Respiratory volume-time relationships during resistive loading in the cat.

The first-breath (neural) effects of graded resistive loads added separately during inspiration and expiration was studied in seven anesthetized cats before and after bilateral vagotomy. Additions of airflow resistance during inspiration reduced the volume inspired (VI) and increased inspiratory duration (TI). The duration of the ensuing unloaded expiration (TE) was unchanged. Vagotomy eliminated the TI modulation with inspiratory loads. Tracheal occlusion at the onset of inspiration yielded TI values similar to the fixed values observed following vagotomy. Resistive loads added during expiration produced similar results. Expired volume (VE) decreased and (TE) increased approaching the values obtained after vagotomy. Unlike the inspiratory resistive loads, loading during expiration results in an upward shift in the functional residual capacity (FRC). The FRC shift produces a time lag between the onset of diaphragmatic (EMG) activity and the initiation of airflow of the next (unloaded) inspiration. These studies suggest separate volume-time relationships for the inspiratory and expiratory phases of the breathing cycle. Both relationships are dependent upon vagally mediated volume feedback.     

Effect of expiratory loading on glottic dimensions in humans

We examined the effects of external mechanical loading on glottic dimensions in 13 normal subjects. When flow-resistive loads of 7, 27, and 48 cmH2O X l-1 X s, measured at 0.2 l/s, were applied during expiration, glottic width at the mid-tidal volume point in expiration (dge) was 2.3 +/- 12, 37.9 +/- 7.5, and 38.3 +/- 8.9% (means +/- SE) less than the control dge, respectively. Simultaneously, mouth pressure (Pm) increased by 2.5 +/- 4, 3.0 +/- 0.4, and 4.6 +/- 0.6 cmH2O, respectively. When subjects were switched from a resistance to a positive end-expiratory pressure at comparable values of Pm, both dge and expiratory flow returned to control values, whereas the level of hyperinflation remained constant. Glottic width during inspiration (unloaded) did not change on any of the resistive loads. There was a slight inverse relationship between the ratio of expiratory to inspiratory glottic width and the ratio of expiratory to inspiratory duration. Our results show noncompensatory glottic narrowing when subjects breathe against an expiratory resistance and suggest that the glottic dimensions are influenced by the time course of lung emptying during expiration. We speculate that the glottic constriction is related to the increased activity of expiratory medullary neurons during loaded expiration and, by increasing the internal impedance of the respiratory system, may have a stabilizing function.     

Effect of resistive loads on pattern of respiratory muscle recruitment during exercise.

In healthy subjects, we compared the effects of an expiratory (ERL) and an inspiratory (IRL) resistive load (6 cmH2O.l-1.s) with no added resistive load on the pattern of respiratory muscle recruitment during exercise. Fifteen male subjects performed three exercise tests at 40% of maximum O2 uptake: 1) with no-added-resistive load (control), 2) with ERL, and 3) with IRL. In all subjects, we measured breathing pattern and mouth occlusion pressure (P0.1) from the 3rd min of exercise, in 10 subjects O2 uptake (VO2), CO2 output (VCO2), and respiratory exchange ratio (R), and in 5 subjects we measured gastric (Pga), pleural (Ppl), and transdiaphragmatic (Pdi) pressures. Both ERL and IRL induced a high increase of P0.1 and a decrease of minute ventilation. ERL induced a prolongation of expiratory time with a reduction of inspiratory time (TI), mean expiratory flow, and ratio of inspiratory to total time of the respiratory cycle (TI/TT). IRL induced a prolongation of TI with a decrease of mean inspiratory flow and an increase of tidal volume and TI/TT. With ERL, in two subjects, Pga increased and Ppl decreased more during inspiration than during control suggesting that the diaphragm was the most active muscle. In one subject, the increases of Ppl and Pga were weak; thus Pdi increased very little. In the two other subjects, Ppl decreased more during inspiration but Pga also decreased, leading to a decrease of Pdi. This suggests a recruitment of abdominal muscles during expiration and of accessory and intercostal muscles during inspiration. With IRL, in all subjects, Ppl again decreased more, Pga began to decrease until 40% of TI and then increased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of expiratory loading on expiratory duration and pulmonary stretch receptor discharge

