ROLE OF HYPERCHOLESTEROLEMIA IN ACCELERATED TRANSPLANT CORONARY VASCULOPATHY - RESULTS OF SURGICAL THERAPY WITH PARTIAL ILEAL BYPASS IN RABBITS UNDERGOING HETEROTOPIC HEART-TRANSPLANTATION

Background: We tested the hypothesis that plasma cholesterol lowering action of partial ileal bypass (PIB) is beneficial in mitigating accel erated transplantation coronary vasculopathy. Methods: Forty-one New Z ealand white rabbits were randomized to receive a normal (n = 21) or 1 % cholesterol diet (n = 20). They underwent heterotopic heart transpla ntation with sham-PIB (n = 19) or PIB (n = 22) and immunosuppression w ith cyclosporine A (CyA). Results: CyA increased plasma cholesterol of rabbits receiving a normal diet. This effect was mitigated by PIB (10 1 +/- 50 mg/dl CyA vs baseline 24 +/- 8, p < 0.001; vs 54 +/- 25 mg/dl with PIB, p < 0.05). In cholesterol-fed rabbits, PIB decreased plasma cholesterol levels (520 +/- 236 mg/dl PIB vs baseline 720 +/- 359, p < 0.05; vs 1502 +/- 253 mg/dl with sham PIB, p < 0.00001). Coronary ar teries (CA) of 21 5-week survivors were evaluated by light microscopy and digital morphometry. No rejection was noted. Histologic study reve aled vasculopathy in 3% of 705 native and 18% of 654 transplant CA (p < 0.05). Graft vasculopathy (GV) was present in 25% of 365 CA of sham- PIB and 10% of 289 CA of PIB rabbits (p = 0.07). In cholesterol-fed ra bbits, GV was characterized by fatty proliferative lesions in 75% of 9 1 pathologic CA of sham and 21% of 28 pathologic CA of PIB rabbits (p < 0.05). Graft intimal hyperplasia was not correlated with cholesterol intake or PIB and was present in 18 of 119 pathologic CA. Conclusions : GV was characterized by fatty intimal proliferation, fibrous intimal hyperplasia, and a ''mixed type.'' Fibrous intimal hyperplasia develo ped in native and transplanted hearts, and CyA seemed to promote this state. Hypercholesterolemia promoted fatty proliferative lesions, wors ening GV. PIE significantly decreased total cholesterol and retarded f atty proliferation of CA of native and transplanted hearts but did not prevent intimal hyperplastic vasculopathy. Therapy of hypercholestero lemia is recommended to at least mitigate the fatty intimal proliferat ion of GV.