Noncompliant Lungs Research Articles

The Effects of Automatic Inspiratory Rise Time and Flow Termination on Operation of Closed-Loop Ventilation.

Adaptive ventilation mode (AVM) is a automated mode of mechanical ventilation. AVM is comprable to adaptive support ventilation (ASV). Both recommend a tidal volume (VT) and breathing frequency (f) combination based on lung mechanics, but AVM also automatically adjusts rise time and flow termination of pressure support breaths. How these added features of AVM affect VT and f recommendations compared to ASV is not clear. The present study compared these 2 modes in a test lung with obstructive and restrictive mechanics. The experiment was performed in a simulated lung model in which the compliance (C) and resistance (R) could be altered independently. The ventilatory parameters at different minute volumes (MinVol%) in AVM or ASV mode were recorded. When MinVol% was set at 100%, AVM provided a similar VT and f combination compared to ASV with decreasing compliance or increasing resistance. However, when MinVol% was increased to 250% simulating hyperventilation, for the severely obstructive lung (C60, R70) model, AVM provided a significantly higher f (26 ± 0.6 breaths/min vs 7.00 ± 0 breaths/min in ASV) and lower VT (240 ± 80 mL vs 491 ± 131 mL in ASV). The addition of automatic control of rise time and flow termination functions did not affect recommended ventilator settings in AVM in the noncompliant or obstructive lung when minute ventilation (V̇E) was low. At higher V̇E, AVM compared to ASV recommended a ventilatory strategy with lower VT and higher f. These results need to be validated in patients.

Serum Surfactant Protein-D (SP-D) Level: Does it Correlates with Pulmonary Compliance and ARDS in Severe Cases of COVID-19?

Acute Respiratory Distress Syndrome (ARDS) happens to 67% of all severe COVID-19 cases with mortality rate of 50-94%. Main characteristics of ARDS are poor oxygenation and non-compliant lungs. The lungs are like inflatable balloons that are actively inflated by the positive pressure within and/or the negative pressure created in the pleural cavity. Compliance is the ability of the lungs to distend at a certain level of transpulmonary pressure. Surfactant lowers the surface tension of the alveoli so that end-expiratory pulmonary collapse could be prevented and pulmonary compliance could be maintained. Surfactants also play an important role in the host's defense against infection. Surfactants comprise of phospholipids, cholesterol and surfactant proteins (SP) SP-A, -B, -C and –D. Previous study showed that concentration of SP-D was significantly higher in ARDS patients. Higher serum SP-D concentrations were associated with a greater risk of death, fewer ventilator-free days, and fewer organ failure-free days. This review highlights the role of surfactant especially SP-D in pulmonary compliance and ARDS in COVID-19.

New insights in ARDS pathogenesis

Acute respiratory distress syndrome (ARDS) is a life-threatening condition in critically ill patients characterized by hypoxemia and non-compliant lung. In this review, we discuss the pathophysiology of ARDS, including the mechanisms involved in the formation of pulmonary edema, the dysregulated inflammatory and immune responses, the activation of procoagulant events, the cellular communication by extracellular vesicles (EVs) between different types of cells and the interaction of the lung with other organs. Activation of inflammation, coagulation, and cell death processes result in the disruption of the alveolar-capillary membrane and the consequent protein-rich edema formation in the alveoli, in which structural and functional alterations of the alveolar epithelium play an essential role. Inflammation and activated endothelial cells trigger coagulation cascades and platelets that generate a procoagulant state in both the airspace and the intravascular compartment with the formation of fibrin in airspaces and thrombi in the microvasculature that aggravate alveolar injury and gas exchange. The crosstalk between epithelial/endothelial cells, platelets, and immune cells is mediated by EVs, whose role in the pathogenesis of ARDS is not known. Finally, the interaction of the lung with other organs has become an important determinant in the development and resolution of ARDS. Understanding the pathophysiological mechanisms involved in ARDS is crucial to developing new therapeutic strategies.

Imagining of Acute Respiratory Distress Syndrome: A Review

Acute respiratory distress syndrome (ARDS) is a life-threatening disorder marked by low oxygen levels and rigid or non-compliant lungs. In the absence of any indication of cardiogenic pulmonary edema, ARDS is defined as an acute disease that begins within 7 days of the triggering event and is marked by bilateral lung infiltrates and severe progressive hypoxemia. ARDS has a significant death rate, and there are few effective treatment options for this life-threatening illness. The management of these severely ill patients in the intensive care unit relies heavily on imaging. Chest radiography, bedside lung ultrasonography, and computed tomography scans can all help with patient care and prognostic variables identification. However, imaging results are not always specific, and other diagnosis should be considered.

