Effects of pulse lung inflation on chest wall expiratory motor activity.

The effects of pulse lung inflation (LI) on expiratory muscle activity and phase duration (Te) were determined in anesthetized, spontaneously breathing dogs (n = 20). A volume syringe was used to inflate the lungs at various times during the expiratory phase. The magnitude of lung volume was assessed by the corresponding change in airway pressure (Paw; range 2-20 cmH(2)O). Electromyographic (EMG) activities were recorded from both thoracic and abdominal muscles. Parasternal muscle EMG was used to record inspiratory activity. Expiratory activity was assessed from the triangularis sterni (TS), internal intercostal (IIC), and transversus abdominis (TA) muscles. Lung inflations <7 cmH(2)O consistently inhibited TS activity but had variable effects on TA and IIC activity and expiratory duration. Lung inflations resulting in Paw values >7 cmH(2)O, however, inhibited expiratory EMG activity of each of the expiratory muscles and lengthened Te in all animals. The responses of expiratory EMG and Te were directly related to the magnitude of the lung inflation. The inhibition of expiratory motor activity was independent of the timing of pulse lung inflation during the expiratory phase. The inhibitory effects of lung inflation were eliminated by bilateral vagotomy and could be reproduced by electrical stimulation of the vagus nerve. We conclude that pulse lung inflation resulting in Paw between 7 and 20 cmH(2)O produces a vagally mediated inhibition of expiratory muscle activity that is directly related to the magnitude of the inflation. Lower inflation pressures produce variable effects that are muscle specific.     

Responses of pulmonary stretch receptors during ramp inflations of the lung

Studies were conducted in anesthetized paralyzed dogs to determine how the dynamic and proportional sensitivity of pulmonary stretch receptors change during lung inflation. The firing of each receptor was examined at multiple levels of static transpulmonary pressure and during multiple identical inflations at each of several rates. The averaged response of the receptor was computed and receptor activity related to transpulmonary pressure. On the basis of a quantitative criterion, employed to distinguish type I from type II receptors, the receptors could not be divided into distinct subpopulations. Thus all receptors were treated as coming from a single population. For all receptors we observed that their proportional sensitivity (increases in firing produced by increases in lung expansion at a constant rate of inflation) declined as the lung was inflated. In contrast, the dynamic sensitivity (increases in firing produced by increased rates of inflation at constant transpulmonary pressure) increased or remained relatively constant with increasing lung expansion. Thus, as inflation volume increases, the pulmonary stretch receptor acts increasingly as a rate receptor. The rate of inflation may have a more important role in control of the inspiratory duration than previously realized.     

Influence of pulmonary inflations on discharge patterns of phrenic motoneurons

The purpose of this study was to assess the influence of pulmonary inflations on activities of single phrenic motoneurons. Studies were performed in decerebrate and paralyzed cats; activities of phrenic nerve and single phrenic motoneurons were recorded. Animals were ventilated with a servo-respirator which produced alterations in tracheal pressure in parallel with changes in integrated activity of the phrenic nerve. At end-tidal fractional concentrations of CO2 of 0.05, phrenic motoneurons were distributed into "early" and "late" populations, depending on time of onset of activity. During the late stages of neural inspiration, differences in levels of integrated activity of the phrenic nerve became evident between cycles with and without lung inflations. At a time approximating 90% of the inspiratory duration during inflations, integrated phrenic activity was higher for cycles with inflation. Concomitantly, with lung inflations, the discharge frequencies of early phrenic motoneurons were lower, and late motoneurons began to discharge sooner than when inflations were withheld. Similar results were obtained in hypercapnia. We conclude that reflexes activated by pulmonary inflations may produce augmentation, as well as inhibition of phrenic motoneuronal activities. Factors responsible for eliciting these reflex augmentations and inhibitions are discussed.     

