Steady-state response of quadriplegic subjects to inspiratory resistive load

Normal subjects preserve tidal volume (VT) in the face of added inspiratory resistance by increasing maximal amplitude and duration of the rising phase of respiratory driving pressure (DP) and by changing the shape of this phase to one that is more concave to the time axis. To explore the possible role of chest wall afferents in mediating these responses, we determined averaged DP in eight quadriplegic subjects during steady-state unloaded breathing and while breathing through an inspiratory resistance (8.5 cmH2O X 1(-1) X s). As with normal subjects, quadriplegics preserved VT (loaded VT = 106% control) by utilizing all three mechanisms. However, prolongation of the inspiratory duration derived from the DP waveform (+22% vs. +42%) and shape response were significantly less in the quadriplegic subjects. Shape response was completely absent in subjects with C4 lesions. The results provide strong evidence that respiratory muscle spindles are responsible for shape response and that changes in afferent feedback from the chest wall play an important role in mediating inspiratory prolongation.     

Response of normal subjects to inspiratory resistive unloading

The purpose of this study was to examine the role of the normal inspiratory resistive load in the regulation of respiratory motor output in resting conscious humans. We used a recently described device (J. Appl. Physiol. 62: 2491-2499, 1987) to make mouth pressure during inspiration positive and proportional to inspiratory flow, thus causing inspiratory resistive unloading (IRUL); the magnitude of IRUL (delta R = -3.0 cmH2O.1(-1).s) was set so as to unload most (approximately 86% of the normal inspiratory resistance. Six conscious normal humans were studied. Driving pressure (DP) was calculated according to the method of Younes et al. (J. Appl. Physiol. 51: 963-1001, 1981), which provides the equivalent of occlusion pressure at functional residual capacity throughout the breath. IRUL resulted in small but significant changes in minute ventilation (0.6 1/min) and in end-tidal CO2 concentration (-0.11%) with no significant change in tidal volume or respiratory frequency. There was a significant shortening of the duration (neural inspiratory time) of the rising phase of the DP waveform and the shape of the rising phase became more convex to the time axis. There was no change in the average rate of rise of DP or in the duration or shape of the declining phase. We conclude that 1) the normal inspiratory resistance is an important determinant of the duration and shape of the rising phase of DP and 2) the neural responses elicited by the normal inspiratory resistance are similar to those observed with added inspiratory resistive loads.     

Ventilatory adjustments during sustained resistive unloading in exercising humans

Effect of He-O2-breathing (79.1%:20.9%) compared to air-breathing on inspiratory ventilation (VI) and its different components [tidal volume (VT), the duration of the phases of each respiratory cycle (tI, tTOT)] as well as on inspiratory mouth occlusion pressure (P0.1) were studied in six normal men at rest and during 72 constant-load exercises (90 W) over a much longer period than in previous studies. Results showed that, irrespective of the order of administration of the two gases (7 min air----7 min He-O2 or vice versa): at rest, P0.1 decreased during He-O2 inhalation but no changes in VI and breathing pattern were detectable; during exercise, sustained He-induced hyperventilation was observed without any change in the absolute value of P0.1; increase in P0.1 between the resting period and exercise (delta P0.1) was significantly higher during He-O2-breathing than during air breathing; this He-induced hyperventilation was associated with a sustained increase in VT/tI, but with constant tI/tTOT. Helium-breathing during exercise cannot be a simple situation of resistance unloading, as has been suggested. We conclude that He-O2-breathing, after the initial compensation period, induces reflex changes in ventilatory control with an increase in inspiratory neural drive. Moreover, it appears that exercise P0.1 is not a legitimate index of inspiratory neural drive whenever rest P0.1 changes according to the nature of the inhaled gas mixture.     

