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Several studies have indicated that antigen-presenting endothelial cells represent the primary initiator of acute arterial graft rejection, leading to decreased arterial patency rates. Patency rates dramatically increase upon endothelial removal (denudation) prior to orthotopic transplantation into antigenically disparate hosts. Although patent, the biomechanical and functional changes seen in these allograft vessels (ACI rats to Lewis rats) have not been described. The present investigation examined functional differences between these allograft arteries and normal rat femoral arteries. Moreover, endothelial removal may also alter function; thus, an autograft injury model (Lewis to Lewis) was employed to discern the differences between injury and rejection. The results indicate that denudation injury alone caused no change in the passive stress-strain curve, the muscle length at which stress was maximum (L_o), or in phenylephrine- or nitroglycerin-induced concentration-response curves. Similarly, concentration-response curves were not affected by allograft transplantation; however, both the passive stress-strain curve and L_o values were shifted to significantly longer lengths (0.25 and 0.20 mm, respectively), suggesting an increase in arterial plasticity but not compliance. Furthermore, allografts produced significantly weaker KCl-induced contractions than did autografts (22 vs. 66% of control values, p < 0.05). Acetylcholine maximally relaxed phenylephrine-contracted arteries in the following descending order. ACI > Lewis > autograft > allograft. In conclusion, these data suggest that vascular rejection involves subendothelial tissues, is distinct from vascular injury, and that the denudation allograft transplantation model can be employed to examine this process.

The vascular endothelium plays an important and complex role in vascular allograft rejection. Antigens expressed by the endothelium can act to promote and be the target of rejection reactions, which often lead to thrombosis and ischemic necrosis of the allograft. In this study, segments of femoral artery and femoral vein with or without endothelium were grafted between allogenic or autologous control rats. Immunocompetent Lewis (RT1(1] recipient rats were randomly selected for groups (N = 14 for each) receiving the following: ACI- (RT1a) allografts with intact endothelium, allografts with endothelium removed before operation, autografts with endothelium, and autografts with endothelium removed. Rejection was assessed by graft patency as well as morphologic and ultrastructural changes. At 5 days, the allografts with intact endothelium were totally occluded, whereas allografts without endothelium remained patent, as did autologous control grafts with or without endothelium. Two additional groups (N = 14 each) receiving the de-endothelialized allografts or autografts were examined at 120 days after operation, revealing that grafts in both groups were still patent and had been re-endothelialized. These findings indicate that physical removal of vascular endothelium may depress vessel allograft rejection without immunosuppressive therapy.

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