Total Respiratory Cycle Duration Research Articles

Cardiorespiratory patterns of male South American sea lions (Otaria flavescens) resting on land.

The goal of this study was to characterize the cardiorespiratory patterns of male South American sea lions (SASLs, Otaria flavescens) resting on land. We recorded respiratory and heart rate (n = 360 individuals studied) by observing the nostrils, chest movements and the impact of the heart on the thoracic wall. The sea lions breathe apneustically with a pause on inspiration, representing 74% of the respiratory cycle. The mean breathing frequency was 3.2 ± 1.0breathsmin-1, with a breathing cycle presenting periods of bradypneas, tachypneas, and long-term post-inspiratory pauses. The normal heart rate (nHR) was 73.4 ± 14.5beats min-1 and no significant differences were observed between age classes. All animals showed variability in HR in relation to respiratory phases (Inspiration: 101.2 ± 18.4beatsmin-1; post-inspiratory pause: 73.4 ± 14.5beatsmin-1; expiration: 64.6 ± 17.7beatsmin-1), consistent with respiratory sinus arrhythmia (RSA). The mean HR (measured during all respiratory phases) was 79.9 ± 22.7beatsmin-1, and was significantly different between age classes. The total duration of respiratory cycle, and duration of both inspiration and expiration, decreased with an increment in ambient temperature, with no variation in the pause duration. Heart rate during pause and expiration was significantly higher during high temperatures. Similar changes in cardiorespiratory patterns have been reported in other pinnipeds. Our results showed ontogenetic differences in development and typical variations with environmental and behavioral variables.

Monitoring respiratory rates with a wearable system using a stretchable strain sensor during moderate exercise.

Respiratory rate, a sensitive indicator of respiratory status, is rarely measured during the field walking test. Our objective was to develop and validate a non-invasive, wearable monitoring system using stretchable strain sensors and an accompanying algorithm capable of providing real-time measurements of respiration during exercise. Twenty-four healthy volunteers wore stretchable sensors during a walking test protocol that included standing, sitting, walking, and walking with a stick. Sensors were placed on the ribcage and abdomen. The Bland-Altman method was used to assess the accuracy and precision of breath counts; total respiration time and inspiration time ratio were determined by custom algorithms and compared with measurements obtained with the standard flow sensor. The output signal from the stretchable sensor was highly synchronized with flow signals. The limits of agreement were within 3 breaths/min throughout the test protocol. Differences between sensors for total respiration time and inspiration time ratio were less than 14% and 26%, respectively. The agreement was maintained regardless of respiratory rate or volume. The wearable respiratory monitoring system yielded accurate and precise breath counts and total duration of respiratory cycle during moderate exercise in healthy young individuals, suggesting that it might be useful in clinical practice. Graphical abstract.

Variability of breathing during wakefulness while using CPAP predicts adherence.

The standard therapy for obstructive sleep apnoea (OSA) is continuous positive airway pressure (CPAP) therapy. However, long-term adherence remains at ~50% despite improvements in behavioural and educational interventions. Based on prior work, we explored whether regularity of breathing during wakefulness might be a physiologic predictor of CPAP adherence. Of the 117 consecutive patients who were diagnosed with OSA and prescribed CPAP, 79 CPAP naïve patients were enrolled in this prospective study. During CPAP initiation, respiratory signals were collected using respiratory inductance plethysmography while wearing CPAP during wakefulness in a seated position. Breathing regularity was assessed by the coefficient of variation (CV) for breath-by-breath estimated tidal volume (VT ) and total duration of respiratory cycle (Ttot). In a derivation group (n = 36), we determined the cut-off CV value which predicted poor CPAP adherence at the first month of therapy, and verified the validity of this predetermined cut-off value in the remaining participants (validation group; n = 43). In the derivation group, the CV for estimated VT was significantly higher in patients with poor adherence than with good adherence (median (interquartile range): 44.2 (33.4-57.4) vs 26.0 (20.4-33.2), P < 0.001). The CV cut-off value for estimated VT for poor CPAP adherence was 34.0, according to a receiver-operating characteristic (ROC) curve. In the validation group, the CV value for estimated VT >34.0 confirmed to be predicting poor CPAP adherence (sensitivity, 0.78; specificity, 0.83). At the initiation of therapy, breathing regularity during wakefulness while wearing CPAP is an objective predictor of short-term CPAP adherence.

