Effects of expiratory resistive loading on the sensation of dyspnea

To determine whether an increase in expiratory motor output accentuates the sensation of dyspnea (difficulty in breathing), the following experiments were undertaken. Ten normal subjects, in a series of 2-min trials, breathed freely (level I) or maintained a target tidal volume equal to (level II) or twice the control (level III) at a breathing frequency of 15/min (similar to the control frequency) with an inspiratory load, an expiratory load, and without loads under hyperoxic normocapnia. In tests at levels II and III, end-expiratory lung volume was maintained at functional residual capacity. A linear resistance of 25 cmH2O.1(-1).s was used for both inspiratory and expiratory loading; peak mouth pressure (Pm) was measured, and the intensity of dyspnea (psi) was assessed with a visual analog scale. The sensation of dyspnea increased significantly with the magnitude of expiratory Pm during expiratory loading (level II: Pm = 9.4 +/- 1.5 (SE) cmH2O, psi = 1.26 +/- 0.35; level III: Pm = 20.3 +/- 2.8 cmH2O, psi = 2.22 +/- 0.48) and with inspiratory Pm during inspiratory loading (level II: Pm = 9.7 +/- 1.2 cmH2O, psi = 1.35 +/- 0.38; level III: Pm = 23.9 +/- 3.0 cmH2O, psi = 2.69 +/- 0.60). However, at each level of breathing, neither the intensity of dyspnea nor the magnitude of peak Pm during loading was different between inspiratory and expiratory loading. The augmentation of dyspnea during expiratory loading was not explained simply by increases in inspiratory activity. The results indicate that heightened expiratory as well as inspiratory motor output causes comparable increases in the sensation of difficulty in breathing.     

Effects of changes in inspiratory muscle strength on the sensation of respiratory force

The sensation of respiratory muscle force was compared in seven normal subjects before and after inspiratory muscle strength training. Subjects performed 20 sustained maximal inspiratory maneuvers daily for 6-18 wk. Maximal inspiratory pressures (MIP) increased from 124 +/- 10 to 187 +/- 9 (SE) cmH2O (P less than 0.005). Exponents of the power function relationships between mouth pressure (Pm) and the intensity of the sensation of force, corrected for inspiratory duration, during magnitude scaling of resistive and elastic ventilatory loads were the same before and after training (P greater than 0.05). However, absolute sensation intensity (S) during resistive and elastic loading was reduced significantly after strength training but returned toward baseline levels greater than or equal to 8 wk after the cessation of training when the MIP had fallen to 150 +/- 5 cmH2O. The absolute S at a given Pm during ventilatory loading changed inversely with changes in MIP (P less than 0.001). Furthermore the relationship between absolute S and Pm expressed as a proportion of the MIP (Pm/MIP) was constant over testing periods. These results suggest that the sensation of respiratory muscle force reflects the proportion of the maximum force utilized in breathing and may be based on the level of respiratory motor command signals.     

Effect of expiratory loading on glottic dimensions in humans

We examined the effects of external mechanical loading on glottic dimensions in 13 normal subjects. When flow-resistive loads of 7, 27, and 48 cmH2O X l-1 X s, measured at 0.2 l/s, were applied during expiration, glottic width at the mid-tidal volume point in expiration (dge) was 2.3 +/- 12, 37.9 +/- 7.5, and 38.3 +/- 8.9% (means +/- SE) less than the control dge, respectively. Simultaneously, mouth pressure (Pm) increased by 2.5 +/- 4, 3.0 +/- 0.4, and 4.6 +/- 0.6 cmH2O, respectively. When subjects were switched from a resistance to a positive end-expiratory pressure at comparable values of Pm, both dge and expiratory flow returned to control values, whereas the level of hyperinflation remained constant. Glottic width during inspiration (unloaded) did not change on any of the resistive loads. There was a slight inverse relationship between the ratio of expiratory to inspiratory glottic width and the ratio of expiratory to inspiratory duration. Our results show noncompensatory glottic narrowing when subjects breathe against an expiratory resistance and suggest that the glottic dimensions are influenced by the time course of lung emptying during expiration. We speculate that the glottic constriction is related to the increased activity of expiratory medullary neurons during loaded expiration and, by increasing the internal impedance of the respiratory system, may have a stabilizing function.     