PNEUMOMEDIASTINUM AS A COMPLICATION OF COVID-19: MAY NOT NEED INTERVENTION

SESSION TITLE: Late-breaking Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Evaluate patients with pneumomediastinum (PTM) as a complication of coronavirus 2019 (Covid-19) infection and their outcomes. METHODS: Data was obtained by retrospective analysis of a database of Covid-19 patients, admitted to two New York hospitals from March 25th to April 26th, 2020. Identified 13 patients with PTM as a complication of Covid-19. RESULTS: Median age of patients was 67 years, 7 (54%) were men, and 1 patient had pre-existing emphysema. Presenting symptoms included dyspnea (13/13, 100%), fever (10/13, 77%), and cough (9/13, 69%); none had chest pain. Median presenting SaO2/FiO2 ratio was 359. Pneumomediastinum was diagnosed on presentation in 2 patients (15%), during hospitalization but prior to invasive mechanical ventilation in 4 patients (31%), and after invasive mechanical ventilation in 7 patients (54%). Six patients had CT scans confirming the diagnosis of PTM. Twelve of the 13 patients were initiated on mechanical ventilation at median 5.5 days. Four patients (31%) developed pneumothoraces and 1 patient required bilateral chest tube drainage. Tension pneumothorax, tension pneumopericardium, and chest wall compartment syndrome were not observed in our cohort. Pneumomediastinum self-resolved in 5 patients (38%) while on mechanical ventilation. (Fig. 1) Seven out of 12 intubated patients (58%) underwent prone ventilation without worsening of PTM. One patient was discharged home, 10 patients expired, and 2 patients remain hospitalized. CONCLUSIONS: Pneumomediastinum is a known sequelae of noncompliant lungs in severe acute respiratory distress syndrome (ARDS), typically in the setting of positive pressure delivered with invasive mechanical ventilation. Our cohort had a low prevalence of predisposing risk factors such as emphysema, and a high mortality. Pneumomediastinum was not strongly associated with mechanical ventilation, as nearly half (6/13) of the patients developed PTM prior to intubation. CLINICAL IMPLICATIONS: In our cohort, findings of PTM may be attributed to two main etiologies converging: damage from Covid-19 and self-inflicted increases in transpulmonary pressures. We postulate that impaired surfactant production from type II pneumocytes may predispose to atelectrauma leading to diffuse alveolar injury and risk of rupture, unlike in typical ARDS where barotrauma occurs in the context of poorly compliant lungs. Moreover, the increased work of breathing and pronounced cough seen in Covid-19 pneumonia may lead to increased transpulmonary pressures resulting in PTM. Reductions in transpulmonary pressures after intubation with initiation of sedation and neuromuscular blockade may explain the resolution of PTM in spite of invasive ventilation. Given the high mortality we observed, early identification and initiation of methods to reduce transpulmonary pressures is imperative to reduce risk of further complications. DISCLOSURES: No relevant relationships by Young Im Lee, source=Web Response No relevant relationships by Nan Li, source=Web Response No relevant relationships by Joseph Mathew, source=Web Response No relevant relationships by Lina Miyakawa, source=Web Response No relevant relationships by Paru Patrawalla, source=Web Response No relevant relationships by Paru Patrawalla, source=Web Response No relevant relationships by Adam Rothman, source=Web Response No relevant relationships by Vishad Sheth, source=Web Response No relevant relationships by David Steiger, source=Web Response No relevant relationships by Jigna Zatakia, source=Web Response

Neonatal cardiopulmonary transition in an ovine model of congenital diaphragmatic hernia

ObjectiveInfants with a congenital diaphragmatic hernia (CDH) are at high risk of developing pulmonary hypertension after birth, but little is known of their physiological transition at birth. We aimed to...

