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)     

Respiratory muscle interaction during NREM sleep in patients with occlusive apnea

To study respiratory muscle interaction in patients with occlusive apnea, diaphragmatic electromyogram (EMGdi) and gastric, pleural, and transdiaphragmatic pressures (Pga, Ppl, and Pdi, respectively) were studied in seven patients during non-rapid-eye-movement (NREM) sleep. Diaphragmatic force output, as assessed by Pdi, followed the periodic changes in EMGdi but during the occlusive phase the increase in Pdi was more than the increase in EMGdi. This increase in Pdi was essentially due to an increase in Ppl, since Pga and EMGdi had a linear relationship (r = 0.98, P less than 0.001) that did not change during the occlusive and ventilatory phases. Abdominal muscle recruitment evident in Pga and abdominal motion tracings during the occlusive phase when paradoxical rib cage motion was observed suggested that this increase in diaphragmatic efficiency was likely due to a change in diaphragmatic length-tension characteristics. These results demonstrate that, in patients with occlusive apneas, the diaphragm is the predominant respiratory muscle during NREM sleep and that its function is supported by abdominal muscle recruitment.     

Ventilatory muscle recruitment during unsupported arm exercise in normal subjects

To test the hypothesis that during unsupported arm exercise (UAE) some of the inspiratory muscles of the rib cage partake in upper torso and arm positioning and thereby decrease their contribution to ventilation, we studied 11 subjects to measure pleural (Ppl) and gastric (Pga) pressures, heart rate, respiratory frequency, O2 uptake (VO2), and tidal volume (VT) during symptom-limited UAE. We used leg ergometry (LE) as a reference. Exercise duration was shorter for UAE vs. LE (207 +/- 67 vs. 514 +/- 224 s, P less than 0.05) even though the end-exercise VO2 was lower for UAE (9.3 +/- 1.1 vs. 30.8 +/- 3.2 ml.kg-1.min-1, P less than 0.05). Eight subjects had positive Ppl-Pga slopes and less negative end-inspiratory Ppl during UAE vs. LE (-11.8 +/- 6 vs. -19 +/- 7 cmH2O, P less than 0.05). This was not due to the lower VT's achieved during UAE, since at a similar VT, UAE resulted in a rightward and downward displacement of the Ppl-Pga slopes. Three of the subjects had irregular breathing rhythm and negative Ppl-Pga slopes as early as 1 min after initiation of UAE. They had shorter UAE duration and more dyspnea than the eight with positive Ppl-Pga slopes. In most subjects UAE decreases the ventilatory contribution of some of the inspiratory muscles of the rib cage as they have to partake in nonventilatory functions. This results in a shift of the dynamic work to the diaphragm and abdominal muscles of exhalation. In a few subjects UAE results in an irregular breathing pattern and very short exercise tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lung and chest wall mechanics in microgravity.

We studied the effect of 15-20 s of weightlessness on lung, chest wall, and abdominal mechanics in five normal subjects inside an aircraft flying repeated parabolic trajectories. We measured flow at the mouth, thoracoabdominal and compartmental volume changes, and gastric pressure (Pga). In two subjects, esophageal pressures were measured as well, allowing for estimates of transdiaphragmatic pressure (Pdi). In all subjects functional residual capacity at 0 Gz decreased by 244 +/- 31 ml as a result of the inward displacement of the abdomen. End-expiratory Pga decreased from 6.8 +/- 0.8 cmH2O at 1 Gz to 2.5 +/- 0.3 cmH2O at Gz (P less than 0.005). Abdominal contribution to tidal volume increased from 0.33 +/- 0.05 to 0.51 +/- 0.04 at 0 Gz (P less than 0.001) but delta Pga showed no consistent change. Hence abdominal compliance increased from 43 +/- 9 to 70 +/- 10 ml/cmH2O (P less than 0.05). There was no consistent effect of Gz on tidal swings of Pdi, on pulmonary resistance and dynamic compliance, or on any of the timing parameters determining the temporal pattern of breathing. The results indicate that at 0 G respiratory mechanics are intermediate between those in the upright and supine postures at 1 G. In addition, analysis of end-expiratory pressures suggests that during weightlessness intra-abdominal pressure is zero, the diaphragm is passively tensed, and a residual small pleural pressure gradient may be present.     

