Respiratory Cycle Length Research Articles

Loop gain response to increased cerebral blood flow at high altitude.

To compare loop gain (LG) before and during pharmacological increases in cerebral blood flow (CBF) at high altitude (HA). Loop gain (LG) describes stability of a negative-feedback control system; defining the magnitude of response to a disturbance, such as hyperpnea to an apnea in periodic breathing (PB). "Controller-gain" sensitivity from afferent peripheral (PCR) and central-chemoreceptors (CCR) plays a key role in perpetuating PB. Changes in CBF may have a critical role via effects on central chemo-sensitivity during sleep. Polysomnography (PSG) was performed on volunteers after administration of I.V. Acetazolamide (ACZ-10mg/kg) + Dobutamine (DOB-2-5 μg/kg/min) to increase CBF (via Duplex-ultrasound). Central sleep apnea (CSA) was measured from NREM sleep. The duty ratio (DR) was calculated as ventilatory duration (s) divided by cycle duration (s) (hyperpnea/hyperpnea + apnea), LG = 2π/(2πDR-sin2πDR). A total of 11 volunteers were studied. Compared to placebo-control, ACZ/DOB showed a significant increase in the DR (0.79 ± 0.21 vs 0.52 ± 0.03, P = 0.002) and reduction in LG (1.90 ± 0.23 vs 1.29 ± 0.35, P = 0.0004). ACZ/DOB increased cardiac output (CO) (8.19 ± 2.06 vs 6.58 ± 1.56L/min, P = 0.02) and CBF (718 ± 120 vs 526 ± 110ml/min, P < 0.001). There was no significant change in arterial blood gases, minute ventilation (VE), or hypoxic ventilatory response (HVR). However, there was a reduction of hypercapnic ventilatory response (HCVR) by 29% (5.9 ± 2.7 vs 4.2 ± 2.8 L/min, P = 0.1). Pharmacological elevation in CBF significantly reduced LG and severity of CSA. We speculate the effect was on HCVR "controller gain," rather than "plant gain," because PaCO2 and VE were unchanged. An effect via reduced circulation time is unlikely, as the respiratory-cycle length did not change.

Abstract 040: Bedscales: Non-Contact Home Health Monitor For Longitudinal Characterization Of Periodic Breathing In Chronic Heart Failure

Periodic breathing (PB), including its subtype Cheyne-Stokes respiration, is a pattern of sleep-disordered breathing marked by cyclic modulations in tidal volume and respiratory rate. PB is commonly identified in patients with chronic heart failure (CHF), and portends a worse prognosis. Due to the impracticality of existing monitoring methods, no longitudinal data exist on whether individual patients may experience prognostically significant fluctuations in PB. Here, we present a novel tool enabling long-term in-home investigation of PB. By passively capturing respirations during sleep via mechanical sensors placed under the legs of a bed, the need for patient compliance is circumvented. PB events were identified by computing an amplitude modulation index, and features including respiratory rate, cycle length, and hyperpnea duration were extracted. To demonstrate viability for longitudinal studies, devices were installed in the homes of 25 CHF patients to continuously record respirations, 9 of whom were found to exhibit PB. In an illustrative case, ~15,000 cycles of PB were captured over 3 months in a patient discharged after hospitalization for heart failure with reduced ejection fraction. Bedscales documented the patient’s worsening tachypnea accompanied by changes in PB parameters (shortened cycle and hyperpnea durations). A chest X-ray showed evidence of pneumonia and antibiotics were prescribed, after which tachypnea improved and trends of PB parameters reversed. This case highlights the potential utility of Bedscales in detecting subtle deviations from an individual’s baseline respiratory signatures; future work is needed to assess the predictive power of these parameters. Taken together, these results demonstrate the feasibility of Bedscales as a low-cost, scalable tool for longitudinal population-level studies of PB in relation to chronic diseases such as CHF. Future research could examine whether such data might predict exacerbations and direct early intervention to prevent rehospitalization.

