Pulmonary and chest wall mechanics in anesthetized paralyzed humans

Pulmonary and chest wall mechanics were studied in 18 anesthetized paralyzed supine humans by use of the technique of rapid airway occlusion during constant-flow inflation. Analysis of the changes in transpulmonary pressure after flow interruption allowed partitioning of the overall resistance of the lung (RL) into two compartments, one (Rint,L) reflecting airway resistance and the other (delta RL) representing the viscoelastic properties of the pulmonary tissues. Similar analysis of the changes in esophageal pressure indicates that chest wall resistance (RW) was due entirely to the viscoelastic properties of the chest wall tissues (delta RW = RW). In line with previous measurements of airway resistance, Rint,L increased with increasing flow and decreased with increasing volume. The opposite was true for both delta RL and delta RW. This behavior was interpreted in terms of a viscoelastic model that allowed computation of the viscoelastic constants of the lung and chest wall. This model also accounts for frequency, volume, and flow dependence of elastance of the lung and chest wall. Static and dynamic elastances, as well as delta R, were higher for the lung than for the chest wall.     

Effect of PEEP on the mechanics of the respiratory system in ARDS patients.

In patients with adult respiratory distress syndrome (ARDS) we studied the effect of positive end-expiratory pressure (PEEP) on respiratory mechanics. We used the technique of rapid airway occlusion during constant flow (V) inflation to partition the total respiratory system resistance (Rrs) into the interrupter resistance (Rint,rs) and the additional resistance (delta Rrs) due to viscoelastic pressure dissipations and time constant inequalities. We also measured static (Est,rs) and dynamic (Edyn,rs) elastance of the respiratory system. The procedure was carried out in nine ARDS patients at different inspiratory V and inflation volumes (delta V) at PEEP of 0, 5, 10, and 15 cmH2O. We found that during baseline ventilation (delta V = 0.7 liter and V = 1 l/s), Est,rs, Edyn,rs, and Rint,rs did not change significantly with PEEP, whereas delta Rrs and Rrs increased significantly only with PEEP of 15 cmH2O. The increase of delta Rrs and Rrs with PEEP was positively correlated with the concomitant changes in end-expiratory lung volume (P < 0.001). At all levels of PEEP, under iso-delta V conditions, delta Rrs decreased with increasing V, whereas at a fixed V, delta Rrs increased with increasing delta V. A four-parameter model of the respiratory system failed to fully describe respiratory dynamics in the ARDS patients, probably due to nonlinearities.     

Dependence of lung injury on surface tension during low-volume ventilation in normal open-chest rabbits.

To evaluate the role of pulmonary surfactant in the prevention of lung injury caused by mechanical ventilation (MV) at low end-expiratory volumes, lung mechanics and morphometry were assessed in three groups of eight normal, open-chest rabbits ventilated for 3-4 h at zero end-expiratory pressure (ZEEP) with physiological tidal volumes (Vt = 10 ml/kg). One group was left untreated (group A); the other two received surfactant intratracheally (group B) or aerosolized dioctylsodiumsulfosuccinate (group C) before MV on ZEEP. Relative to initial MV on positive end-expiratory pressure (PEEP; 2.3 cmH(2)O), quasi-static elastance (Est) and airway (Rint) and viscoelastic resistance (Rvisc) increased on ZEEP in all groups. After restoration of PEEP, only Rint (124%) remained elevated in group A, only Est (36%) was significantly increased in group B, whereas in group C, Est, Rint, and Rvisc were all markedly augmented (274, 253, and 343%). In contrast, prolonged MV on PEEP had no effect on lung mechanics of eight open-chest rabbits (group D). Lung edema developed in group C (wet-to-dry ratio = 7.1), but not in the other groups. Relative to group D, both groups A and C, but not B, showed histological indexes of bronchiolar injury, whereas all groups exhibited an increased number of polymorphonuclear leukocytes in alveolar septa, which was significantly greater in group C. In conclusion, administration of exogenous surfactant largely prevents the histological and functional damage of prolonged MV at low lung volumes, whereas surfactant dysfunction worsens the functional alterations, also because of edema formation and, possibly, increased inflammatory response.     

