Experimental Study Of Endovascular Radiation Prevents Restenosis In Rabbits Following Carotid Endarterectomy

Background: Carotid endarterectomy(CEA) is a classical surgery in the prevention of ischemic cerebral vascular disease(CVD),but restenosis(RS) after the surgery appreciably limits its media-long term effects and its extensive clinical application. Object:This study is to investigate the efficacy,feasibility and safety of a radioisotope 32P liquid-filled balloon catheter in the prevention of RS in rabbits following CEA and to explore the possible mechanisms of endovascular radiation(ER) through following two aspects.(l) To observe the changes in the levels of plasma nitric oxide(NO) and endothelin-l(ET-l) and to find the possible mechanisms of ER.(2)To investigate the impact of ER on the proliferation and apoptosis of vascular smooth muscle cells in the injuried arterial walls in rabbits and to observe the effect of ER on intimal hyperplasia and vascular remodeling in injuried rabbits carotid with histopathological examination. Methods:(l)Twenty four rabbits were randomly divided into three groups following carotid endarterectomy each n=8 and were allocated to receive aradiation dose of 0,10,20Gy(32P) respectively.Changes in the levels of plasma nitric oxide(NO) and endothelin-l(ET-l) were measured 3 day before operation and 3 ,7,14,28 day after operation.(2) Forty rabbits following carotid endarterectomy were randomly divided into four groups each n=10 and given a radiation dose of 0,10,20,40Gy(32P) respectively.Rabbits were killed 3 ,7,14,28,56 days after operation The target segments were cut down and histopathologic analysis was conducted.Results:(l)The plasma NO was markedly increased and ET-1 was markedly decreased in endovascular radiation groups compared with the control groups. The results were similar in the two groups(10Gy versus 20Gy).(2)Compared with the control groups,SMCs proliferation in medial was significantly inhibited and SMCs apoptosis in medial was significantly increased in endovascular radiation groups(P<0.01).The effect was much more evident in 20GY and 40GY groups compared with 10GY group(P<0.01). The expressions of PCNA and apoptosis of SMCs in medial were increased 3 days after operation and both reached its peak at the 7th day. Neontimal and medial thickness of carotid were increased gradually,especially evident two weeks after operation. Compared with the control groups,ER with 10GY,20GY and 40GY all significantly reduced neointimal and medial thickness and increased the lumen area after operation(P<0.05). Conclusions:(l)The endovascular radiation may inhibit smooth muscle cell proliferation and migration by increasing NO and decreasing the level of ET-1 and thus prevent restenosis. Changes of the levels of plasma NO and ET-1 could be an indiation of the restenosis. (2)Endovascular radiation is feasible and effective in reducing neointimal formation and improving vascular remodeling preventing RS. ER may prevent restenosis by inhibiting smooth muscle cell proliferation and migration,and inducing SMC apoptosis.The effects was related to the delivered dose. The doses of10GY,20GY and 40GY are all safe and feasible.Smooth muscle cell proliferation and apoptosis were revealed in the early period after balloon injury, while the increasement of neontimal thickness and medial thickness and negative remodeling of vascular lumen were showed later.