The effect of vagal blockade on the variability of ventilation in the awake dog

The present study examined the variability of breathing in five (5) awake tracheostomized dogs with the vagi intact and during complete vagal blockade produced by cooling exteriorized cervical vagal loops (VC). Breath by breath variations in both respiratory timing (assessed from the airflow signal) and the drive to the respiratory muscles (as assessed from the rate of inspiratory airflow (VI/TI) and occlusive pressure (P100) were examined. The degree of variability in the parameters characterizing breathing was evaluated from frequency distribution histograms and by calculation of the standard deviation. VC increased the mean values of VT, TI, TE, TI/TTOT, and decreased VT/TI and occlusion pressure, but had no consistent effect on the mean value of VE. The variability of VE, PACO2, VT, TI, TE, TI/TTOT was greater during VC in 4 of the 5 dogs. The increased variability of VE and PACO2 during VC appeared to be due to a poorer correlation between TI and TE. The present study suggests that vagal mechanoreceptors, presumably pulmonary stretch receptors, minimize breath by breath fluctuations in both the level and pattern of ventilation by controlling respiratory timing. An explanation, based on the model of inspiratory off-switching proposed by Beadley et al. (1975) is invoked.     

Effect of step duration during incremental exercise on breathing pattern and mouth occlusion pressure

We compared the effects of two step durations on breathing pattern, mouth occlusion pressure and "effective" impedance of the respiratory system during incremental exercise. Nine normal subjects (mean age: 27.8+/-1.21 years) performed two incremental exercise tests in randomized order: one test with step increments every 1 min 30s and the other, every 4 min. After a warm-up at 25 W for the 1 min 30 s test, the power was increased by 50 W from 50 W to exhaustion. During the last minute at each power, we measured ventilation (VE), tidal volume (VT), breathing frequency (fR), inspiratory and expiratory time (TI and TE), total time of the respiratory cycle (TTOT), TI/TTOT, mean inspiratory flow (VT/TI), mouth occlusion pressure (P0.1), "effective" impedance of the respiratory system (P0.1/(VT/ TI)) and venous blood lactate concentration ([La]). Our result showed that at maximal exercise the power was significantly higher (p < 0.01) and [La] lower (p < 0.01) in the 1 min 30 s test. At 100, 150 and 200 W, the 4 min test showed significantly higher oxygen uptake (VO2), carbon dioxide output (VCO2), VE, P0.1, fR, VT/TI and HR (p <0.001) and significantly lower TI, TE and TTOT (p<0.01). [La] was significantly higher at 150 W (p<0.05) and 200 W (p<0.001). At the same VCO2, P0.1 was not significantly different between the two tests, whereas VE showed a tendency to be higher (p = 0.08) and P0.1/(VT/TI) was significantly lower during the 4 min test. In conclusion, this study allowed us to quantify the difference in inspiratory neuromuscular output and ventilatory response between 1 min 30s and 4 min tests and showed that different step durations alter the relationship between inspiratory neuromuscular output and mean inspiratory flow.     

Assessment of ventilatory neuromuscular drive in patients with obstructive sleep apnea

The presence of abnormalities of the respiratory center in obstructive sleep apnea (OSA) patients and their correlation with polysomnographic data are still a matter of controversy. Moderately obese, sleep-deprived OSA patients presenting daytime hypersomnolence, with normocapnia and no clinical or spirometric evidence of pulmonary disease, were selected. We assessed the ventilatory control and correlated it with polysomnographic data. Ventilatory neuromuscular drive was evaluated in these patients by measuring the ventilatory response (VE), the inspiratory occlusion pressure (P.1) and the ventilatory pattern (VT/TI, TI/TTOT) at rest and during submaximal exercise, breathing room air. These analyses were also performed after inhalation of a hypercapnic mixture of CO2 (delta P.1/delta PETCO2, delta VE/delta PETCO2). Average rest and exercise ventilatory response (VE: 12.2 and 32.6 l/min, respectively), inspiratory occlusion pressure (P.1: 1.5 and 4.7 cmH2O, respectively), and ventilatory pattern (VT/TI: 0.42 and 1.09 l/s; TI/TTOT: 0.47 and 0.46 l/s, respectively) were within the normal range. In response to hypercapnia, the values of ventilatory response (delta VE/delta PETCO2: 1.51 l min-1 mmHg-1) and inspiratory occlusion pressure (delta P.1/delta PETCO2: 0.22 cmH2O) were normal or slightly reduced in the normocapnic OSA patients. No association or correlation between ventilatory neuromuscular drive and ventilatory pattern, hypersomnolence score and polysomnographic data was found; however a significant positive correlation was observed between P.1 and weight. Our results indicate the existence of a group of normocapnic OSA patients who have a normal awake neuromuscular ventilatory drive at rest or during exercise that is partially influenced by obesity.     

