leukotriene-b4 and Respiratory-Distress-Syndrome

Topics: Acute Disease; Animals; Humans; Inflammation; Leukotriene B4; Neutrophils; Respiratory Distress Syndrome; Sheep; SRS-A; Tetradecanoylphorbol Acetate; Vasoconstriction

Topics: Anaphylatoxins; Arachidonic Acid; Arachidonic Acids; Asthma; Eicosanoic Acids; Fatty Acids; Humans; Leukocytes; Leukotriene B4; Lung; Macrophage Activation; Mucus; Platelet Activating Factor; Pneumonia; Prostaglandin-Endoperoxide Synthases; Respiratory Distress Syndrome; SRS-A

Septic pulmonary injury remains a significant cause of morbidity and mortality among hospitalized patients today and is likely to increase in prevalence as advances in medical technology allow the salvage of more critically ill and immunocompromised hosts. Treatment of the host's underlying disease and even of the infection itself has appeared to redeem septic patients only to have them succumb in increasing numbers to the pulmonary injury reaction. Our understanding of the mechanisms and mediators of lung dysfunction in sepsis is in a rapidly expanding phase. Currently we recognize the contributions of several blood elements, lipids, and peptides to pulmonary injury, although the relative importance and points of interaction and interdependence of these mediators remain to be established. It is hoped that a more complete understanding of the process of pulmonary injury in sepsis will suggest effective means of intervention at a stage in which damage may be reversed or minimized.

Topics: Animals; Cell Aggregation; Complement System Proteins; Fibrin; Humans; Leukotriene B4; Lung; Neutrophils; Platelet Aggregation; Prostaglandins; Respiratory Distress Syndrome; Sepsis; SRS-A

Lipid emulsions have been associated with changes in pulmonary function. Although these changes were related to the physical effects of the infusion-induced lipemia on gas exchange, several animal and human studies suggest that the impairment in pulmonary function observed with lipid infusions was mediated by prostaglandins. Prostaglandins are synthesized enzymatically from essential fatty acids. We studied the effects of two lipid emulsions, with different amounts of essential fatty acids (20% long-chain triacylglycerols [LCT] with 55% of linoleic acid and 7% of alpha linolenic acid in 100 g of emulsion, and a physical mixture of 20% medium-chain triacyglycerols [MCT] and LCT with 26% of linoleic acid and 4% of alpha linolenic acid in 100 g of emulsion), on plasma levels of eicosanoids in patients with acute respiratory distress syndrome (ARDS). Although in patients with ARDS, plasma levels of prostanoids were higher than the reference values, neither lipid emulsion, administered at the rate of 2 mg.kg-1.min-1 induced significant changes in the eicosanoids except for a decrease in systemic-pulmonary arterial 6-keto prostaglandin F1 alpha difference.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Double-Blind Method; Eicosanoids; Fat Emulsions, Intravenous; Humans; Leukotriene B4; Middle Aged; Parenteral Nutrition; Prospective Studies; Reference Values; Respiratory Distress Syndrome; Thromboxane B2

Leukotriene B4 (LTB4), a proinflammatory lipid mediator correlates well with the acute phase of Acute Respiratory Distress Syndrome (ARDS). Therefore, LTB4-levels were investigated to determine whether they might be a useful clinical marker in predicting pulmonary complications (PC) in multiply traumatized patients.. Plasma levels of LTB4 were determined in 100 patients on admission (ED) and for five consecutive days (daily). Twenty healthy volunteers served as control. LTB4-levels were measured by ELISA. Thirty patients developed PC (pneumonia, respiratory failure, acute lung injury (ALI), ARDS, pulmonary embolism) and 70 had no PC (ØPC).. LTB4-levels in the PC-group [127.8 pg/mL, IQR: 104-200pg/ml] were significantly higher compared to the ØPC-group on admission [95.6 pg/mL, IQR: 55-143 pg/mL] or control-group [58.4 pg/mL, IQR: 36-108 pg/mL]. LTB4 continuously declined to basal levels from day 1 to 5 without differences between the groups. The cutoff to predict PC was calculated at 109.6 pg/mL (72% specificity, 67% sensitivity). LTB4 was not influenced by overall or chest injury severity, age, gender or massive transfusion. Patients with PC received mechanical ventilation for a significantly longer period of time, and had prolonged intensive care unit and overall hospital stay.. High LTB4-levels indicate risk for PC development in multiply traumatized patients.

Topics: Acute Lung Injury; Adult; Blood Transfusion; Critical Care; Enzyme-Linked Immunosorbent Assay; Female; Hospitalization; Humans; Leukotriene B4; Lung Diseases; Male; Middle Aged; Respiratory Distress Syndrome; Sensitivity and Specificity; Time Factors; Wounds and Injuries

The benefits of beta-adrenergic stimulation have been described in acute lung injury (ALI), but there is still no evidence of its anti-inflammatory effect in these patients. Biomarkers in exhaled breath condensate (EBC) were used to study the effects of salbutamol on lung inflammation in mechanically ventilated patients with ALI.. EBC was collected before and 30 minutes after administration of inhaled salbutamol (800 microg). The following parameters were measured in the samples: volume obtained, conductivity, pH after helium deaeration, and concentration of nitrites, nitrates and 8-isoprostane. The leukotriene B4 concentration was measured after sample lyophilization and reconstitution. Results are expressed as the median (interquartile range).. EBC was obtained from six ALI patients, with a median age of 56 (46 to 76) years. At the time of EBC collection, the Lung Injury Score was 3 (2.3 to 3.1) and the PaO2/FIO2 ratio was 133 (96 to 211) mmHg. A significant increase in deaerated EBC pH was observed after salbutamol administration (7.66 (7.58 to 7.75) versus 7.83 (7.67 to 7.91), P = 0.028). Trends toward decreased nitrosative species (18.81 (13.33 to 49.44) microM versus 21.21 (8.07 to 29.83) microM, P = 0.173) and decreased 8-isoprostane concentration (11.64 (7.17 to 17.13) pg/ml versus 6.55 (4.03 to 9.99) pg/ml, P = 0.068) were detected. No changes in leukotriene B4 concentration were found (1.58 (0.47 to 3.57) pg/ml versus 2.06 (1.01 to 3.01) pg/ml, P = 0.753).. EBC analysis is a noninvasive technique that can be used to monitor ventilated patients. In EBC from a small cohort of patients with ALI, inhaled salbutamol significantly decreased airspace acidosis, a marker of inflammation, and was associated with a trend toward decreased markers of nitrosative and oxidative stress.