Power spectra of inspiratory nerve activity with lung inflations in cats

To investigate the effect of lung inflations on the high-frequency synchrony (70-122 Hz) observed in the inspiratory activity of respiratory motor nerves of decerebrate cats, I applied a step increase in lung inflation pressure at fixed delays into the inspiratory phase and computed power spectra of phrenic neurograms before and during inflation. In 25 decerebrate paralyzed cats the frequency of the high spectral peak was 92.3 +/- 11.1 Hz before and 105.3 +/- 12.1 Hz during the step in inflation pressure, shifting upward by 13.0 +/- 6.0 Hz. For 8 of the 25 cats, the recurrent laryngeal and phrenic neurograms were recorded simultaneously. The high spectral peak was present during inspiration in the recurrent laryngeal power spectra and coherent with the high peak in the phrenic power spectra. In response to lung inflation, the high peak disappeared from the power spectra of the recurrent laryngeal nerve as the inspiratory activity was inhibited; a shift upward in frequency was not detectable. Comparing inspiratory times (TI, based on the phrenic neurograms) for breaths with no lung inflations to those for breaths with lung inflations, I found that lung inflations early in inspiration caused a decrease in TI, lung inflations at intermediates times had no effect on TI, and lung inflations late in inspiration caused an increase in TI. Despite lung inflation decreasing, not affecting, or increasing inspiratory duration and amplitude of the phrenic neurogram, lung inflation always caused a shift upward in the high-frequency peak of the phrenic power density. The fact that lung inflation, a powerful respiratory stimulus, affected the frequency of the high peak in a consistent manner suggests that the high-frequency synchrony is an important and robust feature of the central respiratory pattern generator.     

On defining total lung capacity in the mouse.

Maximal lung volume or total lung capacity in experimental animals is dependent on the pressure to which the lungs are inflated. Although 25-30 cm H2O are nominally used for such inflations, mouse pressure-volume (P-V) curves show little flattening on inflation to those pressures. In the present study, we examined P-V relations and mean alveolar chord length in three strains (C3H/HeJ, A/J, and C57BL/6J) at multiple inflation pressures. Mice were anesthetized, and their lungs were degassed in vivo by absorption of 100% O2. P-V curves were then recorded in situ with increasing peak inflation pressure in 10-cm H2O increments up to 90 cm H2O. Lungs were quickly frozen at specific pressures for morphometric analysis. The inflation limbs never showed the appearance of a plateau, with lung volume increasing 40-60% as inflation pressure was increased from 30 to 60 cm H2O. In contrast, parallel flat deflation limbs were always observed, regardless of the inflation pressure, indicating that the presence of a flat deflation curve cannot be used to justify measurement of total lung capacity in mice. Alveolar size increased monotonically with increasing pressure in all strains, and there was no evidence of irreversible lung damage from these inflations to high pressures. These results suggest that the mouse lung never reaches a maximal volume, even up to nonphysiological pressures >80 cm H2O.     

Responses of pulmonary vagal mechanoreceptors to high-frequency oscillatory ventilation

The discharge of 57 slowly adapting pulmonary stretch receptors (PSR's) and 16 rapidly adapting receptors (RAR's) was recorded from thin vagal filaments in anesthetized dogs. The receptors were localized and separated into three groups: extrathoracic tracheal, intrathoracic tracheal, and intrapulmonary receptors. The influence of high-frequency oscillatory ventilation (HFO) at 29 Hz on receptor discharge was analyzed by separating the response to the associated shift in functional residual capacity (FRC) from the oscillatory component of the response. PSR activity during HFO was increased from spontaneous breathing (49%) and from the static FRC shift (25%). PSR activity during the static inflation was increased 19% over spontaneous breathing. RAR activity was also increased with HFO. These results demonstrate that 1) the increased activity of PSR and RAR during HFO is due primarily to the oscillating action of the ventilator and secondarily to the shift in FRC associated with HFO, 2) the increased PSR activity during HFO may account for the observed apneic response, and 3) PSR response generally decreases with increasing distance from the tracheal opening.     

Inhibitory mechanism of slowly adapting pulmonary stretch receptors after release from hyperinflation in anesthetized rabbits

In anesthetized, artificially ventilated rabbits with vagus nerve section, release from 10 consecutive hyperinflations (inflation volume = 3 tidal volume) caused an inhibition of the slowly adapting pulmonary stretch receptor (SAR) activity for 16-22 sec. Intravenous administration of tetraethylammonium (TEA, 10 and 20 mg/kg), a K+ channel blocker, did not significantly alter either basal SAR discharge or tracheal pressure (PT). Although TEA treatment at 10.0 mg/kg had no significant effect on the magnitude and duration of inhibited SAR activity seen after release from hyperinflation, the increasing dose of this K+ channel blocker up to 20 mg/kg inhibited these effects of the receptor activity but this inhibition was small. The Na+ -K+ ATPase inhibitor ouabain (5 and 10 microg/kg) that had no significant effect on SAR activity and P(T) in the control abolished or attenuated the inhibitory action of SARs in a dose-dependent manner. Furthermore, the changes in dynamic lung compliance (Cdyn) and P(T) in response to post-hyperinflation were not significantly influenced by pretreatment with either TEA or ouabain. These results suggest that the inhibitory action of receptors seen during post-hyperinflation corresponded with the induction of slow afterhyperpolarization (sAHP), and that the mechanism of generating the sAHP of SARs is mainly mediated by the activation of Na+ -K+ pump activity.     