Effect of abdominal compression on maximum transdiaphragmatic pressure

Transdiaphragmatic pressure (Pdi) is lower during maximum inspiratory effort with the diaphragm alone than when maximum inspiratory and expulsive efforts are combined. The increase in Pdi with expulsive effort has been attributed to increased neural activation of the diaphragm. Alternatively, the increase could be due to stretching of the contracted diaphragm. If this were so, Pdi measured during a combined maximum effort would overestimate the capacity of the diaphragm to generate inspiratory force. This study determined the likely contribution of stretching of the contracted diaphragm to estimates of maximum Pdi (Pdimax) obtained during combined inspiratory and expulsive effort. Three healthy trained subjects were studied standing. Diaphragmatic Mueller maneuvers were performed at functional residual capacity and sustained during subsequent abdominal compression by either abdominal muscle expulsive effort or externally applied pressure. Measurements were made of changes in abdominal (Pab) and pleural (Ppl) pressure, Pdi, rib cage and abdominal dimensions and respiratory electromyograms. Three reproducible performances of each maneuver from each subject were analyzed. When expulsive effort was added to maximum diaphragmatic inspiratory effort, Pdimax increased from 86 +/- 12 to 148 +/- 14 (SD) cmH2O within the 1st s and was 128 +/- 14 cmH2O 2 s later. When external compression was added to maximum diaphragmatic inspiratory effort, Pdimax increased from 87 +/- 16 to 171 +/- 19 cmH2O within the 1st s and was 152 +/- 16 cmH2O 2 s later.(ABSTRACT TRUNCATED AT 250 WORDS)     

Targeted resistive ventilatory muscle training in chronic obstructive pulmonary disease

To overcome the problem of altered breathing strategy during resistive ventilatory muscle training (VMT), we used a single-orifice inspiratory resistance together with a target feedback device (TFD) in patients with chronic obstructive pulmonary disease (COPD). In a preliminary study (study A), we showed that the resistance plus TFD was effective in controlling breathing strategy. We subsequently used the resistor plus TFD in a 5-wk study (study B) of VMT in 17 COPD patients who were randomized into high-intensity (HI) and low-intensity (LI) training groups. Compared with the LI group, the HI group showed significant increases in static maximal inspiratory pressure (21.3 vs. 5.0 cmH2O), maximal sustained ventilatory capacity (MSVC, 3.2 vs -0.1 l/min, sustained maximal mouth pressure (12.1 vs. 0.6 cmH2O), mean mouth pressure (6.9 vs. 3.9 cmH2O), peak inspiratory flow rate (12.3 vs. 4.0 l/min), and maximal sustained work rate (12.2 vs. 4.2 cmH2O.l-1.min-1). We conclude that targeted VMT with control of breathing strategy improves both ventilatory muscle strength and endurance.     

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.     

Pleural pressure increases during inspiration in the zone of apposition of diaphragm to rib cage

The zone of apposition of diaphragm to rib cage provides a theoretical mechanism that may, in part, contribute to rib cage expansion during inspiration. Increases in intra-abdominal pressure (Pab) that are generated by diaphragmatic contraction are indirectly applied to the inner rib cage wall in the zone of apposition. We explored this mechanism, with the expectation that pleural pressure in this zone (Pap) would increase during inspiration and that local transdiaphragmatic pressure in this zone (Pdiap) must be different from conventionally determined transdiaphragmatic pressure (Pdi) during inspiration. Direct measurements of Pap, as well as measurements of pleural pressure (Ppl) cephalad to the zone of apposition, were made during tidal inspiration, during phrenic stimulation, and during inspiratory efforts in anesthetized dogs. Pab and esophageal pressure (Pes) were measured simultaneously. By measuring Ppl's with cannulas placed through ribs, we found that Pap consistently increased during both maneuvers, whereas Ppl and Pes decreased. Whereas changes in Pdi of up to -19 cmH2O were measured, Pdiap never departed from zero by greater than -4.5 cmH2O. We conclude that there can be marked regional differences in Ppl and Pdi between the zone of apposition and regions cephalad to the zone. Our results support the concept of the zone of apposition as an anatomic region where Pab is transmitted to the interior surface of the lower rib cage.     

Oxygen cost of exercise hyperpnea: measurement.