Changes in maximal exercise ventilation and breathing pattern in boys during growth: a mixed cross-sectional longitudinal study

The aim of this mixed cross-sectional longitudinal study covering a total age range of 11-17 years, i.e. the entire pubertal growth period, was (1) to specify the changes in maximal breathing pattern during incremental exercise; (2) to determine what parts of the changes are due to anthropometric characteristics, physical fitness and inspiratory or expiratory muscle strength; and (3) to determine if the role of these variables is identical before, during and after pubertal growth spurt. This study was conducted in 44 untrained schoolboys separated into three groups, with an initial age of 11.2 +/- 0.2 years for group A, 12.9 +/- 0.25 years for group B, and 14.9 +/- 0.26 years for group C. These children were subsequently followed for 3 years, during the same time period each year. The maximal inspiratory and expiratory pressures (PI max and PE max) were used as an index of the respiratory muscle strength. During an incremental exercise test, maximal ventilation (VE max), tidal volume (VT max), breathing frequency (fmax), inspiratory and expiratory times (tI max and tE max) and mean inspiratory flow (VT/tI max) were measured at maximal oxygen uptake (VO2max). Our study showed that there was a marked increase with age in VE max, VT max, and VT/tI max, and no significant changes in fmax, tI max and tE max. PI max and PE max showed a general trend towards an increase between 11 and 17 years. The study of the linear correlations between maximal breathing pattern and the anthropometric characteristics, physical fitness and inspiratory or expiratory muscle strength showed that, in the three groups of children, (1) lean body mass was the major determinant of VE max, VT max and VT/tI max and the relationships were significantly different before, during and after the pubertal growth spurt; (2) physical fitness was the main determinant of tI max, tE max and fmax before and after the pubertal growth spurt; and (3) maximal respiratory strength did not play a significant role. In conclusion, this mixed cross-sectional longitudinal study showed, at maximal exercise, a significant increase in VE max during growth due only to a significant increase in VT max and VT/tI max, and that the relationships of anthropometric characteristics and physical fitness with maximal breathing pattern change during growth.     

Social-emotional characteristics of preschool-aged children referred for Child Find screening and assessment: a comparative study

In order to determine changes in breathing patterns brought about by resistive loading, ventilation was recorded in 11 healthy subjects with four linear resistances (3.57, 5.75, 8.76 and 13.13 cmH2O L(-1) sec) added in a random order throughout the entire breath. At steady state, a breath-by-breath analysis of airflow was used to quantify the pattern of breathing in terms of respiratory variables: TI, TE, Tt, VT, VT/TI, TI/Tt, and by taking TI, TE, VT all together (TRIAD) and also the shape of the entire airflow profile quantified by harmonic analysis (ASTER). Group analysis using ANOVA showed significant changes in all variables. There were increasing changes with increasing loads in all variables, the smallest changes being in TI/Tt. Within to between-individual comparisons between two loads showed that only TI/Tt and the ASTER were more similar within than between-individuals for all comparisons. It was concluded that at steady state mechanisms of load compensation come into play inducing changes in the pattern of breathing proportional to the loads while maintaining some of the individual characteristics.     