Robust Deep Learning Framework For Predicting Respiratory Anomalies and Diseases.

This paper presents a robust deep learning framework developed to detect respiratory diseases from recordings of respiratory sounds. The complete detection process firstly involves front end feature extraction where recordings are transformed into spectrograms that convey both spectral and temporal information. Then a back-end deep learning model classifies the features into classes of respiratory disease or anomaly. Experiments, conducted over the ICBHI benchmark dataset of respiratory sounds, evaluate the ability of the framework to classify sounds. Two main contributions are made in this paper. Firstly, we provide an extensive analysis of how factors such as respiratory cycle length, time resolution, and network architecture, affect final prediction accuracy. Secondly, a novel deep learning based framework is proposed for detection of respiratory diseases and shown to perform extremely well compared to state of the art methods.

Increasing Local Excitability of Brainstem Respiratory Nuclei Reveals a Distributed Network Underlying Respiratory Motor Pattern Formation.

The core circuit of the respiratory central pattern generator (rCPG) is located in the ventrolateral medulla, especially in the pre-Bötzinger complex (pre-BötC) and the neighboring Bötzinger complex (BötC). To test the hypothesis that this core circuit is embedded within an anatomically distributed pattern-generating network, we investigated whether local disinhibition of the nucleus tractus solitarius (NTS), the Kölliker-Fuse nuclei (KFn), or the midbrain periaqueductal gray area (PAG) can similarly affect the respiratory pattern compared to disinhibition of the pre-BötC/BötC core. In arterially-perfused brainstem preparations of rats, we recorded the three-phase respiratory pattern (inspiration, post-inspiration and late-expiration) from phrenic and vagal nerves before and after bilateral microinjections of the GABA(A)R antagonist bicuculline (50 nl, 10 mM). Local disinhibition of either NTS, pre-BötC/BötC, or KFn, but not PAG, triggered qualitatively similar disruptions of the respiratory pattern resulting in a highly significant increase in the variability of the respiratory cycle length, including inspiratory and expiratory phase durations. To quantitatively analyze these motor pattern perturbations, we measured the strength of phase synchronization between phrenic and vagal motor outputs. This analysis showed that local disinhibition of all brainstem target nuclei, but not the midbrain PAG, significantly decreased the strength of phase synchronization. The convergent perturbations of the respiratory pattern suggest that the rCPG expands rostrally and dorsally from the designated core but does not include higher mid-brain structures. Our data also suggest that excitation-inhibition balance of respiratory network synaptic interactions critically determines the network dynamics that underlie vital respiratory rhythm and pattern formation.

Ventilatory Cycle Measurements and Loop Gain in Central Apnea in Mining Drivers Exposed to Intermittent Altitude.

By measuring the apnea length, ventilatory phase, respiratory cycle length, and loop gain, we can further characterize the central apneas of high altitude (CAHA). Sixty-three drivers of all-terrain vehicles, working in a Peruvian mine located at 2,020 meters above sea level (MASL), were evaluated. A respiratory polygraph was performed in the first night they slept at high altitude. None of the subjects were exposed to oxygen during the test or acetazolamide in the preceding days of the test. Sixty-three respiratory polygraphs were performed, and 59 were considered for analysis. Forty-six (78%) were normal, 6 (10%) had OSA, and 7 (12%) had CAHA. Key data from subjects include: residing altitude: 341 ± 828 MASL, Lake Louise scoring: 0.4 ± 0.8, Epworth score: 3.4 ± 2.7, apneahypopnea index: 35.7 ± 19.3, CA index: 13.4 ± 14.2, CA length: 14.4 ± 3.6 sec, ventilatory length: 13.5 ± 2.9 sec, cycle length: 26.5 ± 4.0 sec, ventilatory length/CA length ratio 0.9 ± 0.3 and circulatory delay 13.3 ± 2.9 sec. Duty ratio media [ventilatory duration/cycle duration] was 0.522 ± 0 0.128 [0.308-0.700] and loop gain was calculated from the duty ratio utilizing this formula: LG = 2π / [(2πDR-sin(2πDR)]. All subjects have a high loop gain media 2.415 ± 1.761 [1.175-6.260]. Multiple correlations were established with loop gain values, but the only significant correlation detected was between central apnea index and loop gain. Twelve percent of the studied population had CAHA. Measurements of respiratory cycle in workers with CAHA are more similar to idiopathic central apneas rather than Hunter-Cheyne-Stokes respiration. Also, there was a high degree of correlation between severity of central apnea and the degree of loop gain. The abnormal breathing patterns in those subjects could affect the sleep quality and potentially increase the risk for work accidents.

