Effect of the chest wall and blood volume on pulmonary distensibility.

To determine the reason for increased pulmonary distensibility in excised lungs, we performed deflation pressure-volume (PV) studies in 24 dogs. Exponential analysis of PV data gave K, an index of distensibility. Lung volume was measured by dilution of neon. Compared with measurements obtained in the supine position, with the chest closed, and with esophageal pressure (Pes) to obtain transpulmonary pressure, K was not changed significantly with the chest strapped, with pleural pressure to obtain transpulmonary pressure, or with the chest open. From displacement of PV curves obtained in the supine position and with the chest closed or open, we estimated that Pes was 0.18 kPa greater than average lung surface pressure. An increase in K in the prone and head-up positions was attributed to a traction artifact decreasing Pes. Exsanguination increased K and produced a relative increase in gas volume. These results show that overall pulmonary distensibility is unaffected by an intact chest wall. An increase in K and gas volume after exsanguination probably reflects a decreased pulmonary blood volume, with collapse of capillaries increasing the alveolar volume-to-surface ratio.     

Volume infusion produces abdominal distension, lung compression, and chest wall stiffening in pigs.

The effect of severe generalized edema on respiratory system mechanics is not well described. We measured airway pressure, gastric pressure, and four vertical pleural pressures in 13 anesthetized paralyzed pigs ventilated in the upright position. Pressure-volume relationships of the respiratory system, chest wall, and lung were measured on deflation from total lung capacity to residual volume and during tidal breathing both before (control) and 50 min after one of two interventions. In one series of experiments, a volume equal to 15-20% of the pig's body weight was infused intravenously. In a second series, a balloon was placed in the peritoneal space to distend the abdomen to the same gastric pressures as achieved in the first series. Measurements were compared before and after either abdominal balloon inflation or volume infusion. Volume infusion increased the pleural pressure in dependent lung regions, decreased both total lung capacity (34%) and functional residual capacity (62%) (both P less than 0.05), and markedly shifted the respiratory system and chest wall pressure-volume curves to the right, but it only moderately affected the lung deflation curve. Tidal compliances of the respiratory system, chest wall, and lung decreased 36, 31, and 49%, respectively (all P less than 0.05). The effect of abdominal balloon inflation on respiratory system mechanics was similar to that of volume infusion. We conclude that infusing large volumes of fluid markedly alters chest wall mechanics, mainly by causing abdominal distension that prohibits descent of the diaphragm.     

Liquid-filled esophageal catheter for measuring pleural pressure in preterm neonates

The precise measurement of esophageal pressure (Pes) as a reflection of pleural pressure (Ppl) is crucial to the measurement of lung mechanics in the newborn. The fidelity of Pes as a measurement of Ppl is determined by the occlusion test in which, during respiratory efforts against an occlusion at the airway opening, changes in pressure (delta Pao) (Pao is assumed to be equal to alveolar pressure) are shown to be equal to changes in Pes (delta Pes). Eight intubated premature infants (640-3,700 g) with chest wall distortion were studied using a water-filled catheter system to measure Pes. During the occlusion test, all patients had a finite region of the esophagus where delta Pes equaled delta Pao, which corresponded to points in the esophagus above the cardia but below the carina. In conclusion, even in the presence of chest wall distortion, a liquid-filled catheter with the tip between the cardia and carina can provide an accurate measurement of Ppl, even in the very small premature infant with chest wall distortion.     

Effect of PEEP on respiratory mechanics in anesthetized paralyzed humans.

With the use of the technique of rapid airway occlusion during constant flow inflation, respiratory mechanics were studied in eight anesthetized paralyzed supine normal humans during zero (ZEEP) and positive end-expiratory pressure (PEEP) ventilation. PEEP increased the end-expiratory lung volume by 0.49 liter. The changes in transpulmonary and esophageal pressure after flow interruption were analyzed in terms of a seven-parameter "viscoelastic" model. This allowed assessment of static lung and chest wall elastance (Est,L and Est,W), partitioning of overall resistance into airway interrupter (Rint,L) and tissue resistances (delta RL and delta RW), and computation of lung and chest wall "viscoelastic constants." With increasing flow, Rint,L increased, whereas delta RL and delta RW decreased, as predicted by the model. Est,L, Est,W, and Rint,L decreased significantly with PEEP because of increased lung volume, whereas delta R and viscoelastic constants of lung and chest wall were independent of PEEP. The results indicate that PEEP caused a significant decrease in Rint,L, Est,L, and Est,W, whereas the dynamic tissue behavior, as reflected by delta RL and delta RW, did not change.     