Effects of inspiratory flow waveforms on arterial blood gases and respiratory mechanics after open heart surgery

The clinical usefulness of inspiratory flow pattern manipulation during mechanical ventilation remains unclear. The aim of this study was to investigate the effects of different inspiratory flow waveforms, i.e. constant, sinusoidal and decelerating, on arterial blood gases and respiratory mechanics, in mechanically ventilated patients. Eight patients recovering after open heart surgery for valvular replacement and/or coronary bypass were studied. The ventilator inspiratory flow waveform was changed according to a randomized sequence, keeping constant the other variables of the ventilator settings. We measured arterial blood gases, flow, volume and pressure at the proximal (airway opening pressure (Pao)) and distal (Ptr) ends of the endotracheal tubes before and after 30 min of mechanical ventilation with each inspiratory flow waveform. We computed breathing pattern, respiratory mechanics (pressures and dynamic elastance) and inspiratory work, which was then partitioned into its elastic and resistive components. We found that: 1) arterial oxygen tension (Pa,O2) and arterial carbon dioxide tension (Pa,CO2) were not affected by changes in the inspiratory flow waveform; and 2) peak Pao and Ptr were highest with sinusoidal inspiratory flow, whilst mean Pao and Ptr and total work of breathing were least with constant inspiratory flow, mainly because of a concomitant decrease in resistive work during constant flow inflation. The effects of the inspiratory flow profile on Pao, Ptr and total inspiratory work performed by the ventilator were mainly due to the resistive properties of the endotracheal tubes. We conclude that the ventilator inspiratory flow waveform can influence patients' respiratory mechanics, but has no impact on arterial oxygen and arterial carbon dioxide tension.     

NMDA receptors mediate peripheral chemoreceptor afferent input in the conscious rat

N-methyl-D-aspartate (NMDA) glutamate receptors mediate critical components of cardiorespiratory control in anesthetized animals. The role of NMDA receptors in the ventilatory responses to peripheral and central chemoreceptor stimulation was investigated in conscious, freely behaving rats. Minute ventilation (VE) responses to 10% O2, 5% CO2, and increasing intravenous doses of sodium cyanide were measured in intact rats before and after intravenous administration of the NMDA receptor antagonist MK-801 (3 mg/kg). After MK-801, eupcapnic tidal volume (VT) decreased while frequency increased, resulting in a modest reduction in VE. Inspiratory time (TI) decreased, whereas expiratory time remained unchanged. The VE responses to hypercapnia were qualitatively similar in control and MK-801 conditions, with slight reductions in respiratory drive (VT/TI) after MK-801. In contrast, responses to hypoxia were markedly attenuated after MK-801 and were primarily due to reduced frequency changes, whereas VT was unaffected. Sodium cyanide doses associated with significant VE increases were 5 and 50 microg/kg before and after MK-801, respectively. Thus 1-log shift to the right of individual dose-response curves occurred with MK-801. Selective carotid body denervation reduced VE during hypoxia by 70%, and residual hypoxic ventilatory responses were abolished after MK-801. These findings suggest that, in conscious rats, carotid and other peripheral chemoreceptor-mediated hypoxic ventilatory responses are critically dependent on NMDA receptor activation and that NMDA receptor mechanisms are only modestly involved during hypercapnia.     

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 produce periodic breathing (PB) during sleep. We hypothesized that PB will develop when PSV level exceeds the product of spontaneous tidal volume (VT) and elastance (VTsp . E) but that the actual level at which PB will develop [PSV(PB)] will be influenced by the DeltaPCO2 (difference between eupneic PCO2 and CO2 apneic threshold) and by DeltaRR [response of respiratory rate (RR) to PSV]. We also wished to determine the PAV level at which PB develops to assess inherent ventilatory stability in normal subjects. Twelve normal subjects underwent polysomnography while connected to a PSV/PAV ventilator prototype. Level of assist with either mode was increased in small steps (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 by respiratory muscle (Pmus) was calculated. The pressure amplification factor (PAF) at the highest PAV level was calculated from [(DeltaPaw + Pmus)/Pmus], where DeltaPaw is peak Paw - continuous positive airway pressure. PB with central apneas developed in 11 of 12 subjects on PSV. DeltaPCO2 ranged from 1.5 to 5.8 Torr. Changes in RR with PSV were small and bidirectional (+1.1 to -3.5 min-1). With use of stepwise regression, PSV(PB) was significantly correlated with VTsp (P = 0.001), E (P = 0.00009), DeltaPCO2 (P = 0.007), and DeltaRR (P = 0.006). The final regression model was as follows: PSV(PB) = 11.1 VTsp + 0.3E - 0.4 DeltaPCO2 - 0.34 DeltaRR - 3.4 (r = 0.98). PB developed in five subjects on PAV at amplification factors of 1.5-3.4. It failed to occur in seven subjects, despite PAF of up to 7.6. We conclude that 1) a PCO2 apneic threshold exists during sleep at 1.5-5.8 Torr below eupneic PCO2, 2) the development of PB during PSV is entirely predictable during sleep, and 3) the inherent susceptibility to PB varies considerably among normal subjects.     

