Dichloroacetate blocks endogenous opioid effects during inspiratory flow-resistive loading.

Inspiratory flow-resistive loading (IRL) in unanesthetized goats causes central elaboration of endogenous opioids, which is accompanied by inhibition of several respiratory muscles. The peripheral stimulus responsible for mediating this phenomenon is unknown. We hypothesized that lactic acid mediates release of endogenous opioids during IRL. Unanesthetized goats were pretreated with either saline or dichloroacetate (DCA; 50 mg/kg iv), a blocker of lactic acid formation, and subjected to IRL (50 cmH2O.l-1.s) for 120 min followed by naloxone (NLX; 0.3 mg/kg iv). Electromyographic activities of the diaphragm (EMGdi), external oblique (EMGeo), and external intercostal (EMGei) were measured and expressed as a percentage of activity at an end-tidal CO2 of 8%. DCA blocked the NLX-induced augmentation of all EMGs observed after 120 min of IRL as follows (means +/- SE): delta EMGdi from 20.8 +/- 5.6% (saline) to 1.2 +/- 2.7% (DCA), delta EMGeo from 116.6 +/- 30.9% (saline) to 5.3 +/- 11.4% (DCA), and delta EMGei from 43.8 +/- 11.3% (saline) to -4.5 +/- 5.6% (DCA) (all P less than 0.05, DCA vs. saline). We conclude that lactic acid produced by the contracting respiratory muscles is the stimulus responsible for endogenous opioid pathway activation during IRL.     

Chest wall and trunk muscle activity during inspiratory loading.

We measured the electromyographic (EMG) activity in four chest wall and trunk (CWT) muscles, the erector spinae, latissimus dorsi, pectoralis major, and trapezius, together with the parasternal, in four normal subjects during graded inspiratory efforts against an occlusion in both upright and seated postures. We also measured CWT EMGs in six seated subjects during inspiratory resistive loading at high and low tidal volumes [1,280 +/- 80 (SE) and 920 +/- 60 ml, respectively]. With one exception, CWT EMG increased as a function of inspiratory pressure generated (Pmus) at all lung volumes in both postures, with no systematic difference in recruitment between CWT and parasternal muscles as a function of Pmus. At any given lung volume there was no consistent difference in CWT EMG at a given Pmus between the two postures (P > 0.09). However, at a given Pmus during both graded inspiratory efforts and inspiratory resistive loading, EMGs of all muscles increased with lung volume, with greater volume dependence in the upright posture (P < 0.02). The results suggest that during inspiratory efforts, CWT muscles contribute to the generation of inspiratory pressure. The CWT muscles may act as fixators opposing deflationary forces transmitted to the vertebral column by rib cage articulations, a function that may be less effective at high lung volumes if the direction of the muscular insertions is altered disadvantageously.     

Effect of inspiratory muscle fatigue on breathing pattern during inspiratory resistive loading

The purpose of this study was to determine whether induction of either inspiratory muscle fatigue (expt 1) or diaphragmatic fatigue (expt 2) would alter the breathing pattern response to large inspiratory resistive loads. In particular, we wondered whether induction of fatigue would result in rapid shallow breathing during inspiratory resistive loading. The breathing pattern during inspiratory resistive loading was measured for 5 min in the absence of fatigue (control) and immediately after induction of either inspiratory muscle fatigue or diaphragmatic fatigue. Data were separately analyzed for the 1st and 5th min of resistive loading to distinguish between immediate and sustained effects. Fatigue was achieved by having the subjects breathe against an inspiratory threshold load while generating a predetermined fraction of either the maximal mouth pressure or maximal transdiaphragmatic pressure until they could no longer reach the target pressure. Compared with control, there were no significant alterations in breathing pattern after induction of fatigue during either the 1st or 5th min of resistive loading, regardless of whether fatigue was induced in the majority of the inspiratory muscles or just in the diaphragm. We conclude that the development of inspiratory muscle fatigue does not alter the breathing pattern response to large inspiratory resistive loads.     