To quantitate the O2 cost of maximal exercise hyperpnea, we required eight healthy adult subjects to mimic, at rest, the important mechanical components of submaximal and maximal exercise hyperpnea. Expired minute ventilation (VE), transpulmonary and transdiaphragmatic (Pdi) pressures, and end-expiratory lung volume (EELV) were measured during exercise at 70 and 100% of maximal O2 uptake. At rest, subjects were given visual feedback of their exercise transpulmonary pressure-tidal volume loop (WV), breathing frequency, and EELV, which they mimicked repeatedly for 5 min per trial over several trials, while hypocapnia was prevented. The change in total body O2 uptake (VO2) was measured and presumed to represent the O2 cost of the hyperpnea. In 61 mimicking trials with VE of 115-167 l/min and WV of 124-544 J/min, VE, WV, duty cycle of the breath, and expiratory gastric pressure (Pga) integrated with respect to time (integral of Pga.dt/min) were not different from those observed during maximum exercise. integral of Pdi.dt/min was 14% less and EELV was 6% greater during maximum exercise than during mimicking. The O2 cost measurements within a subject were reproducible over 3-12 trials (coefficient of variation +/- 10% range 5-16%). The O2 costs of hyperpnea correlated highly and positively with VE and WV and less, but significantly, with integral of Pdi.dt and integral of Pga.dt. The O2 cost of VE rose out of proportion to the increasing hyperpnea, so that between 70 and 100% of maximal VO2 delta VO2/delta VE increased 40-60% (1.8 +/- 0.2 to 2.9 +/- 0.1 ml O2/l VE) as VE doubled.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventilatory response to fatiguing and nonfatiguing resistive loads in awake sheep

To study the changes in ventilation induced by inspiratory flow-resistive (IFR) loads, we applied moderate and severe IFR loads in chronically instrumented and awake sheep. We measured inspired minute ventilation (VI), ventilatory pattern [inspiratory time (TI), expiratory time (TE), respiratory cycle time (TT), tidal volume (VT), mean inspiratory flow (VT/TI), and respiratory duty cycle (TI/TT)], transdiaphragmatic pressure (Pdi), functional residual capacity (FRC), blood gas tensions, and recorded diaphragmatic electromyogram. With both moderate and severe loads, Pdi, TI, and TI/TT increased, TE, TT, VT, VT/TI, and VI decreased, and hypercapnia ensued. FRC did not change significantly with moderate loads but decreased by 30-40% with severe loads. With severe loads, arterial PCO2 (PaCO2) stabilized at approximately 60 Torr within 10-15 min and rose further to levels exceeding 80 Torr when Pdi dropped. This was associated with a lengthening in TE and a decrease in breathing frequency, VI, and TI/TT. We conclude that 1) timing and volume responses to IFR loads are not sufficient to prevent alveolar hypoventilation, 2) with severe loads the considerable increase in Pdi, TI/TT, and PaCO2 may reduce respiratory muscle endurance, and 3) the changes in ventilation associated with neuromuscular fatigue occur after the drop in Pdi. We believe that these ventilatory changes are dictated by the mechanical capability of the respiratory muscles or induced by a decrease in central neural output to these muscles or both.     

Respiratory muscle oxygen consumption estimated by the diaphragm pressure-time index

The O2 consumption of the respiratory muscles (VO2resp), work of breathing, and the time integral of the transdiaphragmatic pressure (TTdi) were measured in four normal subjects breathing against inspiratory resistance. A total of 39 runs were performed at mean tidal transdiaphragmatic pressures (Pdi) ranging from 15 to 53 cmH2O, respiratory frequencies from 3.5 to 22 breaths/min, and inspiratory time durations (TI) from 32 to 76% of the total breath duration. Each run was maintained from 8 to 17 min and the above parameters were kept constant by the subject via visual feedback of Pdi and TI with an oscilloscope. Most of the runs (36 of 39) were performed at TTdi values below those known to produce respiratory muscle fatigue. We found a strong linear correlation between the VO2resp and the TTdi (r = 0.74, P less than 0.001) and a weaker correlation between VO2resp and W (r = 0.31, P less than 0.05). These data suggest that TTdi is a good estimator of VO2resp over a wide range of respiratory patterns during inspiratory resistance breathing. The high variability seen in respiratory muscle efficiency during resistive breathing may be due to W not being a good indicator of the energy consumed by the respiratory muscles.     

Determinants of exercise performance in normal men with externally imposed expiratory flow limitation.