Breathing patterns in infants and children under halothane anesthesia: effect of dose and CO2

We studied the amplitude, timing, and shape of the airflow waveform at the mouth of spontaneously breathing children under two sets of conditions: 1) in 30 children aged 9 wk-4.5 yr at 2, 1, and 0% inspired halothane concentration and 2) in 22 children aged 5 mo-7 yr during hyperoxic CO2 rebreathing while recovering from anesthesia. Compared with control values, the relative changes in breath parameters at 1 and 2% halothane were, respectively, as follows: total cycle time -19 and -31%, tidal volume (VT) -30 and -44%, minute ventilation -11 and -17%, and VT/inspiratory time (TI) -16 and -20%. Parameters of timing and breath shape did not change except for the significant but small increase in TI/total cycle time (by 6 and 8%, respectively). With CO2 rebreathing, parameters reflecting inspiratory drive increased significantly in all patients as shown by the slopes of the regressions of these parameters against end-tidal PCO2. Mean slopes expressed in %control value per millimeter of mercury CO2 were 12.1 for minute ventilation, 8.3 for VT, and 10.67 for VT/TI. Parameters reflecting the timing and breath shape remained essentially unchanged. Our results suggest that, in children under halothane anesthesia, the amplitude, timing, and shape of the breathing pattern are controlled independently. In particular, the amplitude and timing of the breath may vary widely without any significant change in the shape.     

Respiratory muscle function and control of breathing in patients with acromegaly

Increase in lung size has been described in acromegalic patients, but data on respiratory muscle function and control of breathing are relatively scarce. Lung volumes, arterial blood gas tensions, and respiratory muscle strength and activation during chemical stimulation were investigated in a group of 10 patients with acromegaly, and compared with age- and sex-matched normal controls. Inspiratory muscle force was evaluated by measuring pleural (Ppl,sn) and transdiaphragmatic (Pdi,sn) pressures during maximal sniffs. Dynamic pleural pressure swing (Ppl,sw) was expressed both as absolute value and as percentage of Ppl,sn. Expiratory muscle force was assessed in terms of maximal expiratory pressure (MEP). In 8 of the 10 patients, ventilatory and respiratory muscle responses to hyperoxic progressive hypercapnia and to isocapnic progressive hypoxia were also evaluated. Large lungs, defined as total lung capacity (TLC) greater than predicted (above 95% confidence limits), were found in five patients. Inspiratory or expiratory muscle force was below normal limits in all but three patients. During unstimulated tidal breathing, respiratory frequency (fR) and mean inspiratory flow (tidal volume/inspiratory time (VT/tI)) were greater, while inspiratory time (tI) was shorter than in controls. Minute ventilation (V'E) and mean inspiratory flow response slopes to hypercapnia were normal In contrast, four patients had reduced delta(VT/tI)/arterial oxygen saturation (Sa,O2) and three had reduced deltaV'E/Sa,O2. Ppl,sw(%Ppl,sn) response slopes to increasing end-tidal carbon dioxide tension (PET,CO2) and decreasing Sa,O2 did not differ from the responses of the normal subjects, suggesting normal central chemoresponsiveness. At a PET,CO2 of 8 kPa or an Sa,O2 of 80%, patients had greater fR and lower tI compared with controls. Pdi,sn and Ppl,sn related both to deltaV'E/deltaSa,O2 (r=0.729 and r=0.776, respectively) and delta(VT/tI)/deltaSa,O2 (r=0.860 and r=0.90, respectively). Pdi,sn also related both to deltaV'E/deltaPET,CO2 (r=0.8) and delta(VT/tI)/deltaPET,CO2 (r=0.76). In conclusion, the data suggest the relative independence of pneumomegaly and respiratory muscle strength. Peripheral (muscular) factors appear to modulate a normal central motor output to give a more rapid pattern of breathing.     

