Effects of increased ICAM-1 on reperfusion injury and chronic graft vascular disease.

BACKGROUND: The purpose of this study was to assess the impact of increased donor cardiac intercellular adhesion molecule (ICAM-1) expression on both reperfusion injury and chronic graft vascular disease after transplantation. METHODS: Hearts were harvested from donor rats before and after pretreatment with lipopolysaccharide at -24 hours, underwent 45 minutes of cold ischemia, and were transplanted into ACI recipients with or without anti-ICAM-1 monoclonal antibody treatment. Grafts were procured early for analysis of ICAM-1 expression and reperfusion injury or the recipients were treated with cyclosporin A (to allow long-term graft acceptance) for postoperative days 0 through 9 with procurement on postoperative day 90 to histologically score for chronic graft vascular disease. RESULTS: Lipopolysaccharide-pretreated PVG heart grafts showed increased ICAM-1 expression by Northern blot and immunohistochemical analysis leading to increased reperfusion injury as assessed by neutrophil infiltration (myeloperoxidase), cardiac edema (percentage wet weight), and histologic injury (percentage area of contraction band necrosis), which was reversed by recipient treatment with anti-ICAM-1 monoclonal antibody. After administration of cyclosporin A, 5 mg/kg for 10 days, lipopolysaccharide-treated grafts had significantly worse chronic graft vascular disease scores (2.56 +/- 0.57 versus 1.84 +/- 0.75; p < 0.05 by Mann-Whitney U test). CONCLUSIONS: The induction donor inflammatory state before harvest leading to increased cardiac ICAM-1 expression promotes reperfusion injury and chronic graft vascular disease after transplantation in this rodent heterotopic heart model.