leukotriene-b4 and Respiratory-Insufficiency

Bronchial hyperresponsiveness is a hallmark of asthma and many factors modulate bronchoconstriction episodes. A potential correlation of formaldehyde (FA) inhalation and asthma has been observed; however, the exact role of FA remains controversial. We investigated the effects of FA inhalation on Ovalbumin (OVA) sensitisation using a parameter of respiratory mechanics. The involvement of nitric oxide (NO) and cyclooxygenase-derived products were also evaluated. The rats were submitted, or not, to FA inhalation (1%, 90 min/day, 3 days) and were OVA-sensitised and challenged 14 days later. Our data showed that previous FA exposure in allergic rats reduced bronchial responsiveness, respiratory resistance (Rrs) and elastance (Ers) to methacholine. FA exposure in allergic rats also increased the iNOS gene expression and reduced COX-1. L-NAME treatment exacerbated the bronchial hyporesponsiveness and did not modify the Ers and Rrs, while Indomethacin partially reversed all of the parameters studied. The L-NAME and Indomethacin treatments reduced leukotriene B₄ levels while they increased thromboxane B₂ and prostaglandin E₂. In conclusion, FA exposure prior to OVA sensitisation reduces the respiratory mechanics and the interaction of NO and PGE₂ may be representing a compensatory mechanism in order to protect the lung from bronchoconstriction effects.

Topics: Administration, Inhalation; Airway Resistance; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bronchial Hyperreactivity; Bronchoconstrictor Agents; Cyclooxygenase 1; Dinoprostone; Disease Models, Animal; Eicosanoids; Formaldehyde; Gene Expression Regulation, Enzymologic; Leukotriene B4; Male; Membrane Proteins; Nitric Oxide; Nitric Oxide Synthase Type II; Rats; Rats, Wistar; Respiratory Insufficiency; Respiratory Mucosa; Thromboxane B2

Topics: Animals; Dogs; Extracorporeal Membrane Oxygenation; Hypothermia, Induced; Leukotriene B4; Perfusion; Respiratory Insufficiency

We hypothesized that leukotrienes might contribute to the pathophysiology of acute lung injury induced by oleic acid. Oleic acid (2-20 mg.kg-1.h-1), LY171883 [leukotriene (LT) D4/LTE4 receptor antagonist, 10 mg/kg + 1 mg.kg-1.h-1] + oleic acid (10 mg.kg-1. h-1), or triolein (20 mg.kg-1.h-1) were infused intravenously into anesthetized pigs. Treatment with the cyclooxygenase inhibitor was designed to possibly enhance LT release. Bronchoalveolar lavage fluid concentrations of LTB4, LTC4, LTD4, and LTE4 were measured by reverse-phase high-performance liquid chromatography and radioimmunoassay. Oleic acid caused dose-related hypoxemia and pulmonary hypertension and increased pulmonary vascular resistance, lung water, and alveolar-capillary membrane permeability. Bronchoalveolar lavage fluid levels of LTB4, LTC4, LTD4, and LTE4 showed no significant changes in oleic acid- or indomethacin + oleic acid-treated pigs, compared with triolein-treated controls. Indomethacin modestly attenuated the oleic acid-induced hypoxemia and the early increases (i.e., 0-0.5 h) in mean pulmonary arterial pressure and pulmonary vascular resistance. In contrast, LY171883 provided no protection against any oleic acid-induced cardiopulmonary effect (measured or calculated). We conclude that LTs are not likely to be important mediators of oleic acid-induced lung injury in the pig.

Topics: Acetophenones; Acute Disease; Animals; Autacoids; Blood Pressure; Bronchoalveolar Lavage Fluid; Indomethacin; Leukotriene B4; Leukotriene E4; Leukotrienes; Lung; Oleic Acid; Oleic Acids; Respiratory Insufficiency; SRS-A; Swine; Tetrazoles; Triolein; Vascular Resistance

We hypothesized that leukotriene B4 (LTB4) might be produced during endotoxin-induced acute respiratory failure (ARF) observed in young pigs. We used radioimmunoassay (RIA) and reverse phase-high performance liquid chromatography (RP-HPLC) to determine the presence of LTB4 in plasma and bronchoalveolar lavage fluid (BALF) of saline- and endotoxin-treated pigs. Endotoxin was infused at 5 micrograms/kg for 1 hour (hr) followed by 2 micrograms/kg/hr for an average of 3 hrs. Arterial plasma (collected at 0.5 hr intervals for 4 hrs) immunoreactive (i)-LTB4 was significantly increased from 2.5 to 4 hrs of endotoxemia with the peak value occurring at 3.5 hrs (i.e. 282% of baseline value). Analysis of plasma extracts using RP-HPLC revealed an ultraviolet (UV) absorbance peak (270 nm) that was coincident with authentic LTB4 standard. The levels of i-LTB4 were significantly increased in BALF recovered from endotoxemic pigs (337 +/- 71 vs 53 +/- 13 pg/ml for saline controls). Endotoxin also increased the postmortem wet/dry ratio of bloodless lung and BALF albumin concentration, indicating pulmonary edema and increased permeability of the alveolar-capillary membrane, respectively. We conclude that LTB4 is increased in plasma and BALF recovered from endotoxemic pigs and that this lipoxygenase metabolite could possibly be an important factor contributing to the pathophysiology of endotoxin-induced ARF.

Topics: Animals; Bronchoalveolar Lavage Fluid; Chromatography, High Pressure Liquid; Endotoxins; Leukotriene B4; Radioimmunoassay; Respiratory Insufficiency; Swine

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