Effects of negative upper airway pressure on pattern of breathing in sleeping infants

Negative upper airway (UAW) pressure inhibits diaphragm inspiratory activity in animals, but there is no direct evidence of this reflex in humans. Also, little is known regarding reflex latency or effects of varying time of stimulation during the breathing cycle. We studied effects of UAW negative pressure on inspiratory airflow and respiratory timing in seven tracheostomized infants during quiet sleep with a face mask and syringe used to produce UAW suction without changing lower airway pressure. Suction trials lasted 2-3 s. During UAW suction, mean and peak inspiratory airflow as well as tidal volume was markedly reduced (16-68%) regardless of whether stimulation occurred in inspiration or expiration. Reflex latency was 42 +/- 3 ms. When suction was applied during inspiration or late expiration, the inspiration and the following expiration were shortened. In contrast, suction applied during midexpiration prolonged expiration and tended to prolong inspiration. The changes in flow, tidal volume, and timing indicate a marked inhibitory effect of UAW suction on thoracic inspiratory muscles. Such a reflex mechanism may function in preventing pharyngeal collapse by inspiratory suction pressure.     

Respiratory changes in parasternal intercostal length

In an attempt to understand the role of the parasternal intercostals in respiration, we measured the changes in length of these muscles during a variety of static and dynamic respiratory maneuvers. Studies were performed on 39 intercostal spaces from 10 anesthetized dogs, and changes in parasternal intercostal length were assessed with pairs of piezoelectric crystals (sonomicrometry). During static maneuvers (passive inflation-deflation, isovolume maneuvers, changes in body position), the parasternal intercostals shortened whenever the rib cage inflated, and they lengthened whenever the rib cage contracted. The changes in parasternal intercostal length, however, were much smaller than the changes in diaphragmatic length, averaging 9.2% of the resting length during inflation from residual volume to total lung capacity and 1.3% during tilting from supine to upright. During quiet breathing the parasternal intercostals always shortened during inspiration and lengthened during expiration. In the intact animals the inspiratory parasternal shortening was close to that seen for the same increase in lung volume during passive inflation and averaged 3.5%. After bilateral phrenicotomy, however, the parasternal intercostal shortening during inspiration markedly increased, whereas tidal volume diminished. These results indicate that 1) the parasternal intercostals in the dog are real agonists (as opposed to fixators) and actively contribute to expand the rib cage and the lung during quiet inspiration, 2) the relationship between lung volume and parasternal length is not unique but depends on the relative contribution of the various inspiratory muscles to tidal volume, and 3) the physiological range of operating length of the parasternal intercostals is considerably smaller than that of the diaphragm.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of hypercapnia on inspiratory and expiratory muscle activity during expiration

Persistence of inspiratory muscle activity during the early phase of expiratory airflow slows the rate of lung deflation, whereas heightened expiratory muscle activity produces the opposite effect. To examine the influence of increased chemoreceptor drive and the role of vagal afferent activity on these processes, the effects of progressive hypercapnia were evaluated in 12 anesthetized tracheotomized dogs before and after vagotomy. Postinspiratory activity of inspiratory muscles (PIIA) and the activity of expiratory muscles were studied. During resting breathing, the duration of PIIA correlated with the duration of inspiration but not with expiration. Parasternal intercostal PIIA was directly related to that of the diaphragm. Based on their PIIA, dogs could be divided into two groups: one with prolonged PIIA (mean 0.57 s) and the other with brief PIIA (mean 0.16 s). Hypercapnia caused progressive shortening of the PIIA in the dogs with prolonged PIIA during resting breathing. The electrical activity of the external oblique and internal intercostal muscles increased gradually during CO2 rebreathing in all dogs both pre- and postvagotomy. After vagotomy, abdominal activity continued to increase with hypercapnia but was less at all levels of PCO2. The internal intercostal response to hypercapnia was not affected by vagotomy. The combination of shorter PIIA and augmented expiratory activity with hypercapnia might, in addition to changes in lung recoil pressure and airway resistance, hasten exhalation.     