Topics: Adrenergic beta-Agonists; Aged; Albuterol; Biomarkers; Breath Tests; Dinoprost; Exhalation; Female; Humans; Hydrogen-Ion Concentration; Leukotriene B4; Male; Metered Dose Inhalers; Middle Aged; Nitrates; Nitrites; Prospective Studies; Pulmonary Gas Exchange; Respiration, Artificial; Respiratory Distress Syndrome; Severity of Illness Index

Although acute lung injury (ALI) is an important problem in humans, its pathogenesis is poorly understood. Airway instillation of bacterial LPS, a known complement activator, represents a frequently used model of ALI. In the present study, pathways in the immunopathogenesis of ALI were evaluated. ALI was induced in wild-type, C3(-/-), and C5(-/-) mice by airway deposition of LPS. To assess the relevant inflammatory mediators, bronchoalveolar lavage fluids were evaluated by ELISA analyses and various neutralizing Abs and receptor antagonists were administered in vivo. LPS-induced ALI was neutrophil-dependent, but it was not associated with generation of C5a in the lung and was independent of C3, C5, or C5a. Instead, LPS injury was associated with robust generation of macrophage migration inhibitory factor (MIF), leukotriene B(4) (LTB4), and high mobility group box 1 protein (HMGB1) and required engagement of receptors for both MIF and LTB4. Neutralization of MIF or blockade of the MIF receptor and/or LTB4 receptor resulted in protection from LPS-induced ALI. These findings indicate that the MIF and LTB4 mediator pathways are involved in the immunopathogenesis of LPS-induced experimental ALI. Most strikingly, complement activation does not contribute to the development of ALI in the LPS model.

Topics: Animals; Bronchoalveolar Lavage Fluid; Complement Activation; Complement System Proteins; Disease Models, Animal; HMGB1 Protein; Inflammation Mediators; Leukotriene B4; Lipopolysaccharides; Lung; Macrophage Migration-Inhibitory Factors; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Respiratory Distress Syndrome

Neutrophil apoptosis is an important physiological process in the resolution of pulmonary inflammation. Previous studies have shown that eicosapentaenoic acid (EPA; 20:5n-3) increases the rate of apoptosis in a concentration- and time-dependent manner in HL-60 cells. However, it is not known if the EPA-induced apoptosis involves the lipoxygenase (LO) and cyclooxygenase (COX) enzymes or the downstream metabolic products of these enzymes. Thus, the objective of this study was to determine the effects of inhibitors LO and COX enzymes on apoptosis, viability, and necrosis in EPA-treated HL-60 cells.. Cells were incubated with 50 mum EPA in the presence of an enzyme inhibitor (1-10 microm) for 12 h. Compounds were used to inhibit COX 1 and 2 (ibuprofen), 5-, 12-, 15-LO (NDGA), 12-LO (baicalein), 5-LO (AA-861), and 5-LO activating protein (MK-886). Eicosanoid (0.001-1.0 mum) add-back experiments were also conducted; LTB(4) and 5-HETE with 5-LO inhibition and 12-HETE with 12-LO inhibition. Flow cytometry was used to assess apoptosis.. Inhibition of COX 1 and 2 had no effect on apoptosis. Inhibition of 5-LO and 12-LO significantly increased apoptosis in EPA-treated HL-60 cells. Addition of LTB(4) reduced apoptosis to levels significantly lower than in HL-60 cells treated with EPA alone; 5-HETE and 12-HETE also lowered apoptosis to control levels.. These data indicate that inhibition of LO, particularly 5-LO, increased apoptosis in EPA-treated HL-60 cells. Furthermore, this study demonstrated that the products of the LO enzymes, particularly LTB(4), are critical in the regulation of apoptosis in EPA-treated HL-60 cells.

Topics: Apoptosis; Arachidonate 12-Lipoxygenase; Arachidonate 15-Lipoxygenase; Arachidonate 5-Lipoxygenase; Cyclooxygenase Inhibitors; Eicosapentaenoic Acid; Enzyme Inhibitors; Fatty Acids, Unsaturated; Flavanones; Guaiacol; HL-60 Cells; Humans; Hydroxyeicosatetraenoic Acids; Ibuprofen; Indoles; Leukotriene B4; Lignans; Lipoxygenase Inhibitors; Neutrophils; Respiratory Distress Syndrome

Recently, evidence implicating the roles of the anti-human leucocyte antigen (HLA) class II antibody in the development of transfusion-related acute lung injury (TRALI), which is one of the most serious possible side effects of transfusion, has been accumulating. The aim of this study is to clarify the roles of the anti-HLA DR alloantibody in TRALI development. Cultured human lung microvascular endothelial (LME) cells were incubated with either HLA-DR15-positive or HLA-DR15-negative monocytes together with serum from a single multiparous donor previously implicated in a clinical case of TRALI and known to contain anti-HLA DR15 antibody. Production of soluble leukotriene B(4) (LTB(4)) was measured in the supernatant and found to be markedly increased in the presence of HLA-DR15-positive monocytes but not with the HLA-DR15-negative monocytes or in the absence of LME cells. The vascular cell adhesion molecule-1 expression in LME cells and leucocyte-function-associated molecule-1 (LFA-1) expression in HLA-DR15-positive monocytes were notably enhanced after combined culture of LME cells, HLA-DR15-positive monocytes and TRALI-inducing anti-HLA DR15 antibody-positive serum. In conclusion, anti-HLA DR alloantibodies may be implicated in LME dysfunction that leads to TRALI, in a monocyte-dependent manner.

Topics: Blood Grouping and Crossmatching; Cell Adhesion Molecules; Cells, Cultured; Coculture Techniques; Endothelial Cells; Female; Histocompatibility Antigens Class II; Histocompatibility Testing; HLA-DR Antigens; HLA-DR Serological Subtypes; Humans; Isoantibodies; Leukotriene B4; Lymphocyte Function-Associated Antigen-1; Monocytes; Respiratory Distress Syndrome; Transfusion Reaction; Vascular Cell Adhesion Molecule-1

Antibodies to human leucocyte antigens (HLA) and human polymorphonuclear neutrophil (PMN) antigens are considered etiologic agents of transfusion-related acute lung injury (TRALI). The aim of this study was to clarify the role of anti-HLA DR antibodies in the pathophysiology of TRALI and the ability of purified soluble HLA DR (psHLA DR) to inhibit the release of cytokines in an in vitro model.. A coculture of human pulmonary microvascular endothelial cells (HMVEC) and monocytes in the presence of serum containing anti-HLA DR alloantibodies previously associated with cases of TRALI was used as an in vitro TRALI model. The release of leukotriene B(4) (LTB(4)) and tumour necrosis factor-alpha (TNF-alpha), the apoptosis of HMVECs were measured.. The release of LTB(4) and TNF-alpha and apoptosis of HMVECs were observed in the model. The addition of psHLA DR markedly reduced the release of LTB(4) and TNF-alpha and inhibited apoptosis of HMVECs.. These results support the critical role of anti-HLA DR alloantibodies in the pathogenesis of TRALI and suggest that the soluble HLA DR could inhibit TRALI development caused by anti-HLA DR alloantibodies.