Effect of fatigue on maximal inspiratory pressure-flow capacity.

The inspiratory muscles can be fatigued by repetitive contractions characterized by high force (inspiratory resistive loads) or high velocities of shortening (hyperpnea). The effects of fatigue induced by inspiratory resistive loaded breathing (pressure tasks) or by eucapnic hyperpnea (flow tasks) on maximal inspiratory pressure-flow capacity and rib cage and diaphragm strength were examined in five healthy adult subjects. Tasks consisted of sustaining an assigned breathing frequency, duty cycle, and either a "pressure-time product" of esophageal pressure (for the pressure tasks) or peak inspiratory flow rate (for the flow tasks). Esophageal pressure was measured during maximal inspiratory efforts against a closed glottis (Pesmax), maximal transdiaphragmatic pressure was measured during open-glottis expulsive maneuvers (Pdimax), and maximal inspiratory flow (VImax) was measured during maximal inspiratory efforts with no added external resistance before and after fatiguing pressure and flow tasks. The reduction in Pesmax) with pressure fatigue (-25 +/- 7%) was significantly greater than the change in Pesmax with flow fatigue (-8 +/- 8%, P less than 0.01). In contrast, the reductions in Pdimax (-11 +/- 8%) and VImax (-16 +/- 3%) with flow fatigue were greater than the changes in Pdimax (-0.6 +/- 4%, P less than 0.05) or VImax (-3 +/- 4%, P less than 0.05) with pressure fatigue. We conclude that respiratory muscle performance is dependent not only on the presence of fatigue but whether fatigue was induced by pressure tasks or flow tasks. The specific impairment of Pesmax and not of Pdimax or flow with pressure fatigue may reflect selective fatigue of the rib cage muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of inspiratory muscle strength training on inspiratory motor drive and RREP early peak components.

This study investigated the effect of inspiratory muscle strength training (IMST) on inspiratory motor drive [mouth occlusion pressure at 0.1 s (P(0.1))] and respiratory-related evoked potentials (RREP). It was hypothesized that, if IMST increased inspiratory muscle strength, inspiratory motor drive would decrease. If motor drive were related to the RREP, it was further hypothesized that an IMST-related decrease in drive would change RREP latency and/or amplitude. Twenty-three subjects received IMST at 75% of their maximal inspiratory pressure (Pi(max)) with the use of a pressure threshold valve. IMST consisted of four sets of six breaths daily for 4 wk. P(0.1) and the RREP were recorded before and after IMST. Posttraining, Pi(max) increased significantly by 36.0 +/- 2.7%. P(0.1) decreased significantly by 21.9 +/- 5.2%. The increase in Pi(max) was significantly correlated to the decrease in P(0.1). RREP peaks P(1a), N(f), P(1), and N(1) were identified pre- and post-IMST, and there was no difference in either amplitude or latency for those peaks. These results demonstrate that high-intensity IMST significantly increased Pi(max), decreased P(0.1), but did not change the RREP.     

Accelerated decay of inspiratory pressure during hypercapnic endurance trials in humans

Seven normal human subjects inspired a CO2-O2 mixture from a constant-flow generator while performing maximal inspiratory maneuvers from functional residual capacity. End-tidal CO2 (ETCO2) was maintained at either 5.5 (normocapnia), 3.5 (hypocapnia), or 7% (hypercapnia) on separate testing days. Subjects attained maximal mouth pressure (Pm) while breathing at either 1.25 or 1 l/s, utilizing a fixed breathing pattern (duty cycle 0.43) with an inspiratory time of 1.5 s. Maximal Pm was measured at rest and then during a 10-min endurance trial in which subjects repeated maximal voluntary inspirations with constant flow and breathing pattern. The endurance Pm data were fit to nonlinear exponential regression. The results indicated that 1) maximal Pm at rest was unaffected by changing ETCO2; 2) the rate of Pm decay over time was accelerated by hypercapnia, whereas hypocapnia showed no consistent effects; and 3) "sustainable" Pm, attained toward the end of the endurance trial, was not decreased; therefore sustainable force output was preserved in response to changing ETCO2.     

