Cellular adhesion molecules changes in myocardium during first year post heart transplant

The increased presence of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) in the myocardium after orthotropic heart transplantation (OHT) has been implicated in early and late organ rejection. The aim of this study was to investigate the changes in ICAM-1 and VCAM-1 during the first years post-OHT. Accordingly, we studied multiple endomyocardial biopsy specimens collected from 11 randomly selected patients (all males, mean age 46 +/- 11 years). Qualification criteria for OHT included: ischemic cardiomyopathy in 6 pts (55%) and idiopathic dilated cardiomyopathy in 5 pts (45%). All patients were receiving triple immunosuppressive regimen. The therapy consisted of cyclosporine, azathioprine, and prednisolone. Multiple endomyocardial biopsy specimens were collected at 7, 30, 90 and 360 days post OHT from all patients (pts), and examined routinely for histologic signs of organ rejection. To assess levels of adhesion molecules we used monoclonal antibodies (murine anti-human ICAM-1 and VCAM-1) on frozen sections. Immunoreactivity (IR) was detected using a commercially available kit. Intensity of IR was assessed based on a semiquantitative scoring system. In this study, IR scores > or = 2 + were considered positive for ICAM-1, and scores > or = 1 + were considered positive for VCAM-1. IR scores in specimens obtained from consecutive biopsies were compared with the initial biopsy collected at the day 7. The results were analyzed using nonparametric statistics. The routine evaluation revealed histological signs of organ rejection (> or = 2) in 2 pts at 7 days, in 5 pts at 30 days, in 3 pts at 90 days, and in 1 patient at 360 days. On the other hand, ICAM-1 and VCAM-1 expression were absent in the majority of patients at 7, 30 and 90 days, but their presence was significantly increased at 360 days (p < 0.05). Absence of the early expression of ICAM-1 and VCAM-1 may be related to the protective effect of triple immunosuppressive therapy in these patients. The expression of ICAM-1 and VCAM-1 strongly emerging at 1 year post OHT may reflect chronic rejection in myocardium. In conclusion, the immunohistological monitoring of the adhesion molecules in biopsy specimens during routine biopsy schedule may be helpful for the discovery of chronic rejection.