Topics: Antibody Formation; Apoptosis; Cells, Cultured; Endothelial Cells; HLA-DR Antigens; Humans; Isoantibodies; Leukotriene B4; Lung; Models, Biological; Monocytes; Neutrophils; Respiratory Distress Syndrome; Tumor Necrosis Factor-alpha

To study the major eicosanoids implicated in the pathophysiology of acute respiratory distress syndrome (ARDS) in order to estimate their relative prognostic values.. We conducted a prospective study in a consecutive series of patients with ARDS admitted to a university hospital intensive care unit. We measured the plasma concentrations of 3 inflammatory mediators (thromboxane B(2), 6-keto prostaglandin F(1alpha), and leukotriene B(4)) in peripheral arterial and mixed venous plasma samples.. We studied 16 patients with ARDS, who had a mean alpha SD baseline ratio of P(aO(2)) to fraction of inspired oxygen (P(aO(2))/F(IO(2))) of 147 +/- 37 mm Hg and a mean +/- SD baseline lung injury score of 2.9 +/- 0.37. The plasma concentrations of thromboxane B(2), 6-keto prostaglandin F(1alpha), and leukotriene B(4) were greater than the general-population reference levels in both arterial and mixed venous plasma, but only leukotriene B(4) was higher in arterial plasma than in mixed venous plasma (401 +/- 297 pg/mL vs 316 +/- 206 pg/mL, p = 0.04). When we correlated the eicosanoid concentrations with specific indicators of clinical severity, we found correlations only between the baseline P((aO2))/F(IO(2)) and the arterial thromboxane B(2) level (r = -0.57, p = 0.02), the arterial leukotriene B(4) level (r = -0.59, p = 0.01), and the transpulmonary gradient of leukotriene B(4) level (r = -0.59, p = 0.01). We also found a correlation between the transpulmonary gradient of leukotriene B(4) and the lung injury score (r = 0.51, p = 0.04). The thromboxane B(2) concentration in arterial plasma and the leukotriene B(4) concentration in both arterial and mixed venous plasma were the only baseline plasma eicosanoid concentrations that predicted significant differences in outcome. When looking at the transpulmonary gradient of the eicosanoids studied, we found that only the gradient of leukotriene B(4) showed significant differences of clinical interest. Among survivors we observed practically no gradient (-4.9%), whereas among nonsurvivors we found a substantial positive gradient of 41.6% for the elevated arterial (post-pulmonary) values, compared with the pulmonary-artery (pre-pulmonary) values, and this difference was statistically significant (p = 0.02).. The pro-inflammatory eicosanoid leukotriene B(4) showed the best correlation with lung-injury severity and outcome in patients with ARDS.

Topics: Adult; Aged; Female; Humans; Leukotriene B4; Male; Middle Aged; Prospective Studies; Respiratory Distress Syndrome; Spain

To investigate whether the release of lipid mediators is suppressed in rats with experimentally induced acute lung injury managed with partial liquid ventilation (PLV) using FC-77.. Prospective, randomized controlled study.. Research laboratory in a university.. Male Sprague-Dawley rats.. After tracheostomy was performed under general anesthesia, lung injury was induced by intratracheal instillation of HCl. The PLV group was then subjected to conventional gas ventilation for 30 mins, followed by PLV using FC-77. The control group was subjected to conventional gas ventilation throughout the study period.. In the PLV group the following results were obtained: a) impaired oxygenation was markedly improved; b) the increase in the serum levels of lipid mediators such as leukotriene B4, thromboxane A2, and 6-keto-prostaglandin F1alpha was suppressed; and c) the increase in the concentrations of leukotriene B4, thromboxane A2, and 6-keto-prostaglandin F1alpha in the total lung homogenate at 180 mins after lung injury was also suppressed.. This study indicates that PLV using FC-77 suppresses the release of lipid mediators in our rat model of acute lung injury. However, further investigation is needed to clarify the precise mechanism of this effect.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acids; Fluorocarbons; Hydrochloric Acid; Inflammation Mediators; Leukotriene B4; Liquid Ventilation; Male; Models, Animal; Rats; Rats, Sprague-Dawley; Respiratory Distress Syndrome; Thromboxane A2

This study evaluated whether prostacyclin is a necessary mediator of inflammation in graded bacteremia or is sufficient alone in pathophysiologic concentrations to cause the pulmonary derangement of bacteremic shock.. Experimental.. Laboratory.. Twenty-three anesthetized adult swine. INTERVENSIONS: Swine were studied in four groups for 4 hrs: a) an anesthesia control group (n = 6); b) a septic control group (n = 6), in which 1010/mL Aeromonas hydrophila was infused intravenously at 0.2 mL.kg-1.hr-1 and increased to 4.0 mL.kg-1.hr-1 over 3 hrs; c) a prostacyclin infusion group (n = 6), which received prostacyclin infusion to match septic control plasma concentrationsclm without bacteremia; and d) an antiprostacyclin antibody group (n = 5), which received continuous Aeromonas hydrophila infusion plus antiprostacyclin antibody infusion.. Pulmonary hemodynamics, arterial blood gases, and plasma concentrations of arachidonate metabolites were measured hourly over a 4-hr period. In the septic control group and antiprostacyclin antibody group, elevated pulmonary vascular resistance index and pulmonary artery pressure with decreased Pao2, as well as lower pH, were documented after 1 and 3 hrs of graded bacteremia compared with the anesthesia control group and prostacyclin infusion group (p <.05). Thromboxane B2 concentration increased significantly in all groups during septic shock. In the antiprostacyclin antibody group, leukotriene B4 increased immediately after starting antiprostacyclin antibody infusion and reached significance at 3 hrs compared with the septic control group (p <.05). The prostacyclin infusion group had consistently lower concentrations of leukotrienes C4, D4, and E4 than all other groups.. Prostacyclin does not mediate blood gas changes, alterations of pulmonary hemodynamics, or platelet abnormalities in porcine septic shock, because antiprostacyclin antibody infusion did not change the pulmonary hypertension and hypoxemia, and infusion of prostacyclin to pathophysiologic blood concentrations did not reproduce such changes. Antiprostacyclin blockade during bacteremia significantly increased concentrations of leukotrienes C4, D4, and E4 and leukotriene B4, whereas prostacyclin infusion suppressed concentrations of leukotrienes C4, D4, and E4, suggesting that endogenous prostacyclin may blunt leukotriene release.