Relationship between diaphragm length and abdominal dimensions

We examined the relationship between changes in abdominal cross-sectional area, measured by respiratory inductive plethysmography, and changes in length in the costal and crural parts of the diaphragm, measured by sonomicrometry, in nine supine, anesthetized dogs. During passive inflation, both parts of the diaphragm shortened and abdominal cross-sectional area increased. During passive deflation, both parts of the diaphragm lengthened and abdominal cross-sectional area decreased. We subsequently used the relationship between costal and crural diaphragmatic length, respectively, and abdominal cross-sectional area during passive inflation-deflation to predict the length changes in the costal and crural diaphragm during quiet breathing before and after bilateral phrenicotomy. In the intact animal the inspiratory shortening in the crural diaphragm was almost invariably greater than predicted from the relationship during passive inflation. During inspiration after phrenicotomy the crural diaphragm invariably lengthened, whereas the costal diaphragm often shortened. In general there was a good correlation between the measured and predicted length change for the crural diaphragm (r = 0.72 before and 0.79 after phrenicotomy) and a poor one for the costal diaphragm (r = 0.05 before and 0.19 after phrenicotomy).     

Transverse abdominis length changes during eupnea, hypercapnia, and airway occlusion

The abdominal muscles accelerate airflow during expiration and may also influence the end-expiratory volume and configuration of the thorax. Although much is known about their electrical activity, the degree to which they change length during the respiratory cycle has not been previously assessed. In the present study we measured respiratory changes in transverse abdominis length using sonomicrometry in 14 pentobarbital sodium-anesthetized supine dogs and compared length changes to simultaneously recorded tidal volume and transverse abdominis electromyograms (EMG). To determine muscle resting length at passive functional residual capacity (LFRC), the animals were hyperventilated to apnea. The transverse abdominis was electrically active in all animals during resting O2 breathing (eupnea). During inspiration the transverse abdominis lengthened above resting length in all 14 dogs by a mean of 3.7 +/- 1.1% LFRC; during expiration the transverse abdominis shortened below resting length in 13 of 14 dogs by a mean of 4.2 +/- 0.9% LFRC. Increasing hyperoxic hypercapnia (produced in 9 animals) progressively heightened transverse abdominis EMG and progressively increased the extent of muscle shortening below resting length (to 12.6 +/- 3.2% LFRC at a PCO2 of 90 Torr). During single-breath airway occlusion substantial inspiratory lengthening of the transverse abdominis occurred, both during O2 breathing and during CO2 rebreathing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ratio of active to passive muscle shortening in the canine diaphragm.

Active and passive shortening of muscle bundles in the canine diaphragm were measured with the objective of testing a consequence of the minimal-work hypothesis: namely, that the ratio of active to passive shortening is the same for all active muscles. Lengths of six muscle bundles in the costal diaphragm and two muscle bundles in the crural diaphragm of each of four bred-for-research beagle dogs were measured by the radiopaque marker technique during the following maneuvers: a passive deflation maneuver from total lung capacity to functional residual capacity, quiet breathing, and forceful inspiratory efforts against an occluded airway at different lung volumes. Shortening per liter increase in lung volume was, on average, 70% greater during quiet breathing than during passive inflation in the prone posture and 40% greater in the supine posture. For the prone posture, the ratio of active to passive shortening was larger in the ventral and midcostal diaphragm than at the dorsal end of the costal diaphragm. For both postures, active shortening during quiet breathing was poorly correlated with passive shortening. However, shortening during forceful inspiratory efforts was highly correlated with passive shortening. The average ratios of active to passive shortening were 1.23 +/- 0.02 and 1.32 +/- 0.03 for the prone and supine postures, respectively. These data, taken together with the data reported in the companion paper (T. A. Wilson, M. Angelillo, A. Legrand, and A. De Troyer, J. Appl. Physiol. 87: 554-560, 1999), support the hypothesis that, during forceful inspiratory efforts, the inspiratory muscles drive the chest wall along the minimal-work trajectory.     