Ventilatory pattern variability predicts long‐term survival following cardiac arrest and resuscitation in rats

Ventilatory pattern variability (VPV) reflects brainstem function with respect to cardio‐respiratory regulation. We applied linear and nonlinear tools to assess VPV following cardiac arrest and resuscitation with the goal of predicting long‐term survival. Spontaneous breathing (plethysmography) was recorded for 1h for VPV analysis at baseline and after cardiac arrest (12 min) and resuscitation in male Wistar rats. VPV was similar before cardiac arrest but differed between survivors (survived for 4d, n = 15) and non‐survivors (died before 4d, n = 12) after resuscitation. The nonlinear complexity index (NLCI), a measure of deterministic structure in ventilatory patterns, was similar between survivors and non‐survivors (0.08 ± 0.03 vs.0.07 ± 0.03 bits) before cardiac arrest. On day 0 and day 1 post‐resuscitation NLCI was significantly increased (~3 folds) in the non‐survivors while remained unchanged from baseline in the survivors. Traditional measures such as respiratory rate and coefficient of variation of respiratory cycle length cannot distinguish the difference in ventilatory pattern between the survivors and non‐survivors. The characteristic changes in VPV early in recovery distinguished the survivors from non‐survivors, suggesting that VPV could be a predictor of long‐term survival following cardiac arrest and resuscitation. Supported by NS 38632, HL 087377, VA Research Service (I01BX000873).

High‐altitude hypoxia and periodic breathing during sleep: gender‐related differences

High-altitude exposure is characterized by the appearance of periodic breathing during sleep. Only limited evidence is available, however, on the presence of gender-related differences in this breathing pattern. In 37 healthy subjects, 23 male and 14 female, we performed nocturnal cardio-respiratory monitoring in the following conditions: (1) sea level; (2) first/second night at an altitude of 3400m; (3) first/second night at an altitude of 5400m and after a 10day sojourn at 5400m. At sea level, a normal breathing pattern was observed in all subjects throughout the night. At 3400m the apnea-hypopnea index was 40.3±33.0 in males (central apneas 77.6%, central hypopneas 22.4%) and 2.4±2.8 in females (central apneas 58.2%, central hypopneas 41.8%; P<0.01). During the first recording at 5400m, the apnea-hypopnea index was 87.5±35.7 in males (central apneas 60.0%, central hypopneas 40.0%) and 41.1±44.0 in females (central apneas 73.2%, central hypopneas 26.8%; P<0.01), again with a higher frequency of central events in males as seen at lower altitude. Similar results were observed after 10days. With increasing altitude, there was also a progressive reduction in respiratory cycle length during central apneas in males (26.9±3.4s at 3400m and 22.6±3.7s at 5400m). Females, who displayed a significant number of central apneas only at the highest reached altitude, were characterized by longer cycle length than males at similar altitude (30.1±5.8s at 5400m). In conclusion, at high altitude, nocturnal periodic breathing affects males more than females. Females started to present a significant number of central sleep apneas only at the highest reached altitude. After 10days at 5400m gender differences in the apnea-hypopnea index similar to those observed after acute exposure were still observed, accompanied by differences in respiratory cycle length.