Invited Commentary

Reed and colleagues [1Reed M.F. Gilbert C.R. Taylor M.D. Toth J.W. Endobronchial valves for challenging air leaks.Ann Thorac Surg. 2015; 100: 1181-1187Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar] describe their single-institution experience over an 18-month period using endobronchial valves in the management of 21 patients with prolonged air leaks, including 10 patients who had postoperative air leaks after lung resection or lung volume reduction operations and 11 patients with pneumothorax associated with significant underlying lung disease. Prolonged air leaks in any setting are challenging and a significant source of morbidity, resource use, and frustration for patients, families, and all members of the health care team. Most patients can be managed effectively with meticulous attention to placement of adequately sized and positioned chest tubes as well as active monitoring of radiographs and regulation of suction applied to achieve pleural apposition and ultimately pleurodesis and closure. Underlying restrictive chronic lung disease with poor compliance and postoperative pleural space problems may severely undermine efforts to achieve and maintain pleural apposition. Endobronchial valves (EBVs) offer another tool in managing these challenging patients, as demonstrated by the group from Penn State. The limitations of EBVs include the need for 2 procedures, usually with a general anesthetic, to place and remove the valves; difficulties in localizing the air leak because of cross-ventilation between lung segments; and the cost associated with placing multiple valves in each patient, as is usually required and demonstrated in the article by Reed and colleagues (median, 3.6 valves/procedure; range, 1–12), all of which may limit health care value added. EBVs by design decrease ventilation and therefore increase atelectasis in the treated segments and could theoretically aggravate efforts to improve expansion of the noncompliant lung and eliminate space problems. Most likely, using a combination of multiple techniques, tailoring treatment to each patient based on the underlying acute and chronic pathophysiologic features, and meticulous attention to basic chest tube management will be required to favorably improve outcomes and decrease cost in managing this diverse, complicated, and challenging group of patients. Endobronchial Valves for Challenging Air LeaksThe Annals of Thoracic SurgeryVol. 100Issue 4PreviewProlonged air leaks may result in increased morbidity and mortality. Endobronchial valves have been used as a nonoperative treatment. We evaluated the efficacy of endobronchial valves at achieving chest tube removal and hospital discharge for air leaks resulting from varied etiologies. Full-Text PDF

EXPIRATORY TIME CONSTANTS BY ELECTRICAL IMPEDANCE TOMOGRAPHY IN HYPOXEMIC AND HYPERCAPNIC ACUTE LUNG FAILURE - A FEASIBILITY STUDY

During relaxed breathing expiration can be compared to a RC-circuit with R being the airway resistance, C the respiratory system compliance and τ = R∙C the expiratory time constant. For the adult respiratory system, the normal τ is around 0.8 s. Different lung pathologies have different time constants. Two common disease types are the acute respiratory distress syndrome (ARDS) and the chronic obstructive pulmonary disease (COPD). ARDS is characterized by stiff or noncompliant lungs with low compliance and normal or lower resistance which results in shorter τ. COPD is characterized by impaired airflow or high airways resistance and high compliance which results higher τ. τ reveals information about respiratory mechanics and the time required for the lungs to empty. Traditional pulmonary function tests provide global information only. EIT is a non-invasive real-time imaging technology which determines changes of lung volumes on a regional basis assuming that local impedance changes are proportional to local changes in lung volume. Pikkemaat [1] introduced the method to calculate regional τ, what we improved and applied in 10 patients.

Development and Remodeling of the Vertebrate Blood-Gas Barrier

During vertebrate development, the lung inaugurates as an endodermal bud from the primitive foregut. Dichotomous subdivision of the bud results in arborizing airways that form the prospective gas exchanging chambers, where a thin blood-gas barrier (BGB) is established. In the mammalian lung, this proceeds through conversion of type II cells to type I cells, thinning, and elongation of the cells as well as extrusion of the lamellar bodies. Subsequent diminution of interstitial tissue and apposition of capillaries to the alveolar epithelium establish a thin BGB. In the noncompliant avian lung, attenuation proceeds through cell-cutting processes that result in remarkable thinning of the epithelial layer. A host of morphoregulatory molecules, including transcription factors such as Nkx2.1, GATA, HNF-3, and WNT5a; signaling molecules including FGF, BMP-4, Shh, and TFG-β and extracellular proteins and their receptors have been implicated. During normal physiological function, the BGB may be remodeled in response to alterations in transmural pressures in both blood capillaries and airspaces. Such changes are mitigated through rapid expression of the relevant genes for extracellular matrix proteins and growth factors. While an appreciable amount of information regarding molecular control has been documented in the mammalian lung, very little is available on the avian lung.

