Inspiratory Flow-resistive Loading Research Articles

Flow-resistive loading and diaphragmatic muscle function in term and preterm infants.

We aimed to assess diaphragmatic function in term and preterm infants with and without history of bronchopulmonary dysplasia (BPD), before and after the application of inspiratory flow resistive loading. Forty infants of a median (range) gestational age of 34 (25-40) weeks were studied. BPD was defined as supplemental oxygen requirement for >28 days of life. Seventeen infants were term, 17 preterm without history of BPD, and six preterm with a history of BPD. The diaphragmatic pressure-time index (PTIdi) was calculated as the mean to maximum trans-diaphragmatic pressure ratio times the inspiratory duty cycle. The PTIdi was calculated before and after the application of an inspiratory-flow resistance for 120 s. Airflow was measured by a pneumotachograph and the transdiaphragmatic pressure by a dual pressure catheter. The median (interquartile range [IQR]) pre-resistance PTIdi was higher in preterm infants without BPD (0.064 [0.050-0.077]) compared with term infants (0.052 [0.044-0.062], p = .029) and was higher in preterm infants with BPD (0.119 [0.086-0.132]) compared with a subgroup of preterm infants without BPD (0.062 [0.056-0.072], p = .004). The median (IQR) postresistance PTIdi was higher in preterm infants without BPD (0.101 [0.084-0.132]) compared with term infants (0.067 [0.055-0.083], p < .001) and was higher in preterm infants with BPD [0.201(0.172-0.272)] compared with the preterm subgroup without BPD (0.091 [0.081-0.108],p = .004). The median (IQR) percentage change of the PTIdi after the application of the resistance was higher in preterm infants without BPD (65 [51-92] %) compared with term infants (34 [20-39] %, p < .001). Preterm infants, especially those recovering from BPD, are at increased risk of diaphragmatic muscle fatigue under conditions of increased inspiratory loading.

Influence of respiratory mechanics and drive on genioglossus movement under ultrasound imaging.

Genioglossus is the largest upper airway dilator and its dilatory movement can be measured non-invasively with magnetic resonance imaging and ultrasound. The present study used a novel ultrasound method to assess genioglossus movement in conditions in which ventilatory drive or respiratory mechanics were changed.MethodsTwenty healthy subjects (10 males, age 28±5 years [mean ± SD]) lay supine, awake, with the head in a neutral position. Ventilation was monitored with inductance bands. Real-time B-mode ultrasound movies were analysed. We measured genioglossus motion (i) during spontaneous breathing, voluntary targeted breathing (normal tidal volume Vt), and voluntary hyperpnoea (at 1.5Vt and 2 Vt); (ii) during inspiratory flow resistive loading; (iii) with changes in end-expiratory lung volume (EELV).ResultsAverage peak inspiratory displacement of the infero-posterior region of genioglossus was 0.89±0.56 mm; 1.02±0.88 mm; 1.27±0.70 mm respectively for voluntary Vt, and during voluntary hyperpnoea at 1.5Vt and 2Vt. A change in genioglossus motion was observed with increased Vt. During increasing inspiratory resistive loading, the genioglossus displaced less anteriorly (p = 0.005) but more inferiorly (p = 0.027). When lung volume was altered, no significant changes in genioglossus movement were observed (p = 0.115).ConclusionIn healthy subjects, we observed non-uniform heterogeneous inspiratory motion within the inferoposterior part of genioglossus during spontaneous quiet breathing with mean peak displacement between 0.5–2 mm, with more displacement in the posterior region than the anterior. This regional heterogeneity disappeared during voluntary targeted breathing. This may be due to different neural drive to genioglossus during voluntary breathing. During inspiratory resistive loading, the observed genioglossus motion may serve to maintain upper airway patency by balancing intraluminal negative pressure with positive pressure generated by upper airway dilatory muscles. In contrast, changes in EELV were not accompanied by major changes in genioglossus motion.