Threshold effects of respiratory muscle work on limb vascular resistance

The purpose of this study was to determine whether the human diaphragm, like limb muscle, has a threshold of force output at which a metaboreflex is activated causing systemic vasoconstriction. We used Doppler ultrasound techniques to quantify leg blood flow (Q(L)) and utilized the changes in mouth twitch pressure (DeltaP(M)T) in response to bilateral phrenic nerve stimulation to quantify the onset of diaphragm fatigue. Six healthy male subjects performed four randomly assigned trials of identical duration (8 +/- 2 min) and breathing pattern [20 breaths/min and time spent on inspiration during the duty cycle (time spent on inspiration/total time of one breathing cycle) was 0.4] during which they inspired primarily with the diaphragm. For trials 1-3, inspiratory resistance and effort was gradually increased [30, 40, and 50% maximal inspiratory pressure (MIP)], diaphragm fatigue did not occur, and Q(L), limb vascular resistance (LVR), and mean arterial pressure remained unchanged from control (P > 0.05). The fourth trial utilized the same breathing pattern with 60% MIP and caused diaphragm fatigue, as shown by a 30 +/- 12% reduction in P(M)T with bilateral phrenic nerve stimulation. During the fatigue trial, Q(L) and LVR were unchanged from baseline at minute 1, but LVR rose 36% and Q(L) fell 25% at minute 2 and by 52% and 30%, respectively, during the final minutes of the trial. Both LVR and Q(L) returned to control within 30 s of recovery. In summary, voluntary increases in inspiratory muscle effort, in the absence of fatigue, had no effect on LVR and Q(L), whereas fatiguing the diaphragm elicited time-dependent increases in LVR and decreases in Q(L). We attribute the limb vasoconstriction to a metaboreflex originating in the diaphragm, which reaches its threshold for activation during fatiguing contractions.     

Effect of inspiratory muscle fatigue on breathing pattern

Our aim was to determine whether inspiratory muscle fatigue changes breathing pattern and whether any changes seen occur before mechanical fatigue develops. Nine normal subjects breathed through a variable inspiratory resistance with a predetermined mouth pressure (Pm) during inspiration and a fixed ratio of inspiratory time to total breath duration. Breathing pattern after resistive breathing (recovery breathing pattern) was compared with breathing pattern at rest and during CO2 rebreathing (control breathing pattern) for each subject. Relative rapid shallow breathing was seen after mechanical fatigue and also in experiments with electromyogram evidence of diaphragmatic fatigue where Pm was maintained at the predetermined level during the period of resistive breathing. In contrast there was no significant difference between recovery and control breathing patterns when neither mechanical nor electromyogram fatigue was seen. It is suggested that breathing pattern after inspiratory muscle fatigue changes in order to minimize respiratory sensation.     

Preferential fatigue of the rib cage muscles during inspiratory resistive loaded ventilation

Because the inspiratory rib cage muscles are recruited during inspiratory resistive loaded breathing, we hypothesized that such loading would preferentially fatigue the rib cage muscles. We measured the pressure developed by the inspiratory rib cage muscles during maximal static inspiratory maneuvers (Pinsp) and the pressure developed by the diaphragm during maximal static open-glottis expulsive maneuvers (Pdimax) in four human subjects, both before and after fatigue induced by an inspiratory resistive loaded breathing task. Tasks consisted of maintaining a target esophageal pressure, breathing frequency, and duty cycle for 3-5 min, after which the subjects maintained the highest esophageal pressure possible for an additional 5 min. After loading, Pinsp decreased in all subjects [control, -128 +/- 14 (SD) cmH2O; with fatigue, -102 +/- 18 cmH2O; P less than 0.001, paired t test]. Pdimax was unchanged (control, -192 +/- 23 cmH2O; fatigue, -195 +/- 27 cmH2O). These data suggest that 1) inability to sustain the target during loading resulted from fatigue of the inspiratory rib cage muscles, not diaphragm, and 2) simultaneous measurement of Pinsp and Pdimax may be useful in partitioning muscle fatigue into rib cage and diaphragmatic components.     

Effects of dichloroacetate on VO2 and intramuscular 31P metabolite kinetics during high-intensity exercise in humans.

