Clinical And Experimental Study On Prevent And Therapy For Restenosis After Extremity Artery Bypass Grafting

Background:Vascular bypass grafting is the most common procedure for peripheral artery disease(PAD). Restenosis and obliterans is the first and foremost complication of extremity artery bypass grafting. How to deal with this complication, resume limbs blood supply, increase the patency of reoperation, is a troublesome problem which vascular surgeon must face. Irrelevant surgical treatment, do not settle the symptom of ischemia, on the contrary may be amputation, even threaten patient's life. Section I:Clinical study of extremity artery bypass graftingObjective:To evaluate the effect of arterial bypass grafting on arteriosclerosis obliterans and its influencing factors.Methods:Retrospectively reviewed the 150 patients with extremity arteriosclerosis obliterans, who undenvent arterial bypass grafting,11Omales,40 females. All the patients do the Doppler ultrasound or (and) angiography. We selected three variables for statistic analysis:(1) procedure of vascular bypass grafting:routine procedure /unroutine procedure; (2) surgical site:above-kneel/below-kneel; (3) run-off satuts:excellent or good or poor run-off。Results:In the 150 patients, there were no significant difference in patinets age (P>0.05). risk factors (including:hypertention, diabetes, smoking) were no significant difference (P>0.05). The postreoperative complications Included:graft restenosis(62) and infection(2);1 month effect after operation of different surgical site after treatment were significant difference (χ2=8.4673, P=0.0373),different run-off satuts were significant difference (χ2=73.2098, P<0.0001),different procedure were no significant difference (χ2=4.1443, P=0.2463); Patency of different surgical site after treatment were significant difference (χ2=10.7771, P=0.0010),different run-off satuts were significant difference (χ2=15.9497, P=0.0003),different procedure were no significant difference (χ2=0.0656, P=0.7978). different procedure of 1 month effect after operation for aorto-iliac occlusive were significant difference (χ2=20.4775, P=0.0001), patency were no significant difference (χ2=3.2454, P=0.0716)conclusions:Artery bypass grafting can improve the quality of life, to save the severe ischemia, gangrene of the limb; run-off, the distal anastomosis site are the key factor which affecting effect and patency rate post-peration.Section II:Clinical study on surgical therapy for restenosis after artery bypass graftingObjective:To analyse factors of reoperation success rate for arterial bypass occlusion, search reasonable surgical therapy, improve limb salvage rates and decrease mortality.Methods:Retrospectively reviewed the 33 patients(331imbs) with restenosis and obliterans after arterial bypass grafting who undenvent reoperation,21 males,12 females, with a mean age of 63.97 years (range from 28 years to 80 years). Reviewed general information,occlusion condition(the boundary is 30 d of postoperation, within 30 d is early failure,after 30 d is middle and late failure),preoperation imaging examination,surgery record, postoperation follow-up.We selected four dichotomous variables according to the risk factors and surgical treament for statistic analysis:(1)grafts used:saphenous vein or synthetic grafts; (2) previous procedure of vascular bypass grafting:routine procedure /unroutine procedure; (3) reoperation procedure:construction of a new graft/thrombectomy with or without local revision;(4) reoperation run-off satuts:excellent or good or poor run-off。Results:In the 33 patients, there were no significant difference in patinets age and gender(P>0.05). risk factors including:hypertention(17), diabetes(11), hyperlipidemia(13), smoking(19);grafts used:saphenous vein(10), synthetic grafts(23); previous procedure of vascular by pass graft in:routine procedure(25), unroutine procedure(8); early failure(7), middle and late failure(26); The indications for reoperations were nonhealing ulcer or gangrene (7),ischemic rest Pain (23), severe claudication(3); reoperation procedure:I stage amputation(2), take out synthetic graft(1),new vascular bypass grafting (20) thrombectomy with or without local revision(10). reoperation run-off satuts:excellent run-off(8),good run-off(12), poor run-off(10). The postreoperative complicatinos Included:graft infection(4),amputation wound necorsis(1), acute renal failure (1), respire failure (1). In the first operation, average patency of routine procedure was higher than unroutine procedure, saphenous vein was higher