Effects of nasal continuous positive airway pressure on breathing pattern and respiratory drive in patients with obstructive sleep apnea syndrome

To examine the influence of continuous positive airway pressure (CPAP) therapy on respiratory center drive in patients with obstructive sleep apnea syndrome (OSAS), 20 normocapnic OSAS patients (group 0) and 20 simple snoring patients were studied. In the first night, diagnostic polysomnography (PSG) was performed. Before and after PSG monitoring, mouth occlusion pressure (P0.1), tidal volume (VT), minute ventilation (VE), respiratory rate (RR), inspiratory time (Ti), expiratory time (Te), total cycle duration (Ttot), inspiratory duty cycle (Ti/Ttot), mean inspiratory flow (VT/Ti) and effective inspiratory impedance (P0.1/VT/Ti, Ieff) were measured while they were breathing room air. In the following night the OSAS patients were treated with nasal CPAP and PSG monitoring and the above mentioned measurements were repeated. The results showed that pre-PSG values of P0.1, RR and P0.1/VT/Ti in the OSAS patients were significantly higher than those in the snoring patients, while VT, Ti, Te and Ttot values were lower. In the first night, the post-PSG P0.1 value in the OSAS patients increased markedly as compared with the pre-PSG. After overnight nasal CPAP therapy, the respiratory disorder index in the OSAS patients decreased markedly, the nadir SaO2 increased markedly, but the post-PSG P0.1 value did not increase significantly. It is concluded that, before sleep, OSAS patients exhibit a higher respiratory drive and a shallow and frequent breathing pattern as compared with simple snoring patients. After nocturnal sleep, the respiratory drive of OSAS patients increases significantly, the breathing pattern becomes more shallow and frequent. Nasal CPAP may effectively relieve the sleep apnea and hypopnea as well as the resulting hypoxemia and therefore correct the changes in breathing pattern and respiratory drive through nocturnal sleep in patients with OSAS.     

Effect of sleep on changes in breathing pattern accompanying sigh breaths

We studied the effect of sleep on the characteristics of sigh breaths and the associated changes in breathing pattern in breaths following spontaneous sighs in 4 unrestrained dogs with an intact upper airway. The sigh breath was characterized by its large tidal volume (VT), long TI and TE in comparison with the control breath. The volume of the sigh breath was larger in awake sighs than in those recorded during non-REM (NREM) and REM sleep. The strength of Hering-Breuer reflex as determined by duration of the post-sigh apnea was similar in NREM and REM sleep. Sighs occurring during wakefulness, NREM and REM sleep were associated with augmented activity of the parasternal muscles during inspiration, and a persistent tonic abdominal muscle activity during the expiratory period. Breathing pattern in the post-sigh period was characterized by a smaller VT and longer TE in the first post-sigh breath in all sleep states (compared with the control breath), but the pattern returned to control level within the second or third post-sigh breath in both NREM and REM sleep. Sighs did not precipitate periodic breathing or other forms of abnormal breathing patterns in either wakefulness or sleep. We conclude that the respiratory control mechanisms stabilizing breathing after a sigh in the awake dog are intact in NREM and REM sleep.     

Effectiveness of controlled and spontaneous modes in nasal two-level positive pressure ventilation in awake and asleep normal subjects