Traditional control theories of muscle O2 consumption are based on an "inertial" feedback system operating through features of the ATP splitting (e.g., [ADP] feedback, where brackets denote concentration). More recently, however, it has been suggested that feedforward mechanisms (with respect to ATP utilization) may play an important role by controlling the rate of substrate provision to the electron transport chain. This has been achieved by activation of the pyruvate dehydrogenase complex via dichloroacetate (DCA) infusion before exercise. To investigate these suggestions, six men performed repeated, high-intensity, constant-load quadriceps exercise in the bore of an magnetic resonance spectrometer with each of prior DCA or saline control intravenous infusions. O2 uptake (Vo2) was measured breath by breath (by use of a turbine and mass spectrometer) simultaneously with intramuscular phosphocreatine (PCr) concentration ([PCr]), [Pi], [ATP], and pH (by 31P-MRS) and arterialized-venous blood sampling. DCA had no effect on the time constant (tau) of either Vo2 increase or PCr breakdown [tauVo2 45.5 +/- 7.9 vs. 44.3 +/- 8.2 s (means +/- SD; control vs. DCA); tauPCr 44.8 +/- 6.6 vs. 46.4 +/- 7.5 s; with 95% confidence intervals averaging < +/-2 s]. DCA, however, resulted in significant (P < 0.05) reductions in 1). end-exercise [lactate] (-1.0 +/- 0.9 mM), intramuscular acidification (pH, +0.08 +/- 0.06 units), and [Pi] (-1.7 +/- 2.1 mM); 2). the amplitude of the fundamental components for [PCr] (-1.9 +/- 1.6 mM) and Vo2 (-0.1 +/- 0.07 l/min, or 8%); and 3). the amplitude of the Vo2 slow component. Thus, although the DCA infusion lessened the buildup of potential fatigue metabolites and reduced both the aerobic and anaerobic components of the energy transfer during exercise, it did not enhance either tauVo2 or tau[PCr], suggesting that feedback, rather than feedforward, control mechanisms dominate during high-intensity exercise.     

Effects of augmented respiratory muscle pressure production on locomotor limb venous return during calf contraction exercise.

We determined effects of augmented inspiratory and expiratory intrathoracic pressure or abdominal pressure (Pab) excursions on within-breath changes in steady-state femoral venous blood flow (Qfv) and net Qfv during tightly controlled (total breath time = 4 s, duty cycle = 0.5) accessory muscle/"rib cage" (DeltaPab <2 cmH2O) or diaphragmatic (DeltaPab >5 cmH2O) breathing. Selectively augmenting inspiratory intrathoracic pressure excursion during rib cage breathing augmented inspiratory facilitation of Qfv from the resting limb (69% and 89% of all flow occurred during nonloaded and loaded inspiration, respectively); however, net Qfv in the steady state was not altered because of slight reductions in femoral venous return during the ensuing expiratory phase of the breath. Selectively augmenting inspiratory esophageal pressure excursion during a predominantly diaphragmatic breath at rest did not alter within-breath changes in Qfv relative to nonloaded conditions (net retrograde flow = -9 +/- 12% and -4 +/- 9% during nonloaded and loaded inspiration, respectively), supporting the notion that the inferior vena cava is completely collapsed by relatively small increases in gastric pressure. Addition of inspiratory + expiratory loading to diaphragmatic breathing at rest resulted in reversal of within-breath changes in Qfv, such that >90% of all anterograde Qfv occurred during inspiration. Inspiratory + expiratory loading also reduced steady-state Qfv during mild- and moderate-intensity calf contractions compared with inspiratory loading alone. We conclude that 1) exaggerated inspiratory pressure excursions may augment within-breath changes in femoral venous return but do not increase net Qfv in the steady state and 2) active expiration during diaphragmatic breathing reduces the steady-state hyperemic response to dynamic exercise by mechanically impeding venous return from the locomotor limb, which may contribute to exercise limitation in health and disease.     