To understand how externally applied expiratory flow limitation (EFL) leads to impaired exercise performance and dyspnea, we studied six healthy males during control incremental exercise to exhaustion (C) and with EFL at approximately 1. We measured volume at the mouth (Vm), esophageal, gastric and transdiaphragmatic (Pdi) pressures, maximal exercise power (W(max)) and the difference (Delta) in Borg scale ratings of breathlessness between C and EFL exercise. Optoelectronic plethysmography measured chest wall and lung volume (VL). From Campbell diagrams, we measured alveolar (PA) and expiratory muscle (Pmus) pressures, and from Pdi and abdominal motion, an index of diaphragmatic power (W(di)). Four subjects hyperinflated and two did not. EFL limited performance equally to 65% W(max) with Borg = 9-10 in both. At EFL W(max), inspiratory time (TI) was 0.66s +/- 0.08, expiratory time (TE) 2.12 +/- 0.26 s, Pmus approximately 40 cmH2O and DeltaVL-DeltaVm = 488.7 +/- 74.1 ml. From PA and VL, we calculated compressed gas volume (VC) = 163.0 +/- 4.6 ml. The difference, DeltaVL-DeltaVm-VC (estimated blood volume shift) was 326 ml +/- 66 or 7.2 ml/cmH2O PA. The high Pmus and long TE mimicked a Valsalva maneuver from which the short TI did not allow recovery. Multiple stepwise linear regression revealed that the difference between C and EFL Pmus accounted for 70.3% of the variance in DeltaBorg. DeltaW(di) added 12.5%. We conclude that high expiratory pressures cause severe dyspnea and the possibility of adverse circulatory events, both of which would impair exercise performance.     

Bilateral phrenic stimulation: a simple technique to assess diaphragmatic fatigue in humans

Transdiaphragmatic pressure (Pdi) and the rate of relaxation of the diaphragm (tau) were measured at functional residual capacity (FRC) in six normal seated subjects during single-twitch stimulation of both phrenic nerves. The latter were stimulated supramaximally with needle electrodes with square-wave impulses of 0.1-ms duration at 1 Hz before and after diaphragmatic fatigue produced by resistive loaded breathing. Constancy of chest wall configuration was achieved by monitoring the diameter of the abdomen and the rib cage with a respiratory inductive plethysmograph system. During control the peak Pdi generated during the phrenic stimulation amounted to 34.4 +/- 4.2 (SE) cmH2O and represented in each subject a fixed fraction (17%) of its maximal transdiaphragmatic pressure. After diaphragmatic fatigue the peak Pdi decreased by an average of 45%, amounting to 18.1 +/- 2.7 cmH2O 5 min after the fatigue run, and tau increased from 55.2 +/- 9 ms during control to 77 +/- 8 ms 5 min after the fatigue run. The decrease in peak Pdi and the increase in tau observed after the fatigue run persisted throughout the 30 min of the recovery period studied, the peak Pdi amounting to 18.4 +/- 2.8 and 18.9 +/- 3.3 cmH2O and tau to 81.3 +/- 5.7 and 88.7 +/- 10 ms at 15 and 30 min after the end of the fatigue run, respectively. It is concluded that diaphragmatic fatigue can be detected in man by bilateral phrenic stimulation with needle electrodes without any discomfort for the subject and that the decrease in diaphragmatic strength after fatigue is long lasting.     

Respiratory load compensation in chronic airway obstruction

To assess respiratory neuromuscular function and load compensating ability in patients with chronic airway obstruction (CAO), we studied eight stable patients with irreversible airway obstruction during hyperoxic CO2 rebreathing with and without a 17 cmH2O X l-1 X s flow-resistive inspiratory load (IRL). Minute ventilation (VE), transdiaphragmatic pressure (Pdi), and diaphragmatic electromyogram (EMGdi) were monitored. Pdi and EMGdi were obtained via a single gastroesophageal catheter with EMGdi being quantitated as the average rate of rise of inspiratory (moving average) activity. Based on the effects of IRL on the Pdi response to CO2 [delta Pdi/delta arterial CO2 tension (PaCO2)] and the change in Pdi for a given change in EMGdi (delta Pdi/delta EMGdi) during rebreathing, two groups could be clearly identified. Four patients (group A) were able to increase delta Pdi/delta PaCO2 and delta Pdi/delta EMGdi, whereas in the other four (group B) the IRL responses decreased. All group B patients were hyperinflated having significantly greater functional residual capacity (FRC) and residual volume than group A. In addition the IRL induced percent change in delta Pdi/delta PaCO2, and delta VE/delta PaCO2 was negatively correlated with lung volume so that in the hyperinflated group B the higher the FRC the greater was the decrease in Pdi response due to IRL. In both groups the greater the FRC the greater was the decrease in the ventilatory response to loading. Patients with CAO, even with severe airways obstruction, can effect load compensation by increasing diaphragmatic force output, but the presence of increased lung volume with the associated shortened diaphragm prevents such load compensation.     