Positive end-expiratory pressure and surfactant decrease lung injury during initiation of ventilation in fetal sheep

The initiation of ventilation in preterm, surfactant-deficient sheep without positive end-expiratory pressure (PEEP) causes airway injury and lung inflammation. We hypothesized that PEEP and surfactant treatment would decrease the lung injury from initiation of ventilation with high tidal volumes. Fetal sheep at 128-day gestational age were randomized to ventilation with: 1) no PEEP, no surfactant; 2) 8-cmH(2)O PEEP, no surfactant; 3) no PEEP + surfactant; 4) 8-cmH(2)O PEEP + surfactant; or 5) control (2-cmH(2)O continuous positive airway pressure) (n = 6-7/group). After maternal anesthesia and hysterotomy, the head and chest were exteriorized, and the fetus was intubated. While maintaining placental circulation, the fetus was ventilated for 15 min with a tidal volume escalating to 15 ml/kg using heated, humidified, 100% nitrogen. The fetus then was returned to the uterus, and tissue was collected after 30 min for evaluation of early markers of lung injury. Lambs receiving both surfactant and PEEP had increased dynamic compliance, increased static lung volumes, and decreased total protein and heat shock proteins 70 and 60 in bronchoalveolar lavage fluid compared with other groups. Ventilation, independent of PEEP or surfactant, increased mRNA expression of acute phase response genes and proinflammatory cytokine mRNA in the lung tissue compared with controls. PEEP decreased mRNA for cytokines (2-fold) compared with groups receiving no PEEP. Surfactant administration further decreased some cytokine mRNAs and changed the distribution of early growth response protein-1 expression. The use of PEEP during initiation of ventilation at birth decreased early mediators of lung injury. Surfactant administration changed the distribution of injury and had a moderate additive protective effect.     

Abdominal distension alters regional pleural pressures and chest wall mechanics in pigs in vivo

Abdominal distension (AD) occurs in pregnancy and is also commonly seen in patients with ascites from various causes. Because the abdomen forms part of the "chest wall," the purpose of this study was to clarify the effects of AD on ventilatory mechanics. Airway pressure, four (vertical) regional pleural pressures, and abdominal pressure were measured in five anesthetized, paralyzed, and ventilated upright pigs. The effects of AD on the lung and chest wall were studied by inflating a liquid-filled balloon placed in the abdominal cavity. Respiratory system, chest wall, and lung pressure-volume (PV) relationships were measured on deflation from total lung capacity to residual volume, as well as in the tidal breathing range, before and 15 min after abdominal pressure was raised. Increasing abdominal pressure from 3 to 15 cmH2O decreased total lung capacity and functional residual capacity by approximately 40% and shifted the respiratory system and chest wall PV curves downward and to the right. Much smaller downward shifts in lung deflation curves were seen, with no change in the transdiaphragmatic PV relationship. All regional pleural pressures increased (became less negative) and, in the dependent region, approached 0 cmH2O at functional residual capacity. Tidal compliances of the respiratory system, chest wall, and lung were decreased 43, 42, and 48%, respectively. AD markedly alters respiratory system mechanics primarily by "stiffening" the diaphragm/abdomen part of the chest wall and secondarily by restricting lung expansion, thus shifting the lung PV curve as seen after chest strapping. The less negative pleural pressures in the dependent lung regions suggest that nonuniformities of ventilation could also be accentuated and gas exchange impaired by AD.     

Effect of tidal volume and PEEP in ethchlorvynol-induced asymmetric lung injury.

We examined the effects of positive end-expiratory pressure (PEEP) and tidal volume on the distribution of ventilation and perfusion in a canine model of asymmetric lung injury. Unilateral right lung edema was established in 10 animals by use of a selective infusion of ethchlorvynol. Five animals were tested in the supine position (horizontal asymmetry) and five in the right decubitus position (vertical asymmetry). Raising PEEP from 5 to 12 cmH2O improved oxygenation despite a redistribution of blood flow toward the damage lung and a consistent decrease in total respiratory system compliance. This improvement paralleled a redistribution of tidal ventilation to the injured lung. This was effected primarily by a fall in the compliance of the noninjured lung due to hyperinflation. The effects of higher tidal volume were additive to those of PEEP. We propose that the major effect of PEEP in inhomogeneous lung injury is to restore tidal ventilation to a population of alveoli recruitable only at high airway pressures.     