Effect of inspiratory threshold loading on ventilatory kinetics during constant-load exercise

Humoral factors play an important role in the control of exercise hyperpnea. The role of neuromechanical ventilatory factors, however, is still being investigated. We tested the hypothesis that the afferents of the thoracopulmonary system, and consequently of the neuromechanical ventilatory loop, have an influence on the kinetics of oxygen consumption (VO2), carbon dioxide output (VCO2), and ventilation (VE) during moderate intensity exercise. We did this by comparing the ventilatory time constants (tau) of exercise with and without an inspiratory load. Fourteen healthy, trained men (age 22.6 +/- 3.2 yr) performed a continuous incremental cycle exercise test to determine maximal oxygen uptake (VO2max = 55.2 +/- 5.8 ml x min(-1) x kg(-1)). On another day, after unloaded warm-up they performed randomized constant-load tests at 40% of their VO2max for 8 min, one with and the other without an inspiratory threshold load of 15 cmH2O. Ventilatory variables were obtained breath by breath. Phase 2 ventilatory kinetics (VO2, VCO2, and VE) could be described in all cases by a monoexponential function. The bootstrap method revealed small coefficients of variation for the model parameters, indicating an accurate determination for all parameters. Paired Student's t-tests showed that the addition of the inspiratory resistance significantly increased the tau during phase 2 of VO2 (43.1 +/- 8.6 vs. 60.9 +/- 14.1 s; P < 0.001), VCO2 (60.3 +/- 17.6 vs. 84.5 +/- 18.1 s; P < 0.001) and VE (59.4 +/- 16.1 vs. 85.9 +/- 17.1 s; P < 0.001). The average rise in tau was 41.3% for VO2, 40.1% for VCO2, and 44.6% for VE. The tau changes indicated that neuromechanical ventilatory factors play a role in the ventilatory response to moderate exercise.     

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.     

Pressure-diameter relationships of the upper airway in awake supine subjects

In awake supine normal subjects, dimensional changes of the oropharyngeal airway were measured during exposure to negative intraluminal pressures. The pressure was generated 1) "actively" by subjects inspiring against an externally occluded airway or 2) "passively" by external suction at the mouth during voluntary glottic closure with no inspiratory effort. Airway dimensions were imaged with X-ray fluoroscopy and anteroposterior diameters measured at levels corresponding to cervical vertebra 3 and 4 (C3 and C4). Cephalad axial displacement of the hyoid bone (CDHY) was also measured. During the "active" maneuver, airway diameters and position were maintained at resting levels despite airway pressure up to -15 cmH2O. In contrast, during the passive maneuver at -15 cmH2O, C3 was only 15 +/- 9% and C4 only 47 +/- 8% of control; CDHY was 5.6 +/- 1.8 mm. In three subjects airway wall apposition occurred and persisted until an active inspiratory effort. We conclude that, in the absence of inspiratory effort, negative oropharyngeal airway pressures result in marked narrowing and cephalad displacement of the upper airway, even during wakefulness. Therefore, our data suggest that the complex interaction of upper airway and thoracic muscle activity is critical in determining the effective compliance and patency of the upper airway, which is readily collapsible even in normal subjects.     

Inspiratory muscle work in acute hypoxia influences locomotor muscle fatigue and exercise performance of healthy humans

Our aim was to isolate the independent effects of 1) inspiratory muscle work (W(b)) and 2) arterial hypoxemia during heavy-intensity exercise in acute hypoxia on locomotor muscle fatigue. Eight cyclists exercised to exhaustion in hypoxia [inspired O(2) fraction (Fi(O(2))) = 0.15, arterial hemoglobin saturation (Sa(O(2))) = 81 +/- 1%; 8.6 +/- 0.5 min, 273 +/- 6 W; Hypoxia-control (Ctrl)] and at the same work rate and duration in normoxia (Sa(O(2)) = 95 +/- 1%; Normoxia-Ctrl). These trials were repeated, but with a 35-80% reduction in W(b) achieved via proportional assist ventilation (PAV). Quadriceps twitch force was assessed via magnetic femoral nerve stimulation before and 2 min after exercise. The isolated effects of W(b) in hypoxia on quadriceps fatigue, independent of reductions in Sa(O(2)), were revealed by comparing Hypoxia-Ctrl and Hypoxia-PAV at equal levels of Sa(O(2)) (P = 0.10). Immediately after hypoxic exercise potentiated twitch force of the quadriceps (Q(tw,pot)) decreased by 30 +/- 3% below preexercise baseline, and this reduction was attenuated by about one-third after PAV exercise (21 +/- 4%; P = 0.0007). This effect of W(b) on quadriceps fatigue occurred at exercise work rates during which, in normoxia, reducing W(b) had no significant effect on fatigue. The isolated effects of reduced Sa(O(2)) on quadriceps fatigue, independent of changes in W(b), were revealed by comparing Hypoxia-PAV and Normoxia-PAV at equal levels of W(b). Q(tw,pot) decreased by 15 +/- 2% below preexercise baseline after Normoxia-PAV, and this reduction was exacerbated by about one-third after Hypoxia-PAV (-22 +/- 3%; P = 0.034). We conclude that both arterial hypoxemia and W(b) contribute significantly to the rate of development of locomotor muscle fatigue during exercise in acute hypoxia; this occurs at work rates during which, in normoxia, W(b) has no effect on peripheral fatigue.     