Slowly adapting pulmonary stretch receptors have been hypothesized to be the afferents mediating the vagally dependent, volume-related prolongation of expiratory time (TE) during expiratory loading. It has been further suggested that the vagal component of this prolongation of TE is due to the temporal summation of pulmonary stretch receptor (PSR) activity during expiratory loading. This hypothesis was tested in rabbits exposed to resistive and elastic single-breath expiratory loading while PSR's were simultaneously recorded. Both types of loads resulted in a decreased expired volume (VE) and increased expiratory duration (TE). The TE for resistive loads were significantly greater than for elastic loads for equivalent VE. Thus two different VE-TE relationships were found for resistive and elastic loads. When TE was plotted against the area under the expired volume trajectory, a single linear relationship was observed. PSR activity recorded during expiratory loading increased as VE decreased and TE increased. A single linear relationship resulted when the number of PSR spikes during the expiration was plotted against the associated TE for all types of loads. These findings demonstrate that the volume-related prolongation of TE with single-breath expiratory loads is associated with an increase in PSR discharge. These results support the hypothesis that the vagal component of load-dependent prolongation of TE is a function of both the temporal and spatial summation of PSR activity during the expiratory phase.     

Effects of expiratory loading on respiration in humans

We examined the effects of expiratory resistive loads of 10 and 18 cmH2O.l-1.s in healthy subjects on ventilation and occlusion pressure responses to CO2, respiratory muscle electromyogram, pattern of breathing, and thoracoabdominal movements. In addition, we compared ventilation and occlusion pressure responses to CO2 breathing elicited by breathing through an inspiratory resistive load of 10 cmH2O.l-1.s to those produced by an expiratory load of similar magnitude. Both inspiratory and expiratory loads decreased ventilatory responses to CO2 and increased the tidal volume achieved at any given level of ventilation. Depression of ventilatory responses to Co2 was greater with the larger than with the smaller expiratory load, but the decrease was in proportion to the difference in the severity of the loads. Occlusion pressure responses were increased significantly by the inspiratory resistive load but not by the smaller expiratory load. However, occlusion pressure responses to CO2 were significantly larger with the greater expiratory load than control. Increase in occlusion pressure observed could not be explained by changes in functional residual capacity or chemical drive. The larger expiratory load also produced significant increases in electrical activity measured during both inspiration and expiration. These results suggest that sufficiently severe impediments to breathing, even when they are exclusively expiratory, can enhance inspiratory muscle activity in conscious humans.     

Changes in respiratory movements of the human vocal cords during hyperpnea

Five healthy young subjects were studied to assess the changes in vocal cord movements that occur between resting breathing and hyperpnea. Both hypercapnia and exercise induced decreases in the extent of narrowing of the glottic aperture occurring during expiration. In addition, four of the subjects showed a significant positive rank correlation between the extent of narrowing of the glottis and the observed length of the expiratory phase of the respiratory cycle. These results indicate that the braking of expiratory airflow by movements of the vocal cords toward the midline is reduced during hyperpnea at the same time that expiratory time is decreased.     

O2 cost of inspiratory and expiratory resistive breathing in humans

In six normal male subjects we compared the O2 cost of resistive breathing (VO2 resp) between equivalent external inspiratory (IRL) and expiratory loads (ERL) studied separately. Each subject performed four pairs of runs matched for tidal volume, breathing frequency, flow rates, lung volume, pressure-time product, and work rate. Basal O2 uptake, measured before and after pairs of loaded runs, was subtracted from that measured during resistive breathing to obtain VO2 resp. For an equivalent load, the VO2 resp during ERL (184 +/- 17 ml O2/min) was nearly twice that obtained during IRL (97 +/- 9 ml O2/min). This twofold difference in efficiency between inspiratory and expiratory resistive breathing may reflect the relatively lower mechanical advantage of the expiratory muscles in overcoming respiratory loads. Variable recruitment of expiratory muscles may explain the large variation of results obtained in studies of respiratory muscle efficiency in normal subjects.     

