thromboxane-a2 and Lung-Diseases

Topics: Anaphylaxis; Animals; Asthma; Bronchi; Dinoprost; Dinoprostone; Dogs; Epoprostenol; Guinea Pigs; Humans; In Vitro Techniques; Lung; Lung Diseases; Models, Biological; Muscle, Smooth; Prostaglandin D2; Prostaglandins; Prostaglandins D; Prostaglandins E; Prostaglandins F; SRS-A; Thromboxane A2

Chronic non-specific pulmonary diseases are frequently followed by the development of inflammatory-degenerative and erosive-ulcerative processes in the mucous membrane of the stomach and duodenum. The literature date are presented on the frequency of combination of these conditions, the attempt is made to assess their link from the viewpoint of pathogenesis. Disturbances of respiratory lung function and hypoxia as well as non-respiratory metabolic functions of the pulmonary tissue are regarded as etiological factors of pathological processes in the gastro-duodenal area.

Topics: Adult; Angiotensins; Arachidonic Acid; Arachidonic Acids; Chronic Disease; Duodenal Diseases; Duodenitis; Female; Gastritis; Histamine; Humans; Hypoxia; Leukotriene B4; Lung; Lung Diseases; Male; Middle Aged; Peptic Ulcer; Prostaglandins; SRS-A; Stomach Diseases; Thromboxane A2

Topics: Animals; Humans; Lung; Lung Diseases; Prostaglandins; Thromboxane A2; Thromboxane B2

Pulmonary vascular disease, a serious complication of many congenital heart lesions, has three major components: increased muscularity of small pulmonary arteries; intimal hyperplasia, scarring and thrombosis; and reduced numbers of intraacinar arteries. The muscularity is due to increased stress on the vessel wall, and is reversible. The intimal changes may be due to endothelial damage, causing an imbalance between prostacyclin and thromboxane A2 production and leading to local platelet aggregation. This, in turn, may stimulate migration and division of myointimal cells, which thicken the intima and lead to scarring and thrombosis. Extensive intimal changes are probably irreversible, but the possibility of preventing them by use of agents that inhibit platelet aggregation needs to be considered. The mechanism of a decrease in numbers of intraacinar arteries is unexplained. The potential for growth of new vessels after corrective surgery of the cardiac defect is an important factor in restoring pulmonary vascular resistance to normal. Available evidence suggests that this growth potential is reduced after 2 years of age and argues for early surgical relief of pulmonary vascular stresses.

Topics: Animals; Child; Child, Preschool; Dogs; Ductus Arteriosus, Patent; Epoprostenol; Female; Heart Defects, Congenital; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Humans; Hyperplasia; Infant; Lung Diseases; Muscle, Smooth; Platelet Aggregation; Pregnancy; Pulmonary Artery; Tetralogy of Fallot; Thromboxane A2; Transposition of Great Vessels; Vascular Diseases; Vascular Resistance

Patients undergoing total hip replacement surgery who developed pulmonary dysfunction (PD) demonstrated evidence of complement activation and increased thromboxane A2 (TXA2) synthesis. In a double-blind study nifedipine (Adalat; Bayer-Miles) was shown to inhibit complement activation and TXA2 synthesis and thus appears to offer protection against PD.

Topics: Aged; Aged, 80 and over; beta-Thromboglobulin; Clinical Trials as Topic; Complement C5; Double-Blind Method; Epoprostenol; Female; Hip Joint; Hip Prosthesis; Humans; Intraoperative Period; Lung Diseases; Male; Nifedipine; Postoperative Complications; Postoperative Period; Random Allocation; Thromboxane A2