Airway obstruction during periodic breathing in premature infants

To characterize changes in pulmonary resistance, timing, and respiratory drive during periodic breathing, we studied 10 healthy preterm infants (body wt 1,340 +/- 240 g, postconceptional age 35 +/- 2 wk). Periodic breathing in these infants was defined by characteristic cycles of ventilation with intervening respiratory pauses greater than or equal to 2 s. Nasal airflow was recorded with a pneumotachometer, and esophageal or pharyngeal pressure was recorded with a fluid-filled catheter. Pulmonary resistance at half-maximal tidal volume, inspiratory time (TI), expiratory time (TE), and mean inspiratory flow (VT/TI) were derived from computer analysis of five cycles of periodic breathing per infant. In 80% of infants periodic breathing was accompanied by completely obstructed breaths at the onset of ventilatory cycles; the site of airway obstruction occurred within the pharynx. The first one-third of the ventilatory phase of each cycle was accompanied by the highest airway resistance of the entire cycle (168 +/- 98 cmH2O.l-1.s). In all infants TI was greatest at the onset of the ventilatory cycle, VT/TI was maximal at the midpoint of the cycle, and TE was longest in the latter two-thirds of each cycle. A characteristic increase and subsequent decrease of 4.5 +/- 1.9 ml in end-expiratory volume also occurred within each cycle. These results demonstrate that partial or complete airway obstruction occurs during periodic breathing. Both apnea and periodic breathing share the element of upper airway instability common to premature infants.     

Respiratory mechanics during halothane anesthesia and anesthesia-paralysis in humans

In six spontaneously breathing anesthetized subjects [halothane approximately 1 maximum anesthetic concentration (MAC), 70% N2O-30% O2], we measured flow (V), volume (V), and tracheal pressure (Ptr). With airway occluded at end-inspiration tidal volume (VT), we measured Ptr when the subjects relaxed the respiratory muscles. Dividing relaxed Ptr by VT, total respiratory system elastance (Ers) was obtained. With the subject still relaxed, the occlusion was released to obtain the V-V relationship during the ensuing relaxed expiration. Under these conditions, the expiratory driving pressure is V X Ers, and thus the pressure-flow relationship of the system can be obtained. By subtracting the flow resistance of equipment, the intrinsic respiratory flow resistance (Rrs) is obtained. Similar measurements were repeated during anesthesia-paralysis (succinylcholine). Ers averaged 23.9 +/- 4 (+/- SD) during anesthesia and 21 +/- 1.8 cmH2O X 1(-1) during anesthesia-paralysis. The corresponding values of intrinsic Rrs were 1.6 +/- 0.7 and 1.9 +/- 0.9 cmH2O X 1(-1) X s, respectively. These results indicate that Ers increases substantially during anesthesia, whereas Rrs remains within the normal limits. Muscle paralysis has no significant effect on Ers and Rrs. We also provide the first measurements of inspiratory muscle activity and related negative work during spontaneous expiration in anesthetized humans. These show that 36-74% of the elastic energy stored during inspiration is wasted in terms of negative inspiratory muscle work.     

Ventilatory response to high-frequency airway oscillation in humans

To investigate respiratory control during high-frequency oscillation (HFO), ventilation was monitored in conscious humans by respiratory inductive plethysmography during application at the mouth of high-frequency pressure oscillations. Studies were conducted before and after airway and pharyngeal anesthesia. During HFO, breathing became slow and deep with an increase in tidal volume (VT) of 37% (P less than 0.01) and inspiratory duration (TI) of 34% (P less than 0.01). Timing ratio (TI/TT) increased 14% (P less than 0.05) and respiratory frequency (f) decreased 12% (P less than 0.01). Mean inspiratory flow (VT/TI) did not change during HFO. Following airway anesthesia, VT increased only 26% during HFO (P less than 0.01), whereas significant changes in TI, TI/TT, and f were not observed. Pharyngeal anesthesia failed to diminish the effect of HFO on TI, TT, or f, although the increase in VT was reduced. These results indicate that 1) HFO presented in this manner alters inspiratory timing without affecting the level of inspiratory activity, and 2) receptors in the larynx and/or lower airways may in part mediate the response.     

Airway anesthesia effects on hypercapnic breathing pattern in humans

Minute ventilation (VE) and breathing pattern during an abrupt increase in fractional CO2 were compared in 10 normal subjects before and after airway anesthesia. Subjects breathed 7% CO2-93% O2 for 5 min before and after inhaling aerosolized lidocaine. As a result of airway anesthesia, VE and tidal volume (VT) were greater during hypercapnia, but there was no effect on inspiratory time (TI). Therefore, airway anesthesia produced an increase in mean inspiratory flow (VT/TI) during hypercapnia. The increase in VT/TI was compatible with an increase in neuromuscular output. There was no effect of airway anesthesia on the inspiratory timing ratio or the shape and position of the curve relating VT and TI. We also compared airway resistance (Raw), thoracic gas volume, forced vital capacity, forced expired volume at 1s, and maximum midexpiratory flow rate before and after airway anesthesia. A small (0.18 cmH2O X l-1 X s) decrease in Raw occurred after airway anesthesia that did not correlate with the effect of airway anesthesia on VT/TI. We conclude that airway receptors accessible to airway anesthesia play a role in hypercapnic VE.     