Characteristics of inspiratory inhibition by phasic volume feedback in cats

The dependence of phrenic efferent discharge on vagal-volume feedback was examined in barbiturate-anesthetized, paralyzed cats ventilated by a phrenic-driven servo respirator. The characteristics of the respiratory were altered for a single breath, and the resulting change in phrenic activity was quantitated by comparison with phrenic activity without phasic volume feedback. The relation between volume feedback and phrenic inhibition was determined both when inspiratory termination occurred during the rising phase of phrenic discharge and during the plateau observed with barbiturate-induced apneusis. Inhibition of inspiratory activity occurred only when lung volume exceeded a time-dependent threshold. Above this threshold, andextending over a substantial volume range, volume feedback caused graded and reversible inhibition of phrenic discharge. The threshold for graded inhibition declined progressively during the inspiratory phase, showing no obvious relation to the level of inspiratory activity. At any particular time, the relation between volume and phrenic inhibition was convex to the volume axis, and the slope of the relationship increased with inspiratory time. The results indicate that a) volume feedback inhibits inspiration in a graded manner, b) partial inhibition of phrenic activity renders it more susceptible to additional inhibition, and c) inhibitory effectiveness of volume feedback increases with time.     

Adaptation to reflex effects of prolonged lung inflation

Adaptation to the reflex effects of sustained changes in lung volume on inspiratory duration (TI), expiratory duration (TE), and the phrenic neurogram was examined. Test inflations in gallamine-paralyzed dogs anesthetized with pentobarbital sodium were made during a 6-min trial while the animal was not ventilated: 2 min at functional residual capacity (FRC), 2 min at elevated airway pressure, and 2 min back at FRC. The dogs were hyperoxygenated and arterial PCO2 was kept constant by an infusion of tris (hydroxymethyl) aminomethane. The maintained inflations produced minimal changes in TI. On return to FRC, TI was prolonged in proportion to the magnitude of the prior inflation. In contrast, inflation produced marked prolongation of TE, which then adapted back toward preinflation values. On return to FRC, TE shortened initially to values below control. This shortening increased with greater prior lung inflations. The times to reestablish steady-state values upon return to FRC differed for TI (14.8 +/- 4.6 s) and TE (33.8 +/- 12.7 s). The magnitude of the phrenic neurogram at a fixed time from onset of inspiration and its slope were unchanged with inflation. These results indicate that respiratory phase durations are influenced not only by pulmonary afferent input within each respiratory cycle but also by prior vagal afferent activity that engages central processes with long, although different, time constants. Afferent input to the slow central process controlling TI is not gated to only one phase of the respiratory cycle.     

Pulmonary receptors in reptiles: discharge patterns of receptor populations in snakes versus turtles

This study examines the effects of lung inflation/deflation with and without CO2 on the entire population of pulmonary receptors in the vagus nerve in two species of snakes and two species of turtles. We asked the question, "how does the response of the entire mixed population of pulmonary stretch receptors (PSR) and intrapulmonary chemoreceptors (IPC) in species possessing both differ from that in species with only PSR"? This was studied under conditions of artificial ventilation with the secondary goal of extending observations on the presence/absence of IPC to a further three species. Our results indirectly illustrate the presence of IPC in the Burmese python and South American rattlesnake but not the side necked turtle, adding support to the hypothesis that IPC first arose in diapsid reptiles. In both species of snake, CO2-sensitive discharge (presumably from IPC) predominated almost to the exclusion of CO2-insensitive discharge (presumably arising from PSR) while the opposite was true for both species of turtle. The data suggest that for animals breathing air under conditions of normal metabolism there is little to distinguish between the discharge profiles of the total population of receptors arising from the lungs in the different groups. Interestingly, however, under conditions of elevated environmental CO2 most volume-related feedback from the lungs is abolished in the two species of snakes, while under conditions of elevated metabolic CO2, it is estimated that volume feedback from the lungs would be enhanced in these same species.     