Topics: 6-Ketoprostaglandin F1 alpha; Analysis of Variance; Animals; Antihypertensive Agents; Bacteremia; Epoprostenol; Gram-Negative Bacterial Infections; Hemodynamics; Hypertension, Pulmonary; Leukotriene B4; Lung Diseases; Matched-Pair Analysis; Pulmonary Gas Exchange; Respiratory Distress Syndrome; Shock, Septic; SRS-A; Swine; Thromboxane B2

Topics: Animals; Biomarkers; Disease Models, Animal; Humans; Leukotriene B4; Prognosis; Respiratory Distress Syndrome

Recently, eicosapentaenoic acid (EPA) was found to have an anti-inflammatory effect attributable to diminished synthesis of arachidonic acid metabolites that initiate acute lung injury. We evaluated the ability of dietary EPA supplementation to prevent endotoxin-induced acute lung injury in rats.. Rats fed a standard diet were divided randomly into two groups: for 2 weeks one group additionally was fed 1000 mg/kg/day of EPA ethyl ester emulsion (EPA rats), while in the other group the diet was supplemented with vehicle alone (control rats). Fatty acid components of alveolar macrophages (AM) were measured, as well as leukotriene (LT) B(4) and LTB(5) production by AM exposed in vitro to calcium ionophore A23187. Plasma concentrations of thromboxane (Tx) B(2), a stable metabolite of TxA(2), were examined 1 h after inducing lung injury with endotoxin (2 mg/kg iv). At 6 h, wet/dry (W/D) weight ratios were calculated for the lungs to assess pulmonary edema, and neutrophils were counted in pulmonary parenchyma and peripheral blood.. Arachidonic acid content and LTB(4) generation in AM were significantly lower in EPA rats than in controls; conversely, EPA content and LTB(5) generation in AM were significantly higher in the EPA group. Neutrophil counts in lung parenchyma and peripheral blood did not differ between groups, but W/D and plasma TxB(2) concentrations were significantly lower in EPA rats.. EPA supplementation depressed arachidonic acid content and LTB(4) generation in AM and plasma TxB(2) in our model, leading to decreased pulmonary edema.

Topics: Animals; Arachidonic Acid; Eicosapentaenoic Acid; Endotoxemia; Fatty Acids; Leukotriene B4; Male; Neutrophils; Pulmonary Edema; Rats; Rats, Wistar; Respiratory Distress Syndrome; Thromboxane B2

Group IIA secretory phospholipase A(2) (sPLA(2)) has been implicated in a variety of inflammatory diseases including acute lung injury (ALI); however, the role of sPLA(2) in this disorder remains unclear. The aim of the present investigation was to examine the role of this enzyme in a model of ALI induced by oleic acid (OA) in rabbits by testing human group IIA phospholipase A(2) (PLA(2)) inhibitor, S-5920/LY315920Na. Experimental groups consisted of a saline control group (n = 8), an OA control group (n = 10) infused intravenously with OA (0.1 ml/kg/h for 2 h), and three groups given OA + S-5920/LY315920Na (three different doses, n = 8, respectively). Infusion of OA provoked pulmonary hemorrhage and edema formation, protein leakage, and massive neutrophil infiltration, resulting in severe hypoxemia and impaired lung compliance. PLA(2) activity was detected in the bronchoalveolar lavage fluid (BALF), but not plasma, which correlated well with severity of lung injury in this model. Pretreatment with S-5920/LY315920Na diminished the OA-induced PLA(2) activity in the BALF and dose-dependently attenuated the previously described lung injury induced by OA, accompanied by protection against lung surfactant degradation and production of thromboxane A(2) (TXA(2)) and leukotriene B(4) (LTB(4)). S-5920/LY315920Na also inhibited the OA-induced production of interleukin-8 (IL-8), both in plasma and BALF. Thus, sPLA(2) appears to play a key role in OA-induced lung injury, suggesting that the group IIA PLA(2) inhibitor may be a promising agent for patients with acute respiratory distress syndrome (ARDS).

Topics: Acetates; Animals; Bronchoalveolar Lavage Fluid; Capillary Permeability; Dose-Response Relationship, Drug; Enzyme Inhibitors; Extravascular Lung Water; Group II Phospholipases A2; Indoles; Interleukin-8; Keto Acids; Leukotriene B4; Lung; Lung Compliance; Male; Oleic Acid; Oxygen; Phospholipases A; Phospholipids; Pulmonary Edema; Rabbits; Respiratory Distress Syndrome; Thromboxane A2

We have studied prospectively the clinical course and serum concentrations of thromboxane B2 (TxB2) and leukotriene B4 (LTB4) in patients developing adult respiratory distress syndrome (ARDS) after oesophagectomy. The clinical course was assessed according to a validated ARDS score, and intra- and postoperative measurements of TxB2 and LTB4 in pre- and post-pulmonary blood were performed in 18 patients undergoing oesophagectomy for oesophageal carcinoma and 11 control patients undergoing thoracotomy and pulmonary resection. Six of 18 patients undergoing oesophagectomy, but no control patient, developed ARDS. The ARDS score was highest on day 8 after operation. Only patients with ARDS had a significant postoperative increase in post-pulmonary, but not pre-pulmonary, TxB2 concentrations (P < 0.05 vs patients without ARDS). This study provides evidence that TxA2, originating from the lungs, was associated with the development of ARDS after oesophageal resection. In view of the high incidence of ARDS after oesophagectomy (10-30%), prophylactic treatment of patients undergoing oesophageal resection with clinically applicable thromboxane synthetase inhibitors may be warranted.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Esophageal Neoplasms; Esophagectomy; Female; Humans; Leukotriene B4; Male; Middle Aged; Postoperative Period; Prospective Studies; Respiratory Distress Syndrome; Risk Factors; Thromboxane B2

A 75-year-old man was admitted to the hospital due to acute onset of a dry cough and dyspnea on exertion. Arterial blood gas analysis showed hypoxemia (PaO2 = 63 Torr) on room air. Chest radiography and computed tomography showed diffuse bilateral infiltrates. Adult respiratory distress syndrome was diagnosed from the findings described above and from the lack of evidence of left heart failure. Diffuse alveolar damage was confirmed at autopsy. During the course of his illness, the patient underwent bronchoalveolar lavage five times. The recovered fluid had high concentrations of interleukin-8 (IL-8), with a maximum of 6260 pg/ml and a minimum of 190 pg/ml, and these values correlated with the number of polymorphonuclear cells in the fluid. Levels of leukotriene B4, another chemotactic factor for PMN, in the lavage fluid were not high. We conclude that IL-8 was a major chemoattractant for PMN in the alveoli of this patient.

