Introduction: Reperfusion injury is an inflammatory cell-mediated response that causes tissue damage immediately following transplantation, and has been implicated in the development of acute and chronic rejection. NF-κB is a transcription factor that upregulates adhesion molecules ICAM-1, VCAM-1, and ELAM-1 following reperfusion. We hypothesized that treatment with sulfasalazine, a potent inhibitor of NF-κB, would decrease adhesion molecule expression, decrease reperfusion injury, and prolong allograft survival in rat cardiac transplants.MethodsHeterotopic rat heart transplants were performed. Donor allografts were treated with saline, sulfasalazine (SSA), or lipopolysaccharide (LPS), a potent inducer of NF-κB activity. Reperfusion injury was assessed with cardiac edema (percent wet weight), neutrophil infiltration (MPO activity), and histologic damage (contraction band necrosis). Immunohistochemistry was performed to analyze protein expression. Acute rejection was determined by daily palpation.ResultsTreatment with a single 100 mg/kg intraperitoneal injection of sulfasalazine decreased reperfusion injury compared to saline controls (MPO activity, saline: 2.1 ± 0.3, SSA: 1.2 ± 0.31, P < 0.005; % wet weight, saline 77.6 ± 1.1%; SSA 75.8 ± 1.0%, P < 0.005; contraction band necrosis, saline: 13.1 ± 2.5%, SSA: 6.1 ± 3.4%, P < 0.001). LPS administration increased all parameters of reperfusion injury. Treatment with sulfasalazine prior to LPS also decreased reperfusion injury compared to LPS and saline groups. Sulfasalazine treatment decreased ICAM-1 and VCAM-1 protein expression. Administration of 500 mg/kg sulfasalazine increased graft survival to 15.4 ± 1.8 days compared to saline (6.8 ± 1.4 days, P < 0.005).ConclusionTreatment with sulfasalazine is an effective method to decrease reperfusion injury and prolong allograft survival in a rat cardiac transplantation model. Copyright (C) 1999 International Society for Heart and Lung Transplantation.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cardiology and Cardiovascular Medicine