An intravenous injection of oleic acid into animals can produce a lung injury with hypoxaemia and pulmonary vascular hyper-permeability. Although oleic acid lung injury is used as a model of acute respiratory distress syndrome (ARDS), the precise mechanisms of the lung injury are still unclear. We have investigated whether thromboxane A(2) (TXA(2)) participated in the lung injury and have evaluated the efficacy of ozagrel, a TXA(2) synthase inhibitor, on the lung injury in guinea-pigs. Oleic acid injection increased the plasma level of TXB(2), a stable metabolite of TXA(2), and the time-course of plasma TXB(2) was similar to that of the decreased partial oxygen pressure of arterial blood (Pao(2)) induced with oleic acid. Ozagrel administered intravenously 30 min before oleic acid injection prevented the decrease in Pao(2) and pulmonary vascular hyper-permeability. It also prevented increases in lactate dehydrogenase activity, a measure of lung cell injury, TXB(2 )and its weight ratio to 6-keto prostaglandin F(1alpha) in bronchoalveolar lavage fluid. Although ozagrel administered simultaneously with oleic acid ameliorated the decrease in Pao(2), post treatment showed little effect. We suggest that TXA(2) participated in the oleic acid lung injury, as an "early phase" mediator, and rapidly-acting TXA(2) synthase inhibitors were effective in the prevention of acute lung injury.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Bronchoalveolar Lavage Fluid; Enzyme Inhibitors; Guinea Pigs; L-Lactate Dehydrogenase; Lung Diseases; Methacrylates; Oleic Acid; Thromboxane A2; Thromboxane B2; Vascular Resistance

To evaluate the in vivo production of prostacyclin and thromboxane A2 during the initial phase of experimental fat embolism as assessed, respectively, by determinations of urine 2,3-dinor-6-ketoprostaglandin F1alpha and 11-dehydrothromboxane B2 excretion.. Randomized, controlled trial.. Animal laboratory.. Twenty seven domestic pigs, weighing 24 to 31 kg.. All pigs were anesthetized and mechanically ventilated during the experiment. Eighteen pigs were subjected to an intracaval infusion of 10% allogeneic bone marrow suspension at a dose of 100 mg/kg over 5 mins. Nine pigs received only bone marrow suspension (fat embolism group). Nine pigs were given an intravenous bolus of aspirin (300 mg) 1 hr before the bone marrow suspension infusion. After the induction of fat embolism, intravenous aspirin was administered at a dose of 150 mg/hr for 2 hrs (aspirin-treated group). Nine pigs were infused with saline (control group).. In the fat embolism group, cardiac index decreased within 30 mins, while mean arterial pressure remained unchanged. Central venous pressure and pulmonary artery occlusion pressure remained relatively stable over time in the animals with fat embolism. Mean pulmonary arterial pressure and pulmonary vascular resistance increased immediately after the bone marrow suspension infusion from 23 +/- 0.8 (SEM) to 34 +/- 1.3 mm Hg and from 305 +/- 28 to 585 +/- 45 dyne x sec/cm5, respectively; these variables remained increased throughout the study period. Simultaneously, pulmonary shunt in the fat embolism group increased persistently from the baseline of 12.3 +/- 2.8%, and reached its maximum of 26.1 +/- 4.8% at the end of the experiment. Instant and gradual decreases in PaO2 (from 95 +/- 4 to 67 +/- 5 torr [12.6 +/- 0.5 to 8.9 +/- 0.7 kPa]), hemoglobin oxygen saturation (from 97.2 +/- 0.4 to 91.8 +/- 1.8%), and oxygen delivery (from 16.3 +/- 1.0 to 12.6 +/- 0.4 mL/min/kg) were observed in the fat embolism group. In the bone marrow suspension-infused animals, urine 2,3-dinor-6-ketoprostaglandin F1alpha excretion increased transiently from 451 +/- 63 up to 1466 +/- 499 pg/micromol creatinine, while urine 11-dehydrothromboxane B2 excretion increased transiently from 385 +/- 36 up to 2307 +/- 685 pg/micromol creatinine. In the aspirin-treated animals, urinary excretion of these prostanoid metabolites was reduced by 81% and 88%, respectively. The changes in mean pulmonary arterial pressure and PaO2 were ameliorated, and the alterations in pulmonary shunt and SaO2 were abolished in the animals with aspirin treatment.. Pulmonary hypertension, increased pulmonary vascular tone, and increased pulmonary shunt are hallmarks of the present fat embolism model. These hemodynamic responses may, at least partly, be related to the changed balance between prostacyclin and thromboxane A2 production.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aspirin; Cyclooxygenase Inhibitors; Embolism, Fat; Epoprostenol; Evaluation Studies as Topic; Hemodynamics; Hypertension, Pulmonary; Lung Diseases; Random Allocation; Swine; Thromboxane A2; Thromboxane B2

