Postinspiratory Inspiratory Activity Research Articles

Sex differences in the evolution of net respiratory muscle pressures during incremental exercise

The respiratory muscle pressure (Pmus) waveform lends insight into the patterns of net inspiratory v expiratory muscle recruitment under a wide variety of conditions, including mechanical ventilation, spontaneous breathing, and during exercise. On this last point, inspection of the Pmus waveform during incremental and constant work rate cycling reveals that inspiratory and expiratory muscle recruitment systematically increase with rising minute ventilations, and that the duration of post‐inspiratory inspiratory activity (PIIA) gradually disappears from low to high levels of respiratory motor output. In recent years, it has become increasingly evident that the work of breathing is systematically higher for women compared with men at a given minute ventilation during exercise. Yet, no study has examined the potential sex differences in the evolution of Pmus (and its components; e.g., PIIA) during exercise. Thus, a comprehensive assessment of the Pmus waveform during exercise between sexes is warranted.PurposeTo compare the evolution of inspiratory and expiratory Pmus between men and women during incremental cycling.MethodsThirteen men (21 ± yrs; 181 ± 5 cm; 82 ± 11 kg) and 10 women (21 ± 1 yrs; 165 ± 6 cm; 62 ± 6 kg) visited the laboratory on two separate occasions. The first occasion was used to obtain informed consent and to screen participants for normal pulmonary function (>85% age‐predicted). On the second visit, participants were instrumented with an esophageal balloon catheter to estimate variations in pleural pressure (Ppl). Quasi‐static relaxation curves were obtained to measure chest wall recoil pressure (Pcw). Participants then completed an incremental cycling protocol until volitional exhaustion. Pmus was calculated at given minute ventilations during the exercise protocol as follows: Pmus = Pcw – Ppl.ResultsThe peak inspiratory Pmus were significantly greater in females compared with men at a given minute ventilation during incremental cycling (P < 0.05), yet peak expiratory Pmus was similar between sexes. The average rates of change (slope) in Pmus during inspiration & expiration were significantly faster in females than males at a given minute ventilation (P < 0.05). Finally, the duration of PIIA (expressed as a fraction of expiratory time) gradually decreased with increasing minute ventilation during exercise (P < 0.05). This reduction in PIIA was however similar between men and women.ConclusionThe primary finding of this study was that the pattern of respiratory muscle recruitment was different between sexes during incremental cycling, insofar as women displayed systematically larger inspiratory Pmus, and faster rates of net inspiratory & expiratory pressure‐development compared with men at matched ventilations. However, no differences in PIIA between sexes were observed.Support or Funding InformationThis research was funded by preliminary data funds provided by Northern Arizona University (JWD). TJC was supported by the Irene Diamond Fund/American Federation for Aging Research Postdoctoral Transition Award during the time of this study.

Effect of laparotomy on respiratory muscle activation pattern.

Muscular tone of the abdominal wall is important in maintaining transdiaphragmatic pressures and its loss can lead to decreased lung volumes. Patients who are status postlaparotomy are at risk of developing atelectasis. The compensatory role of respiratory muscle activity in postlaparotomy is not well studied. Normally, inspiratory muscles are active during inspiration and passive during expiration to allow for lung recoil. However, electrical activities of the inspiratory muscles continue during early expiratory phase to prevent rapid loss of lung volume. This activity is known as post-inspiratory inspiratory activity (PIIA). In this study, we hypothesized that laparotomy will elicit an increase in PIIA, which is enhanced by respiratory chemical loading. Experiments were conducted in cats under three different conditions: intact abdomen (n=3), open abdomen (n=10), and post abdominal closure (n=10) during eupnea and hypercapnia (10% CO2). Electromyography (EMG) activities of the diaphragm and parasternal muscles were recorded and peak EMG amplitude, PIIA time, and area under the curve were measured. Intraesophageal pressure was also obtained. PIIA was significantly higher under open abdominal conditions in comparison to intact abdomen during eupnea. Our data indicates that PIIA is increased during open abdomen and may be an important compensatory mechanism for altered respiratory mechanics induced by laparotomy. Also, PIIA remained elevated after abdominal closure. However, under hypercapnia, PIIA was significantly higher during intact abdomen in comparison to open abdomen, which is thought to be due to respiratory muscle compensation under chemical loading.

Ventilatory response of the cat to hypoxia in sleep and wakefulness.

