BW755C modifies endotoxin-induced respiratory failure in pigs.
The porcine pulmonary response to endotoxemia was evaluated before and after 3-amino-1-(3-trifluoromethylphenyl)-2-pyrazoline hydrochloride (BW755C), a dual inhibitor of the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism. Escherichia coli endotoxin (055-B5) was infused IV into anesthetized 10- to 14-week-old pigs at 5 micrograms/kg the first hour, followed by 2 micrograms/kg/hr for 3.5 hours. The BW755C was infused at 20 mg/kg before endotoxin was administered and at 2.2 mg/kg during endotoxemia. During phase 1 (ie, 0 to 2 hours), the endotoxin-induced pulmonary hypertension, increased pulmonary vascular resistance and alveolar-arterial oxygen gradient, and decreased cardiac index and lung dynamic compliance were blocked or modified by BW755C. During phase 2 endotoxemia (ie, 2 to 4.5 hours), BW755C modified or blocked the increases in pulmonary vascular pressures, pulmonary vascular resistance, alveolar dead space ventilation, alveolar-arterial oxygen gradient, lung water, and bronchoalveolar lavage albumin concentration. The BW755C also modified the phase 2 decreases in cardiac index, lung dynamic compliance, and aortic platelet count. With regard to the endotoxin-induced pulmonary vasoconstriction, bronchoconstriction, and impairment of gas exchange, the data do not support a role for lipoxygenase metabolites, because the modified blockade (provided by BW755C) was of no greater magnitude than that reported for indomethacin (cyclooxygenase blocker). However, the data supports a possible role for lipoxygenase metabolites with regard to altering vascular permeability, cardiac index, and aortic platelet count.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001784:Blood Gas Analysis / Q000662:veterinary; D002302:Cardiac Output / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000662:veterinary; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D012131:Respiratory Insufficiency / Q000188:drug therapy / Q000209:etiology / Q000662:veterinary*; D013552:Swine; D013553:Swine Diseases / Q000188:drug therapy*; D014655:Vascular Resistance / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine