Susceptibility to periodic breathing with assisted ventilation during sleep in normal subjects

Assisted ventilation with pressure support (PSV)or proportional assist (PAV) ventilation has the potential to produceperiodic breathing (PB) during sleep. We hypothesized that PB willdevelop when PSV level exceeds the product of spontaneous tidal volume (VT) and elastance(VT_sp · E)but that the actual level at which PB will develop[PSV(PB)] will be influenced by thePCO₂ (difference between eupneicPCO₂ andCO₂ apneic threshold) and by RR[response of respiratory rate (RR) to PSV]. We also wishedto determine the PAV level at which PB develops to assess inherentventilatory stability in normal subjects. Twelve normal subjectsunderwent polysomnography while connected to a PSV/PAV ventilatorprototype. Level of assist with either mode was increased in smallsteps (2-5 min each) until PB developed or the subject awakened.End-tidal PCO₂,VT, RR, and airway pressure (Paw) were continuously monitored, and the pressure generated byrespiratory muscle (Pmus) was calculated. The pressure amplification factor (PAF) at the highest PAV level was calculated from[(Paw + Pmus)/Pmus], where Paw is peak Paw  continuous positive airway pressure. PB with central apneas developedin 11 of 12 subjects on PSV. PCO₂ranged from 1.5 to 5.8 Torr. Changes in RR with PSV were small andbidirectional (+1.1 to 3.5min¹). With use ofstepwise regression, PSV(PB) was significantly correlated withVT_sp(P = 0.001), E(P = 0.00009),PCO₂ (P = 0.007), and RR(P = 0.006). The final regressionmodel was as follows: PSV(PB) = 11.1 VT_sp + 0.3E  0.4 PCO₂  0.34 RR  3.4 (r = 0.98). PBdeveloped in five subjects on PAV at amplification factors of1.5-3.4. It failed to occur in seven subjects, despite PAF of upto 7.6. We conclude that 1) aPCO₂ apneic threshold exists duringsleep at 1.5-5.8 Torr below eupneicPCO₂,2) the development of PB during PSVis entirely predictable during sleep, and3) the inherent susceptibility to PBvaries considerably among normal subjects.

     

Effect of breath holding on ventilation maldistribution during tidal breathing in normal subjects

To test the hypothesis that during the course of a multiple-breath N2 washout (MBNW) diffusion-dependent ventilation maldistribution is more apparent in the early breaths, whereas convection-dependent maldistribution predominates in the later breaths, we performed MBNW with 0-, 1-, and 4-s end-inspiratory breath holds (BH0, BH1, BH4, respectively) in five normal subjects. Each subject breathed with a constant tidal volume of 1 liter, at 10-12 breaths/min and at constant flow rates. For each breath we computed the slope of the alveolar plateau normalized by the mean expired N2 concentration (Sn), the Bohr dead space (VDB), and an index analogous to the Fowler dead space (V50). In all five subjects, Sn, VDB, and V50 decreased with breath holding, indicating diffusion dependence of these indexes. Over the first five breaths the rate of increase of Sn as a function of cumulative expired volume (delta Sn/delta sigma VE) decreased by 29 and 54% during BH1 and BH4, respectively, compared with BH0. In contrast, from breath 5 to the end of the washout there was no significant change in delta Sn/delta sigma VE during BH1 and BH4 compared with BH0. Our results provide further experimental support for the hypothesis that the increase of Sn as a function of cumulative expired volume after the fifth breath constitutes a diffusion-independent index of ventilation inhomogeneity. It therefore reflects alveolar gas inequalities among larger units.(ABSTRACT TRUNCATED AT 250 WORDS)     

Similar ventilation distribution in normal subjects prone and supine during tidal breathing.

Multiple-breath washout (MBW) tests, with end-expiratory lung volume at functional residual capacity (FRC) and 90% O(2), 5% He, and 5% SF(6) as an inspired gas mixture, were performed in healthy volunteers in supine and prone postures. The semilog plot of MBW N(2) concentrations was evaluated in terms of its curvilinearity. The MBW N(2) normalized slope analysis yielded indexes of acinar and conductive ventilation heterogeneity (Verbanck S, Schuermans D, Van Muylem A, Paiva M, Noppen M, and Vincken W. J App Physiol 83: 1907-1916, 1997). Also, the difference between SF(6) and He normalized phase III slopes was computed in the first MBW expiration. Only MBW tests with similar FRC in the prone and supine postures (P > 0.1; n = 8) were considered. Prone and supine postures did not reveal any significant differences in curvilinearity, N(2) normalized slope-derived indexes of conductive or acinar ventilation heterogeneity, nor SF(6)-He normalized phase III slope difference in the first MBW expiration (P > 0.1 for all). The absence of significant changes in any of the MBW indexes suggests that ventilation heterogeneity is similar in the supine and prone postures of normal subjects breathing near FRC.     