Effect of mechanical loading on displacements of chest wall during breathing in humans

Using a respiratory inductive plethysmograph (Respitrace) we studied thoracoabdominal movements in eight normal subjects during inspiratory resistive (Res) and elastic (El) loading. The magnitude of loads was chosen so as to produce a fall in inspiratory mouth pressure of 20 cmH2O. The contribution of rib cage (RC) to tidal volume (VT) increased significantly from 68% during quiet breathing (QB) to 74% during El and 78% during Res. VT and breathing frequency did not change significantly. During loading a phase lag was present on inspiration so that the abdomen led the rib cage. However, outward movement of the abdomen ceased in the latter part of inspiration, and the RC became the sole contributor to VT. These observations suggest greater recruitment of the inspiratory musculature of the RC than the diaphragm during loading, although changes in the mechanical properties of the chest wall may also have contributed. Indeed, an increase in abdominal end-expiratory and end-inspiratory pressures was observed in five out of six subjects, indicating abdominal muscle recruitment which may account for part of the reduction in abdominal excursion. Both Res and El increased the rate of emptying of the respiratory system during the ensuing unloaded expiration as a result of a reduction in rib cage expiratory-braking mechanisms. The time course of abdominal displacements during expiration was unaffected by loading.     

Breathlessness during exercise with and without resistive loading

The purpose of this study was to quantify the intensity of breathlessness associated with exercise and respiratory resistive loading, with the specific purpose of isolating the quantitative contributions of inspiratory pressure, length, velocity, and frequency of inspiratory muscle shortening and duty cycle to breathlessness. The intensity of inspiratory pressure was quantified by measurement of estimated esophageal pressure (Pes = pressure at the mouth plus lung pressure), the extent of shortening by tidal volume (VT), and the velocity of shortening by inspiratory flow rate (VI). Six normal subjects underwent five incremental (100 kpm X min-1 X min-1) exercise tests on a cycle ergometer to maximum capacity. The first and last test were unloaded and the intervening tests were performed with external added resistances of 33, 57, and 73 cm H2O X l-1 X s in random order. The resistances were selected to provide a range of pressures, tidal volumes, flow rates, and patterns of breathing. At rest and at the end of each minute during exercise the subjects estimated the intensity of breathlessness (psi) by selecting a number ranging from 0 to 10 (Borg rating scale, 0 indicating no appreciable breathlessness and 10 the maximum tolerable sensation). Breathlessness was significantly and independently related to Pes (P less than 0.0001), VI (P less than 0.0001), frequency of breathing (fb) (P less than 0.01), and duty cycle [ratio of inspiratory duration to total breath duration (TI/TT)] (P less than 0.01): psi = 0.11 Pes + 0.61 VI + 1.99 TI/TT + 0.04 fb - 2.60 (r = 0.83). The results suggest that peak pressure (tension), VI (velocity of inspiratory muscle shortening), TI/TT, and fb contribute independently and collectively to breathlessness. The perception of respiratory muscle effort is ideally suited to subserve this sensation. The neurophysiological mechanism purported is a conscious awareness of the intensity of the outgoing motor command by means of corollary discharge within the central nervous system.     

Induction of periodic breathing during sleep causes upper airway obstruction in humans

To test the hypothesis that occlusive apneas result from sleep-induced periodic breathing in association with some degree of upper airway compromise, periodic breathing was induced during non-rapid-eye-movement (NREM) sleep by administering hypoxic gas mixtures with and without applied external inspiratory resistance (9 cmH2O X l-1 X s) in five normal male volunteers. In addition to standard polysomnography for sleep staging and respiratory pattern monitoring, esophageal pressure, tidal volume (VT), and airflow were measured via an esophageal catheter and pneumotachograph, respectively, with the latter attached to a tight-fitting face mask, allowing calculation of total pulmonary system resistance (Rp). During stage I/II NREM sleep minimal period breathing was evident in two of the subjects; however, in four subjects during hypoxia and/or relief from hypoxia, with and without added resistance, pronounced periodic breathing developed with waxing and waning of VT, sometimes with apneic phases. Resistive loading without hypoxia did not cause periodicity. At the nadir of periodic changes in VT, Rp was usually at its highest and there was a significant linear relationship between Rp and 1/VT, indicating the development of obstructive hypopneas. In one subject without added resistance and in the same subject and in another during resistive loading, upper airway obstruction at the nadir of the periodic fluctuations in VT was observed. We conclude that periodic breathing resulting in periodic diminution of upper airway muscle activity is associated with increased upper airway resistance that predisposes upper airways to collapse.     