Low-volume ventilation causes peripheral airway injury and increased airway resistance in normal rabbits.

Lung mechanics and morphometry of 10 normal open-chest rabbits (group A), mechanically ventilated (MV) with physiological tidal volumes (8-12 ml/kg), at zero end-expiratory pressure (ZEEP), for 3-4 h, were compared with those of five rabbits (group B) after 3-4 h of MV with a positive end-expiratory pressure (PEEP) of 2.3 cmH(2)O. Relative to initial MV on PEEP, MV on ZEEP caused a progressive increase in quasi-static elastance (+36%) and airway (Rint; +71%) and viscoelastic resistance (+29%), with no change in the viscoelastic time constant. After restoration of PEEP, quasi-static elastance and viscoelastic resistance returned to control levels, whereas Rint remained elevated (+22%). On PEEP, MV had no effect on lung mechanics. Gas exchange on PEEP was equally preserved in groups A and B, and the lung wet-to-dry ratios were normal. Both groups had normal alveolar morphology, whereas only group A had injured respiratory and membranous bronchioles. In conclusion, prolonged MV on ZEEP induces histological evidence of peripheral airway injury with a concurrent increase in Rint, which persists after restoration of normal end-expiratory volumes. This is probably due to cyclic opening and closing of peripheral airways on ZEEP.     

Analysis of behavior of the respiratory system in ARDS patients: effects of flow, volume, and time

The effects of inspiratory flow (V) and inflation volume (delta V) on the mechanical properties of the respiratory system in eight ARDS patients were investigated using the technique of rapid airway occlusion during constant-flow inflation. We measured interrupter resistance (Rint,rs), which in humans represents airway resistance, the additional resistance (delta Rrs) due to viscoelastic pressure dissipations and time constant inequalities, and static (Est,rs) and dynamic (Edyn,rs) elastance. The results were compared with a previous study on 16 normal anesthetized paralyzed humans (D'Angelo et al. J. Appl. Physiol. 67: 2556-2564, 1989). We observed that 1) resistance and elastance were higher in ARDS patients; 2) with increasing V, Rint,rs and Est,rs did not change, delta Rrs decreased progressively, and Edyn,rs increased progressively; 3) with increasing delta V, Rint,rs decreased slightly, delta Rrs increased progressively, and Est,rs and Edyn,rs showed an initial decrease followed by a secondary increase noted only in the ARDS patients. The above findings could be explained in terms of a model incorporating a standard resistance in parallel with a standard elastance and a series spring-and-dashpot body that represents the stress adaptation units within the tissues of the respiratory system.     

Transmission of airway pressure to pleural space during lung edema and chest wall restriction

To investigate the influence of positive end-expiratory pressure (PEEP) on hemodynamic measurements we examined the transmission of airway pressure to the pleural space during varying conditions of lung and chest wall compliance. Eight ventilated anesthetized dogs were studied in the supine position with the chest closed. Increases in pleural pressure were similar for both small and large PEEP increments (5-20 cmH2O), whether measured in the esophagus (Pes) or in the juxtacardiac space by a wafer sensor (Pj). Increments in Pj exceeded the increments in Pes at all levels of PEEP and under each condition of altered lung and chest wall compliance. When chest wall compliance was reduced by thoracic and abdominal binding, the fraction of PEEP sensed in the pleural space increased as theoretically predicted. Acute edematous lung injury produced by oleic acid (OA) did not alter the deflation limb pressure-volume characteristics of the lung, provided that end-inspiratory volume was adequate. With the chest and abdomen restricted OA was associated with less than normal transmission of airway pressure to the pleural space, most likely because the end-inspiratory volume required to restore normal deflation characteristics was not attained. Together these results indicate that the influence of acute edematous lung injury on the transmission of airway pressure to the pleural space depends importantly on the peak volume achieved during inspiration.     

Inspiratory lung impedance in COPD: effects of PEEP and immediate impact of lung volume reduction surgery.