Triangularis sterni muscle use in supine humans

The electrical activity of the triangularis sterni (transversus thoracis) muscle was studied in supine humans during resting breathing and a variety of respiratory and nonrespiratory maneuvers known to bring the abdominal muscles into action. Twelve normal subjects, of whom seven were uninformed and untrained, were investigated. The electromyogram of the triangularis sterni was recorded using a concentric needle electrode, and it was compared with the electromyograms of the abdominal (external oblique and rectus abdominis) muscles. The triangularis sterni was usually silent during resting breathing. In contrast, the muscle was invariably activated during expiration from functional residual capacity, expulsive maneuvers, "belly-in" isovolume maneuvers, static head flexion and trunk rotation, and spontaneous events such as speech, coughing, and laughter. When three trained subjects expired voluntarily with considerable recruitment of the triangularis sterni and no abdominal muscle activity, rib cage volume decreased and abdominal volume increased. These results indicate that unlike in the dog, spontaneous quiet expiration in supine humans is essentially a passive process; the human triangularis sterni, however, is a primary muscle of expiration; and its neural activation is largely coupled with that of the abdominals. The triangularis sterni probably contributes to the deflation of the rib cage during active expiration.     

Parasternal and external intercostal responses to various respiratory maneuvers.

Recent studies suggest that the external intercostal (EI) muscles of the upper rib cage, like the parasternals (PA), play an important ventilatory role, even during eupneic breathing. The purpose of the present study was to further assess the ventilatory role of the EI muscles by determining their response to various static and dynamic respiratory maneuvers and comparing them with the better-studied PA muscles. Applied interventions included 1) passive inflation and deflation, 2) abdominal compression, 3) progressive hypercapnia, and 4) response to bilateral cervical phrenicotomy. Studies were performed in 11 mongrel dogs. Electromyographic (EMG) activities were monitored via bipolar stainless steel electrodes. Muscle length (percentage of resting length) was monitored with piezoelectric crystals. With passive rib cage inflation produced either with a volume syringe or abdominal compression, each muscle shortened; with passive deflation, each muscle lengthened. During eupneic breathing, each muscle was electrically active and shortened to a similar degree. In response to progressive hypercapnia, peak EMG of each intercostal muscle increased linearly and to a similar extent. Inspiratory shortening also increased progressively with increasing PCO2, but in a curvilinear fashion with no significant differences in response among intercostal muscles. In response to phrenicotomy, the EMG and degree of inspiratory shortening of each intercostal muscle increased significantly. Again, the response among intercostal muscles was not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diaphragm length adjustments with body position changes in the awake dog

Sonomicrometry was used to measure end-expiratory length and tidal shortening of the costal and crural diaphragm in awake chronically instrumented dogs in the right lateral decubitus, standing, and sitting postures. End-expiratory length did not change significantly in standing but fell by 11.5% for the costal and by 14.4% for the crural segment in sitting, when compared with decubitus position. Tidal shortening of both segments did not change significantly in the three postures. From decubitus to sitting, diaphragmatic electromyogram (EMG) activity increased only in some dogs, not significantly for the group. The inspiratory swing of abdominal pressure was always positive in decubitus and negative in standing and sitting. In the latter two postures, abdominal pressure increased gradually during expiration and fell in inspiration, suggesting a phasic expiratory contraction of abdominal muscles. We conclude that diaphragmatic tidal shortening is maintained in the different postures assumed by the awake dog during resting breathing. It seems that the main compensatory mechanism for changes in diaphragmatic operational length is a phasic expiratory contraction of the abdominal muscles rather than an increase in diaphragmatic EMG activity.     

Postinspiratory activity of costal and crural diaphragm.