Control of breathing at elevated lung volumes in anesthetized cats

We monitored the steady-state ventilatory responses of anesthetized cats to increases in lung volume produced by expiratory threshold loads (ETL) to study the roles of peripheral and central neural mechanisms in controlling respiration at elevated lung volumes. Application of an ETL of 5 cmH2O produced a significant decrease in respiratory frequency (-18%) but no change in minute ventilation (VE) due to a significant increase in tidal volume (VT) (19.3%). The drop in frequency was due solely to an increase in expiratory duration. ETL of 10 cmH2O significantly reduced VE (-17.5%) for the same reason. VT was maintained or increased at elevated lung volumes due to both an increase in the rate of rise of phrenic activity and a maintenance of inspiratory duration (TI) despite increases in both chemical drive and pulmonary stretch receptor (PSR) activity. No PSR adapted completely to the maintained change in lung volume. The sensitivity of the inspiratory off-switch mechanism to increases in lung volume, given by the reciprocal of the VT-TI relationship, decreased significantly during breathing on ETL. The results are consistent with the hypothesis that central habituation, not just peripheral adaptation of PSR, determines breathing pattern at elevated lung volumes.     

Surfactant replacement partially restores the activity of pulmonary stretch receptors in surfactant-depleted cats.

Single units of slowly adapting pulmonary stretch receptors (PSRs) were investigated in anesthetized cats during spontaneous breathing on continuous positive airway pressure (2-5 cmH2O), before and after lung lavage and then after instillation of surfactant to determine the PSR response to surfactant replacement. PSRs were classified as high threshold (HT) and low threshold (LT), and their instantaneous impulse frequency (f imp) was related to transpulmonary pressure (Ptp) and tidal volume (Vt). Both the total number of impulses and maximal f imp of HT and LT PSRs decreased after lung lavage (55 and 45%, respectively) in the presence of increased Ptp and decreased Vt. While Ptp decreased markedly and Vt remained unchanged after surfactant instillation, all except one PSR responded with increased total number of impulses and maximal f imp (42 and 26%, respectively). Some HT PSRs ceased to discharge after lung lavage but recovered after surfactant instillation. The end-expiratory activity of LT PSRs increased or was regained after surfactant instillation. After instillation of surfactant, respiratory rate increased further with a shorter inspiratory time, resulting in a lower inspiratory-to-expiratory time ratio. Arterial pH decreased (7.31 +/- 0.04 vs. 7.22 +/- 0.06) and Pco2 increased (5.5 +/- 0.7 vs. 7.2 +/- 1.3 kPa) after lung lavage, but they were the same after as before instillation of surfactant (pH = 7.21 +/- 0.08 and Pco2 = 7.6 +/- 1.4 kPa) during spontaneous breathing. In conclusion, surfactant instillation increased lung compliance, which, in turn, increased the activity of both HT and LT PSRs. A further increase in respiratory rate due to a shorter inspiratory time after surfactant instillation suggests that the partially restored PSR activity after surfactant instillation affected the breathing pattern.     

Inhibition of breathing after surfactant depletion is achieved at a higher arterial PCO2 during ventilation with liquid than with gas

Background

Inhibition of phrenic nerve activity (PNA) can be achieved when alveolar ventilation is adequate and when stretching of lung tissue stimulates mechanoreceptors to inhibit inspiratory activity. During mechanical ventilation under different lung conditions, inhibition of PNA can provide a physiological setting at which ventilatory parameters can be compared and related to arterial blood gases and pH.

Objective

To study lung mechanics and gas exchange at inhibition of PNA during controlled gas ventilation (GV) and during partial liquid ventilation (PLV) before and after lung lavage.

Methods

Nine anaesthetised, mechanically ventilated young cats (age 3.8 ± 0.5 months, weight 2.3 ± 0.1 kg) (mean ± SD) were studied with stepwise increases in peak inspiratory pressure (PIP) until total inhibition of PNA was attained before lavage (with GV) and after lavage (GV and PLV). Tidal volume (V_t), PIP, oesophageal pressure and arterial blood gases were measured at inhibition of PNA. One way repeated measures analysis of variance and Student Newman Keuls-tests were used for statistical analysis.

Results

During GV, inhibition of PNA occurred at lower PIP, transpulmonary pressure (Ptp) and Vt before than after lung lavage. After lavage, inhibition of inspiratory activity was achieved at the same PIP, Ptp and Vt during GV and PLV, but occurred at a higher PaCO₂ during PLV. After lavage compliance at inhibition was almost the same during GV and PLV and resistance was lower during GV than during PLV.