STUDY OBJECTIVES: The purpose of the present study was to compare in awake and asleep healthy subjects, under nasal intermittent positive pressure ventilation (nIPPV) with a two-level intermittent positive pressure device (two-level nIPPV), the efficacy of the controlled and spontaneous modes, and of different ventilator settings in increasing effective minute ventilation (VE). PARTICIPANTS: Eight healthy subjects were studied. SETTING: In the controlled mode, inspiratory positive airway pressure (IPAP) was kept at 15 cm H2O, expiratory positive airway pressure (EPAP) at 4 cm H2O, and the inspiratory/expiratory (I/E) time ratio at 1. The respirator frequencies were 17 and 25/min. In the spontaneous mode experiment, IPAP was started at 10 cm H2O and progressively increased to 15 and 20 cm H2O; EPAP was kept at 4 cm H2O. MEASUREMENTS AND RESULTS: We measured breath by breath the effective tidal volume (VT with respiratory inductive plethysmography), actual respiratory frequency (f), and effective VE. Using the controlled mode, effective VE was significantly higher on nIPPV than during spontaneous unassisted breathing, except in stage 2 nonrapid eye movement sleep at 17/min of frequency; increases in f from 17 to 25/min led to a significant decrease in VT reaching the lungs, during wakefulness and sleep; effective VE was higher at 25 than at 17/min of frequency only during sleep; periodic breathing was scarce and apneas were never observed. Using the spontaneous mode, with respect to awake spontaneous unassisted breathing, two-level nIPPV at 10 and 15 cm H2O of IPAP did not result in any significant increase in effective VE either in wakefulness or in sleep; only IPAP levels of 20 cm H2O resulted in a significant increase in effective VE; during sleep, effective VE was significantly lower than during wakefulness; respiratory rhythm instability (ie, periodic breathing and central apneas) were exceedingly common, and in some subjects extremely frequent, leading to surprisingly large falls in arterial oxygen saturation. CONCLUSIONS: It appears that two-level nIPPV should be used in the controlled mode rather than in the spontaneous mode, since it seems easier to increase effective VE with a lower IPAP at a high frequency than at a high pressure using the spontaneous mode. We suggest that the initial respirator settings in the controlled mode should be an f around 20/min, an I/E ratio of 1, 15 cm H2O of IPAP, and EPAP as low as possible.     

Respiratory electromyographic estimates of ventilatory functions in piglets

The best electromyographic (EMG) predictors of respiratory drive (P100), tidal volume (VT) and ventilation (VE) were determined from diaphragmatic (DI) and posterior cricoarytenoid (PCA) EMG measures in 8-48-day-old, anesthetized piglets. Progressive hypercapnia was employed to obtain a wide range of muscle activity. A custom-designed, microcomputer-based system was employed to measure the duration, peak amplitude, rate of rise (initial slope) as well as the summed total and initial (first 100 ms) EMG activity from the DI and the PCA. For each respiratory function, the following combinations of EMG measures were identified as significant predictors using regression analyses: (1) for P100, DI amplitude, PCA initial area and PCA rate of rise; (2) for VT, DI amplitude, PCA duration and DI duration; (3) for VE, DI amplitude, DI initial area, PCA initial area, PCA rate of rise, PCA duration, DI area and DI rate of rise. Thus, whereas the traditionally employed measure of DI amplitude is an important correlate of P100, VT or VE, a complete estimate of these respiratory functions requires the inclusion of initial EMG measures and duration.     

Clincal, immunologic, and genetic features of an autoimmune lymphoproliferative syndrome associated with abnormal lymphocyte apoptosis

To examine the effect of elastic loading on variational activity of breathing, we studied 11 healthy subjects breathing at rest and with inspiratory elastic loads of 9 and 18 cm H2O/L, applied randomly for 1 h each. Compared with rest, a load of 18 cm H2O/L decreased gross variability, quantitated as standard deviation, of tidal volume (VT) and expiratory time (TE) (p < 0.01 in both instances) but increased that of inspiratory time (TI) (p < 0.03). The autocorrelation coefficients at a lag of 1 breath for each breath component were not altered by elastic loading, although the number of breath lags with significant serial correlations for TE tended to increase with a load of 18 cm H2O/L (p = 0.08). A load of 18 cm H2O/L decreased only the fraction of variational activity of VT and TE due to uncorrelated, random behavior (white noise), while it increased that fraction for TI (p < 0.05 in each instance); the correlated and oscillatory fractions did not change. Uncorrelated random behavior constituted > 87% of the variance of each breath component, correlated behavior represented 3 to 11%, and oscillatory behavior represented < 1.5% during both rest and loaded breathing. Elastic loading changed the gross variability of each primary breath component by altering the random fraction of variational activity; it had no significant effect on the structured, correlated fraction. We speculate that the observed changes in variational activity may reflect an attempt by the controller to compensate for the increased load while simultaneously minimizing load-induced dyspnea.     