Increased fatigue resistance of respiratory muscles during exercise after respiratory muscle endurance training

Respiratory muscle fatigue develops during exhaustive exercise and can limit exercise performance. Respiratory muscle training, in turn, can increase exercise performance. We investigated whether respiratory muscle endurance training (RMT) reduces exercise-induced inspiratory and expiratory muscle fatigue. Twenty-one healthy, male volunteers performed twenty 30-min sessions of either normocapnic hyperpnoea (n = 13) or sham training (CON, n = 8) over 4-5 wk. Before and after training, subjects performed a constant-load cycling test at 85% maximal power output to exhaustion (PRE(EXH), POST(EXH)). A further posttraining test was stopped at the pretraining duration (POST(ISO)) i.e., isotime. Before and after cycling, transdiaphragmatic pressure was measured during cervical magnetic stimulation to assess diaphragm contractility, and gastric pressure was measured during thoracic magnetic stimulation to assess abdominal muscle contractility. Overall, RMT did not reduce respiratory muscle fatigue. However, in subjects who developed >10% of diaphragm or abdominal muscle fatigue in PRE(EXH), fatigue was significantly reduced after RMT in POST(ISO) (inspiratory: -17 +/- 6% vs. -9 +/- 10%, P = 0.038, n = 9; abdominal: -19 +/- 10% vs. -11 +/- 11%, P = 0.038, n = 9), while sham training had no significant effect. Similarly, cycling endurance in POST(EXH) did not improve after RMT (P = 0.071), while a significant improvement was seen in the subgroup with >10% of diaphragm fatigue after PRE(EXH) (P = 0.017), but not in the sham training group (P = 0.674). However, changes in cycling endurance did not correlate with changes in respiratory muscle fatigue. In conclusion, RMT decreased the development of respiratory muscle fatigue during intensive exercise, but this change did not seem to improve cycling endurance.     

Influence of airway resistance on hypoxia-induced periodic breathing.

We studied the effects of changing upper airway pressure on the variability of the dynamic response of ventilation to a hypoxic disturbance in 11 spontaneously breathing dogs. Supralaryngeal pressure, instantaneous inspiratory flow, end-expiratory lung volume, and the inspiratory and expiratory O2 and CO2 concentrations were continuously recorded at baseline and after a 1.5-min hypoxic stimulus (abrupt normoxic recovery). Arterial blood gases were obtained at baseline, at the end of the hypoxic period, and after 1 min of recovery. Airway resistances were modified during the recovery by changing the composition of the inspired gas (all with an inspiratory O2 fraction of 20.9%) among four different trials: two trials were realized with air (density 1.12 g/l), and the other two were with He or SF6 (respective density 0.42 and 4.20) in random order. There was no difference between baseline minute ventilation, arterial blood gases, and supralaryngeal resistance values preceding the trials. The hypoxemic and hypocapnic levels and the hypoxia-induced hyperventilation reached during the hypoxic tests were identical for the different hypoxic stimuli. The supralaryngeal resistance measured at peak flow was dramatically influenced by the composition of the inspired gas: 8.8 +/- 1.8 and 6.9 +/- 1.7 (SE) cmH2O.l-1.s with air, 7.2 +/- 2.2 with He, 21.9 +/- 5.5 with SF6 (P less than 0.05). Ventilatory fluctuations were consistently seen during the posthypoxic period. They were characterized by a strength index value (M) (Waggener et al. J. Appl. Physiol. 56: 576-581, 1984).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pressure-time product, flow, and oxygen cost of resistive breathing in humans

