Effects of a bradykinin B(2) receptor antagonist, FR173657, on pulmonary ischemia-reperfusion injury in dogs.
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.
Hashimoto
Naoki
N
Second Department of Surgery, Gunma University School of Medicine, Japan.
Takeyoshi
Izumi
I
Tsutsumi
Hirofumi
H
Sunose
Yutaka
Y
Tokumine
Masahiko
M
Totsuka
Osamu
O
Ohwada
Susumu
S
Yokoe
Takao
T
Matsumoto
Koshi
K
Morishita
Yasuo
Y
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D065168:Bradykinin Receptor Antagonists; D015777:Eicosanoids; C105311:FR 173657; D011804:Quinolines; D043782:Receptor, Bradykinin B2