Activation of respiratory muscles during respiratory muscle training

It is unknown which respiratory muscles are mainly activated by respiratory muscle training. This study evaluated Inspiratory Pressure Threshold Loading (IPTL), Inspiratory Flow Resistive Loading (IFRL) and Voluntary Isocapnic Hyperpnea (VIH) with regard to electromyographic (EMG) activation of the sternocleidomastoid muscle (SCM), parasternal muscles (PARA) and the diaphragm (DIA) in randomized order.Surface EMG were analyzed at the end of each training session and normalized using the peak EMG recorded during maximum inspiratory maneuvers (Sniff nasal pressure: SnPna, maximal inspiratory mouth occlusion pressure: PImax).41 healthy participants were included. Maximal activation was achieved for SCM by SnPna; the PImax activated predominantly PARA and DIA. Activations of SCM and PARA were higher in IPTL and VIH than for IFRL (p<0.05). DIA was higher applying IPTL compared to IFRL or VIH (p<0.05).IPTL, IFRL and VIH differ in activation of inspiratory respiratory muscles. Whereas all methods mainly stimulate accessory respiratory muscles, diaphragm activation was predominant in IPTL.

Inspiratory flow resistive loading improves respiratory muscle function and endurance capacity in recreational runners

The purpose of this study was to assess the efficacy of inspiratory flow resistive loading (IFRL) on respiratory muscle function, exercise performance and cardiopulmonary and metabolic responses to exercise. Twenty-four recreational road runners (12 male) were randomly assigned from each gender into an IFRL group (n=8) and sham-IFRL group (n=8), which performed IFRL for 6 weeks, or a control group (n=8). Strength (+43.9%Delta), endurance (+26.6%Delta), maximum power output (+41.9%Delta) and work capacity (+38.5%Delta) of the inspiratory muscles were significantly increased (P<0.05) at rest following the study period in IFRL group only. In addition, ventilation (-25.7%Delta), oxygen consumption (-13.3%Delta), breathing frequency (-11.9%Delta), tidal volume (-16.0%Delta), heart rate (HR) (-13.1%Delta), blood lactate concentration (-38.9%Delta) and the perceptual response (-33.5%Delta) to constant workload exercise were significantly attenuated (P<0.05), concomitant with a significant improvement (P<0.05) in endurance exercise capacity (+16.4%Delta) during a treadmill run set at 80% VO2max in IFRL group only. These data suggest that IFRL can alter breathing mechanics, attenuate the oxygen cost, ventilation, HR, blood lactate and the perceptual response during constant workload exercise and improve endurance exercise performance in recreational runners.

An additive interaction between different qualities of dyspnea produced in normal human subjects

We evaluated the sensation of dyspnea induced by hypercapnia alone and a combination of hypercapnia and flow-resistive loading by the use of visual analogue scale (VAS) and the use of 13 listed descriptors in 23 healthy subjects. Hypercapnia alone caused a modest degree of dyspnea characterized by both air hunger and work/effort sensations. An addition of inspiratory flow-resistive loading (IRL) caused an increase in inspiratory difficulty and some attenuation of 'work/effort.' The addition of expiratory flow-resistive loading (ERL) caused an increase in expiratory difficulty and attenuation of 'air hunger.' The addition of both IRL and ERL caused a marked increase in dyspnea, the amount of which was close to the sum of the increases obtained individually by IRL and by ERL, while the quality of dyspnea was characterized predominantly by work/effort. These results suggest that despite the difference in quality of sensations, the intensity of dyspnea would sum linearly when the two kinds of loads are presented at the same time.

Ventilatory compensation for inspiratory resistive loads during anaesthesia with halothane or isoflurane

We have analysed the ventilatory response to sustained inspiratory resistive loads in 14 patients, while awake and during halothane (n = 7) or isoflurane (n = 7) anaesthesia. Patients breathed halothane or isoflurane in oxygen at 1.2 minimum alveolar concentration (MAC). Inspiratory resistances of 0, 12 and 37 cm H2O litre-1 s were applied. Tidal volume (VT) was maintained with the greater loads. At the greatest resistance, a significant reduction in minute ventilation occurred in both awake (-18.9%) and anaesthetized states, with both halothane (-10.4%) and isoflurane (-14.5%). Ventilatory frequency decreased significantly from mean 14.6 (SD 4.7) to 12.5 (4.3) bpm in the awake state and during anaesthesia, with increasing inspiratory resistance (29.5 (3.6) to 23.7 (7.2) bpm and 25.8 (3.3) to 23.4 (4.0) bpm, respectively, for halothane and isoflurane) because inspiratory time (TI) was significantly longer (P < 0.01). End-tidal PCO2 increased by 0.3 kPa, on average, from baseline to the highest level of resistance (P < 0.01). Inspiratory occlusion pressure at 100 ms increased significantly with increased loading in all situations (P < 0.001). We found a similar pattern of ventilatory adaptation to sustained inspiratory flow resistive loads both in awake and anaesthetized states. VT was maintained at increased loads because of an increase in inspiratory neuromuscular output and inspiratory duration.

