[The effectiveness of ulinastatin on granulocyte H2O2 production in acute lung injury rat model].
Oxygen radicals produced by granulocytes play an important role in acute lung injury. The effectiveness of ulinastatin in adult respiratory distress syndrome and an acute lung injury animal model has been reported. We investigated the effect of ulinastatin on oxygen radical production in the intact pulmonary circulation of a rat acute lung injury model using our new method, which demonstrated the granulocyte adhesion and H2O2 production in vivo. The pulmonary microcirculation was observed by intravital fluorescence microscopy and a TV monitor using a SIT TV camera. Then images were recorded on a videotape. The granulocytes and H2O2 were stained with an intravenous injection of acridine red and dichlorofluorescin diacetate, respectively. The images which were recorded on the videotape were digitized by a computer image digitizer and analyzed with a personal computer and the software Ripp II. When the rat received a continuous infusion of endotoxin (4.5 mg/kg/hour) for 2 hours, the granulocytes adhered to the pulmonary capillaries and generated H2O2 (n = 25 p < 0.001 respectively, compared with the control rat which received saline alone). Then, the acute lung injury model rat was infused with 50,000 U/kg of ulinastatin just before endotoxin infusion and also received a continuous infusion of ulinastatin (50,000 U/kg/hour) for 2 hours. Ulinastatin inhibited the granulocyte adhesion to the pulmonary capillaries (n = 25, inhibition rate: 46% p < 0.001) and H2O2 production (n = 25, inhibition rate; 51% p < 0.001) caused by the continuous infusion of endotoxin. In conclusion, ulinastatin significantly inhibits the granulocyte adhesion and H2O2 production in the intact pulmonary circulation of a rat acute lung injury model.
Manamiya
Y
Y
Second Department of Surgery, Akita University School of Medicine, Japan.
Abo
S
S
Kitamura
M
M
Izumi
K
K
Sato
H
H
Kimura
Y
Y
Saito
S
S
D000208:Acute Disease; D000818:Animals; D004731:Endotoxins; D006023:Glycoproteins / Q000627:therapeutic use*; D006098:Granulocytes / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008171:Lung Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008833:Microcirculation; D011652:Pulmonary Circulation; D051381:Rats; D017208:Rats, Wistar
D004731:Endotoxins; D006023:Glycoproteins; D006861:Hydrogen Peroxide; C028665:urinastatin