Experimental Study Of Local Intra-vascular Administration With Paclitaxel To Inhibit Venous Intima-media Hyperplasia To Prevent Stenosis

Background In the field of diagnosis and treatment for vascular disease, scholarsdomestic and abroad paid more attention to arterial diseases. Drug-elutingballoon(DEB), as the latest research findings of vascular re-stenosis after PTA, has beensuccessfully applied to clinic, however, little attention has been paid to prevent venousre-stenosis after PTA. Therefore, we performed this study to prevent and treat venousstenosis and re-stenosis after PTA by local administration with paclitaxel.Objective To evaluate the efficacy and safety of a novel method to prevent and treatvenous stenosis by local administration with paclitaxel.Materials and methods Twenty-four male New Zealand white rabbits, aged5monthsand weighing2.5kg～3.0kg, were randomly divided into2groups: Group A(controlgroup, n=12) and Group B(experimental group, n=12). Balloon dilatation wasperformed on the right femoral vein of group A and group B and rabbits of group Bwere locally infused the admixture of paclitaxel and iopromide subsequently(total dose0.8mg～1.2mg). Both Group A and B were received the same treatment ofanti-infection and antiplatlete after operation. Liver function and renal function werechecked at pre-operation and1week、1month post-operation; vascular ultrasound wasperformed at pre-operation and1week、1month、2months post-operation; DSA wasperformed at pre-operation and3months post-operation; pathologic examination wasperformed at3months post-operation, HE stain、Masson stain and elastic tissue stainwere preformed to observed the changes of histological of the femoral vein wall.Results2rabbits of Group A were died of air embolization during operation,1rabbit of Group A was died with unclearly reason,1rabbit of Group B was died of hemorrhage,2rabbits of both Group A and B were died of infection. Vascular ultrasound: at1week、1month and2months post-operation, vessel lumen stenosis of two groups were observedand the dilated femoral vein wall of group A and B was much thicker than that beforeoperation. DSA:3months post-operation, the vessel diameter of two groups wasdecreased significantly (PA=0.001，PB=0.001), and the decreasing degree of vesseldiameter of Group A was significant higher than that of Group B (PA-B=0.001).Pathologic examination: HE stain、Masson stain and elastic tissue stain showed that theintima-media thickness of Group A was significant higher than that of Group B; thevolume of VSMC of intima and media of Group A was significant bigger than that inGroup B; the quantity of collagen fiber and elastic fiber of intima and media of Group Awas more than that in Group B as well. Liver function and renal function: ALT、AST、TBIL、DBIL、BUN and Cr, there is no significant difference between2groups beforeoperation(PALT=0.579、PAST=0.6、PTBIL=0.86、PDBIL=1、PBUN=0.611、PCr=0.579);the levels of ALT and AST were increased in the both of Group A and Group B afteroperation one week, the differences have statistically significant(Group A: PALT=0.001、PAST=0.002, Group B: PALT=0.001、PAST=0.001), the differences of otherindicators have no significant (Group A: PTBIL=0.549、PDBIL=0.504、PBUN=0.35、PCr=0.315, Group B: PTBIL=0.775、PDBIL=0.84、PBUN=0.864、PCr=0.475); thedifferences of all the indicators have no significant after operation one month in the twogroups respectively(Group A: PALT=0.651、PAST=0.395、PTBIL=0.104、PDBIL=1、PBUN=1、PCr=1, Group B: PALT=0.442、PAST=0.847、PTBIL=0.343、PDBIL=1、PBUN=0.439、PCr=1); comparison between Group A and Group B, the differences ofall the indicators have no significant during the same period of post-operation(afteroperation1week: PALT=0.492、PAST=0.569、PTBIL=0.715、PDBIL=0.622、PBUN=0.948、PCr=0.995，after operation1month: PALT=0.514、PAST=0.862、PTBIL=0.743、PDBIL=1、PBUN=0.672、PCr=0.572).Conclusion The novel way of intra-venous administration with paclitaxel caneffectively inhibit proliferation, migration and exocytosis of VSMC, inhibit neointimal and medial hyperplasia and reduce the rate of re-stenosis. There is no significant changeof liver and renal function between pre-operation and post-operation.