ug/kg) were given to naive rats (n = 4-5) and 1 hour later this dose was repeated. The resultant cardiovascular and respiratory effects were compared. At all doses there was a significant (p less than 0.05) depression of mean arterial pressure and heart rate after the initial dose of alfentanil. At doses of 50, 130, and 260 ug/kg, the second administration elicited significantly less depression of cardiovascular parameters than the initial dose. Maximum changes in respiratory parameters (PaCO2 and PaO2) were also significantly less after the second administration of alfentanil. This difference, in maximum respiratory depression, was not seen at the highest doses (500 ug/kg). These results indicate that tolerance, to the cardiorespiratory side effects seen after alfentanil, can occur in as little as 1 hour after subsequent bolus injections.     

Cardiovascular effects of cocaine in anesthetized and conscious rats

This study examined the cardiovascular and respiratory effects of cocaine and procaine in anesthetized and conscious rats. Intravenous cocaine (0.16-5 mg/Kg) elicited a rapid, dose dependent increase in mean arterial pressure of relatively short duration. In pentobarbital anesthetized (65 mg/Kg, i.p.) animals, the pressor phase was generally followed by a more prolonged depressor phase. These effects on arterial pressure were generally accompanied by a significant tachypnea and at larger doses (2.5 and 5 mg/Kg, i.v.), bradycardia. Procaine (0.31 and 1.25 mg/Kg, i.v.) produced similar cardiovascular and respiratory effects (depressor phase, tachypnea) in pentobarbital anesthetized animals. In conscious-restrained animals, both cocaine and procaine (1.25 mg/kg, i.v.) produced pressor responses. The subsequent depressor response was, however, absent in both cases. The cardiovascular effects of cocaine (0.25-1 mg/Kg, i.v.) in urethane anesthetized (1.25 g/Kg, i.p.) animals were essentially similar to those observed in conscious animals. Procaine (1mg/Kg) did not produce any significant cardiovascular effects in urethane anesthetized animals, but did elicit tachypnea. Reserpine pretreatment (10 mg/Kg, i.p.) did not significantly attenuate the pressor response in urethane anesthetized animals. Phentolamine pretreatment (3 mg/Kg, i.v.) did significantly antagonize the pressor effect in urethane anesthetized animals. These results suggest that: the depressor phase is likely due to a interaction between local anesthetic activity (cocaine and procaine) and barbiturate anesthesia, the cardiovascular effects of cocaine in conscious animals are more similar to those observed in urethane anesthetized rats than in pentobarbital anesthetized rats and the pressor effect in urethane anesthetized rats is apparently due to a reserpine resistant catecholaminergic mechanism.     

Respiratory sinus arrhythmia: noninvasive measure of parasympathetic cardiac control.

The degree of parasympathetic heart rate control, PC, was defined as the decrease in average heart period (RR interval) caused by the elimination of parasympathetically mediated influences on the heart while keeping sympathetic activity unchanged. By reviewing published results on the interaction of sympathetic and parasympathetic heart rate control, the prediction was made that PC should be directly proportional to VHP, the peak-to-peak variations in heart period caused by spontaneous respiration. In sevel chloralose/urethan-anesthetized dogs the vagi were reversibly blocked by cooling, and PC (the difference between average heart period before and after cooling) and VHP (without cooling) were determined under a variety of conditions that included a) increasing vagal activity by elevating the blood pressure b) sympathetic blockade, and c) parasympathetic blockade. The relationship between VHP and PC was linear with an average correlation coefficient of 0.969 +/- 0.024 (SD) and a PC-axis intercept of 15.2 +/- 25.9 ms. In each dog the correlation coefficient between VHP and PC was higher than between VHP and the average heart period (avg correlation coef: 0.914 +/- 0.044). These results suggest that the degree of respiratory sinus arrhythmia may be used as a noninvasive indicator of the degree of parasympathetic cardiac control.     

Effects of hypercapnia and hypoxemia on respiratory sinus arrhythmia in conscious humans during spontaneous respiration

Normally, at rest, the amplitude of respiratory sinus arrhythmia (RSA) appears to correlate with cardiac vagal tone. However, recent studies showed that, under stress, RSA dissociates from vagal tone, indicating that separate mechanisms might regulate phasic and tonic vagal activity. This dissociation has been linked to the hypothesis that RSA improves pulmonary gas exchange through preferential distribution of heartbeats in inspiration. We examined the effects of hypercapnia and mild hypoxemia on RSA-vagal dissociation in relation to heartbeat distribution throughout the respiratory cycle in 12 volunteers. We found that hypercapnia, but not hypoxemia, was associated with significant increases in heart rate (HR), tidal volume, and RSA amplitude. The RSA amplitude increase remained statistically significant after adjustment for respiratory rate, tidal volume, and HR. Moreover, the RSA amplitude increase was associated with a paradoxical rise in HR and decrease in low-frequency-to-high-frequency mean amplitude ratio derived from spectral analysis, which is consistent with RSA-vagal dissociation. Although hypercapnia was associated with a significant increase in the percentage of heartbeats during inspiration, this association was largely secondary to increases in the inspiratory period-to-respiratory period ratio, rather than RSA amplitude. Additional model analyses of RSA were consistent with the experimental data. Heartbeat distribution did not change during hypoxemia. These results support the concept of RSA-vagal dissociation during hypercapnia; however, the putative role of RSA in optimizing pulmonary perfusion matching requires further experimental validation.     