Measurement of pulmonary mechanics in the newborn lamb: a comparison of three techniques

Although recent interest in neonatal respiratory mechanics has led to the development of a plethora of techniques for measuring lung compliance and resistance, a critical appraisal of the limitations of these techniques in the newborn has not been performed to date. We evaluated three techniques of measuring respiratory mechanics in the newborn lamb, with the reference method (method 1) being the Mead-Whittenberger technique using flow, volume, and esophageal pressure (Pes) by water-filled catheter, and the other two methods entailing the measurement of mouth pressure (Pm) during airway occlusion (method 2 using end-expiratory occlusion; method 3 using end-inspiratory occlusion). Each technique was evaluated during eupnea and tachypnea in intubated and nonintubated newborn lambs. We found that the use of Pes for the measurement of resistance and compliance gave the most reliable results during both eupnea and tachypnea in both the intubated and nonintubated subjects. The airway occlusion techniques that use Pm to derive resistance and compliance (methods 2 and 3) gave more variable results under all conditions of testing. Method 2 was the least precise method of measurement with a variability of greater than 30% compared with a variation of less than 20% for method 1. For all three methods, it was found that the number of breaths needed for reproducible measurements of mechanics was four to six during eupnea and seven to nine during tachypnea.     

Effects of acute pleural effusion on respiratory system mechanics in dogs

We determined regional (Vr) and overall lung volumes in six head-up anesthetized dogs before and after the stepwise introduction of saline into the right pleural space. Functional residual capacity (FRC), as determined by He dilution, and total lung capacity (TLC) decreased by one-third and chest wall volume increased by two-thirds the saline volume added. Pressure-volume curves showed an apparent increase in lung elastic recoil and a decrease in chest wall elastic recoil with added saline, but the validity of esophageal pressure measurements in these head-up dogs is questionable. Vr was determined from the positions of intraparenchymal markers. Lower lobe TLC and FRC decreased with added saline. The decrease in upper lobe volume was less than that of lower lobe volume at FRC and was minimal at TLC. Saline increased the normal Vr gradient at FRC and created a gradient at TLC. During deflation from TLC to FRC before saline was added, the decrease in lung volume was accompanied by a shape change of the lung, with greatest distortion in the transverse (ribs to mediastinum) direction. After saline additions, deflation was associated with deformation of the lung in the cephalocaudal and transverse directions. The deformation with saline may be a result of upward displacement of the lungs into a smaller cross-sectional area of the thoracic cavity.     

A comparison of changes in esophageal pressure and regional juxtacardiac pressures

The relationship between esophageal pressure and juxtacardiac pressures was studied during positive end-expiratory pressure (PEEP) ventilation applied to both lungs or selectively to one lung. The experiments were performed in eight anesthetized dogs with balloon catheters in the esophagus and in the left and right pericardial and overlying pleural cavities and with an open-ended liquid-filled catheter in the pleural cavity. Bilateral PEEP (10, 20, and 30 cmH2O) caused progressive and similar increments in left and right pleural pressure. Selective PEEP, however, increased ipsilateral pleural balloon pressure more than contralateral pressure. The increase in ipsilateral pleural balloon pressure markedly exceeded the increase in esophageal pressure. There was a small increase in pleural open-ended catheter pressure that approximated the increase in esophageal pressure. During selective PEEP, pericardial balloon pressure remained uniform because of a decrease in ipsilateral pericardial transmural pressure. In conclusion, selective PEEP caused nonuniform increments in regional pleural balloon pressure. Left and right pericardial balloon pressure, however, increased uniformly with selective PEEP because of reduced ipsilateral pericardial transmural pressure. The esophageal balloon did not reflect the marked regional increments in pleural balloon pressure with selective PEEP and consistently underestimated the changes in pleural balloon pressure with general PEEP.     