Effect of mechanical loading on expiratory and inspiratory muscle activity during NREM sleep

We investigated the effect of acute and sustained inspiratory resistive loading (IRL) on the activity of expiratory abdominal muscles (EMGab) and the diaphragm (EMGdi) and on ventilation during wakefulness and non-rapid-eye-movement (NREM) sleep in healthy subjects. EMGdi and EMGab were measured with esophageal and transcutaneous electrodes, respectively. During wakefulness, EMGdi increased in response to acute loading (18 cmH2O.l-1.s) (+23%); this was accompanied by preservation of tidal volume (VT) and minute ventilation (VE). During NREM sleep, no augmentation was noted in EMGdi or EMGab. Inspiratory time (TI) was prolonged (+5%), but this was not sufficient to prevent a decrease in both VT and VE (-21 and -20%, respectively). During sustained loading (12 cmH2O.l-1 s) in NREM sleep, control breaths (C) were compared with the steady-state loaded breaths (SS) defined by breaths 41-50. Steady-state IRL was associated with augmentation of EMGdi (12%) and EMGab (50%). VT returned to control levels, expiratory time shortened, and breathing frequency increased. The net result was the increase in VE above control levels (+5%, P less than 0.01). No change was noted in end-tidal CO2 or O2. We concluded that 1) wakefulness is a prerequisite for immediate load compensation (in its absence, TI prolongation is the only compensatory response) and 2) during sustained IRL, the augmentation of EMGdi and EMGab can lead to complete ventilatory recovery without measurable changes in chemical stimuli.     

Phrenic activity and intercostal muscle emg during inspiratory loading in newborn kittens

The effects of airway occlusions at functional residual capacity (FRC) on both "integrated" phrenic activity (Phr) and intercostal muscle electromyogram (intEMG) were studied in intact and vagotomized spontaneously breathing kittens during the 1st wk of life. Animals were anesthetized im with a mixture of ketamine (30 mg/kg) and acepromazine (1.1 mg/kg). In the intact kittens, inspiratory loading led to a significant increase in peak amplitudes of both Phr and intEMG and prolongation of inspiratory (TI) and expiratory (TE) times. Mean values of rate of rise of Phr and intEMG measured at 200 ms (intEMG200) from the onset of inspiration were unaffected. The results indicated that in newborns the vagal component of the load compensation is of great importance. Following vagotomy, airway occlusion produced a significant increase in mean values of TI and intEMG only. These small but significant changes suggest that most of the load compensation reflex is dependent on prolongation of TI. Increased intEMG200 during loading in the vagotomized kittens, observed during several trials, implies that the intercostal fusion-alpha interaction may operate in newborns.     

Respiratory muscle function during CO2 rebreathing with inspiratory flow-resistive loading

We investigated the respiratory muscle contribution to inspiratory load compensation by measuring diaphragmatic and intercostal electromyograms (EMGdi and EMGic), transdiaphragmatic pressure (Pdi), and thoracoabdominal motion during CO2 rebreathing with and without 15 cmH2O X l-1 X s inspiratory flow resistance (IRL) in normal sitting volunteers. During IRL compared with control, Pdi measured during airflow and during airway occlusion increased for a given change in CO2 partial pressure and EMGdi, and there was a greater decrease in abdominal (AB) end expiratory anteroposterior dimensions with increased expiratory gastric pressure (Pga), this leading to an inspiratory decline in Pga with outward AB movement, indicating a passive component to the descent of the abdomen-diaphragm. The response of EMGic to IRL was similar to that of EMGdi, though rib cage (RC)-Pga plots did infer intercostal muscle contribution. We conclude that during CO2 rebreathing with IRL there is improved diaphragmatic neuromuscular coupling, the prolongation of inspiration promoting a force-velocity advantage, and increased AB action serving to optimize diaphragm length and configuration, as well as to provide its own passive inspiratory action. Intercostal action provides increased assistance also. Therefore, compensation for inspiratory resistive loads results from the combined and integrated effort of all respiratory muscle groups.     

