Increase In Pulmonary Capillary Permeability Research Articles

Vascular hyperpermeable molecules potentially contributing to the development of pulmonary edema in sepsis-associated ARDS

The acute respiratory distress syndrome (ARDS) is an important cause of respiratory failure in critically ill patients and may become a life-threatening condition where inflammation of the lungs may begin in one lung but eventually affects both, leading to damage to the alveoli and surrounding small blood vessels. ARDS is particularly characterized by noncardiogenic pulmonary edema caused by an increase in pulmonary capillary permeability. Several clinical disorders can precipitate in ARDS, including pneumonia, sepsis, aspiration of gastric contents, and major trauma. The most common cause of ARDS is sepsis, which is a serious and widespread infection of the bloodstream and is now defined as life-threatening organ dysfunction due to a dysregulated reponse of the host to infection. In sepsis, a number of vascular hyperpermeable factors, such as histamine, nitric oxide, thromboxane A2, and vascular endothelial growth factor, can be overproducted and contribute to the development of pulmonary edema. Given that sepsis can be regarded as a gene-related disorder, the nucleic-acid based gene therapeutic strategy to regulate some transcription factors involved in expression of vascular hyperpermeable genes may be considered to be a promising novel approach for treatment of ARDS in sepsis.

Role of Toll-like receptor 4 in mechanical ventilation-induced increase in pulmonary capillary permeability in diabetic mice

Objective To evaluate the role of Toll-like receptor 4 (TLR4) in mechanical ventilationinduced increase in pulmonary capillary permeability in diabetic mice.Methods Two types of mice,aged 8-10 weeks,weighing 20-25 g,were used in this study:free wild type mice (C3H/HeN) and TLR4 gene mutation type (C3H/HeJ).Diabetes was induced by intraperitoneal streptozotocin 150 mg/kg (in citric acid buffer solution 0.1 mol/L) and confirmed by blood glucose level ＞ 16 mmol/L.Each type of diabetic mice was randomly divided into 2 groups (n =14 each):group diabetes + sham operation (group DS) and group diabetes + mechanical ventilation (group DM).The animals were anesthetized with intraperitoneal ketamine,midazolam and atropine.Tracheal intubation was performed and the animals kept spontaneous breathing in group DS.The animals were mechanically ventilated (FiO2 50％,RR 70 bpm,VT 15 ml/kg,PEEP 2 cmH2O) for 4 h in group DM.Arterial blood samples were obtained at 4 h of ventilation for blood gas analysis,PaO2 and PaCO2 were recorded,and NO concentration in the serum was measured.Then the animals were sacrificed and the lungs were removed for determination of W/D lung weight ratio (W/D ratio),content of evans blue (EB),and expression of caveolin-1,endothelial nitric oxide synthase (eNOS) and phosphor-eNOS (p-eNOS) (by Western blot).The ratio of p-eNOS/eNOS was calculated.Results Compared with group DS,PaO2,PaCO2 and p-eNOS/eNOS ratio were significantly decreased,and W/D ratio,EB content and caveolin-1 expression were increased in group DM (P ＜ 0.05).Compared with C3H/HeN mice,W/D ratio,caveolin-1 expression and EB content were significantly decreased,peNOS/eNOS ratio and serum NO concentrations were increased (P ＜ 0.05),and no significant changes in PaO2 and PaCO2 were found in C3H/HeJ mice in group DM (P ＞ 0.05).Conclusion TLR4 increases the pulmonary capillary permeability after mechanical ventilation in diabetic mice through effectively combining with caveolin-1 and reducing NO bioavailability. Key words: Toll-like receptor 4 ; Respiratory distress syndrome, adult; Diabetes mellitus; Capillary permeability

The effect of blood transfusion on pulmonary permeability in cardiac surgery patients: a prospective multicenter cohort study

