title: Effects of a bradykinin B(2) receptor antagonist, FR173657, on pulmonary ischemia-reperfusion injury in dogs.
abstract: BACKGROUND
  This study investigated the effects of a bradykinin B(2) receptor antagonist, FR173657 (FR), on pulmonary ischemia-reperfusion (I/R) injury.
  
  
  METHODS
  Twenty-four mongrel dogs were divided into four groups (n = 6 each). In Groups I, II and III, FR doses of 33, 100 and 300 nmol/kg per hour, respectively, were administered continuously beginning 30 minutes before ischemia and continuing for 2 hours after reperfusion. In Group IV, vehicle alone was administered. Warm ischemia was induced for 3 hours by clamping the left pulmonary artery and veins. Simultaneously, the left stem bronchus was bisected and then anastomosed before reperfusion. Fifteen minutes after reperfusion, the right pulmonary artery and bronchus were ligated. Left pulmonary vascular resistance (L-PVR), cardiac output (CO), arterial oxygen pressure (PaO(2)) and the alveolar - arterial oxygen pressure difference (A-aDO2) were measured for 4 hours after reperfusion. Lung tissue was harvested for wet-to-dry weight ratio (WDR) measurements, histopathologic studies and polymorphonuclear neutrophil (PMN) counts. Serum thromboxane (TX) B(2), 6-keto-prostaglandin (PG) F(1alpha) and leukotriene (LT) B(4) levels were also measured.
  
  
  RESULTS
  PaO(2), A-aDO2, L-PVR and CO were significantly (p < 0.05) improved and WDR was significantly (p < 0.05) lower in Groups II and III than in Group IV. Histologic tissue edema was mild, and PMN infiltration was significantly (p < 0.05) reduced in Groups I, II and III compared with Group IV. TXB(2) levels were significantly (p < 0.05) lower in Group II than in Group IV, whereas 6-keto-PGF(1alpha) levels were not significantly different. LTB(4) levels were significantly (p < 0.05) lower in Groups II and III than in Group IV.
  
  
  CONCLUSIONS
  FR appears to have a protective effect on pulmonary I/R injury stemming from the inhibition of eicosanoid release.
authors.affiliation: Second Department of Surgery, Gunma University School of Medicine, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Izumi
authors.initials: I
authors.lastname: Takeyoshi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tsutsumi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sunose
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tokumine
authors.forename: Osamu
authors.initials: O
authors.lastname: Totsuka
authors.forename: Susumu
authors.initials: S
authors.lastname: Ohwada
authors.forename: Takao
authors.initials: T
authors.lastname: Yokoe
authors.forename: Koshi
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishita
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D004285:Dogs; D015777:Eicosanoids / Q000378:metabolism; D008168:Lung / Q000187:drug effects*; D008171:Lung Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D011659:Pulmonary Gas Exchange / Q000187:drug effects / Q000502:physiology; D011804:Quinolines / Q000494:pharmacology*; D043782:Receptor, Bradykinin B2; D015427:Reperfusion Injury / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D065168:Bradykinin Receptor Antagonists; D015777:Eicosanoids; C105311:FR 173657; D011804:Quinolines; D043782:Receptor, Bradykinin B2