Frequency-dependent characteristics of lung resistance (RL) and elastance (EL) are sensitive to different patterns of airway obstruction. We used an enhanced ventilator waveform (EVW) to measure inspiratory RL and EL spectra in ventilated patients during thoracic surgery. The EVW delivers an inspiratory flow waveform with enhanced spectral excitation from 0.156 to 8.1 Hz. Estimates of the coefficients in a trigonometric approximation of the EVW flow and transpulmonary pressure inspirations yielded inspiratory RL and EL spectra. We applied the EVW in a group with mild obstruction undergoing various thoracoscopic procedures (n = 6), and another group with severe chronic obstructive pulmonary disease undergoing lung volume reduction surgery (n = 8). Measurements were made at positive end-expiratory pressure (PEEP) of 0, 3, and 6 cmH(2)O. Inspiratory RL was similar in both groups despite marked differences in spirometry. The chronic obstructive pulmonary disease patients demonstrated a pronounced frequency-dependent increase in inspiratory EL consistent with severe heterogeneous peripheral airway obstruction. PEEP appears to have beneficial effects by reducing peripheral airway resistance. Lung volume reduction surgery resulted in increased inspiratory RL and EL at all frequencies and PEEPs, possibly due to loss of diseased lung tissue, pulmonary edema, increased mechanical heterogeneity, and/or an improvement in airway tethering.     

Dependence of lung injury on inflation rate during low-volume ventilation in normal open-chest rabbits.

Lung mechanics and morphometry were assessed in two groups of nine normal open-chest rabbits mechanically ventilated (MV) for 3-4 h at zero end-expiratory pressure (ZEEP) with physiological tidal volumes (Vt; 11 ml/kg) and high (group A) or low (group B) inflation flow (44 and 6.1 ml x kg(-1) x s(-1), respectively). Relative to initial MV on positive end-expiratory pressure (PEEP; 2.3 cmH(2)O), MV on ZEEP increased quasi-static elastance and airway and viscoelastic resistance more in group A (+251, +393, and +225%, respectively) than in group B (+180, +247, and +183%, respectively), with no change in viscoelastic time constant. After restoration of PEEP, quasi-static elastance and viscoelastic resistance returned to control, whereas airway resistance, still relative to initial values, remained elevated more in group A (+86%) than in group B (+33%). In contrast, prolonged high-flow MV on PEEP had no effect on lung mechanics of seven open-chest rabbits (group C). Gas exchange on PEEP was equally preserved in all groups, and the lung wet-to-dry ratios were normal. Relative to group C, both groups A and B had an increased percentage of abnormal alveolar-bronchiolar attachments and number of polymorphonuclear leukocytes in alveolar septa, the latter being significantly larger in group A than in group B. Thus prolonged MV on ZEEP with cyclic opening-closing of peripheral airways causes alveolar-bronchiolar uncoupling and parenchymal inflammation with concurrent, persistent increase in airway resistance, which are worsened by high-inflation flow.     

Effects of mechanical ventilation at low lung volume on respiratory mechanics and nitric oxide exhalation in normal rabbits.

Lung mechanics, exhaled NO (NOe), and TNF-alpha in serum and bronchoalveolar lavage fluid were assessed in eight closed and eight open chest, normal anesthetized rabbits undergoing prolonged (3-4 h) mechanical ventilation (MV) at low volume with physiological tidal volumes (10 ml/kg). Relative to initial MV on positive end-expiratory pressure (PEEP), MV at low volume increased lung quasi-static elastance (+267 and +281%), airway (+471 and +382%) and viscolelastic resistance (+480 and +294%), and decreased NOe (-42 and -25%) in closed and open chest rabbits, respectively. After restoration of PEEP, viscoelastic resistance returned to control, whereas airway resistance remained elevated (+120 and +31%) and NOe low (-25 and -20%) in both groups of rabbits. Elastance remained elevated (+23%) only in closed-chest animals, being associated with interstitial pulmonary edema, as reflected by increased lung wet-to-dry weight ratio with normal albumin concentration in bronchoalveolar lavage fluid. In contrast, in 16 additional closed- and open-chest rabbits, there were no changes of lung mechanics or NOe after prolonged MV on PEEP only. At the end of prolonged MV, TNF-alpha was practically undetectable in serum, whereas its concentration in bronchoalveolar lavage fluid was low and similar in animals subjected or not subjected to ventilation at low volume (62 vs. 43 pg/ml). These results indicate that mechanical injury of peripheral airways due to their cyclic opening and closing during ventilation at low volume results in changes in lung mechanics and reduction in NOe and that these alterations are not mediated by a proinflammatory process, since this is expressed by TNF-alpha levels.     