Event-related potentials to inspiratory flow-resistive loads in young adults: stimulus magnitude effects

Event-related potentials were recorded to brief presentations of four levels of inspiratory flow-resistive loads in young adults. We labeled the loads according to the level of resistance they provided subjectively: sub-threshold (0.34 cmH 2O/l per s), near-threshold (4.01 cmH 2O/l per s), intermediate (10.4 cmH 2O/l per s), and near-occlusion (57.5 cmH 2O/l per s). No discernible ERPs were elicited by the undetected, sub-threshold stimulus but late components of the ERP (P2, N2, and P3) were observed to each of the three larger stimuli. They were related, in part, to behavioral judgments obtained during the stimulus periods. Both the latency and amplitude of the ERP components varied systematically as a function of stimulus magnitude, in a manner comparable to that observed in ERP paradigms using auditory and visual stimuli. Thus, the data show that event-related potentials to breathing are sensitive to physiologic effects of resistive loads present at the onset of inspiration. Respiratory ERPs may be used to infer sensory and perceptual responses to increases in airflow resistance and, accordingly, may relate to the perception of airflow obstruction in patient populations.

Resistive Loading and Pulmonary Capillary Volume in Asthma

We recently observed that an inspiratory flow-resistive load can worsen airflow obstruction in supine asthmatic patients. As such loads reportedly augment intrapulmonary blood volume, we examined the effect of a prolonged inspiratory resistive load on pulmonary capillary volume (corrected for alveolar volume—Vc/Va) in 15 asthmatic and 4 normal subjects. Subjects inspired continuously while supine through increasing resistances (hour 1, 9.0; hour 2, 17.0, and hours 3 and 4, 21.5 cm H2O/L/s).

Breathing route and ventilatory responses to inspiratory resistive loading in humans.

In response to ventilatory loading, a number of compensatory mechanisms can serve to maintain ventilation at or near control levels. To test the hypothesis that respiratory compensation for inspiratory flow-resistive load during nasal breathing may be different from that during oral breathing, we investigated the ventilatory responses to four different magnitudes of inspiratory flow-resistive loads ("control," "light," "moderate," and "severe" loads: 3.5, 15.0, 51.8, 83.3 cm H2O/L/s at a flow rate of 30 L/min, respectively) during nasal breathing and during oral breathing in 11 conscious subjects. With the control, light, and moderate loads, there were no significant differences in tidal volume (VT), respiratory frequency (f), minute ventilation (VI), and end-tidal (partial) carbon dioxide pressure (PETCO2) between nasal and oral breathing. With the severe load, however, VI and f were significantly lower and PETCO2 was significantly higher during nasal breathing than during oral breathing. Occlusion pressure (P0.1) progressively increased during both nasal and oral breathing with increasing magnitudes of loading. However, the value of P0.1 during oral breathing at the severe loading was significantly higher than that during nasal breathing. Our results indicate that ventilatory compensation for the inspiratory flow-resistive load is better during oral breathing than during nasal breathing.

Respiratory Load Compensation During Hypercapnic Ventilatory Response in Pulmonary Emphysema

The purpose of this study is to examine the relationship between mechanical factors and the load compensation during hypercapnia in emphysema. In 36 clinically stable patients, we conducted pulmonary function tests and hypercapnic ventilatory response (HCVR) tests with and without inspiratory flow-resistive loading (IRL) (17 cm H2O/L/s). The mean value of HCVR significantly decreased with IRL, while that of the mouth occlusion pressure (P0.1) response increased. Regardless of IRL, the HCVR values were correlated with FEV1/FVC and airway resistance. The load compensation, evaluated by the ratio of the HCVR value and the P0.1 response before and after IRL, was inversely correlated with percent FRC (r = -0.38, r = -0.39; both p < 0.05). Breathing pattern analysis at the end-tidal pressure of carbon dioxide of 55 mm Hg elicited the decrease of (tidal volume/inspiratory time (VT/TI) and the increase of TI and TI/TTOT. Although the absolute changes of VT and f were inconsistent among subjects, each relative ratio before and after IRL was correlated again with percent FRC (r = -0.46, r = 0.44: both p < 0.01). Therefore, the position of the inspiratory muscles at the onset of inspiration may influence the load compensation during hypercapnia in emphysema.