An Ill Wind‐Iatrogenic Air Embolus Around Pacing Leads During Defibrillator Implant with Coexisting Pulmonary Fibrosis

We present a case of air embolism during biventricular defibrillator implantation in a 58-year-old man with pulmonary fibrosis. To prevent air entry after the dilator was removed, the subclavian venous sheath was covered before the lead was introduced. Air embolism occurred during inspiration around the lead body in the appropriate sized sheath but without a hemostatic valve. Extraordinary swings in intrathoracic pressure due to noncompliant lungs may have contributed to this unusual complication.

Airflow Distribution in the Human Lung and its Influence on Particle Deposition

Realistic descriptions of lung geometry and physiology are the primary determinants of accurate predictions of inhaled particle deposition and distribution in the human lung. While there have been considerable efforts devoted to geometry reconstruction, little attention has been given to lung ventilation as applied to particle deposition applications. Models of lung ventilation based on pressure differential between extrathoracic airways and the pleural cavity were developed and used to calculate lobar and regional deposition of particles in the human lung. Local airflow in the lung varied in accordance with regional physiological properties. Calculations showed that airflow rate entering each lobe was different for compliant and noncompliant lung models and similar for uniform and nonuniform lung expansions. Regional particle deposition predictions were almost identical between the two compliance models. However, differences in lobar depositions were observed. The coupled lung ventilation and deposition models can be used in site-specific deposition predictions of inhaled particles in the human lungs.

Effect of Artificial Lung Compliance on Right Ventricular Load

Artificial lungs may serve as transplant alternatives to patients with respiratory failure. To provide a pulmonary replacement, the device cannot significantly alter right ventricular afterload. We sought to characterize cardiac load using a prototype artificial lung as a pulmonary replacement. An artificial lung was implanted into 13 adult sheep, 7 using a noncompliant original prototype and 6 using a modified device with a compliance chamber. Inflow was from the pulmonary artery and outflow into the left atrium. Pulmonary impedance was determined and pulse wave reflections analyzed. Resistance was similar in the original prototype artificial lung and in the native pulmonary circulation (3.0 vs 3.2 Woods units, p = 0.5). First harmonic impedance was significantly increased in the original prototype artificial lung (0.4 vs 5.9 Woods units, p < 0.01). High-amplitude pulse wave reflections were identified and right ventricular function was altered. The addition of compliance to the artificial lung reduced impedance at the first harmonic (5.9 vs 1.9 Woods units, p < 0.01), decreased the amplitude of pulse wave reflections, and normalized right ventricular function. A low-resistance but noncompliant artificial lung increases pulmonary impedance and alters right ventricular function. Addition of a compliance chamber reduces pulse wave reflections and normalizes ventricular function.

ABC of preterm birth: Respiratory complications of preterm birth

Respiratory complications of preterm birth are an important cause of infant mortality and morbidity. This article looks at how advances in perinatal care have improved outcomes for preterm infants with respiratory distress syndrome and chronic lung disease. ### Preparation for home oxygen treatment Respiratory distress syndrome of prematurity is a major cause of morbidity and mortality in preterm infants. Primarily, respiratory distress syndrome is caused by deficiency of pulmonary surfactant. Surfactant is a complex mixture of phospholipids and proteins that reduces alveolar surface tension and maintains alveolar stability. As most alveolar surfactant is produced after about 30-32 weeks' gestation, preterm infants born before then will probably develop respiratory distress syndrome. In addition to short gestation, several other clinical risk factors have been identified. ### Risk factors for respiratory distress syndeome Preterm infants with respiratory distress syndrome present immediately or soon after birth with worsening respiratory distress. The presenting features include tachypnoea (respiratory rate > 60 breaths per minute); intercostals, subcostal, and sternal recession; expiratory grunting; cyanosis; and diminished breath sounds. If untreated, infants may become fatigued, apnoeic, and hypoxic. They may progress to respiratory failure and will need assisted ventilation. High airway pressures may be required to ventilate the stiff, non-compliant lungs, thereby increasing the risk of acute respiratory complications, such as pneumothorax, pneumomediastinum, and pulmonary interstitial emphysema. ### Indications for mechanical ventilation in preterm infants with respiratory distress syndrome Over the past 20-30 years, two major advances in perinatal …

Bleeding, Dysphagia, Dysphonia, Dysarthria, Severe Sore Throat, and Possible Recurrent Laryngeal, Hypoglossal, and Lingual Nerve Injury Associated with Routine Laryngeal Mask Airway Management: Where Is the Vigilance?