Pattern variability in a computational model of respiratory rhythm generation

Variability is inherent to rhythmic physiological patterns. Fluctuations in neural patterns are often regarded as noise. However it has been suggested that neurally generated rhythms result from systems that are not homeostatic but instead are homeodynamic [1][2]. In this view, excessive variability may indicate an instability while insufficient variability could result from an inability to adapt to environmental stressors. Understanding the inherent mechanisms of variability in the nervous system may enable us to use statistical measures to evaluate stability and robustness. Studies have addressed the presence of variability of the neural control of respiration in both the clinical context [3] as well as the experimental context [4]. Experimental studies have primarily focused on in vivo models that incorporate chemosensory and mechanosensory feedback which are likely to be necessary mechanisms of respiratory variability. A fundamental source of respiratory pattern generation is the preBotzinger complex (preBotC) which is part of the ventral respiratory column located in the brainstem. Here we use a computational model of the preBotC to analyze the variability of behavioral patterns at both the population and single-cell levels. Our model is based on previous computational studies of the in vitro respiratory slice [5][6]. It utilizes Hodgking-Huxley style neurons [7] that are divided into four cell types: hypoglossal motoneurons, premotoneurons, and preBotC cells that are configured for bursting by means of a persistent Na+ current. The architecture consists a feedforward hierarchy such that motoneurons are driven by premotoneurons and premotoneurons are driven by preBotC cells. The preBotC cells receive inputs from each other and also receive random tonic drive in the form of excitatory and inhibitory postsynaptic currents. This tonic drive represents chemosensory and mechanosensory feedback. Hierarchical levels are randomly connected with a fixed connection probability or density. Additionally the model includes extracellular K+ diffusion/buffering and a cellular Na+/ K+ exchange pump. We analyzed the burst patterns of individual cells as well as the spike histogram of the hypoglossal motoneuron population which represents the whole-nerve activity recorded from cranial nerve XII in experiments. Variability was measured for both the single-cell bursts and motoneuron population bursts. Burst properties that were analyzed included respiratory cycle length, inspiratory phase length, and peak burst amplitude for the population spike histogram. Three variability measures were used: the linear measure of coefficient of variation and two nonlinear measures: mutual information and sample entropy. We focused on two network areas and their influence on burst pattern variability. The first was the tonic drive to preBotC cells. We varied the quantity of tonic inputs and connection densities. We found that an increase in the connection density to preBotC cells produced a decrease in overall linear and nonlinear variability. This is due to the increase in postsynaptic event correlation that results from the combined common inputs. The second area that was studied was the interconnection density between the preBotC cells themselves. Again an increase in connection density produced a decrease in overall linear and nonlinear variability. However, this effect was not as pronounced as that of the tonic drive.

Ventilatory pattern variability is associated with long‐term recovery following cardiac arrest and resuscitation in rats

Predicting outcomes is essential for intervening to prevent mortality following cardiac arrest and resuscitation. We hypothesize that ventilatory pattern variability (VPV) reflects brainstem cardio‐respiratory regulation and propose to use VPV as a predictor for long‐term survival following cardiac arrest and resuscitation. Spontaneous ventilation was recorded (60 min) using whole‐body plethysmography in male Wistar rats before cardiac arrest (12 min) and 1d after resuscitation. VPV was analyzed including quantification of a nonlinear complexity index (NLCI) by comparing the sample entropy of original and surrogate data sets with similar autocorrelation functions. Overall survival (4d) was determined. VPV was similar before cardiac arrest but differed between survivor (n=5) and non‐survivor (died before 4d, n=2) groups after resuscitation. Non‐survivors had lower respiratory rate and higher coefficient of variation (CV) of respiratory cycle length compared to the survivors (RR: 80±13 vs. 104±11 bpm; CV: 0.27±0.09 vs. 0.15±0.02). NLCI was about 8‐fold higher in non‐survivor as compared to survivor rats (0.3±0.1 vs.0.04±0.02). Changes in VPV might distinguish surviving from non‐surviving rats early in the recovery phase after resuscitation, suggesting that VPV can be used as an outcome predictor following cardiac arrest and resuscitation. Supported by NS 38632, HL 087377, VA Research Service.