Effects of spontaneous swallows on breathing in awake goats.

The effects of spontaneous swallows on breathing before, during, and after solitary swallows were investigated in 13 awake goats. Inspiratory (TI) and expiratory (TE) time and respiratory output were determined from inspiratory airflow [tidal volume (VT)] and peak diaphragmatic activity (Dia(peak)). The onset time for 1,128 swallows was determined from pharyngeal muscle electrical activity. During inspiration, the later the swallowing onset, the greater increase in TI and VT, whereas there was no significant effect on TE and Dia(peak). Swallows in early expiration increased the preceding TI and reduced TE, whereas later in expiration swallows increased TE. After expiratory swallows, TI and VT were reduced whereas minimal changes in Dia(peak) were observed. Phase response analysis revealed a within-breath, phase-dependent effect of swallowing on breathing, resulting in a resetting of the respiratory oscillator. However, the shift in timing in the breaths after a swallow was not parallel, further demonstrating a respiratory phase-dependent effect on breathing. We conclude that, in the awake state, within- and multiple-breath effects on respiratory timing and output are induced and/or required in the coordination of breathing and swallowing.     

Factors influencing glottic dimensions during forced expiration

To examine the relationship between expiratory effort, expiratory flow, and glottic aperture, we compared the effects of actively and passively produced changes in flow in six normal subjects. During flow transients of 1.08 +/- 0.08 l/s produced by voluntary expiratory effort, glottic width (dg) increased by 54 +/- 13% (mean +/- SE). In contrast transient increases in expiratory flow, produced passively by chest compression, were not accompanied by increases in glottic dimensions. Similarly, when subjects expired through a resistance, transient passive increases in mouth pressure of 8.1 +/- 0.8 cmH2O failed to increase glottic width. However, when similar positive-pressure transients were produced actively, dg increased by 97 +/- 36% even though the expiratory efforts were accompanied by relatively small increases in flow (0.20 +/- 0.05 l/s). During tidal breathing glottic widening commenced 160 +/- 60 ms before the onset of inspiratory flow, whereas the widening associated with active flow and pressure transients did not measurably precede the onset of the change in flow or pressure. Our results indicate that transient expulsive efforts are associated with synchronous increases in dg, regardless of whether expiratory flow increases. The findings are most readily explained by a centrally determined synchronous recruitment of intrinsic laryngeal and expiratory muscles that facilitates lung emptying by minimizing airway resistance during forced exhalation.     

Regulation of end-expiratory lung volume during sleep in premature infants

To investigate the regulation of end-expiratory lung volume (EEV) in premature infants, we recorded airflow, tidal volume, diaphragm electromyogram (EMG), and chest wall displacement during sleep. In quiet sleep, EEV during breathing was 10.8 +/- 3.6 (SD) ml greater than the minimum volume reached during unobstructed apneas. In active sleep, no decrease in EEV was observed during 28 of 35 unobstructed apneas. Breaths during quiet sleep had a variable extent of expiratory airflow retardation (braking), and inspiratory interruption occurred at substantial expiratory flow rates. During active sleep, the expiratory flow-volume curve was nearly linear, proceeding nearly to the volume axis at zero flow, and diaphragm EMG activity terminated near the peak of mechanical inspiration. Expiratory duration (TE) and inspiratory duration (TI) were significantly shortened in quiet sleep vs. active sleep although tidal volume was not significantly different. In quiet sleep, diaphragmatic braking activity and shortened TE combined to maintain EEV during breathing substantially above relaxation volume. In active sleep, reduced expiratory braking and prolongation of TE resulted in an EEV that was close to relaxation volume. We conclude that breathing strategy to regulate EEV in premature infants appears to be strongly influenced by sleep state.     