Because the first stage of expiration or "postinspiration" is an active neurorespiratory event, we expect some persistence of diaphragm electromyogram (EMG) after the cessation of inspiratory airflow, as postinspiratory inspiratory activity (PIIA). The costal and crural segments of the mammalian diaphragm have different mechanical and proprioceptive characteristics, so postinspiratory activity of these two portions may be different. In six canines, we implanted chronically EMG electrodes and sonomicrometer transducers and then sampled EMG activity and length of costal and crural diaphragm segments at 4 kHz, 10.2 days after implantation during wakeful, resting breathing. Costal and crural EMG were reviewed on-screen, and duration of PIIA was calculated for each breath. Crural PIIA was present in nearly every breath, with mean duration 16% of expiratory time, compared with costal PIIA with duration -2. 6% of expiratory time (P < 0.002). A linear regression model of crural centroid frequency vs. length, which was computed during the active shortening of inspiration, did not accurately predict crural EMG centroid frequency values at equivalent length during the controlled relaxation of postinspiration. This difference in activation of crural diaphragm in inspiration and postinspiration is consistent with a different pattern of motor unit recruitment during PIIA.     

Effect of mechanical loading on displacements of chest wall during breathing in humans

Using a respiratory inductive plethysmograph (Respitrace) we studied thoracoabdominal movements in eight normal subjects during inspiratory resistive (Res) and elastic (El) loading. The magnitude of loads was chosen so as to produce a fall in inspiratory mouth pressure of 20 cmH2O. The contribution of rib cage (RC) to tidal volume (VT) increased significantly from 68% during quiet breathing (QB) to 74% during El and 78% during Res. VT and breathing frequency did not change significantly. During loading a phase lag was present on inspiration so that the abdomen led the rib cage. However, outward movement of the abdomen ceased in the latter part of inspiration, and the RC became the sole contributor to VT. These observations suggest greater recruitment of the inspiratory musculature of the RC than the diaphragm during loading, although changes in the mechanical properties of the chest wall may also have contributed. Indeed, an increase in abdominal end-expiratory and end-inspiratory pressures was observed in five out of six subjects, indicating abdominal muscle recruitment which may account for part of the reduction in abdominal excursion. Both Res and El increased the rate of emptying of the respiratory system during the ensuing unloaded expiration as a result of a reduction in rib cage expiratory-braking mechanisms. The time course of abdominal displacements during expiration was unaffected by loading.     

Inspiratory and expiratory muscle function during continuous positive airway pressure in dogs

Continuous positive airway pressure (CPAP) is known to produce activation of the expiratory muscles. Several factors may determine whether this activation can assist inspiration. In this study we asked how and to what extent expiratory muscle contraction can assist inspiration during CPAP. Respiratory muscle response to CPAP was studied in eight supine anesthetized dogs. Lung volume and diaphragmatic initial length were defended by recruitment of the expiratory muscles. At the maximum CPAP of 18 cmH2O, diaphragmatic initial lengths were longer than predicted by the passive relationship by 52 and 46% in the costal and crural diaphragmatic segments, respectively. During tidal breathing after cessation of expiratory muscle activity, a component of passive inspiration occurred before the onset of inspiratory diaphragmatic electromyogram (EMG). At CPAP of 18 cmH2O, passive inspiration represented 24% of the tidal volume (VT) and tidal breathing was within the relaxation characteristic. Diaphragmatic EMG decreased at CPAP of 18 cmH2O; however, VT and tidal shortening were unchanged. We identified passive and active components of inspiration. Passive inspiration was limited by the time between the cessation of expiratory activity and the onset of inspiratory activity. We conclude that increased expiratory activity during CPAP defends diaphragmatic initial length, assists inspiration, and preserves VT. Even though breathing appeared to be an expiratory act, there remained a significant component of active inspiratory diaphragmatic shortening, and the major portion of VT was produced during active inspiration.     