Changes in breathing pattern at loads near perceptual threshold at different work levels

Five subjects were tested to determine the threshold for detection of an added resistance to inspiration in three tests, one at rest and two with exercise (mild = 50 W; moderate = 100 W) on a cycle ergometer. Changes in the breathing pattern were examined at added resistances near the perceptual threshold. Added inspiratory resistances with a 50% probability of detection were very variable at rest; they decreased significantly from rest (250 Pa.l-1.s-1) to moderate exercise (98 Pa.l-1.s-1) in four subjects. It is suggested that physical exercise may cause discomfort even when workers wearing a respirator do not have any abnormal sensation during sedentary work. Breathing patterns were compared between resistance loaded and unloaded breathing during each test. Decreases in inspiratory peak flow and acceleration of flow early in inspiration were found in resistance loaded breathing in almost all tests and a tendency for tidal volume to decrease was found during moderate exercise only. The ratios of resistance loaded to unloaded breathing for inspiratory time (ti) and total time (tt) tended to be greater in the detected than in the undetected responses at rest and during mild exercise but not during moderate exercise. This would imply that further prolongation of ti and tt in the detected responses was attributable to conscious or subconscious aspects of the resistance leading responses: however, these adjustments in breathing, which reduce frequency, would be less likely to occur as the work rate increases.     

Influence of inspiratory flow rate and frequency on O2 cost of resistive breathing in humans

We examined the combined effect of an increase in inspiratory flow rate and frequency on the O2 cost of inspiratory resistive breathing (VO2 resp). In each of three to six pairs of runs we measured VO2 resp in six normal subjects breathing through an inspiratory resistance with a constant tidal volume (VT). One of each pair of runs was performed at an inspiratory muscle contraction frequency of approximately 10/min and the other at approximately 30/min. Inspiratory mouth pressure was 45 +/- 2% (SE) of maximum at the lower contraction frequency and 43 +/- 2% at the higher frequency. Duty cycle (the ratio of contraction time to total cycle time) was constant at 0.51 +/- 0.01. However, during the higher frequency runs, two of every three contractions were against an occluded airway. Because VT and duty cycle were kept constant, mean inspiratory flow rate increased with frequency. Careful selection of appropriate parameters allowed the pairs of runs to be matched both for work rate and pressure-time product. The VO2 resp did not increase, despite approximately threefold increases in both inspiratory flow rate and contraction frequency. On the contrary, there was a trend toward lower values for VO2 resp during the higher frequency runs. Because these were performed at a slightly lower mean lung volume, a second study was designed to measure the VO2 resp of generating the same inspiratory pressure (45% maximum static inspiratory mouth pressure at functional residual capacity) at the same frequency but at two different lung volumes. This was achieved with a negligibly small work rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxygen cost of inspiratory loading: resistive vs. elastic

We measured the O2 cost of breathing (VO2resp) against external inspiratory elastic (E) and resistive loads (R) when end-expiratory lung volume, tidal volume, breathing frequency, work rate, and pressure-time product were matched in each of six pairs of runs in six subjects. During E, peak inspiratory mouth pressure was 65.7 +/- 1.8% (SD) of the maximum at functional residual capacity. However, during resistive runs, peak inspiratory mouth pressure was 41.1 +/- 2.8% of the maximum at functional residual capacity. In 36 paired runs, where both work rate and pressure-time product were within 10%, VO2resp for E was less than for R (81 and 96 ml/min, respectively; P less than 0.01). During loaded and unloaded breathing with the same tidal volume, we measured the changes in anteroposterior diameter of the lower rib cage in five subjects. In four subjects we also recorded the electromyograms of several fixator and stabilizing muscles. During E and R, the change in anteroposterior diameter of the lower rib cage was -116 +/- 5 and -45 +/- 4% (SE), respectively, of the unloaded value (P less than 0.01), indicating greater deformation during E. Although the peak electromyographic activity was 72 +/- 16% greater during E (P less than 0.01), there was no difference between the loads for area under the electromyogram time curve (P greater than 0.05). However, the time to 50% peak activity was less during R (P less than 0.02). We conclude that, even when work rate and pressure-time product are matched, VO2resp during R is greater than that during E. This difference may be due to preferential recruitment of faster and less efficient muscle fibers.     