Cystic fibrosis mice display different breathing patterns than non‐CF mice

Cystic fibrosis (CF) mouse models are used to understand disease physiology, but the CF mouse displays only mild pulmonary pathology. Changes in respiratory pattern are associated with health and disease, but ventilatory pattern has not been investigated in mouse models of CF.Breathing patterns were recorded (200Hz) and quantified in CF mouse models (common mutation ΔF508 (n=22); CF mice complemented with human CFTR in the gastrointestinal tract (FABP‐CFTR, n=11); and wild type (WT, n=24)) using whole body plethysmography. If ANOVA p&lt;0.05, then differences between groups were determined using a multiple comparisons procedure.Respiratory rate was higher in ΔF508 as compared to WT mice (203 [187, 263 vs. 179 [164, 197] bpm; p&lt;0.05). ΔF508 mice also exhibited greater coefficient of variation (CV) of respiratory cycle length (0.28±0.08 vs. 0.20±0.06; p&lt;0.01). Similarly, the FABP mouse group had a respiratory rate (261 [216, 284] bpm) and CV (0.36±0.08) that were significantly greater than the WT group (p&lt;0.05 for both).CF mouse lines exhibited faster respiratory rates and greater ventilatory pattern variability than WT mice. Altered breathing patterns in FABP mice which do not succumb to intestinal obstruction suggest that these differences are not the result of the fragile state of the ΔF508 animals. CF mice may be a good model of pre‐clinical pulmonary disease in humans.

TU‐C‐303A‐04: Slow Gantry Rotation Acquisition Protocol for Four‐Dimensional Digital Tomosynthesis

Purpose: Four‐dimensional digital tomosynthesis (4D‐DTS) was recently introduced as a novel on‐board 4D imaging technique. The purpose of this study is to develop and implement a slow gantry rotation acquisition protocol for 4D‐DTS. A formalism for determining appropriate acquisition parameters based on patients' respiratory characteristics was derived and tested. Methods &amp; Materials: Equations were derived to explain the relationships between slow gantry acquisition parameters (scan speed, frame rate and scan angle) and respiratory characteristics (average period and regularity). Additional equations relate acquisition parameters with resultant scan times, projection numbers and the distribution of projections within phase bins once sorting and binning are complete. Phantom studies were conducted to test the new protocol. A body phantom was mounted on a moving platform to simulate short and long respiratory cycles (3 and 6‐s) and scanned using the slow gantry protocol with a 1.1‐deg/sec scan speed and a 7.8‐fps frame rate. Projections were binned and sorted into 10 phases with 10% phase windows. Resultant distributions of projections within phase bins were compared with expected distributions based on the derived formalism. Reconstructions were completed to investigate dependence on respiratory period. Results: The maximum angular intervals between projections within phase bins were estimated by the formalism to be 3.5 and 6.8° for the 3 and 6‐s profiles, respectively. Actual values ranged 3.4 to 3.6° for the 3‐s profile and from 6.8 to 7.16° for the 6‐s profile. Reconstructions demonstrated the importance of adjusting scan speed according to respiratory cycle length. Conclusion: A 4D‐DTS slow gantry rotation acquisition protocol was developed, implemented, and tested. The derived formalism has proven useful for determining appropriate acquisition parameters based on respiratory characteristics and will be used as a framework for further optimization and testing of the protocol.Conflict of Interest: Partially supported by a Varian research grant.