This study characterized ventilation, the airflow waveform, and diaphragmatic activity in response to hypoxia in the intact adult cat during sleep and wakefulness. Exposure to hypoxia for up to 3 h caused sustained hyperventilation during both wakefulness and sleep. Hyperventilation resulted from significant increases in minute ventilation due to increases in both tidal volume and frequency. Diaphragmatic activity changed significantly from augmenting activity with little postinspiratory-inspiratory activity (PIIA) in normoxia to augmenting activity with increased PIIA in hypoxia. The increase in PIIA was least in rapid eye movement sleep. These changes in diaphragmatic activity were associated with changes in airflow waveforms in inspiration and expiration. We conclude that the ventilatory response to hypoxia involves a change in the output of the central pattern generator and that the change is dependent in part on the state of consciousness.

Biphasic Ventilatory Response to Hypoxia in Unanesthetized Rats

To determine the role of postinspiratory inspiratory activity of the diaphragm in the biphasic ventilatory response to hypoxia in unanesthetized rats, we examined diaphragmatic activity at its peak (DI), at the end of expiration (DE), and ventilation in adult unanesthetized rats during poikilocapnic hypoxia (10 % O2) sustained for 20 min. Hypoxia induced an initial increase in ventilation followed by a consistent decline. Tidal volume (VT), frequency of breathing (fR), DI and DE at first increased, then VT and DE decreased, while fR and DI remained enhanced. Phasic activation of the diaphragm (DI - DE) increased significantly at 10, 15 and 20 min of hypoxia. These results indicate that 1) the ventilatory response of unanesthetized rats to sustained hypoxia has a typical biphasic character and 2) the increased end-expiratory activity of the diaphragm limits its phasic inspiratory activation, but this increase cannot explain the secondary decline in tidal volume and ventilation.

Evolution of inspiratory and expiratory muscle pressures during endurance exercise.

We investigated the relationship between minute ventilation (VE) and net respiratory muscle pressure (Pmus) throughout the breathing cycle [Total Pmus = mean Pmus, I (inspiratory) + mean Pmus, E (expiratory)] in six normal subjects performing constant-work heavy exercise (CWHE, at approximately 80% maximum) to exhaustion on a cycle ergometer. Pmus was calculated as the sum of chest wall pressure (elastic + resistive) and pleural pressure, and all mean Pmus variables were averaged over the total breath duration. Pmus, I was also expressed as a fraction of volume-matched, flow-corrected dynamic capacity of the inspiratory muscles (P(cap, I)). VE increased significantly from 3 min to the end of CWHE and was the result of a significantly linear increase in Total Pmus (Delta = 43 +/- 9% from 3 min to end exercise, P < 0.005) in all subjects (r = 0. 81-0.99). Although mean Pmus, I during inspiratory flow increased significantly (Delta = 35 +/- 10%), postinspiratory Pmus, I fell (Delta = -54 +/- 10%) and postexpiratory expiratory activity was negligible or absent throughout CWHE. There was a greater increase in mean Pmus, E (Delta = 168 +/- 48%), which served to increase VE throughout CWHE. In five of six subjects, there were significant linear relationships between VE and mean Pmus, I (r = 0.50-0.97) and mean Pmus, E (r = 0.82-0.93) during CWHE. The subjects generated a wide range of Pmus, I/P(cap, I) values (25-80%), and mean Pmus, I/P(cap, I) increased significantly (Delta = 42 +/- 16%) and in a linear fashion (r = 0.69-0.99) with VE throughout CWHE. The progressive increase in VE during CWHE is due to 1) a linear increase in Total Pmus, 2) a linear increase in inspiratory muscle load, and 3) a progressive fall in postinspiratory inspiratory activity. We conclude that the relationship between respiratory muscle pressure and VE during exercise is linear and not curvilinear.

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.