Effects of expiratory muscle work on muscle sympathetic nerve activity.

We hypothesized that contractions of the expiratory muscles carried out to the point of task failure would cause an increase in muscle sympathetic nerve activity (MSNA). We measured MSNA directly in six healthy men during resisted expiration (60% maximal expiratory pressure) leading to task failure with long [breathing frequency (f(b)) = 15 breaths/min; expiratory time (TE)/total respiratory cycle duration (TT) = 0.7] and short (f(b) = 30 breaths/min; TE/TT = 0.4) TE. Both of these types of expiratory muscle contractions elicited time-dependent increases in MSNA burst frequency that averaged +139 and +239%, respectively, above baseline at end exercise. The increased MSNA coincided with increases in mean arterial pressure (MAP) for both the long-TE (+28 +/- 6 mmHg) and short-TE (+22 +/- 14 mmHg) trials. Neither MSNA nor MAP changed when the breathing patterns and increased tidal volume of the task failure trials were mimicked without resistance or task failure. Furthermore, very high levels of expiratory motor output (95% maximal expiratory pressure; f(b) = 12 breaths/min; TE/TT = 0.35) and high rates of expiratory flow and expiratory muscle shortening without task failure (no resistance; f(b) = 45 breaths/min; TE/TT = 0.4; tidal volume = 1.9 x eupnea) had no effect on MSNA or MAP. Within-breath analysis of the short-expiration trials showed augmented MSNA at the onset of and throughout expiration that was consistent with an influence of high levels of central expiratory motor output. Thus high-intensity contractions of expiratory muscles to the point of task failure caused a time-dependent sympathoexcitation; these effects on MSNA were similar in their time dependency to those caused by high-intensity rhythmic contractions of the diaphragm and forearm muscles taken to the point of task failure. The evidence suggests that these effects are mediated primarily via a muscle metaboreflex with a minor, variable contribution from augmented central expiratory motor output.

Bifurcations of the respiratory pattern produced with phasic vagal stimulation in the rat

Geometric methods from nonlinear dynamics are employed to evaluate dynamic processing of vagal afferent information by the respiratory central pattern generator (RCPG). While measuring airflow and diaphragm EMG, we applied brief electrical stimuli (40- to 130-ms duration) to one afferent vagus of bilaterally vagotomized urethan-anesthetized rats during every breath at various phases of the respiratory cycle. Stimuli applied during early or late inspiration of every breath evoke highly predictable one-dimensional responses: reversible (graded inhibition) or irreversible (off-switching) inhibition of inspiratory activity, respectively. Stimulation during midinspiration produces higher-dimensional oscillations that wander unpredictably over a continuum of graded inhibition and off-switching; "spiral" attractors and "horseshoe" return maps at this phase are characteristic of Silnikov's bifurcation. Stimuli applied during early expiration always prolonged expiratory duration, but those delivered during midexpiration evoked unpredictable wandering between prolongations and shortening of expiratory duration. A narrow time window surrounds the expiratory-inspiratory (E-I) transition, where stimuli elicit either breaths of short duration and low amplitude (irreversible E-I transition, decreased total respiratory cycle duration) or transient bursts of inspiratory activity at the E-I transition followed by a prolonged breath (reversible E-I transition, increased total respiratory cycle duration). We conclude that RCPG "gating" of and adaptation to vagal feedback combine to produce complex breath-to-breath dynamics in the rat that are consistent with low-dimensional chaos.

Retrofacial lesions: effects on CO2-sensitive phrenic and sympathetic nerve activity.