Decay of inspiratory muscle pressure during expiration in conscious humans

In eight conscious spontaneously breathing adults we studied the decay of pressure developed by the inspiratory muscles during expiration (PmusI). PmusI was obtained according to the following equation: PmusI(t) = Ers X V(t) - Rrs X V(t), where V is volume and V is flow at any instant t during spontaneous expiration, and Ers and Rrs are, respectively, the passive elastance and resistance of the total respiratory system. Ers was determined with the relaxation method, and resistance with the interrupter method. All subjects showed marked braking of expiratory flow by PmusI. The mean time for PmusI to reduce to 50 and 0% amounted, respectively, to 23 and 79% of expiratory time. During expiration, 24-55% of the elastic energy stored during inspiration was used as resistive work and the remainder (45-76%) as negative work.     

Mechanical impedance as determinant of inspiratory neural drive during exercise in humans

Five healthy males exercised progressively with small 2-min increments in work load. We measured inspiratory drive (occlusion pressure, P0.1), pulmonary resistance (RL), dynamic pulmonary compliance (Cdyn), transdiaphragmatic pressure (Pdi), and diaphragmatic electromyogram (EMGdi). Minute ventilation (VE), mean inspiratory flow rate (VT/TI), and P0.1 all increased exponentially with increased work load, but P0.1 increased at a faster rate than did VT/TI or VE. Thus effective impedance (P0.1/VT/TI) rose throughout exercise. The increasing P0.1 was mostly due to augmented Pdi and coincided with increased EMGdi during this initial portion of inspiration. We found no consistent change in RL or Cdyn throughout exercise. With He breathing (80% He-20% O2), RL was reduced at all work loads; P0.1 fell in comparison with air-breathing values and VE, VT, and VT/TI rose in moderate and heavy work; and P0.1/VT/TI was unchanged with increasing exercise loads. Step reductions in gas density at a constant work load of any intensity showed an immediate reduction in the rate of rise of EMGdi and Pdi followed by increased VT/TI, breathing frequency, and hypocapnia. These changes were maintained during prolonged periods of unloading and were immediately reversible on return to air breathing. These data are consistent with the existence of a reflex effect on the magnitude of inspiratory neural drive during exercise that is sensitive to the load presented by the normal mechanical time constant of the respiratory system. This "load" is a significant determinant of the hyperpneic response and thus of the maintenance of normocapnia during exercise.     

Respiratory volume-time relationships during resistive loading in the cat.

The first-breath (neural) effects of graded resistive loads added separately during inspiration and expiration was studied in seven anesthetized cats before and after bilateral vagotomy. Additions of airflow resistance during inspiration reduced the volume inspired (VI) and increased inspiratory duration (TI). The duration of the ensuing unloaded expiration (TE) was unchanged. Vagotomy eliminated the TI modulation with inspiratory loads. Tracheal occlusion at the onset of inspiration yielded TI values similar to the fixed values observed following vagotomy. Resistive loads added during expiration produced similar results. Expired volume (VE) decreased and (TE) increased approaching the values obtained after vagotomy. Unlike the inspiratory resistive loads, loading during expiration results in an upward shift in the functional residual capacity (FRC). The FRC shift produces a time lag between the onset of diaphragmatic (EMG) activity and the initiation of airflow of the next (unloaded) inspiration. These studies suggest separate volume-time relationships for the inspiratory and expiratory phases of the breathing cycle. Both relationships are dependent upon vagally mediated volume feedback.     

Effect of respiratory apparatus on respiration

A mouthpiece plus noseclip (MP + NC) is frequently used in performing measurements of breathing patterns. Although the effects the apparatus exerts on breathing patterns have been studied, the mechanism of the changes it causes remains unclear. The current study examines the effects on respiratory patterns of a standard (17-mm-diam) MP + NC during room air (RA) breathing and the administration of 2 and 4% CO2 in normal volunteers and in patients 2-4 days after abdominal operation. When compared with values obtained with a noninvasive canopy system, the MP + NC induced increases in minute ventilation (VE), tidal volume (VT), and mean inspiratory flow (VT/TI), but not frequency (f) or inspiratory duty cycle, during both RA and CO2 administration. The percentage increase in VE, VT, and VT/TI caused by the MP + NC decreased as the concentration of CO2 increased. During RA breathing, the application of noseclip alone resulted in a decrease in f and an increase in VT, but VE and VT/TI were unchanged. The changes were attenuated during the administration of 2 and 4% CO2. Reducing the diameter of the mouthpiece to 9 mm abolished the alterations in breathing pattern observed with the larger (17-mm) diameter MP.     