Topics: Aged; Bronchoalveolar Lavage Fluid; Fatal Outcome; Humans; Interleukin-8; Leukocyte Count; Leukotriene B4; Male; Neutrophils; Pulmonary Alveoli; Respiratory Distress Syndrome

To evaluate the clinical usefulness of steroids for septic lung injury, we investigated the effects of methylprednisolone (MP) on this disorder using an experimental rat model of cecal ligation and puncture (CLP). While 92% of the rats that underwent CLP (CLP rats) died within 30 h, those given high-dose MP (30 mg/kg) just after the operation (CLP + MP rats) survived for a significantly longer period (p < 0.01). Concentrations of endotoxin (ET) in arterial blood were significantly higher in the CLP + MP rats than in the CLP rats, while those in the bronchoalveolar lavage fluid (BALF) were significantly lower. Alveolar macrophages (AM) obtained from the CLP rats (CLP-AM) generated more O2-than did AM from sham-operated rats (sham-AM) following stimulation. However, the administration of MP did not reduce the upregulated generation of O2-by CLP-AM. While CLP-AM produced less leukotriene (LT)B4 than did sham-AM following stimulation with A23187, the administration of MP further reduced LTB4 production. When AM were cultured with [3H]arachidonic acid (3H-AA), the uptake of the isotope and the 3H release were significantly less in CLP-AM than in sham-AM. The administration of MP did not cause recoveries in the uptake and release of 3H-AA by CLP-AM. Although the survival time of CLP rats was significantly prolonged and the translocation of ET into BALF was reduced by steroid administration, the steroid effects were not explained by those on altered AM function. The upregulated generation of O2- and reduced LTB4 production from CLP-AM were not reversed by the treatment of this drug.

Topics: Animals; Arachidonic Acid; Bronchoalveolar Lavage Fluid; Endotoxins; Leukotriene B4; Leukotriene C4; Lipoxygenase; Lung; Macrophages, Alveolar; Male; Methylprednisolone; Rats; Rats, Wistar; Respiratory Distress Syndrome; Sepsis; Steroids

Gc-globulin has been found in bronchoalveolar lavage fluid in patients with chronic obstructive pulmonary disease (COPD) and adult respiratory distress syndrome (ARDS) and has been shown to enhance neutrophil chemotaxis to C5-derived peptides in vitro. We proposed that Gc-globulin may enhance the inflammatory response in lungs by influencing monocyte chemotaxis to C5-derived peptides as it does with neutrophils. Monocyte chemotaxis was measured in blind well chambers by a leading-front technique. Purified human Gc-globulin had no intrinsic chemotactic activity for monocytes at concentrations ranging from 1 fM to 1 microM. However, Gc-globulin, at concentrations as low as 10 pM, increased monocyte chemotaxis over 10-fold in a concentration-dependent fashion when added to non-chemotactic doses of C5a (0.1 nM) and C5a des Arg (0.5 nM). The chemotaxis-enhancing effect of Gc-globulin was specific for C5-derived peptides, as Gc-globulin did not enhance monocyte chemotaxis to other chemoattractants such as leukotriene B4 or formyl-Met-Leu-Phe. The enhancement of monocyte chemotaxis to C5-derived peptides by Gc-globulin was not a nonspecific effect of anionic proteins, as other serum proteins of similar size and charge did not enhance monocyte chemotaxis to C5a des Arg. These results indicate that Gc-globulin enhances the monocyte response to C5-derived peptides and, together with previous work, indicates that its presence in the airways of patients with COPD and ARDS may up-regulate the monocyte inflammatory response in the lungs.

Topics: Antibodies; Cells, Cultured; Chemotactic Factors; Chemotaxis; Complement C5a; Complement C5a, des-Arginine; Dose-Response Relationship, Drug; Humans; Leukotriene B4; Lung Diseases, Obstructive; Monocytes; N-Formylmethionine Leucyl-Phenylalanine; Respiratory Distress Syndrome; Vitamin D-Binding Protein

To evaluate the hypothesis that treatment with LY255283, a novel leukotriene B4-receptor antagonist, is beneficial in an animal model of the adult respiratory distress syndrome induced by endotoxin.. Prospective, randomized, controlled trial.. Laboratory at a large university medical center.. Twenty-five, immature, random-bred swine.. Four groups of pigs were studied: the LPS group of animals (n = 6) were infused with Escherichia coli lipopolysaccharide (strain 0111:B4, 250 micrograms/kg) from 0 to 60 mins; the LPS + 255283 group of animals (n = 6) were infused with lipopolysaccharide as above, but were also treated with LY255283 (30 mg/kg, then 10 mg/kg/hr), beginning at -15 mins; the 255283 group of animals (n = 6) were infused with the same dose of LY255283, but were not challenged with lipopolysaccharide; and the RL control group of subjects (n = 7) received only the lactated Ringer's solution vehicle. Beginning at 30 mins, all groups were infused with dextran-70 solution as needed to maintain cardiac output at 90% to 110% of baseline value.. Treatment with LY255283 significantly (p < .05) ameliorated lipopolysaccharide-induced systemic arterial hypotension, pulmonary arterial hypertension, and arterial hypoxemia. Treatment with this drug also abrogated lipopolysaccharide-induced increases in pulmonary extravascular water content and bronchoalveolar lavage fluid protein concentration.. These data suggest that leukotriene B4 may be an important mediator of acute lung injury in this porcine model of septic shock and acute lung injury. Further studies to assess the specificity of LY255283 as a leukotriene B4 antagonist are necessary in order to exclude the possibility that the beneficial effects of this compound are due to pharmacologic actions other than the blockade of LTB4 receptors.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Drug Evaluation, Preclinical; Escherichia coli Infections; Extravascular Lung Water; Hemodynamics; Leukotriene B4; Male; Peroxidase; Proteins; Random Allocation; Respiratory Distress Syndrome; Shock, Septic; Swine; Tetrazoles; Thromboxane B2

