The effects of delayed treatment with sialyl Lewis X against lipopolysaccharide-induced acute lung injury in rabbits.
The therapeutic effects of a selectin inhibitor against lipopolysaccharide-induced acute lung injury were studied in rabbits by using sialyl Lewis X-oligosaccharide. Lipopolysaccharide-induced acute lung injury, as characterized by an impairment of pulmonary gas exchange, clinically resembles that of the acute respiratory distress syndrome. Delayed treatments with sialyl Lewis X-oligosaccharide (55 mg kg(-1) i.v. bolus injection 0.5, 1 or 2 h after lipopolysaccharide administration+36 mg kg(-1) h(-1) i.v. infusion for 5.5, 5 or 4 h, respectively) prevented the lipopolysaccharide-induced impairments in pulmonary gas exchange, as well as the accumulation of polymorphonuclear leukocytes in the lung tissue. In contrast, this agent had no significant effects on lipopolysaccharide-induced systemic hypotension, the decrease in the number of circulating white blood cells and platelets or the decline in blood pH. This is the first demonstration that sialyl Lewis X-oligosaccharide is effective against the impairments in pulmonary gas exchange even if administered 0.5, 1 or 2 h following the lipopolysaccharide injection.
Hayashi
H
H
Sumitomo Pharmaceuticals Research Center, 1-98 Kasugadenaka 3-chome, Konohana-ku, Osaka, Japan.
Koike
H
H
Imanishi
N
N
Tojo
S J
SJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D009844:Oligosaccharides / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011817:Rabbits; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D000080506:Sialyl Lewis X Antigen; D013997:Time Factors
D008070:Lipopolysaccharides; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D010100:Oxygen