Bleeding, Dysphagia, Dysphonia, Dysarthria, Severe Sore Throat, and Possible Recurrent Laryngeal, Hypoglossal, and Lingual Nerve Injury Associated with Routine Laryngeal Mask Airway Management: Where Is the Vigilance?

Asymptomatic hydropneumothorax after therapeutic thoracentesis for malignant pleural effusions.

The purpose of this study was to document in a historical cohort the incidence and clinical observations of pneumothorax ex vacuo after therapeutic thoracentesis for malignant pleural effusions in patients with underlying parenchymal lung disease. Forty pneumothoraces resulted from 512 therapeutic thoracentesis performed for malignant pleural effusions over a 3-year period. Twenty-nine patients with pneumothoraces underwent catheter placement in the pleural space for treatment. Of these, 12 pneumothoraces resolved and 17 remained unchanged. We reviewed the charts of these 17 patients to document the cause of malignant pleural effusion, presence of underlying malignant parenchymal disease, volume of fluid aspirated, and improvement in symptoms. Clinical outcome was then evaluated, including size of residual pneumothorax, duration of catheter drainage, and reaccumulation of effusion. No patients' lungs reexpanded despite insertion of large-bore (16- to 35-French) chest tubes. All had pneumothoraces that occupied at least 30% of the hemithorax; all were asymptomatic; all had underlying parenchymal disease and noncompliant lungs. Pleural effusion reaccumulated in all 17 after removal of the chest tube. A subgroup of patients with malignant lung parenchymal disease who undergo therapeutic thoracentesis will develop asymptomatic hydropneumothoraces due to poor lung compliance. These patients do not require further catheter drainage. Pleural effusion will reaccumulate in the residual space over a variable period of time.

Adult respiratory distress syndrome (ARDS): current management, future directions.

The adult respiratory distress syndrome, marked by severe, refractory hypoxemia, noncardiogenic pulmonary edema, and stiff, noncompliant lungs, demands quick recognition and intensive care. This article reviews the disease process and current and experimental treatments for it.

Pneumothorax after small-bore catheter placement for malignant pleural effusions.

The objective of this study was to evaluate the incidence and significance of pneumothorax after small-bore chest tube placement for symptomatic malignant pleural effusions. Over a 2-year period, 90 patients with a known primary malignant tumor and symptomatic pleural effusion were referred to the radiology service at Duke University Medical Center. All patients underwent placement of a small-bore chest tube with fluid drainage in preparation for intrapleural sclerotherapy. Two of these patients were excluded because of coexisting empyema (n=1) and thoracentesis (n=1). The remaining 88 patients (30 men and 58 women; 26-86 years old [mean, 60 years old], who had 90 chest tubes placed, formed our study group. The incidence, duration, and clinical significance of their pneumothoraces and the amount of pleural effusion drained were recorded. Among the 88 patients with 90 chest tubes, 27 patients with 28 chest tubes (31%) were found to have pneumothorax after the procedure. For 23 patients with 24 chest tubes, pneumothorax was evident on chest radiographs taken immediately after tube insertion and fluid drainage. Four patients with four chest tubes were found to have pneumothorax on chest radiographs taken the next day. No significant difference in the amount of fluid drained during the procedure was noted for patients with or without pneumothorax (831 ml versus 853 ml). No relationship between the size of each pneumothorax and the size of each drainage catheter was seen. The duration of pneumothorax ranged from 2 hr to 18 days (average, 3.5 days). Resolution of pneumothorax was seen in 22 (79%) of 28 cases; the remaining six cases of pneumothorax (21%) were stable, and the patients showed eventual fluid reaccumulation after chest tube removal and no sclerotherapy. No patient developed tension pneumothorax, respiratory distress, or other complications. Pneumothorax should be recognized as a common finding after chest tube placement and immediate fluid drainage for malignant pleural effusions. We suggest that this finding is related to rapid removal of fluid from a relatively stiff, noncompliant lung. Patients whose lungs do not fully re-expand in several days will probably not benefit from sclerotherapy. Their tubes may be removed without risk of an enlarging tension pneumothorax.