Posture effects on timing of abdominal muscle activity during stimulated ventilation.

In humans during stimulated ventilation, substantial abdominal muscle activity extends into the following inspiration as postexpiratory expiratory activity (PEEA) and commences again during late inspiration as preexpiratory expiratory activity (PREA). We hypothesized that the timing of PEEA and PREA would be changed systematically by posture. Fine-wire electrodes were inserted into the rectus abdominis, external oblique, internal oblique, and transversus abdominis in nine awake subjects. Airflow, end-tidal CO2, and moving average electromyogram (EMG) signals were recorded during resting and CO2-stimulated ventilation in both supine and standing postures. Phasic expiratory EMG activity (tidal EMG) of the four abdominal muscles at any level of CO2 stimulation was greater while standing. Abdominal muscle activities during inspiration, PEEA, and PREA, were observed with CO2 stimulation, both supine and standing. Change in posture had a significant effect on intrabreath timing of expiratory muscle activation at any level of CO2 stimulation. The transversus abdominis showed a significant increase in PEEA and a significant decrease in PREA while subjects were standing; similar changes were seen in the internal oblique. We conclude that changes in posture are associated with significant changes in phasic expiratory activity of the four abdominal muscles, with systematic changes in the timing of abdominal muscle activity during early and late inspiration.     

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.     

Central inspiratory influence on abdominal expiratory nerve activity

Our purpose was to determine whether the intensity of abdominal expiratory nerve discharge is conditioned by the intensity of the preceding inspiratory phrenic discharge, independent of mechanical and chemical afferent influences. In decerebrate, paralyzed, vagotomized cats with bilateral pneumothoraxes, we recorded phrenic and abdominal (cranial iliohypogastric nerve, L1) nerve activities at hyperoxic normocapnia. We reduced the duration and intensity (i.e., integrated peak height) of phrenic nerve discharge for single cycles by stimulating the cut central end of the superior laryngeal nerve (SLN) during the central inspiratory phase (75 microA, 20-50 Hz, 0.2-ms pulse). Premature termination of inspiration consistently reduced expiratory duration (TE) and abdominal expiratory nerve activity (area of integrated neurogram), but the average reduction in TE was much less than the reduction in abdominal nerve activity (14 vs. 51%). Stimulation of the cut central end of the vagus nerve yielded similar results, as did spontaneous premature terminations of inspiration, which we observed in one cat. SLN stimulation during hyperoxic hypercapnia resulted in more variable responses, and higher stimulation frequencies were usually required to abort inspiration. SLN (or vagal) stimulation during expiration consistently increased abdominal expiratory nerve activity. We speculate that this facilitatory response is gated during inspiration, thereby allowing the inspiratory conditioning effect on the subsequent expiration to be expressed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute effects of incremental inspiratory loads on compartmental chest wall volume and predominant activity frequency of inspiratory muscle

AimThis research aims to analyze the acute effect of incremental inspiratory loads on respiratory pattern and on the predominant activity frequency of inspiratory muscle, taking into account differences in gender responses. Optoelectronic Plethysmography was performed during loads in 39 healthy subjects (20 women), placing 89 markers on the thoracic-abdominal wall to obtain total and regional volumes. Surface electromyography (SEMG) was taken simultaneously on the Sternocleidomastoid and Diaphragm muscles, to calculate the predominant muscle activity frequency through wavelet analysis. Inspiratory loads were performed using Threshold® with 2 min of breathing at different levels, ranging from a load of 10 cmH₂O plus 5 cmH₂O to 40 cmH₂O or fatigue.ResultsInspiratory Time increased during loads. Total and compartmental volumes increased with different regions, changing at different loads. These changes in volume occur earlier in women (20 cmH₂O) than in men (30 cmH₂O). The predominant activity frequency of Sternocleidmastoid muscle decreased at 30 cmH₂O, while Diaphragm activity decreased at 40 cmH₂O.ConclusionThe acute effects of incremental inspiratory loads are increases of total and regional volumes and inspiratory time. As for muscle activity, the predominant activity frequency declined in Sternocleidomastoid and Diaphragm muscles, but at different loads. Such respiratory and SEMG patterns and gender differences should be considered when clinical interventions are performed.     