Both nitric oxide and arachidonic acid metabolites have been implicated in pathogenesis of septic shock. We have recently described a model of endotoxin-induced acute lung injury in rats in which nitric oxide synthase is inhibited. The possible interplay between nitric oxide and eicosanoids (thromboxane A2, prostacyclin) in this model have been presently studied. Animals were randomly assigned to four experimental groups which received the following treatment. 1. Lipopolysaccharide (LPS) infusion only, 2 mg.kg-1min-1 during 10 min (LPS group). 2. N omega-Nitro-L-Arginine 10 mg.kg-1 (L-NNA, nitric oxide synthase inhibitor) pretreatment followed by LPS infusion (L-NNA + LPS group). 3. L-NNA and camonagrel 25 mg.kg-1 (CAM, thromboxane synthase inhibitor) pretreatment followed by LPS infusion (L-NNA + CAM + LPS group). 4. L-NNA and iloprost 0.3 microgram.kg-1.min-1(ILO, stable analog of prostacyclin) pretreatment followed by LPS infusion (L-NNA + ILO + LPS group). LPS infusion resulted in a biphasic response in mean arterial blood pressure. A transient but deep fall in arterial blood pressure was followed by a long-lasting hypotension that led to death after 278 +/- 49 min. L-NNA + LPS rats died within 22 +/- 5 min among the symptoms of systemic hypotension and acute lung injury. In L-NNA + CAM + LPS group a significant attenuation of early phase of hypotension occurred and survival time was comparable with that of the LPS group (298 +/- 68 min). In rats of the L-NNA + ILO + LPS group survival time increased insignificantly to 48 +/- 41 min. It is concluded that immediate deleterious effects of lipopolysaccharide in NO-deficient rats are at least partially mediated by thromboxane A2 while prostacyclin cannot replace NO in its pneumoprotective action.

Topics: Animals; Blood Pressure; Epoprostenol; Escherichia coli; Indans; Lipopolysaccharides; Lung Diseases; Male; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Rats; Rats, Sprague-Dawley; Thromboxane A2; Thromboxane-A Synthase

We have reported recently that lipopolysaccharide endotoxin and platelet activating factor cooperate in priming relationships to elicit lung microvascular injury. Lung injury was associated with elevated serum levels of tumor necrosis factor-alpha (TNF alpha) and histological findings highly reminiscent of the adult respiratory distress syndrome. The present study was designed to examine the role of TNF alpha in lipopolysaccharide/platelet activating factor-induced lung injury by utilizing a highly specific monoclonal antibody which block TNF alpha actions (anti-TNF alpha monoclonal antibody). Pretreatment with anti-TNF alpha monoclonal antibody (2.5-25 mg/kg i.v., n = 5-9) dose-dependently prevented the lipopolysaccharide/platelet activating factor-induced histopathological changes, lung edema (P < .01), lung myeloperoxidase activity (P < .01), elevation of neutrophil count in bronchoalveolar lavage fluid (P < .01) and increased serum thromboxane B2 (P < .01). Indomethacin (6 mg/kg i.v., n = 5) failed to modify the lung injury despite complete inhibition of thromboxane B2 formation (P < .05). These data suggest that TNF alpha might play a key role in initiation of the early inflammatory changes which lead to adult respiratory distress syndrome.

Topics: Animals; Antibodies, Monoclonal; Bronchoalveolar Lavage Fluid; Capillary Permeability; Cricetinae; Indomethacin; Leukocyte Count; Leukocytes; Lipopolysaccharides; Lung; Lung Diseases; Male; Organ Size; Peroxidase; Platelet Activating Factor; Rats; Rats, Sprague-Dawley; Thromboxane A2; Time Factors; Tumor Necrosis Factor-alpha