We made unilateral chemical (10- or 50-nl microinjections; 4.7 mM kainic acid) or electrolytic (5-15 mA; 15 s) lesions in a region of the rostral ventrolateral medulla (VLM) caudal to the retrotrapezoid nucleus in 10 decerebrate, paralyzed, vagotomized, and servo-ventilated cats. The lesions were 3.0-4.2 mm lateral to the midline, within 2 mm caudal to the facial nucleus, and within 2.5 mm of the VLM surface. Four control injections (mock cerebrospinal fluid and fluorescent beads alone) produced small and inconsistent effects over 3-5 h. The predominant effect of the lesions was a significant decrease in baseline integrated phrenic nerve amplitude (PNA) (apnea in 2 cases), total respiratory cycle duration, and the response to increased CO2 (slope < 15% of control in 3 cases). The respiratory-related peak amplitude of the integrated sympathetic signal, blood pressure, and the sympathetic nerve activity response to CO2 were also decreased after the majority of lesions. Not all lesions produced all effects, and some lesions resulted in increased PNA and respiratory cycle duration. The lesioned region appears functionally to represent a caudal extension of the retrotrapezoid nucleus containing neurons necessary for normal baseline PNA and CO2 sensitivity. In addition, it contains neurons involved in the determination of resting respiratory frequency and normal sympathetic activity and blood pressure. The pattern of mixed responses among animals suggests that a heterogeneity of function is present within a relatively small VLM region.

Changes in heart rate during obstructive sleep apnoea

The mechanisms behind the decrease in heart rate during apnoeas in patients with obstructive sleep apnoea (OSA) are little known. Recent findings in animal experiments indicate that stimulation of the upper airway activates postinspiratory and cardiac vagal neurones in the medullary respiratory centre, causing alterations in heart rate and respiratory rhythm. Since OSA leads to a collapse of the airway and consequent stimulation of upper airway receptors, we studied the interrelations between heart rate and respiratory rhythm during apnoea and during negative intrathoracic pressure generated by the Mueller manoeuvre (MM). Fifteen patients with OSA (apnoea hypopnoea index (AHI) 45 +/- 28.h-1) were studied by polysomnography, during a MM and a Valsalva manoeuvre, each of 15 s duration. The heart rate decrease (delta HRA) and the increase in total respiratory cycle duration (TOT) were evaluated during apnoea in non-rapid eye movement (REM) sleep. Patients with OSA demonstrated a decrease in heart rate during apnoea (-14.4 +/- 9.0 beats.min-1), and during MM (-11.5 +/- 13.5 in OSA vs 3.1 +/- 7.8 beats.min-1 in a control group). TOT increased during apnoea (4.6 +/- 3.1 s). There was a significant correlation between delta HRA and AHI (r = -0.64) as well as between delta HRA and increase in TOT (r = 0.62). These findings indicate that upper airway obstruction may cause an activation of receptors at the site of airway collapse or distortion leading to changes in heart rate and respiratory rhythm.

Influence of anthropometric characteristics on changes in maximal exercise ventilation and breathing pattern during growth in boys

The aim of this study was to investigate the effect of growth on ventilation and breathing pattern during maximal exercise oxygen consumption (VO2max) and their relationships with anthropometric characteristics. Seventy six untrained schoolboys, aged 10.5-15.5 years, participated in this study. Anthropometric measurements made included body mass, height, armspan, lean body mass, and body surface area. During an incremental exercise test, maximal ventilation (VEmax), tidal volume (VTmax), breathing frequency (fmax), inspiratory and expiratory times (tImax and tEmax), total duration of respiratory cycle (tTOTmax), mean inspiratory flow (VT/tImax), and inspiration fraction (tI/tTOTmax) were measured at VO2max. A power function was calculated between anthropometric characteristics and ventilatory variables to determine the allometric constants. The results showed firstly, that VEmax, VTmax, tImax, tEmax, tTOTmax, and VT/tImax increased with age and anthropometric characteristics (P less than 0.001), fmax decreased (P less than 0.001), and tI/tTOTmax remained constant during growth; secondly that lean body mass explained the greatest percentage of variance of VEmax (62.1%), VTmax (76.8%), and VT/tImax (70.6%), while anthropometric characteristics explained a slight percentage of variance of fmax and timing; and thirdly that VEmax, VTmax, and VT/tImax normalized by lean body mass did not change significantly with age. We concluded that at VO2max there were marked changes in ventilation and breathing pattern with growth. The changes in VEmax, VTmax, and VT/tImax were strongly related to the changes in lean body mass.