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.     

Effects of Anesthetics on the Renal Sympathetic Response to Anaphylactic Hypotension in Rats

The autonomic nervous system plays an important role in rat anaphylactic hypotension. It is well known that sympathetic nerve activity and cardiovascular function are affected by anesthetics. However, the effects of different types of anesthesia on the efferent renal sympathetic nerve activity (RSNA) during anaphylactic hypotension remain unknown. Therefore, we determined the renal sympathetic responses to anaphylactic hypotension in anesthetized and conscious rats and the roles of baroreceptors in these responses. Sprague-Dawley rats were randomly allocated to anesthetic groups that were given pentobarbital, urethane, or ketamine-xylazine and to a conscious group. The rats were sensitized using subcutaneously injected ovalbumin. The systemic arterial pressure (SAP), RSNA and heart rate (HR) were measured. The effects of sinoaortic baroreceptor denervation on RSNA during anaphylaxis were determined in pentobarbital-anesthetized and conscious rats. In all of the sensitized rats, the RSNA increased and SAP decreased after antigen injection. At the early phase within 35 min of the antigen injection, the antigen-induced sympathoexcitation in the conscious rats was significantly greater than that in the anesthetized rats. Anaphylactic hypotension was attenuated in the conscious rats compared to the anesthetized rats. The anesthetic-induced suppression of SAP and RSNA was greater in the order ketamine-xylazine >urethane = pentobarbital. Indeed, in the rats treated with ketamine-xylazine, RSNA did not increase until 40 min, and SAP remained at low levels after the antigen injection. The baroreceptor reflex, as evaluated by increases in RSNA and HR in response to the decrease in SAP induced by sodium nitroprusside (SNP), was suppressed in the anesthetized rats compared with the conscious rats. Consistent with this finding, baroreceptor denervation attenuated the excitatory responses of RSNA to anaphylaxis in the conscious rats but not in the pentobarbital-anesthetized rats. RSNA was increased markedly in conscious rats during anaphylactic hypotension. Anesthetics attenuated this antigen-induced renal sympathoexcitation through the suppression of baroreceptor function.     

Cardiac rhythm effects of .125-Hz paced breathing through a resistive load: Implications for paced breathing therapy and the polyvagal theory

This study examined the psychophysiological effects of slow-paced breathing while subjects breathed through external respiratory resistive loads. Twenty-four normal volunteers completed four 5-min trials of paced breathing (.125 Hz) through an inspiratory resistive wire mesh screen (0 to 25 cm H₂O/L/s). Each trial was followed by a 5-min rest trial. There was evidence for hyperventilation and/or fatigue during paced breathing. Also, respiratory sinus arrhythmia (RSA) was elevated in the first minute of paced breathing, and then declined toward baseline. Heart period decreased during paced breathing trials, and fell significantly below baseline during rest periods. These data suggest decreased vagus nerve activity and/or sympathetic activation, following an initial increase in parasympathetic activity during paced breathing. They are not consistent with the use of .125-Hz paced breathing as a relaxation technique, particularly during respiratory resistive stress. Finally, although RSA and average heart period changed synchronouslywithin paced breathing and rest conditions, they diverged incomparisons between pacing and rest. This dissociation suggests that different mechanisms mediate these two cardiac parameters. These data are consistent with Porges' theory that vagal influences on tonic heart rate are mediated by the combined effect of vagal projections from both the nucleus ambiguus and the dorsal motor nucleus, while RSA is mediated only through the nucleus ambiguus alone.     

Selective pharmacological blocking of synaptic transmission through the parasympathetic ganglia: Effects on the cardiovascular system

In acute experiments on rats and dogs, compounds IEM-1556 and IEM-1678, the blockers of transmission through the parasympathetic ganglia, reduced the negative chronotropic effect of stimulation of the vagus nerve (VN), while practically not changing the heart rate (HR). In chronic experiments on dogs, these compounds increased the HR, substantially reduced the respiratory heart arrhythmia, did not change the arterial blood pressure (AP), and reduced the chronotropic effects of VN stimulation. IEM-1556 exerted more strong and long-lasting blocking effects on vagal heart control than IEM-1678 did, but in anesthetized animals could evoke a drop in the AP. Acetylcholine, if administered during the action of the above compounds, inhibited heart activity. It is concluded that both IEM-1678 and IEM-1556 are selective parasympatholytics (although IEM-1556 may produce a side effect). The above compounds block synaptic transmission through the intracardiac parasympathetic ganglia and do not affect neuro-effector transmission in the heart.Neirofiziologiya/Neurophysiology, Vol. 28, No. 2/3, pp. 151–159, March–June, 1996.     

