INFLUENCE OF ACUTE OR CHRONIC REJECTION ON MYOCARDIAL COLLAGEN DENSITY IN SERIAL ENDOMYOCARDIAL BIOPSY SPECIMENS FROM CARDIAC ALLOGRAFTS

Background: The knowledge of long-term changes in the transplanted hea rt is still incomplete. Among these changes that could potentially hav e an adverse effect on long-term cardiac function, myocardial fibrosis is of great concern. The aim of this study was to investigate the pos sible influence of acute or chronic rejection on the development of my ocardial fibrosis in cardiac allografts.Methods: We used light microsc opic computer-assisted morphometry of collagen density in 200 right ve ntricular endomyocardial biopsy specimens taken routinely in 21 heart transplant recipients during a mean follow-up period of 36 months (ran ge, 12 to 84). The 21 patients were divided into two groups according to the presence of chronic rejection assessed by coronary angiography. The first group consisted of 11 patients with no chronic rejection; t he second group consisted of 10 patients with chronic rejection. Both groups were divided into four subgroups according to the highest grade of acute rejection reached during the follow-up period (subgroup 1, n o acute rejection or grade 1A; subgroup 2, grade 1B; subgroup 3, grade s 3A or 3B; subgroup 4, grade 4). Patients of both groups were selecte d on the basis of similarity patterns in clinical characteristics and mean follow-up time. Results: Patients with no chronic rejection had r elatively little variation in serial determinations of myocardial coll agen density. During the prechronic and chronic phases in patients wit h chronic rejection, we found no overall increase in myocardial collag en density. In both the chronic rejection and no chronic rejection gro ups there was no consistent relationship between myocardial collagen d ensity and severity of acute rejection. In both groups there were occa sional strikingly elevated myocardial collagen density values that wer e well above the other serial determinations. These elevated values of collagen density were mainly a result of scars, the sequellae of prio r myocyte damage, because neither interstitial nor perivascular fibros is could be detected. Conclusion: During this long-term follow-up stud y of endomyocardial biopsy samples, we found no significant associatio n between either acute or chronic rejection and the later increase in myocardial collagen density.