Multidimensional assessment of graft vascular disease (GVD) in aortic grafts by serial intravascular ultrasound in rhesus monkeys

Background. Graft vascular disease (GVD) is an incompletely understood proc ess and the primary cause of late allograft failure. A nonhuman primate mod el was established to study the progression of GVD by using serial intravas cular ultrasound (IVUS). Methods. Aortic allografts were transplanted below the inferior mesenteric arteries (IMA) into 6 rhesus monkeys. Removed and re-implanted aortic segme nts between renal arteries, and the inferior mesenteric arteries served as autografts. IVUS was performed at days 0, 24, 52, 80, and 98 after transpla ntation. Vessel area (VA) and lumen area (LA) were measured from each cross -section at 0.5 mm intervals. Intimal index (II=100x (VA-LA/VA)) and corres ponding vessel volumes were calculated for the whole grafts. Histologic fea tures were assessed from autopsy samples using computerized morphometric me thod and a score from 6 to 3 for GVD (0=none, 3=severe). Results. In allografts, vessel volume and luminal volume decreased signific antly (P<0.05 for both) and the intimal index increased from 12% to 59% by day 98, These parameters remained unchanged in autografts, Histologic analy sis of allografts showed concentric intimal hyperplasia and scattered monon uclear cell accumulations, whereas the autografts had only occasional eccen tric intimal changes. The GVD-scores were significantly higher in allograft s than in autografts (median 3 vs. 1, P=0.042). Conclusions. We introduce a nonhuman primate model of GVD that enables seri al IVUS assessments of multiple parameters of GVD. Concentric intimal proli feration and decrease of vessel dimensions was observed in allografts as a consequence of alloimmunity. This is a potential new model for studying new therapies to prevent GVD or halt its progression.