title: Beneficial effects of novel nitric oxide donor (FK409) on pulmonary ischemia-reperfusion injury in rats.
abstract: BACKGROUND
  Nitric oxide (NO) seems to play an important role in tissue injury during reperfusion of the lung. FK409 is the first spontaneous NO donor that increases plasma guanosine 3':5'-cyclic monophosphate. It is reported that FK409 prevented myocardial infarction following occlusion and reperfusion in rat coronary arteries. In this study, we evaluated the effects of FK409 on pulmonary ischemia-reperfusion injury in an in situ warm ischemia model of rats.
  
  
  METHODS
  Animals were divided into 2 groups: the FK409 study group that was administered FK409 (0.4 mg/kg) before reperfusion and the control group, administered a saline vehicle only. Following a thoracotomy, the bronchus, pulmonary artery and vein were separately clamped for 1 hour. Arterial oxygen tension (PaO2), arterial oxygen saturation (SaO2), and endothelin-I (ET-I) were measured after 2 hours of reperfusion. Histologic and immunohistochemical studies were performed; polymorphonuclear neutrophils (PMNs) were counted after 2 hours of reperfusion.
  
  
  RESULTS
  PaO2, SaO2, ET-I after 2 hours of reperfusion and the 7-day survival rate were significantly (p < 0.05) better in the FK409 group than the control group. Histologic damage was reduced in the FK409 group compared with the control group. PMN infiltration was also significantly (p < 0.05) lower in the FK409 group than in the control group.
  
  
  CONCLUSIONS
  FK409 seems to protect against ischemia-reperfusion injury of the lung. This effect may be related to a homeostatic effect on pulmonary vascular beds and prevention of PMN sequestration.
authors.affiliation: Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Takeyoshi
authors.forename: Y
authors.initials: Y
authors.lastname: Otani
authors.forename: D
authors.initials: D
authors.lastname: Yoshinari
authors.forename: Y
authors.initials: Y
authors.lastname: Kawashima
authors.forename: S
authors.initials: S
authors.lastname: Ohwada
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Y
authors.initials: Y
authors.lastname: Morishita
mesh_terms: D000818:Animals; D019332:Endothelin-1 / Q000032:analysis; D007150:Immunohistochemistry; D008168:Lung / Q000098:blood supply / Q000473:pathology; D016040:Lung Transplantation / Q000473:pathology; D008297:Male; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000032:analysis; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009574:Nitro Compounds / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood; D011654:Pulmonary Edema / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D019332:Endothelin-1; D020030:Nitric Oxide Donors; D009574:Nitro Compounds; C061872:FK 409; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D010100:Oxygen