Medullary post-inspiratory neuronal and diaphragm post-inspiratory activities during spontaneous augmented breaths in anesthetized rats

To test the hypothesis that during augmented breaths the prolonged expiratory time is correlated with the activity of medullary post-inspiratory neurons, changes in diaphragm electromyogram and post-inspiratory neuronal activities were examined in pentobarbital anesthetized rats. During augmented breaths, the mean total expiratory time significantly increased (from 0.57 ± 0.02 to 1.20 ± 0.07 s, P < 0.01), but the mean duration of post-inspiratory inspiratory activity (PIIA) was significantly decreased (from 0.08 ± 0.01 to 0.02 ± 0.003 s, P < 0.01) compared to control breaths. The mean time which the diaphragm was electrically silent was observed to be significantly prolonged during augmented breaths (from 0.48 ± 0.02 to 1.19 ± 0.07 s, P < 0.01). During significant prolongations of expiratory time in augmented breaths, most of the recorded neurons ( 9 10 ) in the medulla showed sustained discharges. The mean duration of discharges was longer than that of PIIA (0.02 ± 0.003 vs.0.50 ± 0.10 s, P < 0.01). The mean firing frequency/breath significantly increased compared to control breaths (9.45 ± 1.69 vs 37.6 ± 7.13 imp/breath, P < 0.01). These results suggested that during augmented breaths, the prolonged expiratory period may not be mediated by persisting post-inspiratory neuronal activity in the medulla.

Activity of costal and crural diaphragm during progressive hypoxia or hypercapnia.

Because costal and crural diaphragm segments have different functional characteristics, ventilatory stimulation with hypoxia or hypercapnia may elicit differential segmental function. We report measurements of diaphragm segmental length, shortening, and electromyogram (EMG) activity from 11 canines that were chronically implanted with sonomicrometry transducers and EMG electrodes and then studied a mean of 18 days postimplantation while awake and breathing spontaneously during CO2 rebreathing and progressive isocapnic hypoxia. Ventilatory responses to hypercapnia and progressive hypoxia were moderate at 1.13 +/- 0.31 (SD) 1. min-1. mm-1 arterial Pco2 and -0.98 +/- 0.51 l. min-1.%arterial O2 saturation-1. When tidal values for breathing pattern and segmental function were compared at matching tidal volumes that correspond to mean CO2 of 49.4 arterial Pco2 and 77% arterial O2 saturation, there was no significant difference in resting length, tidal shortening, or tidal EMG of costal or crural segments. Intrabreath profiles of flow, shortening, and EMG activity at matched tidal volumes showed that 1) inspiratory flow during hypoxia was significantly greater during early inspiration, 2) crural EMG activity preceded costal EMG activity in early inspiration during both hypercapnia and hypoxia, 3) both segments showed increased postinspiratory inspiratory activity with stimulated ventilation, and 4) postinspiratory shortening and EMG were greatest for the crural segment during hypoxia. These results suggest that costal and crural diaphragm segments exhibit differential function during chemical stimulation, especially during postinspiration.

Costal and crural diaphragm function during CO2 rebreathing in awake dogs

If costal and crural diaphragm segments can perform as separate muscles, then CO2-stimulated ventilation may elicit differential segmental function. We studied diaphragm segmental length, shortening, and electromyogram (EMG) activity in 10 awake dogs chronically implanted with sonomicrometer transducers and EMG electrodes. During CO2 rebreathing, segmental shortening and EMG activity per whole tidal breath progressively increased, but segmental responses could not be differentiated at any level of CO2. With increasing CO2, resting end-expiratory length of both diaphragm segments increased. During the complete intrabreath inspiratory-expiratory cycle, costal and crural diaphragm revealed distinctive segmental function. At rest, crural shortening exceeded costal shortening in earliest inspiration, costal and especially crural shortening persisted into early expiration, and EMG activity of the crural segment was greater than that of the costal segment in earliest inspiration and showed more end-inspiratory/early expiratory [post-inspiratory inspiratory activity (PIIA)] activity. During CO2-stimulated breathing, neither segment shortened during the inspiratory flow of earliest inspiration. During CO2 rebreathing, shortening of the crural segment exceeded that of the costal segment during early inspiration and outlasted costal shortening during expiration; for both segments, shortening persisted after termination of inspiratory airflow. With increased CO2, EMG activity of the crural segment preceded that of the costal segment in earliest inspiration and was dominant into expiration, whereas costal EMG activity terminated abruptly with inspiratory flow. Thus, costal EMG PIIA was not evident during hypercapnia, whereas crural EMG PIIA was significant.(ABSTRACT TRUNCATED AT 250 WORDS)

The inhibitory effects of positive end-expiratory pressure (PEEP) on phrenic motoneuronal activity in cats.

