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 incr eased donor cardiac intercellular adhesion molecule (ICAM-1) expressio n 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, underwen t 45 minutes of cold ischemia, and were transplanted into ACI recipien ts with or without anti-ICAM-1 monoclonal antibody treatment. Grafts w ere procured early for analysis of ICAM-1 expression and reperfusion i njury or the recipients were treated with cyclosporin A (to allow long -term graft acceptance) for postoperative days 0 through 9 with procur ement on postoperative day 90 to histologically score for chronic graf t vascular disease. Results. Lipopolysaccharide-pretreated PVG heart g rafts showed increased ICAM-1 expression by Northern blot and immunohi stochemical analysis leading to increased reperfusion injury as assess ed by neutrophil infiltration (myeloperoxidase), cardiac edema (percen tage wet weight), and histologic injury (percentage area of contractio n band necrosis), which was reversed by recipient treatment with anti- ICAM-1 monoclonal antibody. After administration of cyclosporin A, 5 m d/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 inductio n donor inflammatory state before harvest leading to increased cardiac ICAM-1 expression promotes reperfusion injury and chronic graft vascu lar disease after transplantation in this rodent heterotopic heart mod el. (C) 1997 by The Society of Thoracic Surgeons.