Effects of a single dose of 3-methylindole (3-MI) (250 mg/kg intraperitoneally) were studied at different times ranging from 12 hours to 2 weeks post-treatment (PT). Microscopic study revealed mild Clara cell injury 24 hours PT and mucus hyperplasia 24 hours to 2 weeks PT. Diffuse type I alveolar epithelial cell necrosis occurred at 48 hours, followed by type II cell hyperplasia. Septal edema and accumulation of interstitial and capillary polymorphonuclear leukocytes and perivascular mixed mononuclear inflammatory cells accompanied the injury and repair. A gradual resolution of lesions with persistent mononuclear inflammatory cellular clusters at septal junctions, focal septal fibrosis, and accumulation of alveolar macrophages was evident at 1 and 2 weeks PT. Collagen, measured as hydroxyproline, in 3-MI-treated rats was significantly increased to 130% and 139% of control (3.0 mg/lung) at 1 and 2 weeks PT, respectively. Biphasic peaks of plasma 6-keto-prostaglandin F1 alpha occurred at 12 to 24 hours and at 96 hours PT with 3-MI and thromboxane B2 was elevated 12, 48, and 96 hours PT. Right ventricular/left ventricular and septal weight was increased to 120% and 140% of the control 1 and 2 weeks PT. We concluded that 3-MI induces alveolar septal injury in the rat with relatively complete repair of the alveolar epithelium and residual mild focal septal fibrosis and pulmonary hypertension 2 weeks PT. Arachidonic acid-derived mediators and inflammation are associated with 3-MI-induced lung injury.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Collagen; Dose-Response Relationship, Drug; Drug Administration Schedule; Injections, Intraperitoneal; Lung Diseases; Pulmonary Alveoli; Rats; Rats, Sprague-Dawley; Skatole; Thromboxane A2; Thromboxane B2

Products of cyclooxygenase activity have been proposed to mediate the pulmonary hypertension and increased microvascular permeability associated with phorbol myristate acetate- (PMA) induced acute lung injury. Previously, we reported that thromboxane (Tx) does not mediate PMA-induced pulmonary hypertension in intact anesthetized dogs. In the present study, PMA was administered to isolated canine lungs perfused with autologous blood at constant flow to investigate a possible role for Tx in the PMA-induced increase in microvascular permeability. Changes in permeability were assessed by determining changes in the capillary filtration coefficient (Kfc). In lobes pretreated with papaverine to prevent PMA-induced increases in pulmonary vascular resistance, Kfc increased from a baseline value of 0.2 +/- 0.03 to 1.5 +/- 0.29 ml.min-1.cmH2O-1.100 g wet lobe wt-1 (P < 0.01) 30 min after PMA (5.8 x 10(-8) M, n = 10). Concomitantly, TxB2, the stable metabolite of TxA2, increased from 138 +/- 44 to 1,498 +/- 505 pg/ml (P < 0.05) in the blood. Both the selective Tx synthase inhibitor, OKY-046 (7 x 10(-4) M, n = 6), and the cyclooxygenase inhibitor, indomethacin (10(-4) M, n = 7), prevented the PMA-induced increase in TxB2, but neither compound attenuated the PMA-induced increase in Kfc. ONO-3708 (10(-6) M), a selective prostaglandin (PG) H2/TxA2 receptor antagonist, prevented the vasoconstriction resulting from administration of U-46619, a stable PGH2/TxA2 receptor agonist, but it did not prevent the PMA-induced increases in Kfc (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Capillary Permeability; Dogs; In Vitro Techniques; Indomethacin; Leukocyte Count; Lung Diseases; Male; Methacrylates; Papaverine; Prostaglandin-Endoperoxide Synthases; Tetradecanoylphorbol Acetate; Thromboxane A2; Thromboxane B2; Thromboxane-A Synthase

Rats were killed after 6 weeks of continuous ingestion of the pneumotoxic alkaloid monocrotaline (2.2 mg/kg/day), the neutrophil elastase inhibitor SC39026 (60 mg/kg/day), or both. Pulmonary reactions were evaluated by light and electron microscopy. Lung endothelial function was monitored by angiotensin converting enzyme (ACE) activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Lung hydroxyproline content was measured as an index of interstitial fibrosis. Cardiac right ventricular hypertrophy was determined by the right ventricle to the left ventricle plus septum weight ratio (RV/LV + S). Rats receiving SC39026 alone did not differ significantly from untreated control animals with respect to any of the quantitative endpoints, although rarefaction of Type I pneumocytes was observed in the electron micrographs of these animals. Monocrotaline-treated rats, in contrast, developed a significant increase in RV/LV + S, and exhibited pulmonary edema, inflammation, fibrosis, and muscularization and occlusive mural thickening of the pulmonary small arteries and arterioles. These monocrotaline-induced structural changes were accompanied by decreased lung ACE and PLA activities, and increased PGI2 and TXA2 production, and by an increase in lung hydroxyproline content. Cotreatment with SC39026 ameliorated the monocrotaline-induced pulmonary vascular wall thickening and the cardiac right ventricular hypertrophy. These data suggest that inappropriate neutrophil elastase activity contributes to monocrotaline pulmonary vasculopathy and hypertension. On the other hand, cotreatment with SC39026 had no significant effect on the severity of the monocrotaline-induced lung inflammatory reaction, the pulmonary endothelial dysfunction, or the increase in lung hydroxyproline content.