Response of slowly adapting pulmonary stretch receptors to reduced lung compliance

We examined the steady-state response of slowly adapting pulmonary stretch receptors (SAPSRs) to reduced lung compliance in open-chest cats with lungs ventilated at eupneic rate and tidal volume (VT) and with a positive end-expiratory pressure (PEEP) of 3-4 cmH2O. Transient removal of PEEP decreased compliance by approximately 30% and increased transpulmonary pressure (Ptp) by 1-2.5 cmH2O. Reduction of compliance significantly decreased SAPSR discharge in deflation and caused a small increase in discharge at the peak of inflation; it had little effect on discharge averaged over the ventilatory cycle. Increasing VT to produce a comparable increase in Ptp significantly increased peak discharge. Thus unlike rapidly adapting receptors, whose discharge is increased more effectively by reduced compliance than by increased VT, SAPSRs are stimulated by increased VT but not by reduced compliance. We speculate that the most consistent effect of reduced compliance on SAPSRs (the decrease in deflation discharge) was due to the decreased time constant for deflation in the stiffer lung. This alteration in firing may contribute to the tachypnea evoked as the lungs become stiffer.     

Intrathoracic pressures and left ventricular configuration with respiratory maneuvers

In 12 dogs, we examined the correspondence between esophageal (Pes) and pericardial pressures over the anterior, lateral, and inferior left ventricular (LV) surfaces. Pleural pressure was decreased by spontaneous inspiration, Mueller maneuver, and phrenic stimulation and increased by intermittent positive pressure ventilation (IPPV) and positive end-expiratory pressure (PEEP). To separate effects due to blood flow, we analyzed beating and nonbeating hearts. In beating hearts, there were no significant differences between changes in Pes and pericardial pressures. In arrested hearts, increasing LV pressure by 8 Torr increased pericardial pressures by only 3.6 Torr. With IPPV and PEEP, increases in Pes and pericardial pressures were equal in live hearts and in low-volume arrested hearts (LV pressure = 4 Torr). In high-volume arrested hearts (LV pressure = 12 Torr), the increase in pericardial pressure over the anterior LV surface was less than Pes, whereas that over the lateral and inferior LV surfaces was the same as Pes. At high LV volume, in arrested hearts pericardial pressures decreased less than Pes during negative pressure maneuvers. In another six dogs, external LV configuration and volume were measured. In beating hearts during spontaneous inspiration, Mueller maneuver, and phrenic stimulation (endotracheal tube open), septal-lateral dimension and LV volume decreased by approximately 3% (P less than 0.05). This was also true for PEEP. In arrested hearts, septal-lateral dimension and LV volume decreased only with PEEP. We conclude that 1) the relationship between Pes and pericardial pressures is complex and depends on LV volume, local pericardial compliance, and the means by which Pes is changed, 2) changes in measured pericardial pressures did not completely explain changes in LV configuration, and 3) during different respiratory maneuvers, different forces account for the same observed changes in LV volume and configuration.     

Pleural stress pressure as a force to control liquid accumulation and maintain lung expansion

Total gas pressure in the pleural space is more subatmospheric than that in the alveolar cavity. This pressure difference minus elastic recoil pressure of the lung was termed stress pressure. We investigated the relationship between stress pressure and a force that would hold the lung against the chest wall to prevent accumulation of liquid. The condition was a pleural space with an enlarged pleural surface pressure. Dogs anesthetized with pentobarbital sodium were placed in a box maintained subatmospherically at approximately -30 cmH2O and breathed atmospheric air for 4 h. Liquid volume in the pleural space of the dogs was measured under conditions of thoracotomy. In the normal group, the volume of the pleural liquid was within the normal range of approximately 2.0 ml and the visceral and the parietal pleura made contact. In the pneumothorax group, established by injecting 50 ml of air into the pleural space, the liquid increased significantly in all cases by a mean value of approximately 12 ml. Thus pleural stress pressure seems to be an important force holding the lung against the chest wall and aiding in the control of accumulation of liquid in a more subatmospheric pleural space.     

Clearance of lung edema into the pleural space of volume-loaded anesthetized sheep

To determine whether lung edema leaks into the pleural space, we measured flow rates of visceral pleural liquid from exposed sheep lungs during volume loading and then compared the protein concentration of visceral pleural liquid and lung interstitial liquids (lymph and peribronchovascular cuff liquid). For 4 h, we volume loaded 24 anesthetized ventilated sheep with one side, both sides, or neither side of the chest open. During the experiment, we collected visceral pleural liquid from a bag surrounding the exposed lung and lung lymph; after the experiment, we collected peribronchovascular cuff liquid. We found that during volume loading visceral pleural liquid flow increased significantly by 2 h, and its protein concentration over the final hour was the same as that of lung interstitial liquids. The volume of visceral pleural liquid correlated with excess lung water and wedge pressure elevation. By our estimates, clearance of edema from the lung into the pleural space constituted 23-29% of all edema liquid collected, similar to measured lymph edema clearance. We conclude that edema liquid leaks directly from edematous sheep lungs into the pleural space and that this leakage provides an important additional route of edema clearance.     