Effect of global inspiratory muscle fatigue on ventilatory and respiratory muscle responses to CO2

We evaluated the effect of global inspiratory muscle fatigue on ventilation and respiratory muscle control during CO2 rebreathing in normal subjects. Fatigue was induced by breathing against a high inspiratory resistance until exhaustion. CO2 response curves were measured before and after fatigue. During CO2 rebreathing, global fatigue caused a decreased tidal volume (VT) and an increased breathing frequency but did not change minute ventilation, duty cycle, or mean inspiratory flow. Both esophageal and transdiaphragmatic pressure swings were significantly reduced after global fatigue, suggesting decreased contribution of both rib cage muscles and diaphragm to breathing. End-expiratory transpulmonary pressure for a given CO2 was lower after fatigue, indicating an additional decrease in end-expiratory lung volume due to expiratory muscle recruitment, which leads to a greater initial portion of inspiration being passive. This, combined with the reduction in VT, decreased the fraction of VT attributable to inspiratory muscle contribution; therefore the inspiratory muscle elastic work and power per breath were significantly reduced. We conclude that respiratory control mechanisms are plastic and that the respiratory centers alter their output in a manner appropriate to the contractile state of the respiratory muscles to conserve the ventilatory response to CO2.     

Comparative physiologic effects of noninvasive assist-control and pressure support ventilation in acute hypercapnic respiratory failure

STUDY OBJECTIVE: To compare the effects of noninvasive assist-control ventilation (ACV) and pressure support ventilation (PSV) by nasal mask on respiratory physiologic parameters and comfort in acute hypercapnic respiratory failure (AHRF). DESIGN: A prospective randomized study. SETTING: A medical ICU. PATIENTS AND INTERVENTIONS: Fifteen patients with COPD and AHRF were consecutively and randomly assigned to two noninvasive ventilation (NIV) sequences with ACV and PSV mode, spontaneous breathing (SB) via nasal mask being used as control. ACV and PSV settings were always subsequently adjusted according to patient's tolerance and air leaks. Fraction of inspired oxygen did not change between the sequences. MEASUREMENTS AND RESULTS: ACV and PSV mode strongly decreased the inspiratory effort in comparison with SB. The total inspiratory work of breathing (WOBinsp) expressed as WOBinsp/tidal volume (VT) and WOBinsp/respiratory rate (RR), the pressure time product (PTP), and esophageal pressure variations (deltaPes) were the most discriminant parameters (p<0.001). ACV most reduced WOBinsp/VT (p<0.05), deltaPes (p<0.05), and PTP (0.01) compared with PSV mode. The surface diaphragmatic electromyogram activity was also decreased >32% as compared with control values (p<0.01), with no difference between the two modes. Simultaneously, NIV significantly improved breathing pattern (p<0.01) with no difference between ACV and PSV for VT, RR, minute ventilation, and total cycle duration. As compared to SB, respiratory acidosis was similarly improved by both modes. The respiratory comfort assessed by visual analog scale was less with ACV (57.23+/-30.12 mm) than with SB (75.15+/-18.25 mm) (p<0.05) and PSV mode (81.62+/-25.2 mm) (p<0.01) in our patients. CONCLUSIONS: During NIV for AHRF using settings adapted to patient's clinical tolerance and mask air leaks, both ACV and PSV mode provide respiratory muscle rest and similarly improve breathing pattern and gas exchange. However, these physiologic effects are achieved with a lower inspiratory workload but at the expense of a higher respiratory discomfort with ACV than with PSV mode.     

Occlusion pressures in men rebreathing CO2 under methoxyflurane anesthesia

The effect of general anesthesia on control of breathing was studied by CO2 rebreathing and occlusion pressure measurements in six normal human subjects under methoxyflurane anesthesia. CO2 was found to increase the amplitude of the occlusion pressure wave without changing its shape, so that CO2 responses in terms of the occlusion pressure developed 100 ms after the onset of inspiration (Po/0.1) gave results equivalent to the responses in terms of Po/1.o or any other parameter of the pressure wave. Methoxyflurane depressed the ventilatory response to CO2 but not the occlusion pressure response, implying that the most important action of the anesthetic was to increase the effective elastance of the respiratory system rather than to depress the respiratory centers. The elastance was further increased by CO2, and this mechanical change had the effect of shifting the "apneic threshold" extrapolated from the ventilatory response curve to a lower PAco2. Frequency of breathing, inspiratory and expiratory times were not altered by CO2 in anesthetized subjects.     