Acute inflammatory lung injury (adult respiratory distress syndrome [ARDS]) causes significant morbidity and death in surgical patients. The alveolar macrophage elaborates proinflammatory mediators implicated in acute pulmonary injury. The macrophage products, leukotriene B4 (LTB4), thromboxane A2 (TXA2), and procoagulant activity (PCA), initiate inflammatory cascades that lead to microvascular thrombosis and neutrophil infiltration, two common features of ARDS. One potential method of preventing or attenuating lung injury is to inhibit the production of inflammatory mediators. Preliminary studies indicate that ketoconazole, known primarily for its antifungal properties, may prevent ARDS.. LTB4, TXB2, and PCA production by rabbit alveolar macrophages was measured after treatment with endotoxin or Ca ionophore and ketoconazole or selective 5-lipoxygenase (MK 886) and thromboxane synthetase (imidazole) inhibitors.. Ketoconazole significantly inhibits alveolar macrophage production of LTB4, TXB2, and PCA. Ketoconazole inhibition of PCA is independent of effects on 5-lipoxygenase and thromboxane synthetase.. Ketoconazole inhibition of alveolar macrophage proinflammatory mediators may be of benefit in preventing ARDS by minimizing neutrophil infiltration and microvascular thrombosis. Inhibition of 5-lipoxygenase and thromboxane synthetase, without affecting cyclooxygenase, may offer a selective advantage by allowing production of other homeostatic eicosanoids.

Topics: Animals; Blood Coagulation Factors; Ketoconazole; Leukotriene B4; Macrophages, Alveolar; Rabbits; Respiratory Distress Syndrome; Thromboxane A2

We investigated the pathogenesis of lung injury in sepsis (septic adult respiratory distress syndrome) by focusing on the functional changes of alveolar macrophages (AMs). Sepsis was induced in male WK rats by cecal ligation and puncture. Histological examination of the lungs from this experimental model revealed edematous change at 24 h after the surgery. The protein and endotoxin concentrations in the bronchoalveolar lavage fluid (BALF) increased with time after the surgery. The time course studies of AM function after surgery indicated that AMs from septic rats were activated by endotoxins. Specifically, this was suggested by the finding that AM adherence to and spreading on a plastic dish had increased. On stimulation, these AMs enhanced generation of superoxide anions and increased release of lysosomal enzymes, such as beta-glucuronidase. On the other hand, AMs in sepsis generated much smaller amounts of arachidonate lipoxygenase metabolites, such as leukotriene B4 (LTB4) and 12- and 5-hydroxyeicosatetraenoic acids (HETEs), on stimulation than did AMs from sham rats or untreated rats. However, the concentrations of immunoreactive LTC4 in the BALF of septic rats seemed to be higher than in untreated rats. It is suggested that the AMs of septic rats released lipoxygenase metabolites in alveoli and that these AMs could not be stimulated in vitro. These functional changes in the AMs of septic rats progressed along with the sepsis. These results implicate AMs in the development and progression of septic lung injury by releasing superoxide anions, beta-glucuronidase, and arachidonate metabolites. Furthermore, we speculate that reduced production of LTB4 by septic AMs may increase host susceptibility to severe pulmonary infection during septic ARDS.

Topics: Animals; Bronchoalveolar Lavage Fluid; Endotoxins; Glucuronidase; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Lung; Macrophages, Alveolar; Male; Rats; Rats, Inbred Strains; Respiratory Distress Syndrome; Sepsis; Superoxides

Leukotriene (LT) generation has been implicated in the pathogenesis of the acute respiratory distress syndrome, ARDS. In the present study, we analysed broncho-alveolar lavage fluids of patients on mechanical ventilation because of ARDS (17 samples taken from 9 patients) or because of cardiogenic edema (8 samples taken from 6 patients) and of healthy volunteers (10 samples from different donors). LTs were separated as methylated and non-methylated compounds using different HPLC procedures, and were identified by chromatographic mobility, on-line UV-spectrum analysis and post HPLC immunoreactivity. In the lavage samples of the healthy volunteers and the patients with cardiogenic edema, no LTs were detected by these techniques (detection limit congruent to 0.1-0.2 ng/ml lavage fluid). By contrast, in 15 out of 17 samples from patients with ARDS LTB4 or its metabolites 20-OH-LTB4 and 20-COOH-LTB4 were detected. The endproduct of omega-oxidation, 20-COOH-LTB4, represented the quantitatively predominant compound, detected in the range of 0.3-2.6 ng/ml perfusate. We conclude that the chemotactic agent LTB4 may be involved in the amplification of inflammatory events encountered in ARDS, and that the oxidized metabolites of LTB4 are particularly suitable for monitoring lung leukotriene generation under conditions of neutrophil efflux and oxidative stress.

Topics: Adult; Aged; Bronchoalveolar Lavage Fluid; Female; Heart Diseases; Humans; Leukotriene B4; Male; Middle Aged; Neutrophils; Oxidation-Reduction; Phospholipids; Proteins; Pulmonary Edema; Respiration, Artificial; Respiratory Distress Syndrome; Spectrum Analysis

Topics: Bronchoalveolar Lavage Fluid; Humans; Leukotriene B4; Research Design; Respiratory Distress Syndrome

Leukotriene B4, a potent neutrophil chemotactic factor, is also made by the neutrophil. Neutrophil function was studied in 12 patients at risk for the development of adult respiratory distress syndrome (ARDS) after admission to the surgical intensive care unit (ICU) to test the hypothesis that increased generation by the neutrophil generation of this mediator precedes the development of pulmonary failure. Peripheral blood neutrophils were tested for chemotaxis to f-met-leu-phe (fMLP) and leukotriene B4 (LTB4) and the generation of LTB4. Plasma was collected simultaneously for assay of C3a desArg levels. Five patients had ARDS a mean of 2.2 +/- 0.25 days after admission to the ICU. Neutrophil generation of LTB4 was significantly enhanced on ICU day 1 in these patients as compared with patients at risk for ARDS but not developing the syndrome (119.4 +/- 6.1 versus 101.0 +/- 5.1, per cent control, p less than 0.05). Chemotaxis to fMLP and LTB4 was significantly reduced in both groups of patients. However, neutrophil chemotaxis improved in patients who did not have pulmonary failure during the time in the ICU, whereas neutrophil chemotactic responsiveness worsened in patients who did have pulmonary failure. Plasma C3a desArg levels were significantly elevated over normal laboratory values on ICU day 1 in the ARDS patients (317.2 +/- 74.0 versus 132.0 +/- 16.0 milligrams per milliliter, p less than 0.01). These data indicate that LTB4 production by the neutrophil occurs concomitantly with complement activation, is a predictor of subsequent ARDS and may play a significant role in the development of pulmonary failure in critically ill surgical patients.