Effects of Aging on Respiratory Load Compensation and Dyspnea Sensation

To clarify effects of aging on the load compensation response and the sensation of dyspnea, we examined 28 healthy male volunteers for ventilatory and P0.1 responses to hyperoxic progressive hypercapnia with and without inspiratory flow-resistive loading (17 cm H2O/L/s) while the intensity of dyspnea was simultaneously assessed by visual analogue scaling every 15 s. Of the 28 subjects, 14 were 61 to 79 yr of age and were classified as the older group; the others, 19 to 48 yr of age, were classified as the control group. Neither delta VE/delta PETCO2 nor delta P0.1/delta PETCO2 was different between the two groups without loading. In the control group, the delta P0.1/delta PETCO2 increased with loading (p < 0.01) without a change in the delta VE/delta PETCO2. In the older group, the delta P0.1/delta PETCO2 did not change with loading so that the delta VE/delta PETCO2 decreased with loading (p < 0.01). In the 28 subjects as a whole, the percent change in delta P0.1/delta PETCO2 with loading was inversely correlated with age (r = -0.53, p < 0.01). At PETCO2 levels of 45, 50, and 55 mm Hg, irrespective of loading, the dyspnea intensity was greater in the older group than in the control group, whereas the P0.1 expressed as its ratio to the predicted maximal inspiratory mouth pressure was not different between the two groups. We conclude that aging attenuates the compensatory response to inspiratory flow-resistive loading and it increases the intensity of dyspnea for a given level of PETCO2.

Metabolic, hemodynamic, and ventilatory responses to respiratory load in sedated neonatal piglets

Some neonatal species fail to develop the expected degree of hypercapnia during hypoventilation with mechanical loads. We studied 13 spontaneously breathing, sedated piglets (1-9 days old), grouped by age as young (< or = 3 day old) or old (> 3 day old). Baseline measurements of minute ventilation, arterial blood pressure (BP), cardiac output, and O2 consumption were repeated after continuous (inspiratory and expiratory) flow-resistive loading of 330 cmH2O.l-1 x s for 10 min. Older animals [n = 6, age 6.6 +/- 1.9 (SD) days, wt 1.99 +/- 0.5 kg] increased metabolic rate (9.8 +/- 1.4 to 10.5 +/- 1.3 ml.min-1 x kg-1, P < 0.01), whereas younger animals (n = 7, 2.6 +/- 0.6 days, 1.37 +2- 0.3 kg) invariably decreased metabolic rate with loading (9.7 +/- 1.6 to 7.9 +/- 2.6 ml.min-1 x kg-1); changes were different between groups (P < 0.02). Although ventilation decreased with loading in both groups (P < 0.01), younger animals showed a relatively greater fall from baseline values (38 vs. 27%). Despite differences in the degree of hypoventilation, arterial CO2 tension increased similarly in both groups (21%). BP increased (P < 0.01) with loading in older but not younger animals. We conclude that the decreased metabolic rate and limited hemodynamic response in younger piglets reflect an accomodative response to hypoventilation in contrast to that of older animals, which display an adult pattern of increased metabolic rate and BP with loaded breathing.

Dyspnea sensation and chemical control of breathing in adult twins.

To examine possible genetic influence on the sensation of dyspnea and on load compensation, we conducted a twin study using healthy adult pairs (10 monozygotes, MZ, and 9 dizygotes, DZ). The ventilatory response to progressive hypercapnia (HCVR) was examined under three different conditions: hyperoxia (PETO2 > 150 mm Hg), hypoxia (PETO2 maintained at 50 to 55 mm Hg), and hyperoxia with an inspiratory flow-resistive load (17 mm H2O/L/s), with simultaneous assessment of the dyspnea sensation by visual analog scale (VAS). Although the VDZ/VMZ ratio (VMZ and VDZ are within-pair variances in MZ and DZ, respectively) for the slope value of the minute ventilation-PETCO2 regression line was not different from 1 in hyperoxia either with or without an inspiratory load, it was significantly larger than 1 in hypoxia (F = 5.17, p < 0.05), suggesting that a genetic influence on HCVR existed only in the presence of hypoxia. During 3% CO2 inhalation, the VDZ/VMZ ratio for the tidal volume (VT) was larger than 1 in hyperoxic HCVR with loading (F = 7.89, p < 0.01), and that for respiratory frequency (f) was larger than 1 only in hypoxic HCVR (F = 3.59, p < 0.05). At a PETCO2 of 55 mm Hg, the VT ratio was larger than 1 under all conditions (F = 5.91, p < 0.05; F = 6.99, p < 0.05; F = 3.75, p < 0.05; respectively), and the f ratio was significantly larger than 1 again only in hypoxic HCVR (F = 3.48, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Diaphragmatic failure during loaded breathing: role of neuromuscular transmission.