Conclusion

Inhibition of inspiratory activity occurs at a higher PaCO₂ during PLV than during GV in cats with surfactant-depleted lungs. This could indicate that PLV induces better recruitment of mechanoreceptors than GV.     

Expiratory muscle activity in the awake and sleeping human during lung inflation and hypercapnia.

Expiratory muscle activity has been shown to occur in awake humans during lung inflation; however, whether this activity is dependent on consciousness is unclear. Therefore we measured abdominal muscle electromyograms (intramuscular electrodes) in 13 subjects studied in the supine position during wakefulness and non-rapid-eye-movement sleep. Lung inflation was produced by nasal continuous positive airway pressure (CPAP). CPAP at 10-15 cmH2O produced phasic expiratory activity in two subjects during wakefulness but produced no activity in any subject during sleep. During sleep, CPAP to 15 cmH2O increased lung volume by 1,260 +/- 215 (SE) ml, but there was no change in minute ventilation. The ventilatory threshold at which phasic abdominal muscle activity was first recorded during hypercapnia was 10.3 +/- 1.1 l/min while awake and 13.8 +/- 1 l/min while asleep (P less than 0.05). Higher lung volumes reduced the threshold for abdominal muscle recruitment during hypercapnia. We conclude that lung inflation alone over the range that we studied does not alter ventilation or produce recruitment of the abdominal muscles in sleeping humans. The internal oblique and transversus abdominis are activated at a lower ventilatory threshold during hypercapnia, and this activation is influenced by state and lung volume.     

Effects of hypercapnia on Breuer-Hering threshold for inspiratory termination

The effects of CO2 concentration on the timing of inspiratory duration (TI) and expiratory duration (TE) and the responses to lung inflation were studied in decerebrate paralyzed cats. With lung volume held at functional residual capacity during the breath cycle, hypercapnia (fractional concentration of inspired CO2 = 0.04) caused variable changes in TI and significant increases in TE. To obtain the Breuer-Hering threshold relationship [tidal volume (VT) vs. TI] and the timing relationship between TE and the preceding TI (TE vs. TI), ramp inflations of various sizes were used to terminate inspiration at different times in the breath cycle. Hypercapnia caused the VT vs. TI curves to shift in an upward direction so that at higher lung volumes TI was lengthened. Also, the slope of the TE vs. TI relationship was increased. The results suggest that hypercapnia diminished the sensitivity of the Breuer-Hering reflex to the lung volume, thus allowing volume to increase with little effect on TI. In addition, TE appears to become more sensitive to changes in the preceding TI. A model is presented which provides a possible neural mechanism for these responses.     

Mechanical response to hyperinflation of the two abdominal muscle layers

Abdominal muscle length changes and activity were directly examined in vivo with the use of the techniques of sonomicrometry and electromyography, respectively, in nine supine anesthetized dogs. Expiratory threshold loading was utilized to stimulate recruitment of the abdominal muscles, and lung inflations produced the passive relationships. The internal layer, consisting of the internal oblique and transversus abdominis, shortened more in expiration than the external layer, consisting of the external oblique and rectus abdominis. The internal oblique shortened to approximately 83% of its length at functional residual capacity vs. 98% for the external oblique (P less than 0.05). The results obtained during passive lung inflation indicate these internal muscles are also more influenced by changes in lung volume. The internal oblique lengthened to 115% of its length at functional residual capacity vs. 103% for external oblique at total lung capacity (P less than 0.05). The results suggest that anatomic division of the abdominal muscles into external and internal layers corresponds to functional differences in terms of both passive lengthening and active shortening during ventilation and that these differences imply variable functions of the two layers.     

Firing activity in slow-adapting pulmonary receptors during normal respiration

The firing activity pattern of 50 slow-adapting pulmonary receptors (SAPR) was investigated in anesthetized cats under conditions of normal respiration and quasi-static and dynamic lung inflation. A non-linear relationship was found between change in activity rate and lung capacity during inspiration in 74% of SAPR; the rate rose in proportion to an increase in lung volume in a further 16%, and changes in the rate during the respiratory cycle followed a different atypical pattern in the remaining 10%. A non-linear relationship persisted between rate and volume during quasi-static inflation of the lungs in40% of the SAPR investigated (linear in 50% of cases). During dynamic inflation, nonlinear and linear SAPR numbered 70% and 20% respectively. Summated flow of impulses from all SAPR investigated stood in a non-linear relationship to lung volume during normal breathing. Reasons for the different relationships between the activity rate of individual SAPR and lung volume during normal pulmonary ventilation and during inflation of the lungs are discussed together with possible synaptic connections between pulmonary afferents and bulbar respiratory neurons.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 20, No. 4, pp. 518–525, July–August, 1988.     