There is an association between blood transfusion and pulmonary complications in cardiac surgery. Mediators of increased pulmonary vascular leakage after transfusion are unknown. We hypothesized that factors may include antibodies or bioactive lipids, which have been implicated in transfusion-related acute lung injury. We performed a prospective cohort study in two university hospital intensive care units in the Netherlands. Pulmonary vascular permeability was measured in cardiac surgery patients after receiving no, restrictive (one or two transfusions), or multiple (five or more transfusions) transfusions (n=20 per group). The pulmonary leak index (PLI), using (67) Ga-labeled transferrin, was determined within 3 hours postoperatively. Blood products were screened for bioactive lipid accumulation and the presence of antibodies. The PLI was elevated in all groups after cardiac surgery. Transfused patients had a higher PLI compared to nontransfused patients (33×10(-3) ± 20×10(-3) vs. 23×10(-3) ± 11×10(-3)/min, p<0.01). The amount of red blood cell (RBC) products, but not of fresh-frozen plasma or platelets, was associated with an increase in PLI (β, 1.6 [0.2-3.0]). Concerning causative factors in the blood product, neither the level of bioactive lipids nor the presence of antibodies was associated with an increase in PLI. Patient factors such as surgery risk and time on cardiopulmonary bypass did not influence the risk of pulmonary leakage after blood transfusion. Transfusion in cardiothoracic surgery patients is associated with an increase in pulmonary capillary permeability, an effect that was dose dependent for RBC products. The level of bioactive lipids or the presence of HLA or HNA antibodies in the transfused products were not associated with increased pulmonary capillary permeability.

Fluid management in acute lung injury and ards

ARDS is particularly characterized by pulmonary edema caused by an increase in pulmonary capillary permeability. It is considered that limiting pulmonary edema or accelerating its resorption through the modulation of fluid intake or oncotic pressure could be beneficial. This review discusses the principal clinical studies that have made it possible to progress in the optimization of the fluid state during ARDS. Notably, a randomized, multicenter study has suggested that fluid management with the goal to obtain zero fluid balance in ARDS patients without shock or renal failure significantly increases the number of days without mechanical ventilation. On the other hand, it is accepted that patients with hemodynamic failure must undergo early and adapted vascular filling. Liberal and conservative filling strategies are therefore complementary and should ideally follow each other in time in the same patient whose hemodynamic state progressively stabilizes. At present, although albumin treatment has been suggested to improve oxygenation transiently in ARDS patients, no sufficient evidence justifies its use to mitigate pulmonary edema and reduce respiratory morbidity. Finally, the resorption of alveolar edema occurs through an active mechanism, which can be pharmacologically upregluated. In this sense, the use of beta-2 agonists may be beneficial but further studies are needed to confirm preliminary promising results.

Platelet Transfusion Associated With Acute Lung Injury After Coronary Artery Bypass Grafting

Transfusion-related acute lung injury is a potentially fatal complication of blood and plasma transfusion; however, the incidence relating to platelet use in cardiac surgery is uncommon. In the presence of normal left ventricular function, an acute increase in pulmonary capillary permeability leads to a high protein content pulmonary edema, which leads to a dramatic reduction in pulmonary function due to acute lung injury and also intravascular fluid depletion. The clinical picture is acute and the condition is associated with considerable mortality. Although the exact mechanism of transfusion-related acute lung injury is unknown, it may be due to an antibody-mediated reaction caused by preformed leukocyte antibodies or activation of inflammatory mediators. The signs, diagnosis, and therapeutic interventions are discussed with reference to a case report.

Endothelial Microparticles Induce Myeloperoxidase-Mediated Lung Injury

Background: Endothelial microparticles (EMPs) are produced by activated or apoptotic cells during various human and experimental disease states. Previous experimental work in our lab has shown that exogenous EMPs injected into a murine model cause a significant increase in pulmonary capillary permeability, induce oxidative injury in the respiratory epithelium and vasculature, and inhibit endothelium-mediated vasodilatation and nitric oxide production. Myeloperoxidase (MPO) has been implicated in the propagation of lung injury through the products formed as part of the MPO-mediated antimicrobial system.

Genetic Ablation of Nrf2 Enhances Susceptibility to Acute Lung Injury After Traumatic Brain Injury in Mice

Previous studies have shown that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a unique role in many physiological stress processes. The present study investigated the role of Nrf2 in the regulation of traumatic brain injury (TBI)-induced acute lung injury (ALI). Wild-type Nrf2 (+/+) and Nrf2 (-/-)-deficient mice were subjected to a moderately severe weight-drop impact head injury. Pulmonary capillary permeability (PCP), wet/dry weight ratio, apoptosis, inflammatory cytokines and antioxidant/detoxifying enzymes were measured at 24 h after TBI. Mice lacking Nrf2 were found to be more susceptible to TBI-induced ALI, as characterized by the higher increase in PCP, wet/dry weight ratio and alveolar cells apoptosis after TBI. This exacerbation of lung injury in Nrf2-deficient mice was associated with increased pulmonary mRNA and protein expression of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6); and with decreased pulmonary mRNA expression and enzymatic activities of antioxidant and detoxifying enzymes including NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase alpha1 (GST-alpha1)--as compared with their wild-type Nrf2 (+/+) counterparts after TBI. The results of the present study suggest that Nrf2 reduces TBI-induced acute lung injury, possibly by decreasing pulmonary inflammation and inducing antioxidant and detoxifying enzymes.