Elevated diaphragm electromyogram during neonatal hypoxic ventilatory depression

Diaphragmatic electromyogram (EMG) was obtained in eight 48-h-old unanesthetized monkeys while breathing air and then either of two different hypoxic gas mixtures (12 or 8% O2 in N2) for 5 min. Minute ventilation (VI) rose significantly above control levels by 1 min of hypoxemia while animals were breathing either of the hypoxic gas mixtures as tidal volume (VT) and slope and rate moving average EMG increased. The relative gains in VI were associated with comparable increases in diaphragmatic neural activity per minute (EMG/min = peak EMG X frequency) during this early phase of hypoxemia. VI subsequently fell to control levels (inspired O2 fraction = 12%, arterial PO2 = 23 +/- 3 Torr) or significantly below (inspired O2 fraction = 8%, arterial PO2 = 18 +/- 0.4 Torr) by 5 min of hypoxemia, secondary to changes in VT. Despite the decline in VI, slope and rate moving average EMG, and EMG/min remained statistically above control values by 5 min of hypoxemia, although there was a trend for EMG/min to decrease slightly from the 1-min peak response. These findings demonstrate that hypoxic-induced depression of neural input to the diaphragm is not independently responsible for the biphasic nature of the newborn ventilatory response, although it cannot be ruled out as a contributor. The fall in inspiratory volumes despite constant elevated EMG activity suggests the presence of a change in respiratory mechanics and/or an impairment in diaphragmatic contractile function without offsetting neural compensatory activity.     

Contribution of central and reflex nervous activity to the rapid increase in pulmonary ventilation at the start of muscular exercise in man

To investigate the relative contributions of the central and peripheral neural drive to hyperventilation at the onset of muscular exercise, five volunteers were tested during the first ten breaths while performing both voluntary (VM) and passive (PM) ankle rotations with a frequency of 1 Hz and through an angle of 10 degrees. Resulting breathing patterns for the two movements were compared. Hypocapnic hyperventilation, found in both PM and VM, indicated its neural origin. Respiratory changes were higher in VM than in PM. In both experimental conditions, increases in ventilation (VE) depended more on respiratory frequency (f) than on tidal volume (VT). Moreover, increases in VT adapted, breath-by-breath, to values lower than the initial ones, while increases in f rose progressively. Expiratory time was reduced more than inspiratory time (TI); increases in inspiratory flow (VT/TI) depended to the same extent on changes in both TI and VT. Increases in expiratory tidal volume were initially higher than in inspiratory tidal volume, thereby producing a reduction in functional residual capacity. Because PM respiratory changes could be considered to be of nervous reflex origin only, the identical breathing patterns in PM and VM indicated that the hyperventilation found also in VM was mainly of reflex origin. The increase in VE was considered to be dependent on a greater stimulus from muscle proprioreceptors.     

Mechanisms of respiratory elastic load compensation in anesthetized humans

In anesthetized humans the nature of tidal volume (VT) compensation during elastic loading (as reflected in the difference between passive and effective respiratory elastances (Ers) and (E*rs), respectively) has not been fully elucidated. We assessed the relative contribution of various mechanisms contributing to VT compensation during linear elastic loading in 10 young anesthetized adults free of cardiorespiratory disease. Ers averaged 22.0 cmH2O X 1(-1), representing 64% of E*rs. Most of E*rs (84%) was comprised of the active elastance (E'rs), reflecting the major role played by the addition of force-length properties of inspiratory muscles to the internal impedance, and chest wall distortion played in the defense of VT. Of the remaining 16% of E*rs, the difference between E*rs and isotime E*rs, representing the contribution of prolongation of inspiratory time (TI) via the Hering-Breuer reflex, amounted to only 9%. Finally, the remainder of E*rs, which reflects the difference between E*rs and E'rs in the absence of vagal modulation, and attributed to several factors [shape of driving pressure wave, duration of control TI, and magnitude of E'rs and intrinsic flow resistance plus external resistances (Zin, Rossi, Zocchi, and Milic-Emili. J. Appl. Physiol. 57: 271-277, 1984)], amounted to less than 7%.