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.     

Impedance measurement during air and He-O2 breathing before and after salbutamol in normal subjects

Total respiratory resistance and reactance from 4 to 52 Hz were determined by the method of forced pseudorandom noise oscillation in 20 normal male subjects before and after inhalation of 0.200 mg salbutamol (albuterol) and before and after the subjects were equilibrated with 80% He-20% O2. During air breathing, there was a statistically significant decrease of resistance values at lower frequencies after inhalation of salbutamol. When the subject was equilibrated with 80% He-20% O2, total respiratory resistance markedly decreased at all frequencies, and a negative frequency dependence of resistance was observed between 8 and 20 Hz. Resistance values further decreased during He-O2 breathing after inhalation of salbutamol. After inhalation of salbutamol, reactance values increased during air and He-O2 breathing. The density-dependent decrease of the real part of impedance can be explained by a decrease of turbulence in the larger airways. The bronchodilating effect of salbutamol was not influenced by a change in the physical properties of the inhaled gas. During He-O2 breathing, reactance values significantly decreased, resulting in an increase of resonant frequency due to a decrease of inductive reactance. It is concluded that an increase in the capacitance of the respiratory system must be supposed to explain the increase in reactance values after inhalation of the beta-adrenergic agonist salbutamol.     

Accuracy of the respiratory inductive plethysmograph during loaded breathing

Indirect methods of measuring ventilation, such as the respiratory inductive plethysmograph (RIP), operate on the assumption that the respiratory system possesses two degrees of freedom of motion: the rib cage and abdomen. Accurate measurements have been obtained in many patients with pulmonary disease who possess additional degrees of freedom. Since calibration and validation of the RIP was carried out during quiet breathing in these patients, the amount of asynchronous or paradoxic breathing was presumably similar during the calibration and validation runs. Conversely, accuracy might be lost if following the initial calibration procedure the magnitude of chest wall distortion increased during subsequent validation runs. We calibrated the RIP during quiet breathing and examined its accuracy while subsequently breathing against resistive loads that required the generation of 20-80% of the subject's maximum inspiratory mouth pressure (Pmmax). We compared the relative accuracy of three commonly employed calibration methods: isovolume technique, least-squares technique, and single position loop-area technique. Up to 60% of Pmmax, 89% of the RIP values with the least-squares technique were within +/- 10% of simultaneous spirometric (SP) measurements and 100% were within +/- 20% of SP, compared with 63 and 91%, respectively, for the loop-area technique and 19 and 54%, respectively, for the isovolume technique. At 70 and 80% of Pmmax accuracy deteriorated. Accuracy of respiratory timing was judged in terms of fractional inspiratory time (TI/TT).(ABSTRACT TRUNCATED AT 250 WORDS)     

Thyroarytenoid muscle activity during loaded and nonloaded breathing in adult humans

Previous fiber-optic studies in humans have demonstrated narrowing of the glottic aperture in expiration during application of expiratory resistive loads. Nine healthy subjects were studied to determine the effect of expiratory resistive loads on the electromyographic activity of the thyroarytenoid (TA) muscle, a vocal cord adductor. Four of the nine subjects also underwent the application of inspiratory resistive loads and voluntary prolongation of either inspiratory (TI) or expiratory (TE) time. TA activity was recorded by intramuscular hooked-wire electrodes. During quiet breathing in all subjects, the TA was phasically active on expiration and often tonically active throughout the respiratory cycle. TA expiratory activity progressively increased with increasing levels of expiratory load. Inspiratory loads resulted in increased TA "inspiratory" activity. Voluntary prolongation of TE to times similar to those reached during loaded breathing induced increases in TA expiratory activity similar to those reached during the loaded state. Voluntary prolongation of TI was associated with an increase in TA inspiratory activity. Similar increases in TI during inspiratory loading or voluntary conditions were associated with comparable increases in TA inspiratory activity in three of the four subjects. In conclusion, increased activation of TA during the application of expiratory resistive loads implies that the reported narrowing of glottic aperture during expiratory loading is an active phenomenon. Changes in activation of the TA with resistive loads appear to be related to changes in respiratory pattern.     

Relative contributions of rib cage and abdomen to breathing in normal subjects.