Partitioning of respiratory mechanics in halothane-anesthetized humans

In five spontaneously breathing anesthetized subjects [halothane approximately 1 minimal alveolar concentration (MAC), 70% N2O, 30% O2], flow, changes in lung volume, and esophageal and airway opening pressure were measured in order to partition the elastance (Ers) and flow resistance (Rrs) of the total respiratory system into the lung and chest wall components. Ers averaged (+/- SD) 23.0 +/- 4.9 cmH2O X l-1, while the corresponding values of pulmonary (EL) and chest wall (EW) elastance were 14.3 +/- 3.2 and 8.7 +/- 3.0 cmH2O X l-1, respectively. Intrinsic Rrs (upper airways excluded) averaged 2.3 +/- 0.2 cmH2O X l-1 X s, the corresponding values for pulmonary (RL) and chest wall (RW) flow resistance amounting to 0.8 +/- 0.4 and 1.5 +/- 0.5 cmH2O X l-1 X s, respectively. Ers increased relative to normal values in awake state, mainly reflecting increased EL. Rw was higher than previous estimates on awake seated subjects (approximately 1.0 cmH2O X l-1 X s). RL was relatively low, reflecting the fact that the subjects had received atropine (0.3-0.6 mg) and were breathing N2O. This is the first study in which both respiratory elastic and flow-resistive properties have been partitioned into lung and chest wall components in anesthetized humans.     

Viscoelastic behavior of lung and chest wall in dogs determined by flow interruption

Pulmonary and chest wall mechanics were studied in six anesthetized paralyzed dogs, by use of the technique of rapid airway occlusion during constant flow inflation. Analysis of the pressure changes after flow interruption allowed us to partition the overall resistance of the lung (Rl) and chest wall (Rw) and total respiratory system (Rrs) into two components, one (Rinit) reflecting in the lung airway resistance (Raw), the other (delta R) reflecting primarily the viscoelastic properties of the pulmonary and chest wall tissues. The effects of varying inspiratory flow and inflation volume were interpreted in terms of frequency dependence of resistance, by using a spring-and-dashpot model previously proposed and substantiated by Bates et al. (Proc. 9th Annu. Conf. IEEE Med. Biol. Soc., 1987, vol. 3, p. 1802-1803). We observed that 1) Raw and Rw,init were nearly equal and small relative to Rl and Rw (both were unaffected by flow); 2) Rrs,init decreased slightly with increasing volume; 3) both delta Rl and delta Rw decreased with increasing flow and increased with increasing lung volume. These changes were manifestations of frequency dependence of delta R, as it is predicted by the model; 4) Rrs, Rl, and Rw followed the same trends as delta R. These results corroborate data previously reported in the literature with the use of different techniques to measure airways and pulmonary tissue resistances and confirm that the use of Rl to assess bronchial reactivity is problematic. The interrupter techniques provides a convenient way to obtain Raw values, as well as analogs of lung and chest wall tissue resistances in intact dogs.     

Effect of lung volume on plateau response of airways and tissue to methacholine in dogs.