Topics: Animals; Cardiomegaly; Chlorobenzoates; Epoprostenol; Hydroxyproline; Lung Diseases; Male; Monocrotaline; Organ Size; Pancreatic Elastase; Peptidyl-Dipeptidase A; Pyrrolizidine Alkaloids; Rats; Rats, Inbred Strains; Thromboxane A2; Tissue Plasminogen Activator

Interleukin (IL)-2 administration leads to respiratory dysfunction due to increased vascular permeability. This study examines the role of thromboxane (Tx)A2 in IL-2 induced lung injury in sheep with chronic lung lymph fistulae. This preparation enables evaluation of permeability prior to the development of gross edema. IL-2, 10(5) units/kg (n = 6), or its excipient control (n = 5) was given as an i.v. bolus over 2 min. After 2 h of IL-2 administration, plasma TxB2 increased from 168 to 388 pg/ml (P less than 0.05) and lung lymph TxB2 from 235 to 694 pg/ml (P less than 0.05). Mean pulmonary artery pressure (MPAP) rose from 13 to 29 mm of Hg (P less than 0.05) at 30 min and remained elevated for 4 h while the pulmonary artery wedge pressure was unchanged at 4 mm of Hg. Arterial oxygen tension (PaO2) fell from 88 to 77 mm of Hg (P less than 0.05). Lung lymph flow (QL) rose from 2.2 to 3.8 ml/30 min (P less than 0.05) at 1 h and to 6.4 ml/30 min at 3 h. This rise coincided with an increase in the lymph/plasma (L/P) protein ratio from 0.67 to 0.77 (P less than 0.05). In contrast, the non-IL-2-infused sheep (n = 3) recruitment of the lung vasculature by left atrial balloon inflation led to a rise in QL from 2.4 to 8.2 ml/30 min, whereas the L/P ratio declined from 0.62 to 0.25, suggesting that the protein-rich lymph flow after IL-2 administration reflected increased microvascular permeability. In further proof of an increase in permeability, IL-2 administration into sheep (n = 2) with an inflated left atrial balloon led, after a pressure-independent L/P protein ratio had been achieved, to an increase in L/P protein ratio and decrease in protein reflection coefficient. At 2 h after IL-2, the blood leukocyte count fell from 8156 to 4375/mm3 (P less than 0.05) primarily due to a 73% drop in lymphocytes. The platelet count declined from 292 to 184 x 10(3)/mm3 (P less than 0.05). Body temperature rose from 38.9-40.3 degrees C (P less than 0.05), and shaking chills were common. Pretreatment with the Tx synthetase inhibitor OKY 046 (n = 7) lowered baseline plasma and lymph TxB2 levels to 22 and 52 pg/ml (P less than 0.05) and prevented the IL-2-induced increase in plasma and lung lymph TxB2 (P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Animals; Blood Cell Count; Blood Platelets; Blood Pressure; Capillary Permeability; Female; Interleukin-2; Lung Diseases; Methacrylates; Neutrophils; Pulmonary Circulation; Sheep; Thromboxane A2; Thromboxane B2; Thromboxane-A Synthase; Time Factors

Intravascular complement activation results in thromboxane (TxA2) production, pulmonary hypertension, hypoxemia, and increased lung vascular permeability. The purpose of this study was to determine the role of TxA2 as a mediator of these responses. Experiments were made in anesthetized sheep subjected to intravenous injections of zymosan-activated plasma (ZAP) every 30 min for 4 h. Sheep were pretreated with dazoxiben, a TxA2 synthetase inhibitor, or SK and F 88046, a TxA2 end-organ antagonist, and the results were compared with those from untreated sheep. Dazoxiben, but not SK and F 88046, inhibited TxA2 release. The hypertensive response averaged 74 +/- 3 cm H2O after each injection of ZAP in untreated sheep. Neither drug altered this response. Pao2 decreased an average of 20 +/- 1 mmHg in untreated sheep, 3 +/- 1 mmHg in dazoxiben-treated sheep, and 11 +/- 1 mmHg in SK and F 88046-treated sheep. Increases in lung lymph flow and lymph protein clearance were unaffected by treatment. TxA2 appears to be an important mediator of hypoxemia during intravascular complement activation.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Capillary Permeability; Complement Activation; Hypertension, Pulmonary; Hypoxia; Imidazoles; Leukocytes; Lung Diseases; Plasma; Pulmonary Circulation; Sheep; Sulfonamides; Thromboxane A2; Zymosan

