Abstract
Objective To study the beneficial effects of LMWH on rat cardiac allograft vasculopathy and the underlying mechanisms. Methods Hearts from SD rats were heterotopically grafted into the abdomen of Wistar male recipients. Recipients were divided into 3 groups randomly as follows: control group,LMWH group and HL group with 30 rats in each group. Recipients in control group were treated with cyclosporine A (CsA) for 10 days from 0 to 9 postoperative days to avoid acute rejection and allow for the development of chronic rejection. In addition, recipients in LMWH and HL groups were treated with LMWH (2 mg·kg·d-1) till sacrificed. The NOS inhibitor, L-nitro-arginine methyl ester (L-NAME) was also administered in HL group at a dosage of 10 mg·kg-1·d-.At 30,60 and 90 days post operation, 10 recipients in each group were sacrificed for the harvest of blood sample and the graft. While recipients were sacrificed, hearts were harvested for cardiac allograft vasculopathy (CAV) score,and blood samples were collected for determination of nitric oxide (NO) and endothelin-1 (ET-1). Results As the time passed,CAV score was increased,while NO and ET-1 were decreased gradually. CAV score and ET-1 in LMWH group were lower in all 3 time points. CAV scores were 1.1±0.6,1.6±0.7,2.1±0.6,and ET-1 were (133±26)pg/ml, (106±16)pg/ml,(79±16)pg/ml in 30,60 and 90 days, respectively. NO levels were (171±22) μmol/L, (122±27) μmol/L, and (92±17)μmol/L in 50,60 and 90 days, respectively. Compared with the other two groups, the development of CAV was attenuated in LMWH group at all 3 time points (P<0.05). And recipients in LMWH group had higher NO and lower ET-1 levels (P<0.05). Conclusion LMWH could attenuate but not prevent the development of CAV,and the beneficial effect may be due to the increase of NO and decrease of ET-1. The beneficial effects of LMWH could be prevented by L-NAME. Key words: Heparin, love-molecular-weight; Heart tranaplantation; Coronary stenosis; Nitric oxide; Rats
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