Animal ventilator controlled by central respiratory phases

An animal ventilator based on the principle of constant gas flow is described. The ventilator can operate either in a fixed cycle mode or in cycle-triggered mode. In the first case the built-in generator allows the setting of respiration rate and of the ratio of inspiratory duration to total respiratory cycle duration. When operated in cycle-triggered mode, phrenic nerve activity by means of an external respiratory phase detector controls the action of the pump. An internal circuitry allows precise no-inflation maneuvers. The device provides logical timing signals suitable for cycle-triggered averaging of respiration-related neuronal activity. The ventilator has proven its usefulness in experiments on reflex control of central respiration in paralyzed rabbits.

Respiratory inhibition induced by transient hypertension during sleep in unrestrained cats

The effects of transient blood pressure elevation, induced by intravenous injection of phenylephrine, were studied in drug-free, unrestrained cats during sleep and waking. Transient hypertension evoked an increase in respiratory cycle duration (T tot), an effect which was most prominent during quiet sleep. Transient hypertension evoked no overall change in inspiratory duration (T di) during any sleep-waking state, although reduction of diaphragmatic EMG amplitude was observed. Thus, the ratio of diaphragmatic activity time to total respiratory cycle duration ( T di T tot ) was decreased following blood pressure elevation. Apneic episodes occasionally occurred, and these occurrences were more frequent during sleep states. Apneas induced during quiet sleep were often associated with transient or sustained arousal.

Electrical stimulation of arterial and central chemosensory afferents at different times in the respiratory cycle of the cat: I. Ventilatory responses.

Ventilatory responses to stimulation of chemoreceptor afferents were studied in the anesthetized, spontaneously breathing cat. Short bursts of electrical stimuli were applied, at various times in the inspiratory or expiratory phase of consecutive breaths, to the carotid sinus (CSN) and aortic nerves (AN) and to the ventral medulla (VM), and effects on tidal volume (VT), inspiratory, expiratory and cycle durations (tI, tE, ttot) and in ventilation (VE) were measured. The responses evoked by stimulating CSN, AN and VM were qualitatively the same, although there were quantitative differences. It was found that effects of stimulation in expiration were restricted to the expiratory phase, and vice versa for inspiration. Stimulation during both inspiration and expiration resulted in increased VT, by increasing end-inspiratory or decreasing end-expiratory lung volume, respectively, and also increased ventilation, VE. These effects were most marked in response to stimulation in inspiration. During both phases there was an increasing effect with increasing delay of the stimulus, tSt, from onset of inspiration or expiration, respectively. There was a continuous increase in tI, from below control to above control values, with increasing tSt during inspiration and similarly for tE during expiration. Hence, the total respiratory cycle duration was shortened when a stimulus was applied early in either phase, and was prolonged, when it was applied late. The results show that stimulation of peripheral and of central chemoafferents exerts qualitatively similar effects on respiration. The central neuronal mechanisms generating both inspiration and expiration show the same changes in reactivity in the respiratory cycle.

Occlusion pressure and breathing pattern in healthy children

The breathing pattern was investigated in 62 children aged 4 to 16 years together with the mouth pressure generated 0.1 s after an occlusion at the endexpiratory level (P 0.1). A group of 20 adults (18 to 32 years old) were tested in a similar way. The values of P 0.1 otained during room air breathing at rest in the children decreased with age as a power function P 0.1= 8.51 A −0.62 (where A is age in years), r = −0.74. Adult values of P 0.1 were achieved at about 13 years. After O 2 inhalation P 0.1 decreased in children, but the changes in P 0.1 were independent of age. Respiratory frequency decreased with age while inspiratory time (T i) increased, both reaching adult values at about 13 years. The ratio of T i over the total respiratory cycle duration did not change significantly with age in the entire population. The absolute value of tidal volume (V t) increased with age, but not when normalized for body weight (BW). The mean inspiratory flow (V t/T i) normalized for BW decreased with age in children as did P 0.1. There was a significant relationship between P 0.1 and V t/T i normalized for body weight (r = 0.63).