Modulation of respiratory sinus arrhythmia by respiration rate and volume: Stability across posture and volume variations

We tested the assumption that the slope of the within-individual regression equation of respiratory sinus arrhythmia (RSA) normalized by tidal volume (V(T)) upon respiratory cycle length (T(TOT)) can characterize ventilatory RSA modulation independent of cardiac vagal tone, whereas the intercept is varying as a function of vagal tone. We also explored whether a variation of V(T) is necessary to estimate slopes reliably. Four 3-min sequences paced at 8-18 cycles/min were performed supine and standing. Participants also breathed the same sequences in supine posture with voluntarily varying V(T). The mean slope of RSA/V(T) upon T(TOT) was identical, and the mean intercept was lower for standing than supine (spontaneous V(T)) conditions. Stability of slopes was low between body postures, and was higher between spontaneous V(T) versus varying V(T) at the same body posture. The regression of RSA/V(T) upon T(TOT) allows for a valid estimation of ventilatory influences on RSA.

Cardiorespiratory reflexes in a working heart–brainstem preparation of the house musk shrew, Suncus murinus

In this study, we adapted the working heart–brainstem preparation (WHBP) from rodents to the Insectivore, Suncus murinus. Suncus WHBPs had a baseline heart rate of 333±8 beats min −1, a perfusion pressure of 69±2 mm Hg and a respiratory cycle length of 6.5±0.7 s. Administration of atropine produced an increase in heart rate of 26±9 beats min −1, indicative of the presence of cardiac vagal tone. Activation of baroreceptors produced pressure-dependent reflex falls in heart rate and reduced respiratory cycle length. The baroreceptor reflex sensitivity in Suncus WHBP was a decrease in heart rate of 8.1±1.4 beats min −1 mm Hg −1. Activation of peripheral chemoreceptors with aortic injections of sodium cyanide (0.1–12.5 μg) produced a dose-dependent reflex fall in heart rate and reduced respiratory cycle length. The reflex falls in heart rate evoked by baroreceptor and peripheral chemoreceptor stimulation were both atropine-sensitive. We conclude that viable WHBP can be prepared from Suncus and that Suncus WHBP is a novel non-rodent model in which to study brainstem-mediated reflexes.

Role of the solitary tract nucleus in mediating nociceptive evoked cardiorespiratory responses

We compared the cardiorespiratory reflex responses evoked by noxious stimulation of the forelimb and cornea. Due to the depressant effects of anaesthesia on visceral reflexes we compared data from an unanaesthetised decerebrate rat model — the working heart–brainstem preparation (WHBP), with the anaesthetised rat. In both experimental models stimulation of the forelimb (mechanical pinch) evoked a tachycardia (WHBP: 19±2 bpm) and a decrease in respiratory cycle length (WHBP: from 4.1±0.2 to 2.3±0.1 s). The magnitude of response in anaesthetised animals depended on anaesthetic depth. Mechanical stimulation of the cornea evoked a bradycardia (−49.2±4.8 bpm) and an increase in respiratory cycle length from 4±0.36 to 5.88±0.2 s which was only present in the WHBP. In the WHBP activation of forelimb and corneal nociceptors both elicited significant pressor effects; in anaesthetised rats there were inconsistent changes in arterial pressure. To determine a role for the nucleus of the solitary tract (NTS) in mediating nociceptive evoked responses in the WHBP, synaptic transmission was blocked reversibly following bilateral microinjections of cobalt chloride. The heart rate responses evoked from either forelimb or corneal nociceptors were attenuated by approximately 50% ( P<0.05). A similar effect was observed using isoguvacine, a GABA A receptor agonist, to hyperpolarise NTS neurones. In conclusion, activation of forelimb and corneal nociceptors evoked contrasting patterns of cardiorespiratory response in the WHBP while in the anaesthetised rat the magnitude of the cardiorespiratory response to forelimb stimulation was quantitatively dependent on anaesthetic dose. In the WHBP, NTS neurones appear important for mediating the cardiac component of the reflex response following stimulation of nociceptive reflex pathways.

Brain-derived neurotrophic factor is required for normal development of the central respiratory rhythm in mice.

