Effects of a bradykinin B 2 receptor antagonist on ischemia–reperfusion injury in a canine lung transplantation model

Abstract

Background This study investigated the effects of a bradykinin B 2 receptor antagonist, FR173657 (FR), on ischemia–reperfusion (I/R) injury in a canine lung transplantation model. Methods Eighteen pairs of weight-matched dogs were randomly divided into 3 groups. Six pairs were assigned to the FR(D+R) group, in which FR (100 nmol/kg/h) was administered to the transplant donor continuously beginning 30 minutes before ischemia until the onset of ischemia, and FR was administered to the transplant recipient beginning 30 minutes before reperfusion and continuing for 2 hours after reperfusion. Another 6 pairs of dogs were assigned to the FR(R) group, in which FR was administered only to the recipient in the same manner as in the FR(D+R) group. The other pairs were assigned to the control group, in which vehicle alone was administered. Orthotopic left lung transplantation was performed after 12-hour cold storage in Euro-Collins solution. Fifteen minutes after reperfusion, the right pulmonary artery and the right stem bronchus were ligated. The animals were measured for 4 hours after reperfusion for left pulmonary vascular resistance (L-PVR), cardiac output (CO), arterial oxygen pressure (Pa o 2) and alveolar-arterial oxygen pressure difference (A-aD o 2). Lung specimens were harvested for measurement of the wet-to-dry lung weight ratio (WDR), histopathologic studies and polymorphonuclear neutrophil (PMN) count. Results Compared with the control group, Pa o 2, A-aD o 2, L-PVR and CO were all significantly ( p < 0.05) improved and WDR significantly ( p < 0.05) lower in both the FR(D+R) and FR(R) groups. Moreover, in the FR-treated groups, histologic tissue edema was mild, and PMN infiltration was significantly ( p < 0.05) reduced. Conclusions The bradykinin B 2 receptor antagonist, FR173657, ameliorates I/R injury in lung grafts, indicating that protection of lung grafts can be achieved by the administration of FR solely to the transplant recipient.