Pretreatment of sivelestat sodium hydrate improves the lung microcirculation and alveolar damage in lipopolysaccharide-induced acute lung inflammation in hamsters.
Damage to the lung microcirculation and alveoli caused by activated leukocytes is known to play an important role in the development of acute lung injury (ALI). The aim of this study is to evaluate the difference in the effect of pretreatment and posttreatment of a synthetic neutrophil elastase inhibitor sivelestat on ALI. Hamsters were instilled with 10.0 mg/kg of lipopolysaccharide (LPS) intratracheally for 1 h to simulate ALI. Two milligrams per kilogram of sivelestat was injected intraperitoneally either previously or after LPS infusion. One and 24 hours after the infusion of LPS, pulmonary microcirculation was observed under the intravital microscopy. In another series, the blood cell counts were evaluated. The adhesive leukocyte count on the endothelium was significantly lower in pretreatment group compared with control group (P < 0.01), whereas the difference was not significant in the posttreatment group. Similarly, the number of obstructed capillary was significantly lower in the pretreatment group (P < 0.01). The width of interstitium was significantly lower in the pretreatment and posttreatment group (P < 0.01 and 0.05, respectively). A comparison of white blood cell counts showed a better maintenance in pretreatment group (P < 0.05). Pretreatment of sivelestat demonstrated a protective effect on both intravascular and extravascular damage in the lung, whereas posttreatment only suppressed the latter damage.
Iba
Toshiaki
T
Department of Surgery, Juntendo Urayasu Hospital, Juntendo University School of Medicine, Urayasu, Chiba, Japan. iba-jun@umin.ac.jp
Kidokoro
Akio
A
Fukunaga
Masaki
M
Takuhiro
Kitoji
K
Yoshikawa
Seiichiro
S
Sugimotoa
Kiichi
K
D000208:Acute Disease; D000818:Animals; D006224:Cricetinae; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000494:pharmacology / Q000633:toxicity*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D011014:Pneumonia / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000293:injuries / Q000503:physiopathology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
D008070:Lipopolysaccharides; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D019272:Leukocyte Elastase; D005998:Glycine