To determine whether central or peripheral mechanisms are responsible for diaphragmatic failure during loaded breathing, phrenic nerve activity (iENG), diaphragm muscle electromyogram (iEMG), and transdiaphragmatic pressure (Pdi) were measured in unanesthetized chronically instrumented sheep during inspiratory flow-resistive (IFR) loaded breathing. After placement of the IFR load, Pdi increased initially and remained relatively stable for 10-30 min [Pdi = 69.9 +/- 6.3 (SE) cmH2O, n = 6]; arterial PCO2 also increased from baseline (35.8 +/- 0.9 Torr) to 55.1 +/- 4.7 Torr. During IFR loading, iEMG and iENG also increased from baseline, but during the plateau phase of Pdi, iENG continued to increase at the same time while iEMG was stable, and the M wave, evoked by phrenic nerve stimulation, decreased during this period. After the plateau phase, Pdi decreased and arterial PCO2 increased, at which point the study was terminated (at 82.1 +/- 20.6 min). The observation that iENG increased while Pdi and iEMG were stable demonstrates a reduced efficiency of neuromuscular transmission and suggests that the neuromuscular junction is an important site of diaphragmatic failure in unanesthetized sheep during IFR loaded breathing.

Respiratory Muscle Acidosis Stimulates Endogenous Opioids during Inspiratory Loading

Activation of endogenous opioid pathways during intense inspiratory flow-resistive loading (IRL) results in greater inhibition of EMG activity in the external oblique (EMGeo) relative to the diaphragm (EMGdi). Dichloroacetate (DCA) abolishes opioid-mediated inhibitory influences upon these muscles, suggesting a causal relationship between respiratory muscle lactic acidosis and activation of endogenous opioid pathways, during IRL. We tested the hypothesis that a more intense acidosis of the external oblique relative to the diaphragm may be the signal that determines the differential inhibitory opioid-mediated effect upon the respiratory muscles during IRL. Unanesthetized goats were exposed to IRL (50 cm H2O/1/s) for 120 min, before and after intravenous pretreatment with DCA (50 mg/kg) or saline. We measured peak phasic EMGdi and EMGeo, and respective muscle interstitial pH (pHdi, pHeo) using flexible pH probes. After 120 min IRL with saline, pHdi, and pHeo declined by -0.12 +/- 0.03 (mean +/- SEM) and -0.20 +/- 0.04 units, respectively (p < 0.05, pHdi versus pHeo). Naloxone (NLX), 0.3 mg/kg given intravenously at this time, increased EMGdi by 26.5 +/- 6.1%, but EMGeo by 81.9 +/- 13.3% (p < 0.05, EMGdi versus EMGeo). DCA blunted both the change in pHdi and pHeo during IRL (to -0.01 +/- 0.01 and -0.08 +/- 0.03 units, respectively) (p < 0.05, DCA versus saline) and the increase in EMGdi and EMGeo with NLX (to -1.0 +/- 2.6% and 5.7 +/- 5.8%, respectively) (p < 0.05, DCA versus saline).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood flow to respiratory muscles and major organs during inspiratory flow resistive loads.

To determine whether diaphragmatic fatigue in the intact animal subjected to loaded breathing is associated with a decrease in diaphragmatic blood flow, seven unanesthetized sheep were subjected to severe inspiratory flow resistive (IFR) loads that led to a decrease in transdiaphragmatic pressure (Pdi) and a rise in arterial PCO2 (PaCO2). Blood flow to the diaphragm, other respiratory muscles, limb muscles, and major organs was measured using the radionuclide-labeled microsphere method. With these loads blood flow increased to the diaphragm (621 +/- 242%) and all the other inspiratory and expiratory diaphragm (621 +/- 242%) and all the other inspiratory and expiratory muscles; there was no statistically significant change in blood flow to these muscles at the time when Pdi decreased and PaCO2 rose. Blood flow also increased to the heart (103 +/- 34%), brain (212 +/- 39%), and adrenals (76 +/- 9%), whereas pancreatic flow decreased (-66 +/- 14%). Limb muscle blood flow remained unchanged. We conclude that in unanesthetized sheep subjected to IFR loads 1) we did not demonstrate a decrease in respiratory muscle blood flow associated with diaphragmatic fatigue and ventilatory failure, and 2) there is a redistribution of blood flow among major organs.