Quantitative evaluation of pulmonary stretch receptor activity during high-frequency ventilation.

The purpose of this study was to determine the neural output of pulmonary stretch receptors (PSRs) in response to conditions that, in previous studies (J. Appl. Physiol. 65: 179-186, 1988 and Respir. Physiol. 80: 307-322, 1990), produced apnea in anesthetized cats. These conditions included changes in airway pressure (Paw; 2 or 6 cmH2O), stroke or tidal volume (1-4 ml/kg), frequency [conventional mechanical ventilation (CMV) vs. high-frequency ventilation (HFV) at 10, 15, and 20 Hz], and levels of inspired CO2 (0, 2, and 5%). These data were needed to assess properly the specific contribution of the PSRs to the apnea found with certain combinations of the above variables. Each PSR was subjected to HFV over a range of mechanical and chemical settings, and its activity was recorded. PSRs exhibited continuous activity associated with pump stroke in 11 of 12 fibers tested. PSRs fired more rapidly when mean Paw was 6 cmH2O [45.3 +/- 0.8 (SE) impulses/s] than when it was 2 cmH2O (31.7 +/- 0.9 impulses/s, P = 0.0001). At both pressures, PSR activity increased as the volume of inflation, or tidal volume, was increased from 1 to 4 ml/kg. At Paw of 2 cmH2O, the number of impulses per second for HFV was not different from that for CMV (averaged over the respiratory cycle), under conditions previously demonstrated as apneogenic for both modes of ventilation. Therefore the absolute amount of information being sent to the brain stem processing centers via PSRs during HFV did not differ from that during CMV. Thus any PSR contribution to HFV-induced apnea must have been the result of changes in the pattern of the signal or the central nervous system's processing of it rather than an increase in the amount of inhibitory afferent signal.     

The proximal colonic motor response to rectal mechanical and chemical stimulation

We aimed to determine whether rectal distension and/or infusion of bile acids stimulates propagating or nonpropagating activity in the unprepared proximal colon in 10 healthy volunteers using a nasocolonic manometric catheter (16 recording sites at 7.5-cm spacing). Sensory thresholds and proximal colonic motor responses were assessed following rectal distension by balloon inflation and rectal instillation of chenodeoxycholic acid. Maximum tolerated balloon volume and the volume that stimulated a desire to defecate were both significantly (P < 0.01) reduced after rectal chenodeoxycholic acid. The frequency of colonic propagating pressure wave sequences decreased significantly in response to initial balloon inflations (P < 0.05), but the frequency doubled after subsequent chenodeoxycholic acid infusion (P < 0.002). Nonpropagating activity decreased after balloon inflation, was not influenced by acid infusion, and demonstrated a further decrease in response to repeat balloon inflation. We concluded that rectal chenodeoxycholic acid in physiological concentrations is a potent stimulus for propagating pressure waves arising in the proximal colon and reduces rectal sensory thresholds. Rectal distension inhibits all colonic motor activity.     

Acoustic evidence of airway opening during recruitment in excised dog lungs.

The aim of this study was to test the hypothesis that the mechanism of recruitment and the lower knee of the pressure-volume curve in the normal lung are primarily determined by airway reopenings via avalanches rather than simple alveolar recruitments. In isolated dog lung lobes, the pressure-volume loops were measured, and crackle sounds were recorded intrabronchially during both the first inflation from the collapsed state to total lobe capacity and a second inflation without prior degassing. The inflation flow contained transients that were accompanied by a series of crackles. Discrete volume increments were estimated from the flow transients, and the energy levels of the corresponding crackles were calculated from the sound recordings. Crackles were concentrated in the early phase of inflation, with the cumulative energy exceeding 90% of its final value by the lower knee of the pressure-volume curve. The values of volume increments were correlated with crackle energy during the flow transient for both the first and the second inflations (r(2) = 0.29-0.73 and 0.68-0.82, respectively). Because the distribution of volume increments followed a power law, the correlation between crackle energy and discrete volume increments suggests that an avalanche-like airway opening process governs the recruitment of collapsed normal lungs.