than synthetic grafts (P>0.05). After six months of reoperation, patency was lower than limb salvage rate in no graft and poor run-off; After twelve months of reoperation, patency was lower than limb salvage rate in new graft and good run-off. After reoperation,average patency time of new vascular bypass grafting was higher than no graft (P<0.05),good run-off was higher than poor run-off (P<0.05); average limb salvage time of new vascular bypass grafting was higher than no graft (P> 0.05), good run-off was higher than poor run-off (P< 0.05)conclusions:Positive reoperation for patients with ischemic rest pain or ulcer on rescue limb and life is signality; Reoperation procedure and run-off satuts influent prognosis; effection of new vascular bypass grafting is better. Background:Artery bypass graft is the main surgical method to treat the lower extremity arteriosclerosis obliterans (ASO)disease. Whatever saphenous vein or vascular prosthesis, Some research shows that after the artery bypass graft surgery, the occlusion rate grows annually, Therefore, the method to avoid the grafts'restenosis has become a hotspot. Vascular smooth muscle cell proliferation play a key role in the process of restenosis after reconstructive Vascular Operation. Some research shows that angiotension-II(Ang-II) increases after the artery bypass graft surgery, AngⅡand Angiotensinll type 1 Receptor (AT1R) combination stimulate a series of reactions, then startup cycles of the cells, drive migration and proliferation of VSMC. Angiotension—Ⅱreceptor(AT1R) antagonist is a new kind of antihypertensive agents, as well as a hot point of research in the world. Epidemiological studies have confirmed that hypertension is the occurrence of peripheral atherosclerotic disease were independent risk factors. Some studies also show:in prostate cancer,pancreatic cancer,esophageal cancer and other tumors, AT1R antagonist show a therapeutic effect, subjects were not confined to hypertensive patients. This study is based on the results of these studies,Explore the possibility of the bypss graft patients with AT1R antagonist for prevention and control,regardless of whether hypertensive patients.Objective:To study the influences and mechanism of Valsartan on the effects of proliferation caused by angiotension-II in vascular smooth muscle cells of rats; Can valsartan be a conventional medicine to deal with restenosis after reconstructive Vascular Operation, provide theoretical and experimental evidence for clinical.Methods:Subcultures between 3 and 5(P3-5) VSMC were used in the study. different concentration Ang II was used to stimulate VSMC proliferation, select Ang II experimental concentration. Experiment was divided into four groups:①Control group;②Valsartan group;③AngⅡgroup;④Valsartan+AngⅡgroup. MTT was used to measure existent ratio of cells, Flow cytometer was used to measure cycles of the cells, Flow cytometer was used to measure the apoptosis rate, The levels of different protein in cultured VSMCs were detected by Western blotting. Results:1.Successfully cultured rats smooth muscle cells and they can continuous passage.2. different concentration AngⅡwas used to stimulate VSMC proliferation, select 10-7M Ang II as experimental concentration. After 24 hours, VSMCs number was increased induced by Angll, reached the highest climax at 48 hours, and then droped, but compared with control group at 96 hours, had statistics significant (p<0.05); which affection was inhibited by valsartan at different time point after 24 hours(P<0.05); there is no notable difference compared Control group with Valsartan group(P>0.05)。Flow cytometry analysis showed that the cellcycle:After affection 24 hours, cells proportion of AngⅡgroup in S phase rised, and can be inhibited by valsartan.3.Flow cytometry analysis showed that the rate of apoptosis increased markedly in Valsartan＋Ang II group (P<0.05), and no statistics difference in other groups (p>0.05).after 24 hours of VSMCs induced by Angll, Westernblot test showed that the use of Valsartan can inhibit the expression of MMP-9,MMP-2,STAT3 Protein; the expression of Bax Protein ascend and Bcl-2 Protein drop.conclusions:1)Establish a simple and effective method to culture rat vascular smooth muscle cells, and its cells can consecutive Passages to meet the experimental requirements.2) Alsartan may antagonize AngⅡinduced proliferation in the cultured of VSMC.3) Alsartan may have the effect on the expression of migration,proliferation and apoptosia in vascular smooth muscle cells, and inhibited VSMC proliferation and intimal hyperplasia.