By use of the method of Konno and Mead and the respiratory magnetometer, the partition of respired gas volumes into rib cage and diaphragm-abdomen components was accomplished in 81 normal subjects including 32 young and middle-aged men, 29 young and middle-aged women, and 20 elderly men. Studied were isovolume maneuvers and the relaxation configuration over the inspiratory capacity range, quiet tidal breathing, increased amplitudes of slow breathing, rapid inspirations and expirations, and both quiet and forceful phonation. No major differences were noted between men and women or between the young and the elderly during any respiratory acts. During quiet breathing most normal subjects are abdominal breathers when supine and thoracic breathers when upright. Rapid respiratory maneuvers were accomplished mostly through rib cage displacement suggesting that rib cage muscles are capable of more rapid action than diaphragm and abdominal muscles. Data from deep breathing and rapid maneuvers supported the view that abdominal and rib cage muscles often act to optimize the mechanical (length-tension) advantage of the diaphragm.     

Cardiac output and O2 consumption during inspiratory threshold loaded breathing

In this study, noninvasive measurements of cardiac output and O2 consumption were performed to estimate the blood flow to and efficiency of the respiratory muscles that are used in elevated inspiratory work loads. Five subjects were studied for 4.5 min at a respiratory rate of 18 breaths/min and a duty cycle of 0.5. Studies were performed at rest without added respiratory loads and at elevated inspiratory work loads with the use of an inspiratory valve that permitted flow only when a threshold pressure was maintained. Cardiac output and O2 consumption were calculated using a rebreathing technique. Respiratory muscle blood flow and O2 consumption were estimated as the difference between resting and loaded breathing. Work of breathing was calculated by integrating the product of mouth pressure and volume. Increases in cardiac output and O2 consumption in response of 4.5 min loaded breathing averaged 1.84 l/min and 108 ml/min, respectively. No increases were seen in response to 20-s loaded breathing. In a separate series of experiments on four subjects, though, cardiac output increased for the first 2 min then leveled off. These results indicate that the increase in cardiac output was a metabolic effect of the increased work load and was not caused primarily by the influence of the highly negative intrathoracic pressure on venous return. Efficiency of the respiratory muscles during inspiratory threshold loading averaged 5.9%, which was similar to measurements of efficiency of respiratory muscles using whole-body O2 consumption that have been reported previously in humans and in dogs.     

Effect of inspiratory muscle fatigue on perception of effort during loaded breathing

The present study examined the relationship between the intensity of the sense of effort during inspiratory threshold loading and the severity of inspiratory muscle fatigue. Studies were performed on normal subjects in whom the magnitude of airway pressure developed (Pm) and the duty cycle of breathing (TI/TT) were constrained to achieve a pressure-time integral (i.e., Pm/Pmax X TI/TT) 24% of maximum. In separate trials, the same pressure-time index (24%) was achieved using two widely different patterns of pressure magnitude and duty cycle to allow the effects of changes in the pattern of inspiratory muscle contraction on sensation and fatigue to be assessed. The intensity of the sense of effort was assessed using a category (Borg) scale. The severity of inspiratory muscle fatigue was assessed both from changes in the centroid frequency of the diaphragm electromyogram and from changes in the maximum static inspiratory pressure. Loaded breathing produced inspiratory muscle fatigue and a progressive increase in the sense of effort over time in all subjects. The rate at which the inspiratory muscles fatigued was the same with the two patterns of loading. In contrast, the rate of growth in the intensity of the sense of effort varied significantly as a function of the pattern of loaded breathing. The sense of effort increased at a faster rate with the high pressure-short duty cycle pattern of contraction as compared with the low pressure-long duty cycle pattern. As a result, the intensity of the sense of effort was not uniquely related to the severity of inspiratory muscle fatigue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Activation of the parasternal intercostals during breathing efforts in human subjects

We have tested the possibility that the electromyographic (EMG) activity present in the parasternal intercostal muscles during quiet inspiration was reflexive, rather than agonistic, in nature. Using concentric needle electrodes we measured parasternal EMG activity in four normal subjects during various inspiratory maneuvers. We found that 1) phasic inspiratory activity was invariably present in the parasternal intercostals during quiet breathing, 2) the parasternal EMG activity was generally increased during attempts to perform the tidal breathing maneuver with the diaphragm alone, 3) parasternal EMG activity was markedly decreased or suppressed in the presence of rib cage distortion during diaphragmatic isovolume maneuvers, and 4) that EMG activity could not be voluntarily suppressed during breathing unless the inspired volume was trivial. We conclude that the parasternal EMG activity detected during quiet inspiration in the normal subjects depends on a central involuntary mechanism and is not related to activation of intercostal mechanoreceptors.