Hemodynamic Resuscitation With Arginine Vasopressin Reduces Lung Injury After Brain Death in the Transplant Donor

The autonomic storm accompanying brain death leads to neurogenic pulmonary edema and triggers development of systemic and pulmonary inflammatory responses. Neurogenic vasoplegia exacerbates the pulmonary injury caused by brain death and primes the lung for ischemia reperfusion injury and primary graft dysfunction in the recipient. Donor resuscitation with norepinephrine ameliorates the inflammatory response to brain death, however norepinephrine has deleterious effects, particularly on the heart. We tested the hypothesis that arginine vasopressin is a suitable alternative to norepinephrine in managing the hypotensive brain dead donor. Brain death was induced in Wistar rats by intracranial balloon inflation. Pulmonary capillary leak was estimated using radioiodinated albumin. Development of pulmonary edema was assessed by measurement of wet and dry lung weights. Cell surface expression of CD11b/CD18 by neutrophils was determined using flow cytometry. Enzyme-linked immunosorbent assays were used to measure the levels of TNFalpha, IL-1beta, CINC-1, and CINC-3 in serum and bronchoalveolar lavage. Quantitative reverse-transcription polymerase chain reaction was used to determine the expression of cytokine mRNA (IL-1beta, CINC-1 and CINC-3) in lung tissue. There was a significant increase in pulmonary capillary permeability, wet/dry lung weight ratios, neutrophil integrin expression and pro-inflammatory cytokines in serum (TNFalpha, IL-1beta, CINC-1 and CINC-3), bronchoalveolar lavage (TNFalpha and IL-1beta) and lung tissue (IL-1beta and CINC-1) in braindead animals compared to controls. Correction of neurogenic hypotension with either arginine vasopressin or norepinephrine limits edema, reduces pulmonary capillary leak, and modulates systemic and pulmonary inflammatory responses to brain death. Arginine vasopressin and norepinephrine are equally effective in treating the hypotensive pulmonary donor in this rodent model.

Influence of hydroxyethyl starch 130/0.4 in pulmonary neutrophil recruitment and acute lung injury during polymicrobial sepsis in rats

Acute lung injury (ALI) is a progressive syndrome associated with significant mortality in sepsis patients. Neutrophils are key cells in the inflammatory response that characterizes ALI. This study was designed to explore the effects of hydroxyethyl starch (HES) 130/0.4 (a novel plasma substitute) on pulmonary neutrophil recruitment and associated ALI in a rat sepsis model induced by cecal ligation and puncture (CLP). Animals were randomly assigned to six groups [saline control; CLP and saline; CLP and HES (7.5, 15 and 30 ml/kg); and HES control], subjected to CLP and infused with or without HES 130/0.4 4 h after CLP. Six hours later, the pulmonary capillary permeability (PCP), myeloperoxidase (MPO) activity, lung histological changes, tumor necrosis factor-alpha, interleukin-1beta and cytokine-induced neutrophil chemoattractant levels, P-selectin mRNA expression and nuclear factor-kappa B (NF-kappaB) activation were measured. Resuscitation with HES 130/0.4 significantly attenuated the CLP-induced increase in PCP, MPO activity, cytokine/chemokine levels, mRNA expression of P-selectin and NF-kappaB activation, all of which are involved in the recruitment of neutrophils. Groups receiving the higher doses of HES 130/0.4 (15 and 30 ml/kg) were more adequately resuscitated. HES 130/0.4 can inhibit CLP-induced neutrophil recruitment and subsequent ALI by attenuating cytokines/chemokines, adhesion molecule-mediated inflammation and NF-kappaB activation.

