Leukotrienes in the pathogenesis of pulmonary blast injury.
Our previous studies demonstrate a significant increase of sulfidopeptide leukotriene concentrations in animals exposed to a free air blast. The aim of this study was to analyze the role of leukotrienes in the local response of lung tissue as well as in the general response of organisms to blast overpressure. The study was conducted on adult rabbits exposed to moderate blast overpressure (four pulmonary contusions characterized as confluent ecchymoses involving 30 to 60% of the lungs), generated in laboratory conditions. One group of experimental animals was treated with 5-lipoxygenase (5-LO) inhibitor, diethylcarbamazine (DEC, Sigma, St. Louis, Missouri) (50 mg/kg, i.v.), immediately before blast. The early posttraumatic period was observed (30 minutes after blast). Hemodynamic parameters (mean arterial pressure, heart rate, blood gases) as well as arterial plasma levels of conjugated dienes were observed. The myeloperoxidase activity, lipid peroxidation products levels, and water contents were measured in the lung tissue of injured rabbits. We observed that 5-LO inhibition reduced edema formation, accumulation of neutrophils, and generation of lipid peroxidation products in injured lungs. In this study, we demonstrated that treatment with DEC inhibits the increased systemic generation of conjugated dienes after blast injury. Although DEC exerts local antioxidant activity with beneficial effects on lung tissue, this 5-LO inhibitor intensifies the blast overpressure caused hemodynamic insufficiency.
Cernak
I
I
Military Medical Academy, Institute for Medical Research, Beograd, Yugoslavia.
Savic
J
J
Malicevic
Z
Z
Zunic
G
G
Radosevic
P
P
Ivanovic
I
I
D000818:Animals; D001753:Blast Injuries / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology; D001834:Body Water / Q000502:physiology; D004049:Diethylcarbamazine / Q000494:pharmacology; D006339:Heart Rate / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000502:physiology*; D015227:Lipid Peroxidation / Q000502:physiology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008168:Lung / Q000503:physiopathology; D055370:Lung Injury; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits
D020024:Leukotriene Antagonists; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D009195:Peroxidase; D004049:Diethylcarbamazine