Effect of lung inflation on ventilation and various phases of the respiratory cycle in preterm infants.

The effect of sudden and sustained lung inflation on inspiratory time (Ti), expiratory time (Te) and duration of apnea, as a translation of the Hering-Breuer reflex, has not been systematically analyzed in preterm infants. To examine such effects, 10 infants (body weight 1,550 +/- 110 g; gestational age 31 +/- 1 weeks) were studied. Lung inflation was obtained by applying negative pressure around the chest using a negative pressure incubator. After a control period, lung volume functional residual capacity was increased by an average of 14, 23, 34 and 53%. During lung inflation, Ti, Te, total respiratory cycle duration, incidence and duration of apnea increased. Minute ventilation decreased due to a decrease in frequency. Tidal volume decreased but not significantly. Inspiratory and expiratory flows decreased. These results (1) confirm the presence of the Hering-Breuer reflex in preterm infants, as reflected by increased Te and appearance of apnea during lung inflation; and (2) show that contrary to expectations, Ti increased significantly with lung inflation.

Properties of phrenic nerve activity during experimental periodic breathing in cats.

Periodic breathing was evoked in Nembutal-anesthetized cats by graded hemorrhage and common carotid artery occlusion. The cats were vagotomized, paralyzed, and artificially ventilated, and the integrated phrenic neurogram (IPN) was recorded. In all cases, the periodic breathing was associated with sustained oscillation of blood pressure (Mayer waves). Twelve episodes of periodic breathing were analyzed. End-inspiratory IPN voltage (Vm) showed characteristic quasi-sinusoidal oscillations with a 30-s average period, accompanied in all 12 cases by a synchronous oscillation of IPN slope. Both oscillations persisted after abolishing the blood pressure waves with an α-adrenergic blocking agent, showing that they were not dependent on phasic baroreceptor input. In four cases there were oscillations of inspiratory and total respiratory cycle duration (and in three of these, expiratory duration also) in synchrony with the Vm and slope waves. In two further cases, expiratory duration oscillated 180° out of phase to Vm and slope, while inspiratory duration records showed only irregular variations. In the remaining six cases, inspiratory, expiratory, and total respiratory cycle duration remained relatively constant during the Vm and slope oscillation. The observed modulation of total respiratory cycle duration indicates that the mechanism generating periodic breathing was acting on the brainstem respiratory oscillator, where respiratory cycle duration is set. The slope modulation is also likely to result from an action at the brainstem oscillator level, although a spinal site of action cannot be entirely excluded.

EVIDENCE FOR A TONIC COMPONENT OF THE HERING-BREUER INFLATION REFLEX IN THE TERM NEONATE

Animal studies have shown that an increase in FRC slows respiration, increases expiratory duration and is vagally mediated. To explore whether a similar response occurs in humans, we studied respiratory timing in 10 sleeping, healthy term neonates on days 1, 2 and 3, before and after a change in lung volume accomplished by adding a continuous positive airway pressure(CPAP) of 3 and 6 cm H2O. Using a mask and flowmeter with constant flow to reduce deadspace, we measured inspiratory time(Ti), expiratory time(Te), total respiratory cycle duration (Ttot), and tidal volume. Comparative movements of upper and lower rib cage were recorded via mercury strain gauges and transcutaneous(Tc) PO2, monitored via a skin electrode. Increasing lung volume caused a significant prolongation of Te% (100xTe/Ttot) on all 3 days(mean data in table). As CPAP was raised from 0 to 6. respiratory rate fell from 47 to 42(NS),58 to 42(p<.005) and 50 to 36(p<.005) on days 1, 2, and 3 respectively. CPAP at 6 cm caused a mean increase in FRC of 19±7cc without significant change in tidal volume and there was no change in TcPO2 when compared to the control period. The direction of paradoxical rib cage movement was unaltered by CPAP. These observations suggest that the significant rise in Te% at increased lung volume may be secondary to the stimulation of a tonic inflation reflex.