Effects of Hydroxyethyl Starch 130/0.4 on Pulmonary Capillary Leakage and Cytokines Production and NF-κB Activation in CLP-Induced Sepsis in Rats

Sepsis and resulting multiple system organ failure are the leading causes of mortality in intensive care units. Hydroxyethyl starch (HES) 130/0.4 was a novel preparation, developed to improve the pharmacokinetics of current medium molecular weight HES solutions. This study was designed to explore the effects of HES 130/0.4 on pulmonary capillary permeability (PCP), production of cytokines, and activation of transcription factor in septic rats induced by cecal ligation and puncture (CLP). Adult male Sprague Dawley rats were randomly divided into six groups (six rats/group): saline controls (30 ml/kg); CLP plus saline (30 ml/kg); CLP plus HES (7.5, 15, or 30 ml/kg, respectively), and HES alone (30 ml/kg). Mean arterial blood pressure and heart rate were monitored during the experiment process. Myeloperoxidase (MPO) activity, wet/dry weight ratio, PCP, tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, IL-10, and nuclear factor-kappa B (NF-kappaB) were investigated at 6 h. We demonstrated that CLP could provoke significant injury in lung, characterized by increase in PCP, wet/dry weight ratio, MPO activity, TNF-alpha, IL-6, and IL-10 level, and NF-kappaB activation. Without obvious influence on systemic macro-hemodynamics, HES 15 ml/kg and 30 ml/kg significantly reduced CLP-induced elevation of pulmonary capillary permeability, wet/dry weight ratio, and production of IL-6. Meanwhile, HES 15 ml/kg increased IL-10 level and HES 7.5, 15, and 30 ml/kg suppressed MPO activity, TNF-alpha level, and NF-kappaB activation. HES 130/0.4 can inhibit CLP-induced PCP by attenuating pulmonary inflammation and NF-kappaB activation in vivo.

Part 10.3: Drowning

Drowning is a leading preventable cause of unintentional morbidity and mortality. Although this chapter focuses on treatment, prevention is possible, and pool fencing has been shown to reduce drowning and submersion injury (Class I).1 The most important and detrimental consequence of submersion is hypoxia. Therefore, oxygenation, ventilation, and perfusion should be restored as rapidly as possible. This will require immediate bystander CPR plus immediate activation of the emergency medical services (EMS) system. Victims who have spontaneous circulation and breathing when they reach the hospital usually recover with a good outcome. Victims of drowning may develop primary or secondary hypothermia. If the drowning occurs in icy (<5°C [41°F]) water, hypothermia may develop rapidly and provide some protection against hypoxia. Such effects, however, have typically been reported only after submersion of young victims in icy water (see Part 10.4: “Hypothermia”).2 All victims of drowning (see definitions below) who require any form of resuscitation (including rescue breathing alone) should be transported to the hospital for evaluation and monitoring even if they appear to be alert with effective cardiorespiratory function at the scene. The hypoxic insult can produce an increase in pulmonary capillary permeability with delayed onset of pulmonary complications. A number of terms are used to describe drowning. To aid in the use of consistent terminology and the uniform reporting of data from drowning, the Utstein definition and style of data reporting are recommended3: Drowning . Drowning is a process resulting in primary respiratory impairment from submersion/immersion in a liquid medium. Implicit in this definition is that a liquid/air interface is present at the entrance of the victim’s airway, …

Noninvasive evaluation of acute capillary permeability changes during high-volume ventilation in rats with and without hypercapnic acidosis*

To evaluate whether hypercapnic acidosis attenuates acute alterations of pulmonary capillary permeability due to high lung stretch in rats using a simple, noninvasive, scintigraphic method. Prospective, randomized, controlled animal study. University research laboratory. Male adult Wistar rats weighing 291 +/- 7.5 g. Three groups of rats were studied: controls ventilated with a low (6 mL/kg body weight) tidal volume and rats ventilated with a high (38 mL/kg body weight) tidal volume under normocapnic (Paco(2) = 35.2 +/- 1.65 mm Hg) or hypercapnic (Paco(2) = 102.5 +/- 5.63 mm Hg) conditions. Pulmonary capillary permeability alterations were assessed by monitoring the rate of (111)In-transferrin accumulation in lung tissue. Respiratory system pressure-volume curves were registered and analyzed. High tidal volume ventilation increased In-transferrin plasma to lung flux in such a way that I(111)In-transferrin behaved like a marker of water. The rate of initial (first 30 mins of high tidal volume ventilation) lung transferrin accumulation measured by scintigraphy (standardized lung/heart ratio) was steady, correlated with the percent decrease in respiratory system compliance (a marker of edema progression), and did not differ between normocapnic and hypercapnic groups (18.9 +/- 3.97 vs. 14.2 +/- 2.89%/hr, not significant). However, lung In-tranferrin accumulation rate was highly scattered due to variable interindividual mechanical properties of the respiratory system. This rate was correlated with initial values of volume of the upper inflection point of the pressure-volume curve (r = -.53, p < .001) and end-inspiratory pressure (r = .54, p < .001). Mechanical properties were similar in normocapnic and hypercapnic rats. There was no difference between In-transferrin accumulation rates in these rats when a stringent selection was made based on end-inspiratory pressure (28-32 cm H(2)O) or body weight (330-360 g). Hypercapnic acidosis does not influence in vivo the acute increase in pulmonary capillary permeability due to high-volume ventilation.

