MORPHOMETRIC ANALYSIS OF NEOINTIMAL FORMATION IN MURINE CARDIAC GRAFTS .3. DISSOCIATION OF INTERSTITIAL FIBROSIS FROM NEOINTIMAL FORMATION

Background. This study examined the relationship between transplant va scular sclerosis (TVS) and tissue fibrosis, features of chronic reject ion that can develop rapidly in accepted heterotopic murine cardiac al lografts, Methods. The rate of development of interstitial fibrosis or TVS development was determined by computerized analysis of tissue sec tions from DBA/2-->C57BL/6 heterotopic cardiac allografts after immuno suppression with gallium nitrate. Results. In accepted cardiac allogra fts, neointimal fibrosis developed by 30 days after transplant, wherea s TVS was minimal by day 30, and maximal by day 60. Variable levels of fibrosis were found throughout the allografts. DBA/2-->DBA/2 cardiac isografts never displayed TVS in this time period, but displayed allog raft-like fibrosis within 60 days of transplantation. Conclusions. Int erstitial fibrosis can be dissociated from the TVS development in this experimental model of chronic cardiac allograft rejection. Apparently , it is caused, at least in part, by alloantigen-independent factors o ther than TVS-related tissue ischemia.