Topics: Chemotaxis, Leukocyte; Complement Activation; Complement C3a; Critical Care; Humans; Lactoferrin; Leukotriene B4; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Respiratory Distress Syndrome; Surgical Procedures, Operative

Seven patients with the adult respiratory distress syndrome (ARDS) were studied. As a control group we used 6 surgical patients who underwent minor surgical operation (inguinal hernia). For both groups the same sample collection and analysis was used. The presence of leuktorienes (LTs) B4 and C4 and of their isomers 11-trans LTC4 and delta 6-trans-12-epi LTB4 was determined in arterial, mixed venous blood and in bronchoalveolar lavage (BAL) fluid. The samples, analysed by reverse phase high performance liquid chromatography (RP-HPLC), showed a similar chromatographic picture among ARDS patients, while the control group showed no detectable amounts of LTs in BAL or blood. The distribution of these arachidonic acid metabolites in mixed venous blood, arterial blood and BAL seems to suggest pulmonary metabolism and/or inactivation. It is suggested that these mediators act as humoral factors in pathogenesis of the ARDS.

Topics: Adult; Bronchoalveolar Lavage Fluid; Female; Humans; Leukotriene B4; Male; Middle Aged; Respiratory Distress Syndrome; SRS-A

Thirty multiply injured blunt-trauma patients at high risk for development of ARDS (multisystem trauma including more than one organ or extremity, Injury Severity Score of 26 or more, hypotension and need for 1500 mL or more blood within the first hour after admission, and PaO2 less than or equal to 70 torr) were studied sequentially with blood and physiologic evaluations beginning immediately after injury and every eight hours for eight days, or until death, to study the evolution of the ARDS process. Mixed venous blood samples were obtained for eicosanoids PGE2, PGF2 alpha, thromboxane B2, PGI2 (6-KetoPGF1 alpha) and leukotriene B4 (LTB4). Platelet (PLAT), and neutrophil (WBC) counts were also done and plasma elastase was measured. At 7:00 AM each day patient neutrophils were obtained for a study of zymosan-activated superoxide production using a chemiluminescence assay. These data were correlated with physiologic measurements of the Respiratory Index (RI), per cent pulmonary shunt (QS/QT), and respiratory compliance measures. Seven patients developed a fulminant post-traumatic ARDS syndrome within 96 hours after injury. Twelve patients without ARDS developed sepsis (TS) four or more days after injury, and 11 had uncomplicated postinjury courses (TR). Compared to both TR and TS, ARDS had a significant (p less than 0.01) rise in neutrophil superoxide production beginning on day 2 through day 4 after injury. This was preceded by rises in PGE2 and LTB4, which were significantly correlated with subsequent falls in PLAT and WBC and rises in TXB2, PGF1, and superoxide production and followed by increases in RI, QS/QT, and a fall in compliance. The significant difference in the pattern and sequence of events in ARDS compared to TR and TS patients suggests that in ARDS the earliest event may be related to peripheral release of PGE2 and LTB4 due to platelet activation and lung sequestration with release of PGF2 alpha, and by aggregation and leukocyte adherence with release of elastase. However, fulminant ARDS mortality appears to be related to the subsequent amplification of the LTB4 leukocyte activation with superoxide production that does not achieve significance before the second day after injury and rises to a maximum by day 4 after injury. These data suggest that post-trauma ARDS follows a different evolutionary pattern than that reported in animal models and is also different from that seen in human TS or TR patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Biomechanical Phenomena; Blood Platelets; Cell Communication; Humans; Infections; Leukotriene B4; Neutrophils; Prostaglandins; Respiratory Distress Syndrome; Statistics as Topic; Superoxides; Thromboxane B2; Time Factors; Wounds and Injuries

We investigated the cause of the reduced leukotriene B4 (LTB4) production seen in neutrophils from patients with established adult respiratory distress syndrome compared with control neutrophils. Lymphocytes/monocytes from controls were found to synergistically enhance the amount of LTB4 produced when incubated with neutrophils. This synergistic effect was not seen in cells from patients with adult respiratory distress syndrome. Fatty-acid analysis of neutrophils from patients with adult respiratory distress syndrome and controls showed remarkable similarity in all quantities of fatty acids measured except for arachidonic acid, where there was a 22% reduction in patients' cells compared with controls. Assay of the rate of generation of LTB4 and its degradation product, 20-hydroxy LTB4, revealed that reduced LTB4 generation in patients' neutrophils was not due to increased degradation of LTB4 by hydroxylase enzymes. When the amount of LTB4 being generated per milliliter of whole blood was analyzed in the patients with adult respiratory distress syndrome and compared with controls, it was determined that the potential to generate LTB4 in patients in the intensive care unit was three to five times greater than in controls.

Topics: Fatty Acids; Female; Humans; Leukotriene B4; Lipid Metabolism; Lymphocytes; Male; Middle Aged; Monocytes; Neutrophils; Respiratory Distress Syndrome

We hypothesized that leukotriene B4 (LTB4) might be produced during endotoxemia in pigs and, if so, might play a role in the pathophysiology of acute respiratory failure. Escherichia coli endotoxin (055-B5) was infused intravenously into anesthetized pigs at 5 micrograms/kg the 1st h, followed by 2 micrograms.kg-1.h-1 for 3 h. Endotoxemic pigs were treated with dexamethasone (DEX, iv) 18 h (5 mg/kg) and 1 h (5 mg/kg) before onset of endotoxemia. During phases I (i.e., 0-2 h) and II (i.e., 2-4 h), endotoxin decreased cardiac index, caused granulocytopenia, and increased mean pulmonary arterial pressure, pulmonary vascular resistance, alveolar-arterial O2 gradient, and hematocrit. During phase II, plasma LTB4 levels were increased (as determined by radioimmunoassay, reverse-phase high-performance liquid chromatography, and ultraviolet spectroscopy). Endotoxin increased the levels of LTB4 and albumin in bronchoalveolar lavage fluid (BALF). DEX blocked or greatly attenuated the endotoxin-induced hemodynamic abnormalities and blocked the increases in plasma and BALF LTB4 levels. We conclude that LTB4 is produced during porcine endotoxemia and could possibly play a role in the pathophysiology of endotoxin-induced lung injury in anesthetized pigs.