We examined the effects of positive end-expiratory pressure (PEEP) on phrenic single motoneuronal activity (SMA) in anesthetized, paralyzed, and mechanically ventilated cats. SMA was isolated and recorded from the right C-5 phrenic root. Phrenic nerve compound activity was also recorded simultaneously from the contralateral C-5 phrenic root in each preparation. With the vagus nerve intact, phrenic SMA significantly decreased to 91.5, 76.2, 45.3, and 21.6% of control when PEEP was loaded to levels of 2.5, 5, 7.5, and 10 cm H2O, respectively. Compound activity also decreased. Moreover, not only phrenic single postinspiratory inspiratory activity (PIIA) but also the ratio of PIIA to the inspiratory SMA significantly decreased with increments of PEEP. In contrast, with the vagus nerve sectioned, phrenic nerve activity, including PIIA, remained unchanged when loading PEEP. These results suggest that 1) SMA might be inhibited in lung volume-dependent manner by PEEP, and that 2) the vagal nerve afferents are essential for the inhibition of SMA by PEEP.

Chemosensitivity and breathing pattern regulation of the coatimundi and woodchuck

An analysis of breathing pattern regulation was carried out on the coatimundi and woodchuck who represent two different volume-time patterns. It was found that the coati, with a short expiratory time as a fraction of total breath time, Te/Ttot, has a greater sensitivity to CO 2 as represented by the slope and threshold of its ventilatory response. Breathing air the coati maintains post-inspiratory inspiratory activity (PIIA) of the posterior cricoarytenoid (PCA) through 51% of expiration, while the woodchuck, who is less sensitive to CO 2 and has a long Te/Ttot, exhibits no PIIA of the PCA. The woodchuck also has a greater incidence and duration of end-expiratory pauses (or delayed inspiratory onset). The woodchuck does not demonstrate the usual inverse relationship between Vt and Te in response to 5% CO 2 and does not recruit PIIA of the PCA at this level of CO 2. These data confirm the importance of CO 2 chemosensitivity in regulation of Te. It is further demonstrated that interspecific differences in chemosensitivity among three mammals of the same size are reflected in regulation of Te but not in inspiratory ‘drive’ (as indicated by mean inspiratory flow, Vt/Ti).

Differential timing of respiratory muscles in response to chemical stimuli in awake dogs

We assessed changes in respiratory muscle timing in response to hyperpnea and shortened inspiratory and expiratory times caused by chemoreceptor stimuli in six awake dogs. Durations of postinspiratory inspiratory activity of costal and crural diaphragm (PIIA), the delay in diaphragm electromyogram (EMG) after the initiation of inspiratory airflow, postexpiratory expiratory activity of the transversus abdominis (PEEA), and the delay of abdominal expiratory muscle activity after the initiation of expiratory airflow were measured. In control, four out of six dogs showed PIIA [8-10% of expiratory time (TE)]; all showed delay of diaphragm [19% of inspiratory time (TI)], delay of abdominal muscle activation (21% of TE), and PEEA (24% of TI). Hypercapnia decreased PIIA (4-9% of TE), maintained diaphragm delay at near control values (23% of TI), increased PEEA (36% of TI), eliminated delay of abdominal muscle activation (4% of TE), and decreased end-expiratory lung volume (EELV). Hypocapnic hypoxia increased PIIA (24-25% of TE), eliminated diaphragm delay (3% of TI), eliminated PEEA (3% of TI), reduced delay of abdominal muscle activation (14% of TE), and increased EELV. Most of these effects of hypoxic hypocapnia vs. hypercapnia on the within-breath EMG timing parameters corresponded to differences in the magnitude of expiratory muscle activation. These changes exerted significant influences on flow rates and EELV.

Effects of bronchoconstriction on respiratory muscle activity during expiration.

The effect of methacholine-induced bronchoconstriction on the electrical activity of respiratory muscles during expiration was studied in 12 anesthetized spontaneously breathing dogs. Before and after aerosols of methacholine, diaphragm, parasternal intercostal, internal intercostal, and external oblique electromyograms were recorded during 100% O2 breathing and CO2 rebreathing. While breathing 100% O2, five dogs showed prolonged electrical activity of the diaphragm and parasternal intercostals in early expiration, postinspiratory inspiratory activity (PIIA). Aerosols of methacholine increased pulmonary resistance, decreased tidal volume, and elevated arterial PCO2. During bronchoconstriction, when PCO2 was varied by CO2 rebreathing, PIIA was shorter at low levels of PCO2, and external oblique and internal intercostal were higher at all levels of PCO2. Vagotomy shortened PIIA in dogs with prolonged PIIA. After vagotomy, methacholine had no effects on PIIA but continued to increase external oblique and internal intercostal activity at all levels of PCO2. These findings indicate that bronchoconstriction influences PIIA through a vagal reflex but augments expiratory activity, at least in part, by extravagal mechanisms.