We have recently shown in dogs that much of the increase in lung resistance (RL) after induced constriction can be attributed to increases in tissue resistance, the pressure drop in phase with flow across the lung tissues (Rti). Rti is dependent on lung volume (VL) even after induced constriction. As maximal responses in RL to constrictor agonists can also be affected by changes in VL, we questioned whether changes in the plateau response with VL could be attributed in part to changes in the resistive properties of lung tissues. We studied the effect of changes in VL on RL, Rti, airway resistance (Raw), and lung elastance (EL) during maximal methacholine (MCh)-induced constriction in 8 anesthetized, paralyzed, open-chest mongrel dogs. We measured tracheal flow and pressure (Ptr) and alveolar pressure (PA), the latter using alveolar capsules, during tidal ventilation [positive end-expiratory pressure (PEEP) = 5.0 cmH2O, tidal volume = 15 ml/kg, frequency = 0.3 Hz]. Measurements were recorded at baseline and after the aerosolization of increasing concentrations of MCh until a clear plateau response had been achieved. VL was then altered by changing PEEP to 2.5, 7.5, and 10 cmH2O. RL changed only when PEEP was altered from 5 to 10 cmH2O (P < 0.01). EL changed when PEEP was changed from 5 to 7.5 and 5 to 10 cmH2O (P < 0.05). Rti and Raw varied significantly with all three maneuvers (P < 0.05). Our data demonstrate that the effects of VL on the plateau response reflect a complex combination of changes in tissue resistance, airway caliber, and lung recoil.     

Effects of longitudinal laparotomy on respiratory system, lung, and chest wall mechanics.

In six sedated, anesthetized, paralyzed, and mechanically ventilated guinea pigs, total respiratory system (RT,rs), lung, and chest wall resistances and respiratory system (Est,rs), lung, and chest wall (Est,w) elastances were determined before and after longitudinal laparotomy. Furthermore the resistances were also split into their initial and difference components, with the former reflecting the Newtonian resistances and the latter representing the viscoelastic/inhomogeneous pressure dissipations in the system. For such purpose the end-inflation occlusion during constant inspiratory flow method was used. During laparotomy, a statistically significant increase in respiratory system difference resistance (from 0.086 to 0.101 cmH2O.ml-1.s) significantly augmented RT,rs (from 0.157 to 0.167 cmH2O.ml-1.s). The former was entirely secondary to a significant increase in chest wall difference resistance (0.019 to 0.034 cmH2O.ml-1.s), which naturally raised chest wall total resistance (from 0.030 to 0.047 cmH2O.ml-1.s). Est,rs and Est,w also increased (14.7 and 13.1%, respectively) after abdominal incision. It can be concluded that the midline xiphipubic laparotomy accompanied by the bilateral ventrodorsal infracostal incision increases RT,rs as a consequence of augmented chest wall difference resistance and Est,rs as a result of higher Est,w.     

Effects of elastase-induced emphysema on airway responsiveness to methacholine in rats

We examined the effects of elastase-induced emphysema on lung volumes, pulmonary mechanics, and airway responses to inhaled methacholine (MCh) of nine male Brown Norway rats. Measurements were made before and weekly for 4 wk after elastase in five rats. In four rats measurements were made before and at 3 wk after elastase; in these same animals the effects of changes in end-expiratory lung volume on the airway responses to MCh were evaluated before and after elastase. Airway responses were determined from peak pulmonary resistance (RL) calculated after 30-s aerosolizations of saline and doubling concentrations of MCh from 1 to 64 mg/ml. Porcine pancreatic elastase (1 IU/g) was administered intratracheally. Before elastase RL rose from 0.20 +/- 0.02 cmH2O.ml-1.s (mean +/- SE; n = 9) to 0.57 +/- 0.06 after MCh (64 mg/ml). A plateau was observed in the concentration-response curve. Static compliance and the maximum increase in RL (delta RL64) were significantly correlated (r = 0.799, P less than 0.01). Three weeks after elastase the maximal airway response to MCh was enhanced and no plateau was observed; delta RL64 was 0.78 +/- 0.07 cmH2O.ml-1.s, significantly higher than control delta RL64 (0.36 +/- 0.7, P less than 0.05). Before elastase, increase of end-expiratory lung volume to functional residual capacity + 1.56 ml (+/- 0.08 ml) significantly reduced RL at 64 mg MCh/ml from 0.62 +/- 0.05 cmH2O.ml-1.s to 0.50 +/- 0.03, P less than 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute effects of thixotropy conditioning of inspiratory muscles on end-expiratory chest wall and lung volumes in normal humans.