Decrease in functional residual capacity during inspiratory loading and the sensation of dyspnea.

The purposes of the present study were to determine the changes in functional residual capacity (FRC) during inspiratory loading and to examine their mechanisms. We studied seven normal subjects seated in a body plethysmograph. In both graded inspiratory elastic (35, 48, and 68 cmH2O/l) and resistive (21, 86, and 192 cmH2O.l-1.s) loading, FRC invariably decreased from control FRC and phasic expiratory activity increased. The reduction in FRC was greater with greater loads. A single inspiratory effort against an inspiratory occlusion at three different target mouth pressures (-25, -50, and -75 cmH2O) and durations (1, 2, and 5 s) also resulted in a decrease in FRC with an increase in expiratory electromyogram activity in the following expiration. The decrease in FRC was greater with greater target pressure and duration. This decrease in FRC is qualitatively similar to that during inspiratory loaded breathing, and we suspect that the same mechanisms are at work. Because neither vagal nor chemoreceptor reflex can account for these responses, we suspect conscious awareness of breathing or behavioral control to be responsible. In an additional study, the sensation of discomfort of breathing during elastic loading decreased with a decrease in FRC. These results suggest that the reduced FRC may be due to behavioral control of breathing to reduce the sensation of dyspnea during inspiratory loading.     

Control of larynx during loaded breathing in normal subjects

We examined laryngeal resistance (Rla) in six normal subjects in control and four kinds of loaded breathing: hypercapnia, chest strapping, added external resistance, and inhaled methacholine. Rla was measured with a low-frequency sound methed (Sekizawa et al., J. Appl. Physiol. 55: 591-597, 1983). In control and the four kinds of loaded breathing, changes in Rla were tightly coupled with ventilation and Rla decreased during inspiration and increased during expiration. Hypercapnia and chest strapping significantly decreased Rla in both inspiration and expiration in all subjects. Added external resistance decreased inspiratory Rla in all subjects, but decreased expiratory Rla in three subjects, did not change it in two subjects, and increased it in one subject. Inhaled methacholine increased Rla in both inspiration and expiration in all subjects. The present study suggests that although laryngeal movement is tightly coupled with ventilation, laryngeal aperture may be determined by the complex competition of dilating and constricting mechanisms associated with the activity of the respiratory center and neural reflexes from the airway.     

Expiratory muscle fatigue in normal subjects

We examined expiratory muscle fatigue during expiratory resistive loading in 11 normal subjects. Subjects breathed against expiratory resistances at their own breathing frequency and tidal volume until exhaustion or for 60 min. Respiratory muscle strength was assessed from both the maximum static expiratory and inspiratory mouth pressures (PEmax and PImax). At the lowest resistance, PEmax and PImax measured after completion of the expiratory loaded breathing were not different from control values. With higher resistance, both PEmax and PImax were decreased (P less than 0.05), and the decrease lasted for greater than or equal to 60 min. The electromyogram high-to-low frequency power ratio for the rectus abdominis muscle decreased progressively during loading (P less than 0.01), but the integrated EMG activity did not change during recovery. Transdiaphragmatic pressure during loading was increased 3.6-fold compared with control (P less than 0.05). These findings suggest that expiratory resistive loaded breathing induces muscle fatigue in both expiratory and inspiratory muscles. Fatigue of the expiratory muscles can be attributed directly to the high work load and that of the inspiratory muscles may be related to increased work due to shortened inspiratory time.     