1. Molecular mechanisms underlying maturation of the central respiratory rhythm are largely unknown. Previously, we found that brain-derived neurotrophic factor (BDNF) is required for expression of normal breathing behaviour in newborn mice, raising the possibility that maturation of central respiratory output is dependent on BDNF. 2. Respiratory activity was recorded in vitro from cervical ventral roots (C1 or C4) using the isolated brainstem-spinal cord preparation from postnatal day (P) 0.5-2.0 and P4.5 wild-type mice and mice lacking functional bdnf alleles. 3. Loss of one or both bdnf alleles resulted in an approximately 50% depression of central respiratory frequency compared with wild-type controls. In addition, respiratory cycle length variability was 214% higher in bdnf null (bdnf-/-) animals compared with controls at P4.5. In contrast, respiratory burst duration was unaffected by bdnf gene mutation. 4. These derangements of central respiratory rhythm paralleled the ventilatory depression and irregular breathing characteristic of bdnf mutants in vivo, indicating that central deficits can largely account for the abnormalities in resting ventilation produced by genetic loss of BDNF. BDNF is thus the first growth factor identified that is required for normal development of the central respiratory rhythm, including the stabilization of central respiratory output that occurs after birth.

The coordination and interaction between respiration and deglutition in young pigs.

The anatomical pathways for inspired air and ingested food cross in the pharynx of mammals, implying that breathing and swallowing must be separated either in space or in time. In this study we investigated the time relationship between swallowing and respiration in young pigs, as a model for suckling mammals. Despite the high morphological position of the larynx in young mammals, allowing liquid to pass in food channels lateral to the larynx, respiration and swallowing are not wholly independent events. Although, when suckling on a veterinary teat, the swallows occurred at various points in the respiratory cycle, there was always a period of apnea associated with the swallow. Finally, an increase in the viscosity of the milk altered this coordination, changing respiratory cycle length and also restricting the relative rate at which swallows occurred in some parts of the respiratory cycle. These results suggest that the subsequent changes in respiratory activity at weaning, associated with passage of a solid bolus over the larynx, is preceded by the ability of the animal to alter coordination between respiration and swallowing for a liquid bolus.

Effect of respiration on the QT interval

This clinical study was undertaken to investigate the effect of respiration on the QT interval. The QT interval is affected by a variety of factors, including steady change sin heart rate, instantaneous changes in heart rate as in atrial fibrillation, and changes in autonomic tone. Respiration gives rise to cyclical changes in the instantaneous heart rate and autonomic tone. The effect of respiration on the QT interval was analyzed in 25 subjects in sinus rhythm. Cosinor analysis was used to estimate the amplitude of its change from the mean value, its statistical significance, and the timing of the maximum change. Thirteen (52%) subjects revealed significant respiratory change in the QT interval, being the shortest during inspiration in 10 of them. Its amplitude correlated positively with respiratory cycle length ( r = .58, P < .01), but not with age, mean heart rate, or the amplitude of change in the RR interval. The mean amplitude of change in the QT interval was 0.8% compared to a change of 2.6% in the RR interval. There is a respiratory variation in the QT interval in subjects in sinus rhythm that is more prominent during slower respirations. However, the amplitude of change in the QT interval is small compared to the change in the RR interval.

Mutual interactions of respiratory sinus arrhythmia and the carotid baroreceptor-heart rate reflex.

1. In six healthy subjects the amplitude and phase of respiratory sinus arrhythmia were determined at five different respiratory cycle lengths ranging from 3 to 9.5 s. 2. At each respiratory cycle length the carotid baroreceptor-heart rate reflex response was determined by cyclical neck suction at -40 mmHg at five different cycle lengths covering the same range of 3-9.5 s. 3. The application of cyclical neck suction increased the amplitude of respiratory sinus arrhythmia in all but the longest respiratory cycle lengths. 4. With increasing respiratory cycle length the amplitude of sinus arrhythmia increased, and R-R intervals were at their longest at an earlier phase of the respiratory cycle. Similarly, with increasing suction cycle length the amplitude of the cardiac interval response increased and the phase angle decreased. 5. The cardiac interval responses to respiration and to neck suction at different frequencies were independent of each other, the heart rate at any moment resulting from the algebraic summation of the two responses.