Thixotropy conditioning of inspiratory muscles consisting of maximal inspiratory effort performed at an inflated lung volume is followed by an increase in end-expiratory position of the rib cage in normal human subjects. When performed at a deflated lung volume, conditioning is followed by a reduction in end-expiratory position. The present study was performed to determine whether changes in end-expiratory chest wall and lung volumes occur after thixotropy conditioning. We first examined the acute effects of conditioning on chest wall volume during subsequent five-breath cycles using respiratory inductive plethysmography (n = 8). End-expiratory chest wall volume increased after conditioning at an inflated lung volume (P < 0.05), which was attained mainly by rib cage movements. Conditioning at a deflated lung volume was followed by reductions in end-expiratory chest wall volume, which was explained by rib cage and abdominal volume changes (P < 0.05). End-expiratory esophageal pressure decreased and increased after conditioning at inflated and deflated lung volumes, respectively (n = 3). These changes in end-expiratory volumes and esophageal pressure were greatest for the first breath after conditioning. We also found that an increase in spirometrically determined inspiratory capacity (n = 13) was maintained for 3 min after conditioning at a deflated lung volume, and a decrease for 1 min after conditioning at an inflated lung volume. Helium-dilution end-expiratory lung volume increased and decreased after conditioning at inflated and deflated lung volumes, respectively (both P < 0.05; n = 11). These results suggest that thixotropy conditioning changes end-expiratory volume of the chest wall and lung in normal human subjects.     

Airway closure with high PEEP in vivo.

When airway smooth muscle is contracted in vitro, the airway lumen continues to narrow with increasing concentrations of agonist until complete airway closure occurs. Although there remains some controversy regarding whether airways can close in vivo, recent work has clearly demonstrated that, if the airway is sufficiently stimulated with contractile agonists, complete closure of even large cartilaginous conducting airways can readily occur with the lung at functional residual capacity (Brown RH and Mitzner W. J Appl Physiol 85: 2012-2017, 1998). This result suggests that the tethering of airways in situ by parenchymal attachments is small at functional residual capacity. However, at lung volumes above functional residual capacity, the outward tethering of airways should increase, because both the parenchymal shear modulus and tethering forces increase in proportion to the transpulmonary pressure. In the present study, we tested whether we could prevent airway closure in vivo by increasing lung volume with positive end-expiratory pressure (PEEP). Airway smooth muscle was stimulated with increasing methacholine doses delivered directly to airway smooth muscle at three levels of PEEP (0, 6, and 10 cmH(2)O). Our results show that increased lung volume shifted the airway methacholine dose-response curve to the right, but, in many airways in most animals, airway closure still occurred even at the highest levels of PEEP.     

Chest wall and respiratory system mechanics in cats: effects of flow and volume

The effects of inspiratory flow rate and inflation volume on the resistive properties of the chest wall were investigated in six anesthetized paralyzed cats by use of the technique of rapid airway occlusion during constant flow inflation. This allowed measurement of the intrinsic resistance (Rw,min) and overall dynamic inspiratory impedance (Rw,max), which includes the additional pressure losses due to time constant inequalities within the chest wall tissues and/or stress adaptation. These results, together with our previous data pertaining to the lung (Kochi et al., J. Appl. Physiol. 64: 441-450, 1988), allowed us to determine Rmin and Rmax of the total respiratory system (rs). We observed that 1) Rw,max and Rrs,max exhibited marked frequency dependence; 2) Rw,min was independent of flow (V) and inspired volume (delta V), whereas Rrs,min increased linearly with V and decreased with increasing delta V; 3) Rw,max decreased with increasing V, whereas Rrs,max exhibited a minimum value at a flow rate substantially higher than the resting range of V; 4) both Rw,max and Rrs,max increased with increasing delta V. We conclude that during resting breathing, flow resistance of the chest wall and total respiratory system, as conventionally measured, includes a significant component reflecting time constant inequalities and/or stress adaptation phenomena.     