Nutritional Support in Acute Lung Injury and Acute Respiratory Distress Syndrome

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent points on a spectrum of acute hypoxic respiratory failure that are distinguished by the severity of associated hypoxemia. The hallmark of ALI/ARDS is an increase in pulmonary capillary permeability resulting from epithelial and endothelial injury; a variety of inflammatory mediators are involved in the pathogenesis, including toxic oxygen radicals, cytokines, and eicosanoids. Patients with ALI/ARDS are at high risk for malnutrition because the underlying disease increases caloric expenditure and promotes the loss of lean body mass; this, in turn, has adverse effects on pulmonary and immune function. The type of fatty acids (FA) that comprise the cell membrane of alveolar macrophages and neutrophils is influenced by dietary fat intake; this, in turn, impacts on the nature of eicosanoid mediators produced during ALI/ARDS. Diets high in linoleic acid (LA) promote an inflammatory response by stimulating production of arachidonic acid and its derived eicosanoids. Nutritional supplementation with ω‐3 FA can lessen the inflammatory response and be of therapeutic benefit in patients with ALI/ARDS. This article reviews the pathology and pathophysiology of acute hypoxemic respiratory failure, summarizes animal and human studies that delineate the effects of modified FA solutions, and provides clinical recommendations for the nutrition support of patients with ALI/ARDS.

Part 8: Advanced Challenges in Resuscitation

Part 8: Advanced Challenges in Resuscitation

Neurogenic disorders of heart and lung function in acute cerebral lesions

Incidence and clinical significance of cardiopulmonary complications of acute cerebral lesions are still unclear. Neurogenic pulmonary edema (NPE) is characterized as an acute, protein-rich lung edema occurring shortly after cerebral lesions associated with an acute rise of intracranial pressure. NPE is infrequently diagnosed, usually in association with head trauma. Pathophysiological mechanisms include a rise of the pulmonary vascular hydrostatic pressure either due to sympathetic innervation with pulmonary vasoconstriction or increased left-atrial pressure following systemic arterial hypertension or an increase in pulmonary capillary permeability. In contrast to NPE, cardiac complications are frequently observed, most consistently in patients with subarachnoid hemorrhage. Typical ECG changes are repolarization abnormalities, similar to those observed in coronary heart disease, and cardiac arrhythmias. The CK-MB may be slightly elevated; echocardiographic findings show a depressed left-ventricular function. Pathological examination reveals myofibrillar necrosis. Cardiac complications are explained with overactivity of the sympathetic innervation and high levels of circulating catecholamines. For adequate treatment, close cardiac monitoring is required in all patients with acute cerebral lesions.

Pulmonary oedema in isolated lung lobe after inhalation injury

Pulmonary oedema was produced in isolated lung lobes with steam and provided direct continuous measurements of transudation as it occurred. Transvascular flux (Q f) and weight gain (G w) of the lobe increased immediately and the transudation reached its peak within half an hour after inhalation injury. Studies of protein content, colloid osmotic pressure of bronchial exudate and water content of lung, reconfirmed the increase in pulmonary capillary permeability. Marked haemoconcentration was revealed. Plasma leaked 113g (25 per cent), plasma protein leaked 1.96g (9.7 per cent) during the experiment. Based on the measured arterial pressure (P a), vein pressure (P v), arterial occlusion (P ao), venous occlusion (P vo), double occlusion (P do) and blood flow through the lobe (Q t), the total vascular (R t), arterial (R a), middle compartment (R mid) and venous (R v) resistances were calculated. All the resistances were increased and the Q t showed a decrease after inhalation injury.