Snoring during NREM sleep: Respiratory timing, esophageal pressure and EEG arousal

Eight men who were regular heavy snorers were monitored while awake and during nocturnal sleep. All subjects were known to be free of lung disease, obstructive sleep apnea syndrome, and oxygen drops during sleep. For each subject, two snoring periods of 3–31 min with a mean of 12.7 min were randomly selected for comparison with periods of normal, non-snoring NREM sleep breathing. A mean of 150 respiratory cycles per period were analyzed. For each respiratory cycle, respiratory inductive plethysmography and measurements of peak flow, laryngeal sounds, and esophageal pressure (Pes) were used to calculate breathing frequency (bf), inspiratory time (Ti), expiratory time (Te), total respiratory cycle length (Ttot), and Pes at its nadir. During NREM sleep silent breathing, the Ti/Te ratio was analogous to that already measured in normal subjects. With the onset of snoring, an immediate increase in Ti, Te, and Pes nadir were noted. Mean peak Pes nadir increased 120 ± 37%, and mean Ttot increased by 18%. Through the duration of the snoring period, a further increase in Ti(mean = 10.4 ± 3.4%) and a decrease in Te were noted, with a mean change in Ti/Ttot of 12 ± 3.1%. The shape of the esophageal pressure wave during expiration shifted from its normal dynamics. The percentage of Te decreased by a mean of −9.8 ± 2.3% ( P < 0.0001), and the rise time in Pes increased a mean of 37%. When Pes nadir was the most negative, a mean peak flow decrease of 4.3 ± 13.6% from baseline was observed. Tidal volume had decreased by a mean of 22% and minute ventilation by a mean of 21% at the end of the snoring period. Separate investigation of each subject indicates that the evolutions of Ti, Te and Pes during snoring were not the same for all subjects. At least two different groups of snorers exist; these groups may be differentiated by the evolution of Pes over time during snoring. Modifications in the ‘braking’ role of inspiratory muscles during expiration may explain the changes in the Pes wave dynamics snoring which lead to repetitive EEG arousals, termination of snoring periods, and some sleep fragmentation.

Respiratory sinus arrhythmia is a limited measure of cardiac parasympathetic control in man.

1. Respiratory modulation of cardiac parasympathetic activity and the relationship between respiratory sinus arrhythmia and parasympathetic control has been studied in twenty-nine conscious, healthy young adult subjects. 2. Changes in heart period in propranolol-treated subjects were taken as the measure of changes in cardiac parasympathetic activity; respiratory sinus arrhythmia was quantified as the difference between maximum and minimum heart periods in a given respiratory cycle; cardiac parasympathetic control was defined as the change in heart period after administration of a full dose of atropine. 3. During normal quiet breathing the inspiratory level of cardiac parasympathetic activity was not reduced to zero. The expiratory level was influenced by excitatory inputs whose activation was related to respiratory cycle length. 4. Slow breathing was associated with augmented sinus arrhythmia, but in different individuals the influence on minimum and maximum heart periods varied so that mean heart period was increased in some subjects but decreased in others. This occurred both in control conditions and after administration of a full dose of propranolol. 5. During normal breathing the correlation across subjects between respiratory sinus arrhythmia and parasympathetic control, although significant, was not close (r = 0.61). The relationship was not affected by beta-adrenergic blockade (r = 0.63). The strength of the correlation improved when multiple regression of respiratory sinus arrhythmia was performed on three variables: parasympathetic control, respiratory cycle length and tidal volume (R = 0.93). 6. It is concluded that in conscious human subjects the respiratory modulation of cardiac parasympathetic activity is different from that observed in the anaesthetized dog, and that variations in the amplitude of respiratory sinus arrhythmia do not necessarily reflect proportional changes in cardiac parasympathetic control.