Pleural pressure distribution and its relationship to lung volume and interstitial pressure

The mechanics of the pleural space has long been controversial. We summarize recent research pertaining to pleural mechanics within the following conceptual framework, which is still not universally accepted. Pleural pressure, the force acting to inflate the lung within the thorax, is generated by the opposing elastic recoils of the lung and chest wall and the forces generated by respiratory muscles. The spatial variation of pleural pressure is a result of complex force interactions among the lung and other structures that make up the thorax. Gravity contributes one of the forces that act on these structures, and regional lung expansion and pleural pressure distribution change with changes in body orientation. Forces are transmitted directly between the chest wall and the lung through a very thin but continuous pleural liquid space. The pressure in pleural liquid equals the pressure acting to expand the lung. Pleural liquid is not in hydrostatic equilibrium, and viscous flow of pleural liquid is driven by the combined effect of the gravitational force acting on the liquid and the pressure distribution imposed by the surrounding structures. The dynamics of pleural liquid are considered an integral part of a continual microvascular filtration into the pleural space. Similar concepts apply to the pulmonary interstitium. Regional differences in lung volume expansion also result in regional differences in interstitial pressure within the lung parenchyma and thus affect regional lung fluid filtration.     

Lung pressures and gas transport during high-frequency airway and chest wall oscillation

The major goal of this study was to compare gas exchange, tidal volume (VT), and dynamic lung pressures resulting from high-frequency airway oscillation (HFAO) with the corresponding effects in high-frequency chest wall oscillation (HFCWO). Eight anesthetized paralyzed dogs were maintained eucapnic with HFAO and HFCWO at frequencies ranging from 1 to 16 Hz in the former and 0.5 to 8 Hz in the latter. Tracheal (delta Ptr) and esophageal (delta Pes) pressure swings, VT, and arterial blood gases were measured in addition to respiratory impedance and static pressure-volume curves. Mean positive pressure (25-30 cmH2O) in the chest cuff associated with HFCWO generation decreased lung volume by approximately 200 ml and increased pulmonary impedance significantly. Aside from this decrease in functional residual capacity (FRC), no change in lung volume occurred as a result of dynamic factors during the course of HFCWO application. With HFAO, a small degree of hyperinflation occurred only at 16 Hz. Arterial PO2 decreased by 5 Torr on average during HFCWO. VT decreased with increasing frequency in both cases, but VT during HFCWO was smaller over the range of frequencies compared with HFAO. delta Pes and delta Ptr between 1 and 8 Hz were lower than the corresponding pressure swings obtained with conventional mechanical ventilation (CMV) applied at 0.25 Hz. delta Pes was minimized at 1 Hz during HFCWO; however, delta Ptr decreased continuously with decreasing frequency and, below 2 Hz, became progressively smaller than the corresponding values obtained with HFAO and CMV.     

Effect of PEEP and type of injury on thermal-dye estimation of pulmonary edema

We investigated the effect of positive end-expiratory pressure (PEEP) on the extravascular thermal volume of the lung (ETV) determined by the thermal-dye technique in three canine models of pulmonary edema created by injection of alpha-naphthylthiourea (ANTU) or oleic acid (OA) into the pulmonary circulation or intrabronchial instillation of hydrochloric acid (HCl). ETV was determined before, during, and after ventilation with 14 cmH2O PEEP, and final ETV was compared with the extravascular lung mass (ELM) determined postmortem. Final ETV correctly estimated ELM in 12 animals with ANTU injury, ETV/ELM = 1.04 +/- 0.13, but underestimated after HCl injury (n = 5), ETV/ELM = 0.61 +/- 0.23, and OA injury (n = 6), ETV/ELM = 0.73 +/- 0.19. Whereas PEEP had no consistent effect on extravascular thermal volume in ANTU edema, there was a reversible increase in ETV during PEEP in animals with HCl or OA injury and underestimation of ELM. The increase in ETV during PEEP averaged 9.3 +/- 3.8 ml/kg (62 +/- 42%) over the mean of the pre- and post-PEEP values after HCl injury (P less than 0.01) and 6.7 +/- 4.4 ml/kg (47 +/- 35%) after OA injury (P less than 0.02). There was an inverse correlation between the change in ETV during PEEP and the ETV/ELM ratio for animals with HCl and OA injury (r = -0.94). We conclude that PEEP produces a reversible increase in ETV in some models of lung injury by allowing for distribution of thermal indicator through a larger fraction of the lung water and that this response may be useful to detect underestimation when gravimetric measurements are not available.     