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)     

Electrical and mechanical activity of respiratory muscles during hypercapnia

In nine anesthetized supine spontaneously breathing dogs, we compared moving average electromyograms (EMGs) of the costal diaphragm and the third parasternal intercostal muscles with their respective respiratory changes in length (measured by sonomicrometry). During resting O2 breathing the pattern of diaphragm and intercostal muscle inspiratory shortening paralleled the gradually incrementing pattern of their moving average EMGs. Progressive hypercapnia caused progressive increases in the amount and velocity of respiratory muscle inspiratory shortening. For both muscles there were linear relationships during the course of CO2 rebreathing between their peak moving average EMGs and total inspiratory shortening and between tidal volume and total inspiratory shortening. During single-breath airway occlusions, the electrical activity of both the diaphragm and intercostal muscles increased, but there were decreases in their tidal shortening. The extent of muscle shortening during occluded breaths was increased by hypercapnia, so that both muscles shortened more during occluded breaths under hypercapnic conditions (PCO2 up to 90 Torr) than during unoccluded breaths under normocapnic conditions. These results suggest that for the costal diaphragm and parasternal intercostal muscles there is a close relationship between their electrical and mechanical behavior during CO2 rebreathing, this relationship is substantially altered by occluding the airway for a single breath, and thoracic respiratory muscles do not contract quasi-isometrically during occluded breaths.     

Chest wall motion during epidural anesthesia in dogs

To determine the relative contribution of rib cage and abdominal muscles to expiratory muscle activity during quiet breathing, we used lumbar epidural anesthesia in six pentobarbital sodium-anesthetized dogs lying supine to paralyze the abdominal muscles while leaving rib cage muscle motor function substantially intact. A high-speed X-ray scanner (Dynamic Spatial Reconstructor) provided three-dimensional images of the thorax. The contribution of expiratory muscle activity to tidal breathing was assessed by a comparison of chest wall configuration during relaxed apnea with that at end expiration. We found that expiratory muscle activity was responsible for approximately half of the changes in thoracic volume during inspiration. Paralysis of the abdominal muscles had little effect on the pattern of breathing, including the contribution of expiratory muscle activity to tidal breathing, in most dogs. We conclude that, although there is consistent phasic expiratory electrical activity in both the rib cage and the abdominal muscles of pentobarbital-anesthetized dogs lying supine, the muscles of the rib cage are mechanically the most important expiratory muscles during quiet breathing.     

Differential activation among five human inspiratory motoneuron pools during tidal breathing.

Neural drive to inspiratory pump muscles is increased under many pathological conditions. This study determined for the first time how neural drive is distributed to five different human inspiratory pump muscles during tidal breathing. The discharge of single motor units (n = 280) from five healthy subjects in the diaphragm, scalene, second parasternal intercostal, third dorsal external intercostal, and fifth dorsal external intercostal was recorded with needle electrodes. All units increased their discharge during inspiration, but 41 (15%) discharged tonically throughout expiration. Motor unit populations from each muscle differed in the timing of their activation and in the discharge rates of their motor units. Relative to the onset of inspiratory flow, the earliest recruited muscles were the diaphragm and third dorsal external intercostal (mean onset for the population after 26 and 29% of inspiratory time). The fifth dorsal external intercostal muscle was recruited later (43% of inspiratory time; P < 0.05). Compared with the other inspiratory muscles, units in the diaphragm and third dorsal external intercostal had the highest onset (7.7 and 7.1 Hz, respectively) and peak firing frequencies (12.6 and 11.9 Hz, respectively; both P < 0.05). There was a unimodal distribution of recruitment times of motor units in all muscles. Neural drive to human inspiratory pump muscles differs in timing, strength, and distribution, presumably to achieve efficient ventilation.     