Effect of maturation on the extrathoracic airway stability of infants.

The influence of maturation on extrathoracic airway (ETA) stability during quiet sleep was determined in 13 normal preterm infants of 1.41 +/- 0.14 (SD) kg birth weight and 32 +/- 2 wk estimated gestational age. Studies began in the first week of life and were performed three times at weekly intervals. A drop in intraluminal pressure within the ETA was produced by external inspiratory flow-resistive loading (60 cmH2O.l-1 x s at 1 l/min); an increase in intrinsic resistance, indicating airway narrowing, was sought as a measure of ETA instability. Baseline total pulmonary resistance was not significantly different between weeks 1, 2, and 3 (88 +/- 35, 65 +/- 24, and 61 +/- 17 cmH2O.l-1 x s, respectively) but increased markedly above baseline with loading to 144 +/- 45 cmH2O.l-1.s during week 1 (P < 0.001), 89 +/- 28 cmH2O.l-1 x s at week 2 (P < 0.01), and 74 +/- 25 cmH2O.l-1 x s at week 3 (n = 10). The increment with loading was significantly greater during week 1 than during weeks 2 or 3 (P < 0.02). Similar studies were also done in seven full-term infants in the first week of life to evaluate the influence of gestational maturity on ETA stability. Despite a relatively greater drop in intraluminal pressure within the ETA of term vs. preterm infants with loading (P < 0.001), total pulmonary resistance failed to increase (68 +/- 21 to 71 +/- 32 cmH2O.l-1.s). These data reveal that ETA instability is present in preterm infants at birth and decreases with increasing postnatal age. Full-term neonates, by comparison, display markedly greater ETA stability in the immediate neonatal period.

Glycogen Content in Neonatal Diaphragmatic Fibres in Response to Inspiratory Flow Resistive Loads1

To study intramuscular glycogen use with increased work loads in the neonatal diaphragm, unanesthetized lambs were subjected to severe inspiratory flow resistive loads. With these loads, transdiaphragmatic pressure and arterial CO2 tension increased several fold above baseline and then remained stable for a period of 10-30 min. This was followed by a decrease in transdiaphragmatic pressure and a marked increase in arterial CO2 tension with severe acidosis. Intramuscular glycogen content was determined histochemically by the periodic acid-Schiff reaction and was quantified microphotometrically by the fiber types (type I, IIa, or IIc) present in the lamb costal diaphragm. Glycogen content in the control diaphragm was greatest in type IIa fibers and lowest in type I fibers. With severe inspiratory flow resistive loads, the greatest decrease in glycogen content was in type IIa fibers, followed by type IIc and type I fibers. Therefore, our data suggest that in the neonatal lamb subjected to inspiratory flow resistive loads the diaphragm uses intramuscular glycogen during increased work loads. These data do not indicate that the marked depletion of glycogen in the diaphragm is the cause of the decrease in diaphragmatic force.

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.

Responses of Diaphragm and External Oblique Muscles to Flow-resistive Loads During Sleep

Although it is generally agreed that rapid respiratory compensation for externally applied inspiratory loads is impaired or absent during sleep, the individual components of the "load-compensating reflex" may not be inhibited by sleep to the same degree. We studied the effect of inspiratory flow-resistive loading (18 cm H2O/L/s) for two consecutive breaths on inspiratory (diaphragm) and expiratory (external oblique) muscle activity, and respiratory timing, in six awake and sleeping goats. During the first loaded breath in the awake state, peak integrated diaphragmatic electromyogram activity (EMGdi) increased 16.7 +/- 3.9% (p less than 0.01), peak integrated external oblique EMG activity (EMGeo) increased 21.0 +/- 7.5% (p less than 0.001), and electrical inspiratory time (Ti) increased 18.1 +/- 2.1% (p less than 0.01). In contrast, loading did not significantly change peak EMGdi or EMGeo on the first or second breaths in any sleep state. However, Ti was significantly increased during loading in all sleep states (p less than 0.01) to a similar degree seen during wakefulness. Loading did not significantly alter electrical expiratory time. No significant differences were noted between the first and second loaded breaths. We conclude that the reflex increases in peak EMG of both inspiratory and expiratory muscles in response to inspiratory flow-resistive loading during the awake state are absent during all stages of sleep; however, one aspect of load compensation, prolongation of Ti, is preserved during sleep and aids in maintaining tidal volume.