Reflex control of expiratory duration in newborn infants

We investigated the effect on expiratory duration (TE) of application of graded resistive and elastic loads and total airway occlusions to single expirations in 9 full-term healthy infants studied on the 2nd or 3rd day of life. The infants breathed through a face mask and pneumotachograph, and flow, volume, airway pressure, and diaphragm electromyogram (EMG) were recorded. Loads were applied to the expiratory outlet of a two-way respiratory valve using a manifold system. Application of all loads resulted in expired volumes (VE) decreased from control (P less than 0.05), and changes were progressive with increasing loads. As VE became smaller, end-expiratory volume (EEV) became greater. TE, measured either from the pattern of airflow or airway pressure, or from diaphragm EMG activity, progressively increased with increasing loads and was greatest with total occlusions (P less than 0.05, compared with control). Resistive loading resulted in a greater accumulated VE history than elastic loading to the same EEV. For equivalent changes in EEV, TE was more prolonged with resistive than with elastic loading. Expiratory loading did not change the inspiratory duration determined from the diaphragm EMG activity of the breath immediately following each loaded expiration. These findings in infants are consistent with an integrative neural mechanism that modulates TE in response to the accumulated VE history, including both EEV and rate of lung deflation.     

Posterior cricoarytenoid activity and glottic size during hyperpnea in humans.

We measured the electromyographic activity of the posterior cricoarytenoid (PCA) muscle simultaneously with glottic width (dg) in five normal human subjects during hyperpnea induced by hypoxia (7% CO2 in N2) or hypercapnia (9% CO2 in 50% O2). The glottic aperture was measured during inspiration at the time corresponding to peak inspiratory PCA activity and during expiration at the time corresponding to the minimum tonic activity. During hyperpnea, peak and tonic PCA activity increased simultaneously with widening of the vocal cords in both phases of the respiratory cycle. The PCA activity during both inspiration and expiration showed a single curvilinear relationship with dg of the form dg = A - Be-k.PCA (where A, B, and k are constants) in three of the five subjects. At 50% of maximum PCA activity, dg already reached 95% of its maximum value, which was less than that recorded during a voluntary forced expiratory maneuver. The single curvilinear relationship between PCA activity and dg could be due to the length-tension relationship of the PCA muscle and/or changes in its mechanical coupling, as well as simultaneous agonist and antagonist laryngeal muscle activity during progressive chemical stimulation. Also, further widening of the glottis during forced expiration suggests recruitment of additional muscles, e.g., the arytenoideus.     

Phrenic afferents and ventilatory control at increased end-expiratory lung volumes in cats

The role of phrenic afferents in controlling inspiratory duration (TI) at elevated end-expiratory lung volume (EEV) has been studied in pentobarbital-anesthetized, spontaneously breathing cats with intact vagi. Responses to increases in EEV, induced by imposition of an expiratory threshold load (ETL) of 10 cmH2O, were monitored before and after section of cervical dorsal roots C3-C7. The immediate (first-breath) effect of application of ETL was a prolongation of both TI and expiratory duration (TE). After 10 min of breathing against the ETL, average TI returned to control values but TE remained prolonged. Abolishing feedback from the diaphragm did not affect these responses. When steady-state responses to ETL were compared with those elicited by inhalation of 5-6% CO2 in O2, changes in EEV had, on average, no independent effect on respiratory drive (rate of rise of integrated phrenic activity), although phrenic activity increased greatly in some cats despite little or no change in arterial partial pressure of CO2. These data indicate that diaphragmatic receptors do not contribute to either the immediate (first-breath) or steady-state responses of phrenic motoneurons to increases in EEV in intact cats.     

Expiratory flow pattern and respiratory mechanics

During resting breathing, expiration is characterized by the narrowing of the vocal folds which, by increasing the expiratory resistance, raises mean lung volume and airway pressure. This is even more pronounced in the neonatal period, during which expirations with short complete airway closure are commonly occurring. We asked to which extent differences in expiratory flow pattern may modify the inspiratory impedance of the respiratory system. To this aim, newborn puppies, piglets, and adult rats were anesthetized, paralyzed, and ventilated with different expiratory patterns, (a) no expiratory load, (b) expiratory resistive load, and (c) end-inspiratory pause. The stroke volume of the ventilator and inspiratory and expiratory times were maintained constant, and the loads were adjusted in such a way that inflation always started from the resting volume of the respiratory system. After 1 min of each ventilatory pattern, mean inspiratory impedance and compliance of lung and respiratory system were measured. The values were unchanged or minimally altered by changing the type of ventilation. We conclude that the expiratory laryngeal loading is not primarily aimed to decrease the work of breathing. It is conceivable that the expiratory pattern is oriented to increase and control mean airway pressure in the regulation of pulmonary fluid reabsorption, distribution of ventilation, and diffusion of gases.     