Interrupter technique for measurement of respiratory mechanics in anesthetized cats

In six spontaneously breathing anesthetized cats (pentobarbital sodium, 35 mg/kg ip), airflow, changes in lung volume, and tracheal and esophageal pressures were measured. Airflow was interrupted by brief airway occlusions during relaxed expirations (elicited via the Breuer-Hering inflation reflex) and throughout spontaneous breaths. A plateau in tracheal pressure occurred throughout relaxed expirations and the latter part of spontaneous expirations indicating respiratory muscle relaxation. Measurement of tracheal pressure, immediately preceding airflow, and corresponding volume enabled determination of respiratory system elastance and flow resistance. These were partitioned into lung and chest wall components using esophageal pressure. Respiratory system elastance was constant over the tidal volume range, divided approximately equally between the lung and chest wall. While the passive pressure-flow relationship for the respiratory system was linear, those for the lung and chest wall were curvilinear. Volume dependence of chest wall flow resistance was demonstrated. During inspiratory interruptions, tracheal pressure increased progressively; initial tracheal pressure was estimated by backward extrapolation. Inspiratory flow resistance of the lung and total respiratory system were constant. Force-velocity properties of the contracting inspiratory muscles contributed little to overall active resistance.     

Mechanical aspects of chest wall distortion

During passive inflation of the respiratory system, the rib cage (RC) expands because the pressure applied to it [approximately equal to abdominal pressure (Pab)] increases. Similar Pab-tidal volume (VT) relationships between passive and spontaneous inspirations would occur only if 1) Pab acts on RC equally in the two situations (no distortion) or 2) the extradiaphragmatic inspiratory muscles expand RC, compensating for distortion. In anesthetized adult rats and in sleeping human infants the passive relationships between VT and Pab or abdomen motion (AB) were constructed by occluding the airways during expiration. For a given Pab (or AB) in active breathing VT averaged 55% (rats) and 49% (infants) of the passive volume change. With phrenic stimulation in rats VT was only slightly less than during spontaneous breathing, indicating that, in the latter case, the respiratory system was essentially driven only by the diaphragm. In both species occasional breaths with large RC expansion occurred, and VT was then equal to or larger than the passive volume at iso-Pab. We conclude that 1) RC distortion decreases VT to approximately half of the passive value and 2) being on the relaxation curve reflects "compensated" distortion and not absence of it.     

Total work rate of breathing optimization in CO-2 inhalation and exercise.

The hypothesis that respiratory frequency and the relative durations of inspiration and expiration are regulated according to a total cycle work rate minimization criterion was explored. Effects of negative work performed by the respiratory muscles and dead space variation as a function of tidal volume were included in a formulation which yielded a theoretically predictable optimal frequency and relative duration of inspiration and expiration at all levels of ventilation. Predicted cycle characteristics based on measured mechanical parameters were compared with data taken during CO-2 inhalation (3 and 5%) and moderate exercise (MRR = 3 and 6) in three normal human subjects. No major difference in breathing pattern was observed between CO-2 inhalation and exercise. Results suggest that conditions for minimization of total cycle work rate are achieved asympototically as the level of ventilation rises above the resting level. At rest and at low levels of hyperpnea complete work rate optimization is not achieved.     

Changes in intra-abdominal pressure during postural and respiratory activation of the human diaphragm.

In humans, when the stability of the trunk is challenged in a controlled manner by repetitive movement of a limb, activity of the diaphragm becomes tonic but is also modulated at the frequency of limb movement. In addition, the tonic activity is modulated by respiration. This study investigated the mechanical output of these components of diaphragm activity. Recordings were made of costal diaphragm, abdominal, and erector spinae muscle electromyographic activity; intra-abdominal, intrathoracic, and transdiaphragmatic pressures; and motion of the rib cage, abdomen, and arm. During limb movement the diaphragm and transversus abdominis were tonically active with added phasic modulation at the frequencies of both respiration and limb movement. Activity of the other trunk muscles was not modulated by respiration. Intra-abdominal pressure was increased during the period of limb movement in proportion to the reactive forces from the movement. These results show that coactivation of the diaphragm and abdominal muscles causes a sustained increase in intra-abdominal pressure, whereas inspiration and expiration are controlled by opposing activity of the diaphragm and abdominal muscles to vary the shape of the pressurized abdominal cavity.