MORPHOMETRIC ANALYSIS OF NEOINTIMAL FORMATION IN MURINE CARDIAC ALLOGRAFTS .2. RATE AND LOCATION OF LESION DEVELOPMENT

Background. Transplant vascular sclerosis (TVS) is manifested in trans planted human and murine hearts as a concentric, intimal lesion. The p urpose of this study was to characterize the rate, location, and inten sity of developing TVS lesions in murine cardiac allografts using quan titative morphometric analysis. Methods. Murine cardiac allografts, tr eated with the immunosuppressant gallium nitrate, were explanted at 30 , 60, and 90 days after transplant. The grafts were histologically sta ined and evaluated for intimal thickening by deriving a neointimal ind ex (NI) using a computerized image-analysis system. Results. In cardia c allografts, mild vascular lesions of varying NI were detectable by d ay 30 and lesion severity increased significantly by day 60. Thereafte r, average lesion severity stabilized, although the percentage of affe cted vessels continued to increase from day 30 to day 90. In contrast, day-90 cardiac isografts showed little to no TVS development. Vascula r lesions developed randomly without regard for vessel location or siz e. TVS developed more regularly in vessels of the interventricular sep tum than in the right or left ventricular walls. The degree of TVS dev elopment fluctuated along the length of individual vessels, even as la te as 90 days after transplant. The smaller vessels (<85 mu m in diame ter) appeared to occlude more quickly than the larger vessels.Conclusi ons. TVS developed reproducibly in a random pattern throughout cardiac allografts over a 1-month to 3-month period after transplant. This de velopment can be quantitatively monitored by computerized morphometric analysis. In general, under these experimental conditions, 30-day car diac allografts seem to provide a useful experimental model for studyi ng early aspects of TVS, whereas 60-day allografts may be better suite d for analysis of advanced TVS.