Do voluntary changes in inspiratory-expiratory ratio prevent exercise-induced asthma?

It is often admitted that heat exchange in the airways is a major cause of exercise-induced asthma. Because a decrease in the inspiratory time/expiratory time ratio (TI/TE) decreases these exchanges, we postulated that it might decrease bronchoconstriction as well. Twenty-four asthmatic children, divided into three groups, underwent two exercise provocation tests, 24 hours apart (outdoor running for 6 min). The first test was identical for all the subjects. In the second test, the first group did not receive any instruction concerning breathing pattern. The second group was instructed to adopt equal inspiratory and expiratory times (TI/TE = 1). The third group had to adopt an expiratory time three times longer than inspiratory time (TI/TE = 1/3). The three groups displayed similar pulmonary function tests (FEV1 and FVC), cardiac frequency, and running performances. However, FEV1 significantly improved in the second session. This suggested that familiarization with the task and related psychological factors may influence asthma more than voluntary changes in TI/TE.This work was partly supported by the Institut National de la Santé et de la Recherche Médicale (CJF 89-09) and by the Institut Electricité Santé (grant No. 93 022 CS).     

Immediate response to resistive loading in anesthetized humans

In eight spontaneously breathing anesthetized subjects (halothane: approximately 1 minimal alveolar concn; 70% N2O-30% O2), we determined 1) the inspiratory driving pressure by analysis of the pressure developed at the airway opening (Poao) during inspiratory efforts against airways occluded at end expiration; 2) the active inspiratory impedance; and 3) the immediate (first loaded breath) response to added inspiratory resistive loads (delta R). Based on these data we made model predictions of the immediate tidal volume response to delta R. Such predictions closely fitted the experimental results. The present investigation indicates that 1) in halothane-anesthetized humans the shape of the Poao wave differs from that in anesthetized animals, 2) the immediate response to delta R is not associated with appreciable changes in intensity, shape, and timing of inspiratory neural drive but depends mainly on intrinsic (nonneural) mechanisms; 3) the flow-dependent resistance of endotracheal tubes must be taken into account in studies dealing with increased neuromuscular drive in intubated subjects; and 4) in anesthetized humans Poao reflects the driving pressure available to produce the breathing movements.     

Postnatal maturation of ventilation and breathing pattern in kittens: influence of sleep

Ventilation and breathing pattern were studied in kittens at 1, 2, 3, 4, and 8 wk of life during quiet wakefulness (W), quiet sleep (QS), and active sleep (AS) with the barometric method. Tidal volume (VT), respiratory frequency (f), ventilation (VE), inspiratory time (TI), expiratory time (TE), mean inspiratory flow (VT/TI), and respiratory "duty cycle" (TI/TT) were measured. VT, VE, TI, TE, and VT/TI increased; f decreased and TI/TT remained constant during postnatal development in wakefulness and in both sleep states. No significant difference was observed between AS and QS for all the ventilatory parameters except TI/TT, which was greater in QS than in AS at 2 wk. VE was larger in W than in both AS and QS at all ages. This was mainly due to a greater f, TI/TT remaining constant. VT/TI, which represents an index of the central inspiratory activity, was larger in W than in sleep, VT not being significantly different whatever the stage of consciousness. The results of this study show that in the kitten 1) unlike in the adult cat, ventilation and breathing pattern are similar in QS and in AS; 2) in sleep, the central inspiratory drive appears to be independent of the type of sleep; and 3) in wakefulness, the increase of the central inspiratory activity could be related to important excitatory inputs.