Respiratory muscle fatigue: a cause of ventilatory failure in septic shock

The effect of endotoxic shock on the respiratory muscle performance was studied in spontaneously breathing dogs given Escherichia coli endotoxin (Difco Laboratories, 10 mg/kg). Diaphragmatic (Edi) and parasternal intercostal (Eic) electromyograms were recorded using fishhook electrodes. The recorded signals were then rectified and electrically integrated. Pleural, abdominal, and transdiaphragmatic (Pdi) pressures were recorded by a balloon-catheter system. After a short control period, the endotoxin was administered slowly intravenously (within 5 min). Death was secondary to respiratory arrest in all animals. All animals died within 150-270 min after the onset of endotoxic shock. Within 45-80 min of the endotoxin administration, mean blood pressure and cardiac output dropped to 42.1 +/- 4.1 and 40.1 +/- 6.0% (mean +/- SE) of control values, respectively, with little change afterward. Mean inspiratory flow rate and Pdi increased from control values of 0.27 +/- 0.03 l X s-1 and 5.75 +/- 0.7 cmH2O to mean values of 0.44 +/- 0.3 l X s-1 and 8.70 +/- 1.05 cmH2O and then decreased to 0.17 +/- 0.03 l X s-1 and 3.90 +/- 0.30 cmH2O before the death of the animals. There were no major changes in the mechanics of the respiratory system. Edi and Eic increased progressively to mean values of 360 +/- 21 and 263 +/- 22% of control, respectively, before the death of the animals. None of the dogs were hypoxic. Arterial PCO2 decreased from a control value of 42.9 +/- 1.7 Torr to a mean value of 29.9 +/- 2.8 Torr and then increased to 51 +/- 4.3 Torr before the death of the animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Partitioning of inspiratory pressure swings between diaphragm and intercostal/accessory muscles

We tested the hypothesis that the inspiratory pressure swings across the rib-cage pathway are the sum of transdiaphragmatic pressure (Pdi) and the pressures developed by the intercostal/accessory muscles (Pic). If correct, Pic can only contribute to lowering pleural pressure (Ppl), to the extent that it lowers abdominal pressure (Pab). To test this we measured Pab and Ppl during during Mueller maneuvers in which deltaPab = 0. Because there was no outward displacement of the rib cage, Pic must have contributed to deltaPpl, as did Pdi. Under these conditions the total pressure developed by the inspiratory muscles across the rib-cage pathway was less than Pdi + Pic. Therefore, we rejected the hypothesis. A plot of Pab vs. Ppl during relaxation allows partitioning of the diaphragmatic and intercostal/accessory muscle contributions to inspiratory pressure swings. The analysis indicates that the diaphragm can act both as a fixator, preventing transmission of Ppl to the abdomen and as an agonist. When abdominal muscles remain relaxed it only assumes the latter role to the extent that Pab increases.     

Within-breath electromyographic changes during loaded breathing in adult sheep

To investigate the changes in diaphragm electromyogram (EMG) during the course of severe loaded breathing, we subjected five conscious adult sheep to inspiratory flow resistive breathing (resistance greater than 150 cmH2O X l-1 X s) for up to 2-3 h and studied the total EMG power per breath (iEMG) and the EMG power per unit time after dividing the duration of EMG activity within each breath into three equal parts (iEMG1, iEMG2, and iEMG3). Both total breath iEMG and transdiaphragmatic pressure (Pdi) increased, remained at a high level for a certain period of time, and then started to fall. A change in the pattern of iEMG within a breath was observed during loaded breathing. The increase in total-breath iEMG was associated mostly with an increase in iEMG3, or the last part of the EMG power within each inspiration. Similarly, the decrease in total breath iEMG was primarily due to a decrease in iEMG3. We conclude that, in sheep subjected to severe IFR loads for prolonged periods the marked increase in total-breath iEMG at the beginning of loaded breathing and the marked decrease in this iEMG at the time of decrease in Pdi are largely due to changes in iEMG that occur during the latter third of each breath. We speculate that during loaded breathing the recruitment pattern of diaphragmatic muscle fibers changes during the course of an inspiratory effort.     