Mechanisms of pulmonary edema induced by an organophosphorus compound in anesthetized dogs

To determine the mechanism governing pulmonary edema induced by an organophosphorus compound, S-(2-diisopropylaminoethyl)- O-ethylmethyl phosphonothiolate (VX), lung lymph flow and lymph-to-plasma protein concentration ratio were measured in six anesthetized, open-chest, mechanically ventilated beagle dogs before and after intravenous injection of 6 μg/kg of VX. Systemic and pulmonary hemodynamic data (heart rate, aortic blood flow, and left atrial, systemic arterial, pulmonary arterial, and pulmonary capillary pressures) were continuously recorded. Arterial blood gases and pH were measured every 30 min. Histological examinations and lung water content measurements were also carried out. Following VX injection, lung lymph flow increased (from 109 ± 38 to 179 ± 66 μl/min, p < 0.05) while lymph-to-plasma protein concentration ratio remained unchanged (from 0.64 ± 0.14 to 0.62 ± 0.12, N.S.). Neither systemic nor pulmonary hemodynamics were changed. Lung water content expressed as blood-free wet-to-dry weight ratio increased from 4.31 ± 0.23 to 5.35 ± 0.26 ( p < 0.05). Histological examinations revealed in many cases diffuse congestion of lungs and interstitial edema. These results suggest that VX injection induces an increase in pulmonary capillary permeability which may lead to a high-permeability edema.

Pathogenesis of pulmonary edema during interleukin-2 therapy: correlation of chest radiographic and clinical findings in 54 patients.

The pathogenesis of pulmonary edema that occurs during interleukin-2 therapy has often been attributed to an increase in pulmonary capillary permeability. However, renal insufficiency, fluid overload, and hypotension also develop in many patients. These manifestations of systemic toxicity may contribute to the development of pulmonary edema during therapy. Understanding the cause of pulmonary edema during interleukin-2 therapy could directly affect patients' care. Therefore, we reviewed the chest radiographs and clinical course of 54 patients who received high-dose interleukin-2 therapy and lymphokine-activated killer cells for advanced carcinoma. The type, frequency, and course over time of pulmonary abnormalities were recorded and correlated with clinical measures of renal function, fluid status, and blood pressure. Focal or diffuse parenchymal lung opacities were found on radiographs in 43 (80%) of 54 patients. Findings of interstitial pulmonary edema were most common, occurring in 76% of patients. Weight gain, hypotension, and elevation of the serum creatinine level were not associated statistically with interstitial edema. Diffuse air-space disease developed in 20% of patients. Focal consolidation, which was associated with positive central venous catheter cultures (p less than .03), developed in 28% of patients. Pleural effusion occurred in 48% of patients and was associated with all types of parenchymal disease. These data suggest that the frequent development of pulmonary edema during interleukin-2 therapy is not due to renal insufficiency, fluid overload, or hypotension, but is more likely the result of an interleukin-2-related increase in pulmonary capillary permeability.

The effects of neutrophils and phospholipase A 2 on transvascular albumin flux in isolated rabbit lungs

In this study, addition of phospholipase A 2 (PLA 2) to salt-perfused isolated rabbit lungs containing rabbit polymorphonuclear leukocytes leads to an increase in pulmonary capillary permeability. We add 1.5 × 10 8 polymorphonuclear leukocytes to the perfusate. Next, indomethacin is added to the perfusate and 40 units of PLA 2 are infused into the pulmonary arterial inflow of the lungs. At the end of the study, a lung sample is removed for measurement of transvascular albumin flux using I 125-albumin as a measure of the permeability-surface area product. Control studies demonstrate no increase in transvascular albumin flux. Addition of a dual cyclooxygenase and lipoxygenase inhibitor, BW755C, to the perfusate prevents the increase in transvascular albumin flux. We conclude that PLA 2 interacts with polymorphonuclear leukocytes to increase protein permeability. Since PLA 2 can release endogenous arachidonic acid and platelet-activating factor from cells, this suggests that release of such products may contribute to an increase in pulmonary capillary permeability from polymorphonuclear leukocytes. The ability of BW755C to prevent the increase suggests the possibility that lipoxygenase products contribute.

Increase in pulmonary capillary permeability in dogs exposed to 100% O 2

Increase in pulmonary capillary permeability in dogs exposed to 100% O 2