We injected Escherichia coli endotoxin, 2 micrograms/kg, beneath the eschar of sheep with 25% total body surface full-thickness burns to determine whether burn tissue in the presence of endotoxin releases prostanoids, particularly thromboxane A2, (TxA2), and if increased local TxA2 production can lead to distant lung dysfunction. We compared this response to the lung injury produced by the same dose given intravenously. We noted a marked increase in burn tissue TxA2 production after subeschar endotoxin as reflected in significant increases in burn lymph and pulmonary artery TxB2 levels. Pulmonary artery pressure increased from 22 to 38 mm Hg and PaO2 decreased from 89 to 71 torr while lung lymph flow (QL) increased only modestly with no evidence of increased lung permeability. The TxA2 production and the lung response were prevented by the subeschar injection of ibuprofen, 12.5 mg/kg. Circulating endotoxin was noted in only one of five sheep. After intravenous (endotoxin), a significant increase in lung TxA2 production was noted and a characteristic two-phase lung injury was seen with an initial phase basically identical to that seen with the subeschar injection followed by an increase in lung protein permeability. Burn tissue endotoxin can stimulate local TxA2 production leading to distant lung dysfunction without the need for circulating endotoxin. The source of the TxA2 is the burn, while with endotoxemia the source is the lung.

Topics: Animals; Burns; Endotoxins; Hemodynamics; Ibuprofen; Injections, Intravenous; Lung Diseases; Lymph; Pulmonary Artery; Sheep; Thromboxane A2; Thromboxanes; Time Factors

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Capillary Permeability; Dogs; Endotoxins; Epoprostenol; In Vitro Techniques; Lung; Lung Diseases; Perfusion; Thromboxane A2

Topics: Anti-Inflammatory Agents; Arachidonic Acids; Epoprostenol; Gastrointestinal Diseases; Humans; Kidney Diseases; Lung Diseases; Neoplasms; Prostaglandins; SRS-A; Thromboxane A2; Thromboxanes; Vascular Diseases

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Burns; Fistula; Hemodynamics; Lung Diseases; Lymphatic Diseases; Lymphatic System; Prostaglandins; Sheep; Thromboxane A2; Thromboxane B2; Thromboxanes

The relationship of leukocytes, platelets, and thromboxane A2 (TxA2) to endotoxin-induced lung injury was studied by use of chronic pulmonary lymph fistula in 12 adult female sheep. Endotoxin-induced lung injury in sheep was characterized by an early pulmonary hypertensive phase followed by a phase of increased capillary permeability. A profound leukopenia occurred early after endotoxin infusion and persisted during both phases of the injury. TxA2 levels (measured as its metabolite thromboxane B2) were significantly increased during the hypertensive phase and then returned rapidly to baseline. Levels were higher in lymph than in plasma, implying local generation in lung. Platelet count decreased transiently later in the permeability phase, rapidly returning toward baseline in animals that survived. The decrease in platelets occurred after TxA2 levels had returned to baseline, suggesting that TxA2 may be coming from sources other than platelets. We conclude that leukocytes appear to play a major role in initiating endotoxin-induced lung injury, and TxA2 may be contributing to pulmonary hypertension. Platelets, on the other hand, seem to be transiently sticking to an already damaged endothelium, with the degree of sequestration indicative of the severity of the injury.

Topics: Animals; Endotoxins; Escherichia coli; Female; Leukocyte Count; Lung Diseases; Lymph; Platelet Count; Sheep; Thromboxane A2; Thromboxanes

Topics: Animals; Arachidonic Acids; Biological Transport; Epoprostenol; Humans; Hydroxyprostaglandin Dehydrogenases; Hypoxia; Linolenic Acids; Lung; Lung Diseases; Prostaglandin Endoperoxides; Prostaglandin Endoperoxides, Synthetic; Prostaglandins; Prostaglandins E; Prostaglandins F; Thromboxane A2; Thromboxane B2; Vasomotor System