INOS and peroxynitrite formation during acute rejection after human heart transplantation

Abstract

endomyocardial biopsy (EMB) beyond 2 years post-transplant remains uncertain. We performed a retrospective analysis reflecting our singleinstitution experience with 4041 biopsies (188 patients) from 1986-2001. Late ISHLT grade 3A rejection ocurring beyond 2 years posttransplant was detected in 24% of cardiac transplant recipients (33 of 139 patients) up to 10 years post-transplant. Late rejection could not be attributed to subtherapeutic levels of immunosuppression or other established parameters. Late rejection was only marginally correlated with the incidence of moderate rejection within the first 2 posttransplant years (p 0.09). Unlike the incidence of moderate rejection in the first post-transplant year showing a steady decline toward more recent years (2.1430.13), the incidence of late rejection appeared not to be influenced by transplant era (mean 0.11 0.056) over a 10 year observation period (1989-1999). Spontaneous resolution of moderate rejection beyond 2 years post-transplant occurred in all 17 patients in whom specific anti-rejection therapy had been electively withheld. Mortality beyond 2 years post-transplant was slightly lower (p 0.033) in the late rejecting group (n 33) than in the control group (n 106), no difference was found in the prevalence of transplant vasculopathy diagnosed by coronary angiography. EMB continues to detect episodes of moderate rejection even very late after heart transplantation without a close correlation with the rejection frequency in the early posttransplant period. Late rejection may represent a distinct biological entity as evidenced by its spontaneous resolution, lack of an era effect as is found for early rejection and no negative impact on survival. The future role of late EMB will depend on its predictive value for diagnosis and risk stratification of chronic graft dysfunction.