Analysis of postinspiratory activity of phrenic motoneurons with chemical and vagal reflexes.

We examined the effects of chemical and reflex drives on the postinspiratory inspiratory activity (PIIA) of phrenic motoneurons using a single-fiber technique. Action potentials from "single" fibers were recorded from the C5 phrenic root together with contralateral mass phrenic activity (also from C5) in anesthetized, paralyzed, and artificially ventilated cats with intact vagus and carotid sinus nerves. Nerve fibers were classified as "early" or "late" based on their onset of discharge in relation to mass phrenic activity during hyperoxic ventilation. Only the early fibers displayed PIIA but not the late fibers, even when their activity began earlier in inspiration with increased chemical drives. Isocapnic hypoxia increased, whereas hyperoxic hypercapnia shortened the duration of PIIA. Pulmonary stretch and "irritant" receptors inhibited PIIA. Hypercapnia and stimulation of peripheral chemoreceptors by lobeline excited both early and late units to the same extent, but hypoxic ventilation had a less marked excitatory effect on late fiber activity. Irritant receptor activation increased the activity of early more than late fibers. Hyperoxic hyperventilation eliminated late phrenic fiber activity, whereas early fibers became tonically active. Bilateral vagotomy abolished this sustained discharge in eight of nine early units, suggesting the importance of vagal afferents in producing tonic firing during hyperventilation. These results suggest that early and late phrenic fibers have different responses to chemical stimuli and to vagally mediated reflexes; late units do not discharge in postinspiratory period, whereas early fibers do; the PIIA is not affected in the same way by various chemical and vagal inputs; and early units that exhibit PIIA display tonic activity with hyperoxic hypocapnia.

Increased duration of postinspiratory inspiratory activity during augmented breaths in cats

The duration of diaphragm electrical activity in augmented breaths during early expiration (postinspiratory inspiratory activity, PIIA) was assessed in 12 pentobarbital-anesthetized cats. There were significant prolongations of expiratory time ( P<0.001) and PIIA ( P<0.001) during augmented breaths compared to eupneic breaths, but no alteration in the portion of expiratory time during which the diaphragm was electrically silent. Furthermore, significant linear correlations were found between control and augmented breaths for the duration of PIIA ( r=0.95) and for the ratio of PIIA to expiratory time ( r=0.88). These results suggest that during augmented breaths there is not only an increased motor output to the diaphragm during inspiration, but that the early expiratory activity of the diaphragm is greater as well.

Control of activity of the diaphragm in rapid-eye-movement sleep.

Respiration in rapid-eye-movement sleep (REMS) is known to be highly variable. The purpose of this study was to investigate the source of this variability and to determine which ordering principles remained operative in REM sleep. In unrestrained, naturally sleeping cats we recorded the electroencephalogram, electrooculogram, neck electromyogram, and diaphragmatic electromyogram (EMG) and computed its moving average (MAdi). As a reference, we first examined MAdi during "tonic" REMS, since breathing is fairly regular in this state. "Control" ranges for peak amplitude (PEMG), inspiratory time (TI), duration of postinspiratory inspiratory activity, expiratory time, and the calculated inspiratory slope (PEMG/TI) were determined by overlaying individual breath traces of the time course of MAdi during tonic REMS to form a composite tracing. Next, the time course of the EMG during individual breaths in slow-wave sleep (SWS) and a complete period of consecutive breaths in REMS (both tonic and phasic) were compared with this tonic REMS composite. The number of eye movements per breath was tabulated as an index of phasic activity. The inspiratory slopes during SWS and tonic REMS were similar. However, during phasic REMS, many breaths displayed either increases (excitation) or decreases (inhibition) in slope compared with the "typical" breaths seen in tonic REMS. The occurrence of these altered slopes increased with the frequency of phasic events. TI was inversely related to the slope of the EMG, which tended to minimize changes in PEMG.(ABSTRACT TRUNCATED AT 250 WORDS)