We examined the relationship between the pressure-time product (Pdt) of the inspiratory muscles and the O2 cost of breathing (VO2 resp) in five normal subjects breathing through an external inspiratory resistance with a tidal volume of 800 ml at a constant end-expiratory lung volume [functional residual capacity, (FRC)]. Each subject performed 30-40 runs, each of approximately 30 breaths, with inspiratory flow rates ranging from 0.26 +/- 0.01 to 0.89 +/- 0.04 l/s (means +/- SE) and inspiratory mouth pressures ranging from 10 +/- 1 to 68 +/- 4% of the maximum inspiratory pressure at FRC. In all subjects VO2 resp was linearly related to Pdt when mean inspiratory flow (VI) was constant, but the slope of this relationship increased with increasing VI. Therefore, Pdt is an accurate index of VO2 resp only when VI is constant. There was a linear relationship between the VO2 resp and the work rate across the external resistance (W) for all runs in each subject over the range of W 10 +/- 1 to 137 +/- 21 J/min. Thus, at a constant tidal volume the VO2 resp was related to the mean inspiratory pressure, independent of flow or inspiratory duration. If the VO2 resp were determined mainly during inspiration, then for a given rate of external work or O2 consumption, VI would be inversely related to mean inspiratory pressure. Efficiency (E) was 2.1 +/- 0.2% and constant over a large range of VI, pressure, work rate, or resistance and was not altered by the presence of a potentially fatiguing load. The constant E over such a wide range of conditions implies a complex integration of the recruitment, mechanical function, and energy consumption of the muscles utilized in breathing.     

Effect of respiratory muscle fatigue on subsequent exercise performance.

The purpose of this study was to determine whether induction of inspiratory muscle fatigue might impair subsequent exercise performance. Ten healthy subjects cycled to volitional exhaustion at 90% of their maximal capacity. Oxygen consumption, breathing pattern, and a visual analogue scale for respiratory effort were measured. Exercise was performed on three separate occasions, once immediately after induction of fatigue, whereas the other two episodes served as controls. Fatigue was achieved by having the subjects breathe against an inspiratory threshold load while generating 80% of their predetermined maximal mouth pressure until they could no longer reach the target pressure. After induction of fatigue, exercise time was reduced compared with control, 238 +/- 69 vs. 311 +/- 96 (SD) s (P less than 0.001). During the last minute of exercise, oxygen consumption and heart rate were lower after induction of fatigue than during control, 2,234 +/- 472 vs. 2,533 +/- 548 ml/min (P less than 0.002) and 167 +/- 15 vs. 177 +/- 12 beats/min (P less than 0.002). At exercise isotime, minutes ventilation and the visual analogue scale for respiratory effort were larger after induction of fatigue than during control. In addition, at exercise isotime, relative tachypnea was observed after induction of fatigue. We conclude that induction of inspiratory muscle fatigue can impair subsequent performance of high-intensity exercise and alter the pattern of breathing during such exercise.     

Putative protective effect of inspiratory threshold loading against exercise-induced supraspinal diaphragm fatigue.

The present investigation was intended to assess the consequences of an inspiratory load on the diaphragm central component of fatigue during exercise. We recorded the motor potential evoked (MEP) by transcranial magnetic stimulation of the motor cortex in 10 subjects. The diaphragm and rectus femoris were studied before and 10, 20, and 40 min after two 16-min cycling exercise (E) trials requiring 55% of maximal oxygen uptake: 1) one with an inspiratory threshold load (E + ITL), corresponding to 10% of maximal inspiratory pressure; and 2) the other without the load (E). Dyspnea, heart rate, electromyographic activity of the sternocleidomastoid, and diaphragm work were significantly higher in E + ITL than in E. Neither trial affected the response to phrenic magnetic stimulation, which was performed 15 and 25 min postexercise, or the maximal inspiratory pressure (116 and 120 cm H(2)O before E and E + ITL, respectively, and 110 and 114 cm H(2)O at 30 min postexercise). Whereas the amplitude of the diaphragm MEP was unaffected by E + ITL (+2.1 +/- 29.4%), a significant decrease was observed 10 min after E compared with baseline (-37.1 +/- 22.3%) and compared with E + ITL. The MEP amplitude of rectus femoris remained unchanged with E and E + ITL. The recruitment of synergistic agonists during E + ITL may have normalized the major ventilatory stress and reset up the excitability of the diaphragm pathway.