Respiratory and thermoregulatory responses of rabbits breathing carbon dioxide during heat exposure

1. Rabbits were clipped and exposed in turn to three environmental conditions: control (C), cold exposure (CE) and water deprivation (WD). Following each type of treatment, the rabbits were exposed to an ambient temperature (Ta) of 35 degrees C for 1 hr. Throughout this period they breathed either normal atmospheric air or 6% CO2 in air. 2. During heat exposure, measurements were made of the respiratory responses and of the O2 consumption (Vo2) of the rabbits. Rectal temperature (Tre) was measured immediately before and again immediately after heat exposure. 3. When subjected to cold exposure or water deprivation the rabbits showed an initial decrease in respiratory frequency (RF) and an initial increase in VT when compared with controls. There was no difference in VE. Rabbits breathing 6% CO2 showed an increase in VT and VE and a decrease in RF when compared with rabbits breathing atmospheric air. In all cases a change in VT or RF was associated with a reciprocal change in the other parameter. 4. The respiratory responses to breathing 6% CO2 were essentially similar in treated and control rabbits, from which it is concluded that neither cold exposure nor water deprivation alter the sensitivity of the medullary respiratory centre to the respiratory drive from the central chemosensors. 5. The increase in Tre during heat exposure was significantly less in rabbits breathing 6% CO2 than in rabbits breathing atmospheric air. However, there was no significant over-all difference in VO2 between rabbits breathing CO2 and those breathing air. From this it is concluded that increased ventilation induced by CO2 causes a greater dissipation of heat than does thermally-induced panting. 6. It is concluded that VT is controlled by the level of blood PCO2 whereas RF is controlled by thermoregulatory requirements. It is further concluded that the reciprocal relationship between VT and RF is regulated in such a way as to maintain VE at the appropriate level for effecting gaseous exchange and evaporative heat loss.     

Pressure support ventilation in adult respiratory distress syndrome: short-term effects of a servocontrolled mode

PURPOSE: To assess the short-term effects of pressure support ventilation in adult respiratory distress syndrome (ARDS), we studied 17 patients with moderate to severe ARDS using mandatory rate ventilation (MRV), a servocontrolled mode of PSV having respiratory rate as the targeted parameter. MATERIALS AND METHODS: Based on the duration of ARDS, the patients were divided into two groups: Group 1, early ARDS (duration up to 1 week), 10 patients; Group 2, intermediate ARDS (duration between 1 and 2 weeks). The patients were initially ventilated with assisted mechanical ventilation then with MRV, and finally with controlled mechanical ventilation. After a 20-minute period allowed for stabilization in each mode, ventilatory variables, gas exchange, hemodynamics, and patient's inspiratory effort were evaluated. RESULTS: During MRV blood gases, airway pressures and hemodynamic variables remained within acceptable limits in all patients. Compared with assisted mechanical ventilation, during MRV, patients of group 1 decreased their VT and V (from 0.64 +/- 0.04 to 0.42 +/- 0.03 L/sec) and increased their TI/TT (from 0.39 +/- 0.03 to 0.52 +/- 0.03). f did not change. PAO2 - PaO2 and QS/QT decreased (from 306 +/- 16 to 269 +/- 15 mm Hg, and from 20.2 +/- 1.4 to 17.5 +/- 1.1, respectively), while PaCO2 increased (from 44 +/- 3 to 50 +/- 3 mm Hg). On the contrary, patients of group 2 increased their VT (from 0.69 +/- 0.02 to 0.92 +/- 0.09 L), decreased their f (from 22.3 +/- 0.5 to 19.3 +/- 0.3 b/min), although they did not change their V and TI/TT. PAO2 - PaO2 and QS/QT remained stable. PaCO2 diminished (from 39 +/- 3 to 34 +/- 3 mm Hg). Pressure support level was higher in group 2 than in group 1 (29.4 +/- 3.0 v 19.8 +/- 2.9 cm H2O). CONCLUSIONS: We conclude that (1) PSV delivered by MRV may adequately ventilate patients with moderate to severe ARDS, preserving gas exchange and hemodynamics, at least for the short period tested; (2) early and intermediate ARDS respond in a different manner to MRV in terms of breathing pattern, gas exchange, and level of pressure assistance; and (3) patients with early ARDS are those who have an improvement in intrapulmonary oxygenation probably due, at least in part, to alveolar recruitment augmented by active diaphragmatic contraction.