Influence of lung volume on oxygen cost of resistive breathing

We examined the relationship between the O2 cost of breathing (VO2 resp) and lung volume at constant load, ventilation, work rate, and pressure-time product in five trained normal subjects breathing through an inspiratory resistance at functional residual capacity (FRC) and when lung volume (VL) was increased to 37 +/- 2% (mean +/- SE) of inspiratory capacity (high VL). High VL was maintained using continuous positive airway pressure of 9 +/- 2 cmH2O and with the subjects coached to relax during expiration to minimize respiratory muscle activity. Six paired runs were performed in each subject at constant tidal volume (0.62 +/- 0.2 liters), frequency (23 +/- 1 breaths/min), inspiratory flow rate (0.45 +/- 0.1 l/s), and inspiratory muscle pressure (45 +/- 2% of maximum static pressure at FRC). VO2 resp increased from 109 +/- 15 ml/min at FRC by 41 +/- 11% at high VL (P less than 0.05). Thus the efficiency of breathing at high VL (3.9 +/- 0.2%) was less than that at FRC (5.2 +/- 0.3%, P less than 0.01). The decrease in inspiratory muscle efficiency at high VL may be due to changes in mechanical coupling, in the pattern of recruitment of the respiratory muscles, or in the intrinsic properties of the inspiratory muscles at shorter length. When the work of breathing at high VL was normalized for the decrease in maximum inspiratory muscle pressure with VL, efficiency at high VL (5.2 +/- 0.3%) did not differ from that at FRC (P less than 0.7), suggesting that the fall in efficiency may have been related to the fall in inspiratory muscle strength. During acute hyperinflation the decreased efficiency contributes to the increased O2 cost of breathing and may contribute to the diminished inspiratory muscle endurance.     

O2 metabolism of the sheep diaphragm during flow resistive loaded breathing

To determine whether O2 availability limited diaphragmatic performance, we subjected unanesthetized sheep to severe (n = 11) and moderate (n = 3) inspiratory flow resistive loads and studied the phrenic venous effluent. We measured transdiaphragmatic pressure (Pdi), systemic arterial and phrenic venous blood gas tensions, and lactate and pyruvate concentrations. In four sheep with severe loads, we measured O2 saturation (SO2), O2 content, and hemoglobin. We found that with severe loads Pdi increased to 74.7 +/- 6.0 cmH2O by 40 min of loading, remained stable for 20-30 more min, then slowly decreased. In every sheep, arterial PCO2 increased when Pdi decreased. With moderate loads Pdi increased to and maintained levels of 40-55 cmH2O. With both loads, venous PO2, SO2, and O2 content decreased initially and then increased, so that the arteriovenous difference in O2 content decreased as loading continued. Hemoglobin increased slowly in three of four sheep. There were no appreciable changes in arterial or venous lactate and pyruvate during loading or recovery. We conclude that the changes in venous PO2, SO2, and O2 content may be the result of changes in hemoglobin, blood flow to the diaphragm, or limitation of O2 diffusion. Our data do not support the hypothesis that in sheep subjected to inspiratory flow resistive loads O2 availability limits diaphragmatic performance.     

Effect of elastic loading on ventilatory pattern during progressive exercise

Ventilatory responses to progressive exercise, with and without an inspiratory elastic load (14.0 cmH2O/l), were measured in eight healthy subjects. Mean values for unloaded ventilatory responses were 24.41 +/- 1.35 (SE) l/l CO2 and 22.17 +/- 1.07 l/l O2 and for loaded responses were 24.15 +/- 1.93 l/l CO2 and 20.41 +/- 1.66 l/l O2 (P greater than 0.10, loaded vs. unloaded). At levels of exercise up to 80% of maximum O2 consumption (VO2max), minute ventilation (VE) during inspiratory elastic loading was associated with smaller tidal volume (mean change = 0.74 +/- 0.06 ml; P less than 0.05) and higher breathing frequency (mean increase = 10.2 +/- 0.98 breaths/min; P less than 0.05). At levels of exercise greater than 80% of VO2max and at exhaustion, VE was decreased significantly by the elastic load (P less than 0.05). Increases in respiratory rate at these levels of exercise were inadequate to maintain VE at control levels. The reduction in VE at exhaustion was accompanied by significant decreases in O2 consumption and CO2 production. The changes in ventilatory pattern during extrinsic elastic loading support the notion that, in patients with fibrotic lung disease, mechanical factors may play a role in determining ventilatory pattern.