Chest wall distortion during resistive inspiratory loading

We studied six (1 naive and 5 experienced) subjects breathing with added inspiratory resistive loads while we recorded chest wall motion (anteroposterior rib cage, anteroposterior abdomen, and lateral rib cage) and tidal volumes. In the five experienced subjects, transdiaphragmatic and pleural pressures, and electromyographs of the sternocleidomastoid and abdominal muscles were also measured. Subjects inspired against the resistor spontaneously and then with specific instructions to reach a target pleural or transdiaphragmatic pressure or to maximize selected electromyographic activities. Depending on the instructions, a wide variety of patterns of inspiratory motion resulted. Although the forces leading to a more elliptical or circular configuration of the chest wall can be identified, it is difficult to analyze or predict the configurational results based on insertional and pressure-related contributions of a few individual respiratory muscles. Although overall chest wall respiratory motion cannot be readily inferred from the electromyographic and pressure data we recorded, it is clear that responses to loading can vary substantially within and between individuals. Undoubtedly, the underlying mechanism for the distortional changes with loading are complex and perhaps many are behavioral rather than automatic and/or compensatory.     

Pleural pressure between diaphragm and rib cage during inspiratory muscle activity

We measured the changes in pleural surface pressure (delta Ppl) in the area of apposition of the rib cage to the diaphragm (Aap) in anesthetized dogs during spontaneous breathing, inspiratory efforts after airway occlusion at functional residual capacity, and phrenic stimulation. Intact dogs were in supine or lateral posture; partially eviscerated dogs were in lateral posture. delta Ppl,ap often differed significantly from changes in abdominal pressure (delta Pab); sometimes they differed in sign (except during phrenic stimulation). Changes in transdiaphragmatic pressure in Aap (delta Pdi,ap) could be positive or negative and were less in eviscerated than in intact dogs. delta Pdi,ap could differ in sign among respiratory maneuvers and over different parts of Aap. Hence average delta Pdi,ap should be closer to zero than delta Pdi,ap at a given site. Since delta Ppl,ap = delta Prc,ap, where Prc,ap represents rib cage pressure in Aap, delta Pdi,ap = delta Pab - delta Prc,ap. Hence, considering that delta Pab and delta Prc depend on different factors, delta Pdi,ap may differ from zero. This pressure difference seems related to the interaction between two semisolid structures (contracted diaphragm and rib cage in Aap) constrained to the same shape and position.     

Effects of mechanical loading and hypercapnia on inspiratory muscle EMG.

The electromyograms of the diaphragm and an external intercostal muscle were analyzed to see if the effects of hypercapnia on inspiratory muscle electrical activity could be distinguished from those of mechanical loading and to determine whether changes in inspiratory muscle electrical activity were a sueful measure of CO2 response during mechanical loading. Anesthetized dogs were studied: 1) during progressive hypercapnia without mechanical loading, 2) during flow-resistive and elastic loading at constant PCO2, and 3) during progressive hypercapnia and mechanical loading. Both mechanical loading and hypercapnia increased total inspiratory diaphragmatic and intercostal muscle electrical activity. However, inspiratory duration was increased by mechanical loads but reduced by hypercapnia. Because of these changes in inspiratory duration, the average rate of diaphragmatic electrical activity remained unaffected by mechanical loading before and after vagotomy but was increased by hypercapnia. In contrast, both hypercapnia and mechanical loading increased the average rate of intercostal muscle electrical activity. There was a greater increase in both total and average rate of intercostal muscle electrical activity during hypercapnia in the presence of mechanical loading than during unloaded breathing. However, the change in total and average rate of diaphragmatic electrical activity with PCO2 was unaffected by added mechanical loads. These results suggest that diaphragmatic but not intercostal muscle electrical activity can be used as an index of CO2 response even during mechanical loading.