Activity patterns of cardiac vagal motoneurons in rat nucleus ambiguus

Extracellular recordings were made in the right nucleus ambiguus of urethane-anesthetized rats from 33 neurons that were activated at constant latency from the craniovagal cardiac branch. Their calculated conduction velocities were in the B-fiber range (1.6-13.8 m/s, median 4.2), and most (22/33) were silent. Active units were confirmed as cardiac vagal motoneurons (CVM) by the collision test for antidromic activation and by the presence of cardiac rhythmicity in their resting discharge (9/9). Brief arterial pressure rises of 20-50 mmHg increased the activity in five of five CVM by 0.1 +/- 0.02 spikes. s(-1). mmHg(-1) from a resting 3.8 +/- 1.2 spikes/s; they also recruited activity in two of four previously silent cardiac branch-projecting neurons. CVM firing was modulated by the central respiratory cycle, showing peak activity during inspiration (8/8). Rat CVM thus show firing properties similar to those in other species, but their respiratory pattern is distinct. These findings are discussed in relation to mechanisms of respiratory sinus arrhythmia.     

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.     

Effect of five human anesthetics on respiratory control in cats

The effect of halothane, fentanyl, Innovar, thiopental, and ketamine on inspiratory output, vagal influence, and chest wall reflex was assessed in seven cats lightly anesthetized with pentobarbital, using the method of airway occlusion with and without rapid vagal cooling. All anesthetics depressed inspiratory output, as expressed by deltaP/deltat, of the first occluded inspiration. However, only halothane depressed peak inspiratory output (Pmax). Phasic vagal influence was markedly depressed by 2% halothane but was preserved under other anesthetics. The ability to induce tonic vagal influence (expiratory muscle recruitment) was lost under halothane. Inspiratory inhibitory chest wall reflex was evident in two cats during airway occlusion. Addition of any test anesthetic abolished the reflex. It is concluded that halothane should be avoided in studies dealing with assessment of vagal influence.     

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.     

Comparison of two different approaches in the detection of intermittent cardiorespiratory coordination during night sleep

Background

The objective was to evaluate and to compare two completely different detection algorithms of intermittent (short-term) cardiorespiratory coordination during night sleep. The first method is based on a combination of respiratory flow and electrocardiogram recordings and determines the relative phases of R waves between successive onsets of inspiration. Intermittent phase coordination is defined as phase recurrence with accuracy α over at least k heartbeats. The second, recently introduced method utilizes only binary coded variations of heart rate (acceleration = 1, deceleration = 0) and identifies binary pattern classes which can be assigned to respiratory sinus arrhythmia (RSA). It is hypothesized that RSA pattern class recurrence over at least k heartbeats is strongly related with the intermittent phase coordination defined above.

Results

Both methods were applied to night time recordings of 20 healthy subjects. In subjects <45 yrs and setting k = 3 and α = 0.03, the phase and RSA pattern recurrence were highly correlated. Furthermore, in most subjects the pattern predominance (PP) showed a pronounced oscillation which is most likely linked with the dynamics of sleep stages. However, the analysis of bivariate variation and the use of surrogate data suggest that short-term phase coordination mainly resulted from central adjustment of heart rate and respiratory rate rather than from real phase synchronization due to physiological interaction.

Conclusion

Binary pattern analysis provides essential information on short-term phase recurrence and reflects nighttime sleep architecture, but is only weakly linked with true phase synchronization which is rare in physiological processes of man.     

Breath-by-breath analysis of cardiorespiratory interaction for quantifying developmental maturity in premature infants

In healthy neonates, connections between the heart and lungs through brain stem chemosensory pathways and the autonomic nervous system result in cardiorespiratory synchronization. This interdependence between cardiac and respiratory dynamics can be difficult to measure because of intermittent signal quality in intensive care settings and variability of heart and breathing rates. We employed a phase-based measure suggested by Sch?fer and coworkers (Sch?fer C, Rosenblum MG, Kurths J, Abel HH. Nature 392: 239-240, 1998) to obtain a breath-by-breath analysis of cardiorespiratory interaction. This measure of cardiorespiratory interaction does not distinguish between cardiac control of respiration associated with cardioventilatory coupling and respiratory influences on the heart rate associated with respiratory sinus arrhythmia. We calculated, in sliding 4-min windows, the probability density of heartbeats as a function of the concurrent phase of the respiratory cycle. Probability density functions whose Shannon entropy had a <0.1% chance of occurring from random numbers were classified as exhibiting interaction. In this way, we analyzed 18 infant-years of data from 1,202 patients in the Neonatal Intensive Care Unit at University of Virginia. We found evidence of interaction in 3.3 patient-years of data (18%). Cardiorespiratory interaction increased several-fold with postnatal development, but, surprisingly, the rate of increase was not affected by gestational age at birth. We find evidence for moderate correspondence between this measure of cardiorespiratory interaction and cardioventilatory coupling and no evidence for respiratory sinus arrhythmia, leading to the need for further investigation of the underlying mechanism. Such continuous measures of physiological interaction may serve to gauge developmental maturity in neonatal intensive care patients and prove useful in decisions about incipient illness and about hospital discharge.