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: Naoki Hashimoto, Izumi Takeyoshi, Hirofumi Tsutsumi, Yutaka Sunose, Masahiko Tokumine, Osamu Totsuka, Susumu Ohwada, Takao Yokoe, Koshi Matsumoto, Yasuo Morishita
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 21 Issue 9 Pg. 1022-9 (Sep 2002) ISSN: 1053-2498 [Print] United States
• PMID: 12231374 (Publication Type: Evaluation Study, Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Bradykinin Receptor Antagonists
• Eicosanoids
• FR 173657
• Quinolines
• Receptor, Bradykinin B2

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Bradykinin Receptor Antagonists
• Dogs
• Eicosanoids (metabolism)
• Lung (drug effects)
• Lung Diseases (immunology, metabolism, pathology)
• Pulmonary Circulation (drug effects, physiology)
• Pulmonary Gas Exchange (drug effects, physiology)
• Quinolines (pharmacology)
• Receptor, Bradykinin B2
• Reperfusion Injury (immunology, metabolism, pathology)