Topics: Animals; Dexamethasone; Endotoxins; Escherichia coli; Leukotriene B4; Respiratory Distress Syndrome; Swine

We studied the effects of a 5-lipoxygenase inhibitor, L-651,192, on the pulmonary dysfunction caused by endotoxemia in chronically instrumented unanesthetized sheep. The efficacy and selectivity of L-651,392 were tested by measuring in vivo production of leukotriene B4 (LTB4) and cyclooxygenase products of arachidonic acid after endotoxemia before and after pretreatment with L-651,392 and ex vivo from granulocytes and whole blood stimulated with calcium ionophore from sheep before and 24 h after pretreatment with L-651,392. A novel assay for LTB4 by high-performance liquid chromatography/gas chromatography/mass spectrometry techniques was developed as a measure of 5-lipoxygenase metabolism of arachidonic acid. L-651,392 proved to be an effective in vivo 5-lipoxygenase inhibitor in sheep. L-651,392 blocked the increase in LTB4 observed in lung lymph after endotoxemia in vivo in sheep as well as inhibited by 80% the ex vivo production of LTB4 by granulocytes removed from sheep treated 24 h earlier with L-651,392. Although L-651,392 blocked the increase in cyclooxygenase products of arachidonic acid observed in lung lymph after endotoxemia in vivo in sheep, the drug probably did not function directly as a cyclooxygenase inhibitor. L-651,392 did not attenuate the ex vivo production of thromboxane B2 by whole blood from sheep treated 24 h earlier with the drug. L-651,392 attenuated the alterations in pulmonary hemodynamics, lung mechanics, oxygenation, and lung fluid and solute exchange observed after endotoxemia in sheep. We speculate that 5-lipoxygenase products are a major stimulus for cyclooxygenase metabolism of arachidonic acid after endotoxemia in sheep.

Topics: Animals; Arachidonate 5-Lipoxygenase; Arachidonate Lipoxygenases; Arachidonic Acid; Arachidonic Acids; Endotoxins; Female; Granulocytes; In Vitro Techniques; Leukotriene B4; Lipoxygenase Inhibitors; Lung; Lymph; Male; Phenothiazines; Pulmonary Circulation; Respiratory Distress Syndrome; Sheep; Toxemia

The sulfidopeptide leukotrienes (LT) C4 and D4 have been reported to promote the formation of pulmonary edema when administered into the pulmonary circulation of laboratory animals. As a first step in the evaluation of the hypothesis that these leukotrienes participate in the edema formation of the adult respiratory distress syndrome (ARDS), we investigated whether LTC4 and LTD4 were present in the bronchoalveolar lavage (BAL) fluid of patients with ARDS compared to nonsmoker control subjects and to patients with acute respiratory failure exhibiting no radiographic evidence of widespread pulmonary infiltrates but having a clinical predisposition for developing ARDS, i.e., the "at risk" group. Bronchoscopic lavage was performed with sterile 0.9% NaCl on 32 control subjects, nine patients with ARDS, and nine patients "at risk" for ARDS. Leukotrienes were measured in BAL fluid by radioimmunoassay after methanol extraction and HPLC purification of a 20-ml aliquot of the BAL sample. LTC4 and LTD4 (mean +/- SE) increased from 1.1 +/- 0.2 and 1.2 +/- 0.5 ng/lavage in the BAL fluid of control subjects to 6.3 +/- 2.3 and 20.1 +/- 5.9 ng/lavage in patients "at risk" for ARDS and to 12.5 +/- 3.0 and 30.5 +/- 7.8 ng/lavage in patients with ARDS, respectively. The sulfidopeptide LTs correlated with BAL fluid protein content. These results suggest that increased amounts of LTs in BAL fluid are a general finding in patients with ARDS and those "at risk" for ARDS.

Topics: Acute Disease; Bronchoalveolar Lavage Fluid; Humans; Leukotriene B4; Pulmonary Edema; Radioimmunoassay; Respiratory Distress Syndrome; Respiratory Insufficiency; Risk Factors; SRS-A

Studies were conducted in isolated, buffer-perfused rat lungs to determine if prostaglandin (PG) E1 attenuated pulmonary edema provoked by hydrogen peroxide (H2O2). When lungs were challenged by 60 min of perfusion with H2O2 (generated by the reaction between glucose and glucose oxidase) the wet weight-to-dry weight ratio increased from control by 54%, indicating development of pulmonary edema. In contrast, lungs treated simultaneously with H2O2 plus PGE1 (1 microgram/min) failed to exhibit an elevated wet-to-dry weight ratio. H2O2-injured lungs demonstrated a modest 2 torr increase in pulmonary arterial perfusion pressure that was not influenced by simultaneous treatment with PGE1. Both radioimmunoassay (RIA) and high-performance liquid chromatographic (HPLC) analysis detected increased amounts of (5S)-5-hydroxy-6,8,11,14 eicosatetraenoic acid in the perfusion medium of H2O2-injured lungs (RIA, 48.0 +/- 14.7; HPLC, 54.8 +/- 13.5) relative to controls (RIA, 6.6 +/- 1.6; HPLC, 6.8 +/- 1.9), and simultaneous treatment with PGE1 tended to blunt this increase (RIA, 29.2 +/- 8.3; HPLC, 29.8 +/- 7.6). PGE1 abolished the increase in wet weight-to-dry weight ratio induced by exogenous leukotriene C4. Production of H2O2 by the glucose-glucose oxidase reaction was not influenced by PGE1. Taken together, these observations indicate that PGE1 attenuates H2O2-induced pulmonary edema formation in buffer-perfused rat lungs by mechanisms that may relate to inhibition of lung 5'-lipoxygenase activation and/or to inhibition of the injurious effects of endogenously produced lipoxygenase products.

Topics: Alprostadil; Animals; Glucose Oxidase; Hydrogen Peroxide; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Lung; Male; Neutrophils; Organ Size; Perfusion; Pulmonary Edema; Rats; Respiratory Distress Syndrome

Topics: Calcimycin; Chromatography, High Pressure Liquid; Granulocytes; Humans; Leukotriene B4; Leukotriene E4; Pulmonary Alveoli; Radioimmunoassay; Respiratory Distress Syndrome; SRS-A; Therapeutic Irrigation

Topics: Aged; Cardiopulmonary Bypass; Exudates and Transudates; Humans; Leukotriene B4; Male; Pulmonary Edema; Respiratory Distress Syndrome; SRS-A