Abstract
144 Arterial intimal thickening produced by transplant vascular disease (TVD) is the major complication limiting long-term graft survival after solid organ transplantation. We have shown that PVS-treated heart transplant recipients have decreases in the incidence and progression of TVD. It has been hypothesized that the combination of PVS, an HMGCoA reductase inhibitor, and CS in these patients leads to this reduction in TVD. The purpose of this study is to examine the effects of PVS and CS on arterial intimal thickening in a transplant model. Femoral arteries from Brown-Norway rats were transplanted into Lewis rats. Recipient rats were gavaged with PVS (20mg/kg/d), CS(5mg/kg/d) or a combination of PVS and CS beginning either postoperatively(Grp I) or 3 days preoperatively (Grp II). There were six rats in each treatment arm. The transplanted femoral vessels were harvested at postop day 40 and were examined using morphometric and histopathologic techniques. In Grp I, there were no differences in intimal area (mm2, ± S.E.) comparing PVS, CS or PVS+CS treated rats with controls despite a trend towards less inflammation with CS treatment and sparing of medial necrosis with PVS+CS treatment. In Grp II, there was a synergistic decrease in intimal area in PVS+CS treated rats (p<0.05) compared with controls, CS or PVS alone treated rats (see graph). In addition, in Grp II, CS again showed decreased inflammation and PVS+CS-treated rats had minimal medial necrosis despite significant inflammation. FigureIn conclusion, PVS and CS synergistically inhibit arterial intimal thickening when treatment is begun 3 days prior to transplant. Given the lack of intimal thickening despite the presence of mononuclear inflammation, pretreatment with this combination of agents may prevent the elaboration of growth factors responsible for TVD. These findings may help explain the decreased incidence of TVD noted on our PVS-treated heart transplant patients.
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