Validation of esophageal balloon technique at different lung volumes and postures

The esophageal balloon technique for measuring pleural surface pressure (Ppl) has recently been shown to be valid in recumbent positions. Questions remain regarding its validity at lung volumes higher and lower than normally observed in upright and horizontal postures, respectively. We therefore evaluated it further in 10 normal subjects, seated and supine, by measuring the ratio of esophageal to mouth pressure changes (delta Pes/delta Pm) during Mueller, Valsalva, and occlusion test maneuvers at FRC, 20, 40, 60, and 80% VC with the balloon placed 5, 10, and 15 cm above the cardia. In general, delta Pes/delta Pm was highest at the 5-cm level, during Mueller maneuvers and occlusion tests, regardless of posture or lung volume (mean range 1.00-1.08). At 10 and 15 cm, there was a progressive increase in delta Pes/delta Pm with volume (from 0.85 to 1.14). During Valsalva maneuvers, delta Pes/delta Pm also tended to increase with volume while supine (range 0.91-1.04), but was not volume-dependent while seated. Qualitatively, observed delta Pes/delta Pm fit predicted corresponding values (based on lung and upper airway compliances). Quantitatively there were discrepancies probably due to lack of measurement of esophageal elastance and to inhomogeneities in delta Ppl. At every lung volume in both postures, there was at least one esophageal site where delta Pes/delta Pm was within 10% of unity.     

Pulmonary vascular resistance after cessation of positive end-expiratory pressure

This report describes the pulmonary vascular response of infant lamb lung to abrupt cessation of positive end-expiratory pressure (PEEP) during volume-regulated continuous positive-pressure breathing (CPPB). In an intact, endobronchially ventilated preparation, the increase in left lung blood flow (QL) after abrupt cessation of 11 Torr left lung PEEP was found to be gradual, although peak airway pressure (Pmax) fell promptly from 36 to 14 Torr; 49% of the increase in QL occurred greater than 10 s after cessation of PEEP. Recruitment of zone I vasculature that had been created by balloon occlusion of the left pulmonary artery was found to occur promptly after balloon deflation. Isolated neonatal lamb lungs, perfused at constant flow rate, showed similar persistent elevation of pulmonary vascular resistance after cessation of 15 Torr PEEP, although Pmax fell abruptly from 39 to 12 Torr. This hysteresis was eliminated by calcium channel blockade with verapamil, and the magnitude of the change in pulmonary arterial pressure after either application or cessation of PEEP was reduced (25 and 26%, respectively). These observations suggest that, during CPPB, lung stretch alters neonatal pulmonary vascular tone or, by causing calcium channel-dependent lung volume hysteresis, modulates pulmonary vascular resistance. This interaction exaggerates the effect of airway pressure changes on pulmonary vascular resistance during mechanical ventilation.     

Desmin modulates lung elastic recoil and airway responsiveness

Desmin is a structural protein that is expressed in smooth muscle cells of both airways and alveolar ducts. Therefore, desmin could be well situated to participate in passive and contractile force transmission in the lung. We hypothesized that desmin modulates lung compliance, lung recoil pressure, and airway contractile response. To test this hypothesis, respiratory system complex impedance (Zin,rs) at different positive end-expiratory pressure (PEEP) levels and quasi-static pressure-volume data were obtained in desmin-null and wild-type mice at baseline and during methacholine administration. Airways and lung tissue properties were partitioned by fitting Zin,rs to a constant-phase model. Relative to controls, desmin-null mice showed 1) lower values for lung stiffness and recoil pressure at baseline and induced airway constriction, 2) greater negative PEEP dependence of H and airway resistance under baseline conditions and cholinergic stimulation, and 3) airway hyporesponsiveness. These results demonstrate that desmin is a load-bearing protein that stiffens the airways and consequently the lung and modulates airway contractile response.