DEVELOPMENTAL DIFFERENCES IN PERFLUBRON UPTAKE INTO THE BLOOD DURING TIDAL LIQUID VENTILATION (TLV) IN THE IMMATURE LAMB. † 1310

Tidal liquid ventilation (TLV) with perfluorochemical liquids (PFC) has been shown to provide effective gas exchange in term and preterm lambs with respiratory failure. PFCs have very low surface tensions and have high respiratory gas solubilities. It is these physical characteristics that make PFC an ideal media with which to support gas exchange in the stiff, noncompliant lungs characteristic of Infant Respiratory Distress Syndrome(IRDS). Although PFC is bioinert, nontoxic, and nonbiotransformable, a small quantity does cross into the blood. To determine if there is a developmental difference in PFC uptake in an animal model which resembles the cardiopulmonary development of human neonates currently receiving PFC therapy, 2 groups of premature lambs [Gr 1: 111 ±.23 days; n=6) and Gr 2: 123±.95 days; n=6)] were delivered by caesarean section, anesthetized, paralyzed, tracheotomized, placed on a time-cycled, pressure-limited tidal liquid ventilator, and ventilated with perflubron (Liquivent®: Alliance Pharm. Corp.) for 4 hours. Ventilation was modulated to maintain physiologic blood gases. Blood PFC content was determined by headspace analysis using an electron capture detector gas chromatograph on samples taken in utero, every 15 mins up to 1 hour, and every 30 mins to 4 hrs. These data were compared to that of previously evaluated term lambs (Pediatr Res (37): A1414). Results in μgm/gm (mean ± SE) are presented below:Table These data demonstrate that very minute (all values < 10μgm/gm) but different (*p<.01) quantities cross into the blood of the immature lamb following tidal liquid ventilation. The mean over 4 hrs for Gr 1, Gr 2, and the term lambs were 4.31 ±.29, 6.97±.36, and 7.35 ±.36, respectively, showing comparable levels in term and preterm blood perflubron content. These data suggest that even in the presence of high lung permeability of prematurity, perflubron blood content does not exceed that of a normal, term newborn lamb.(Supp by AlliancePharm Corp,R29HD26341)

Function of the Dräger Oxylog Ventilator at High Altitude

We have assessed the performance of the Dräger Oxylog ventilator at high altitude using a decompression chamber and a lung simulator set to mimic the normal and non-compliant lung. In the normal lung, tidal volume increased by 28% at 2040 metres and by 106% at 9120 metres. A lesser change, but in the opposite direction, occurred in respiratory rate. The net effect was a linear increase in minute volume with altitude. At 2040 and 9144 metres minute volume increased by 13% and by 45%, and rate decreased by 10% and 30% respectively. In the abnormal lung stimulation, similar, but slightly less marked, changes occurred in all variables. These changes are of sufficient magnitude to require frequent observation of tidal volume and respiratory rate during aircraft ascent and descent.

Increased sensitivity to mechanical ventilation after surfactant inactivation in young rabbit lungs.

To study the individual and combined effects of surfactant inactivation and mechanical ventilation on pulmonary microvascular permeability and lung compliance. Prospective, controlled trial. An isolated, perfused, lung model of surfactant inactivation and mechanical ventilation at 15, 30, and 45 cm H2O peak inspiratory pressure was developed in young (4 to 6 wks) New Zealand white rabbits. Laboratory of a university-affiliated medical school. Isolated, perfused lungs were prepared for measurement of the capillary filtration coefficient before and after one of four interventions: instillation of dioctyl succinate, a surfactant inactivator, without ventilation (group 1); ventilation without dioctyl succinate at 15, 30, or 45 cm H2O peak inspiratory pressure (group 2); ventilation after dioctyl succinate pretreatment at 15, 30, or 45 cm H2O peak inspiratory pressure (group 3); and control lungs without dioctyl succinate or ventilation (group 4). A significant increase in the capillary filtration coefficient was noted after dioctyl succinate treatment alone, after ventilation alone at 45 cm H2O peak inspiratory pressure, and after dioctyl succinate plus ventilation at 15, 30, and 45 cm H2O peak inspiratory pressure. Dioctyl succinate plus ventilation produced a significantly greater increase in the capillary filtration coefficient than ventilation alone at 15 and 45 cm H2O peak inspiratory pressure. These data suggest that ventilation after surfactant inactivation is more injurious to the pulmonary microvasculature than ventilation alone, and that generalized lung overdistention is not the primary mechanism for microvascular injury in the diseased, noncompliant lung. The increases seen in the capillary filtration coefficient in postventilated surfactant inactivated lungs, even at low-ventilation pressures, suggest that low peak inspiratory pressures do not overdistend the dioctyl succinate-treated lung.