Vascular and airway effects of endogenous cyclooxygenase products during lung inflation

The influence of lung inflation on lung elasticity and pulmonary resistance (RL) and on pulmonary and bronchial hemodynamics was examined in five anesthetized, mechanically ventilated adult sheep before and after treatment with the cyclooxygenase inhibitor indomethacin (2 mg/kg). Lung inflation was accomplished by increasing levels of positive end-expiratory pressure (PEEP). Measurements of pulmonary vascular resistance (PVR), bronchial blood flow (Qbr), and RL were obtained with a Swan-Ganz catheter, with an electromagnetic flow probe placed around the carinal artery, and by relating airflow to transpulmonary pressure (Ptp), respectively. Before indomethacin, increasing PEEP from 5 to 15 cmH2O increased mean lung volume (VL) to 135% (P less than 0.01), Ptp to 165% (P less than 0.005), and PVR to 132% (P less than 0.05) of base line and decreased mean Qbr (normalized for cardiac output) to 53% (P less than 0.05) of base line. Mean RL showed a tendency to decrease with a mean value of 67% of base line at 15 cmH2O PEEP. After indomethacin the corresponding values were 121% for VL, 155% for Ptp, 124% for PVR, 35% for Qbr, and 31% for RL. The PEEP-dependent changes were not different before and after indomethacin except for mean VL, which increased less (P less than 0.05) after indomethacin. The failure of indomethacin to modify PEEP-induced changes in RL, PVR, and Qbr was also present when these parameters were expressed as a function of Ptp. These findings suggest that the cyclooxygenase products elaborated during lung inflation reduce lung elasticity but fail to influence airflow resistance and pulmonary and bronchial hemodynamics.     

Lung mechanics and end-expiratory lung volume during hypoxia in rats.

We investigated whether an hypoxia-induced increase in airway resistance mediated by vagal efferents participates in the increase in end-expiratory lung volume (EELV) observed in hypoxia. We also assessed the contribution of the end-expiratory activity of the diaphragm (DE) to this phenomenon. Therefore, we measured EELV, total lung resistance (RL), dynamic lung compliance (Cdyn), DE, and minute ventilation (VE) in anesthetized rats during normoxia and hypoxia (10% O(2)) before (control) and after administration of atropine or saline. In the control group, hypoxia increased EELV, Cdyn, DE, and VE but slightly decreased RL. These changes were unaffected by saline or atropine, except that, in the atropine-treated rats, hypoxia did not change RL. These results suggest that 1) the increase in EELV observed in hypoxia cannot result from an increase in airway resistance; 2) the increased and persistent activity of inspiratory muscles during expiration is the most likely cause of the increase in EELV during hypoxia; and 3) the decrease in RL induced by hypoxia could result from the increase in lung volume including EELV.     

Chest wall distortion and discharge of pulmonary slowly adapting receptors.

We assessed the effects of chest wall distortion, changes in lung volume, and abolition of airway smooth muscle tone on the discharge patterns of 92 pulmonary slowly adapting receptors (SAR) in decerebrate, spontaneously breathing cats. Distortion resulted from their inspiratory efforts against an occluded airway at functional residual capacity and at increased end-expiratory lung volumes. Approximately 40% of SAR increased discharge frequencies during occlusions. Modulation of SAR discharge during occlusions persisted after administration of atropine to eliminate airway smooth muscle tone. Phasic modulation of SAR discharge was eliminated during no-inflation tests after paralyzing the cats and ventilating them on a cycle-triggered pump. We conclude 1) parasympathetic modulation of airway smooth muscle tone makes no obvious contribution to SAR discharge in spontaneously breathing cats; 2) the no-inflation test (withholding of lung inflation during neural inspiration) in paralyzed and ventilated cats is a valid test for the presence of projections from SAR to medullary respiratory neurons; and 3) in the absence of tidal volume changes, distortion stimulates some SAR. Sensory feedback from receptors in the lung, not just those in the chest wall, may therefore provide information about abnormal chest wall configurations.