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 heart is still incomplete. Among these changes that could potentially have an adverse effect on long-term cardiac function, myocardial fibrosis is of great concern. The aim of this study was to investigate the possible influence of acute or chronic rejection on the development of myocardial fibrosis in cardiac allografts.


METHODS
We used light microscopic computer-assisted morphometry of collagen density in 200 right ventricular endomyocardial biopsy specimens taken routinely in 21 heart transplant recipients during a mean follow-up period of 36 months (range, 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; the 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, no acute rejection or grade 1A; subgroup 2, grade 1B; subgroup 3, grades 3A or 3B; subgroup 4, grade 4). Patients of both groups were selected on the basis of similarity patterns in clinical characteristics and mean follow-up time.


RESULTS
Patients with no chronic rejection had relatively little variation in serial determinations of myocardial collagen density. During the prechronic and chronic phases in patients with chronic rejection, we found no overall increase in myocardial collagen density. In both the chronic rejection and no chronic rejection groups there was no consistent relationship between myocardial collagen density and severity of acute rejection. In both groups there were occasional strikingly elevated myocardial collagen density values that were well above the other serial determinations. These elevated values of collagen density were mainly a result of scars, the sequellae of prior myocyte damage, because neither interstitial nor perivascular fibrosis could be detected.


CONCLUSIONS
During this long-term follow-up study of endomyocardial biopsy samples, we found no significant association between either acute or chronic rejection and the later increase in myocardial collagen density.
Fornes
P
P
Department of Pathology, Broussais Hôpital, Paris, France.
Heudes
D
D
Simon
D
D
Guillemain
R
R
Amrein
C
C
Bruneval
P
P
D000208:Acute Disease; D000328:Adult; D001706:Biopsy; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism*; D004699:Endocardium / Q000378:metabolism* / Q000473:pathology; D004719:Endomyocardial Fibrosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D016027:Heart Transplantation; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous
D003094:Collagen