Prolonged systemic delivery of tirofiban in a thrombus-laden saphenous vein graft

Results from previous trials have shown conflicting results from local delivery of thrombolytic agents to diminish thrombus burden before intervention in native coronary arteries and saphenous vein grafts. We described a patient with an acute coronary syndrome who was treated for 24 hours with systemic tirofiban (Aggrastat), a glycoprotein IIb/IIIa inhibitor, for the treatment of a degenerated saphenous vein graft with a TIMI grade 4 thrombus (large-sized thrombus). Angiographic evaluation 48 hours later revealed complete resolution of the thrombus with normal coronary blood flow.     

The clopidogrel after surgery for coronary artery disease (CASCADE) randomized controlled trial: clopidogrel and aspirin versus aspirin alone after coronary bypass surgery [NCT00228423]

Background

Saphenous vein graft disease remains a major limitation of coronary artery bypass graft surgery. The process of saphenous vein intimal hyperplasia begins just days after surgical revascularization, setting the stage for graft atherosclerotic disease and its sequalae. Clopidogrel improves outcomes in patients with atherosclerotic disease, and is effective at reducing intimal hyperplasia in animal models of thrombosis. Therefore, the goal of this study will be to evaluate the efficacy of clopidogrel and aspirin therapy versus aspirin alone in the prevention of saphenous vein graft intimal hyperplasia following coronary artery bypass surgery.

Methods

Patients undergoing multi-vessel coronary artery bypass grafting and in whom at least two saphenous vein grafts will be used are eligible for the study. Patients will be randomized to receive daily clopidogrel 75 mg or placebo, in addition to daily aspirin 162 mg, for a one year duration starting on the day of surgery (as soon as postoperative bleeding has been excluded). At the end of one year, all patients will undergo coronary angiography and intravascular ultrasound assessment of one saphenous vein graft as selected by randomization. The trial will be powered to test the hypothesis that clopidogrel and aspirin will reduce vein graft intimal hyperplasia by 20% compared to aspirin alone at one year following bypass surgery.

Discussion

This trial is the first prospective human study that will address the question of whether clopidogrel therapy improves outcomes and reduces saphenous vein graft intimal hyperplasia following cardiac surgery. Should the combination of clopidogrel and aspirin reduce the process of vein graft intimal hyperplasia, the results of this study will help redefine modern antiplatelet management of coronary artery bypass patients.     

High density lipoprotein oxidation: in vitro susceptibility and potential in vivo consequences

Elevated levels of plasma high density lipoprotein (HDL) are strongly predictive of protection against atherosclerotic vascular disease. HDL particles likely have several beneficial actions in vivo, including the initiation of reverse cholesterol transport. The apparent importance of oxidative modification of low density lipoprotein in atherogenesis raises the question of how oxidative modification of HDL might affect its cardioprotective actions. HDL is readily oxidized using numerous models of lipoprotein oxidation. In vitro evidence suggests oxidation might impair some protective actions, but actually enhance other mechanisms induced by HDL that prevent the accumulation of cholesterol in the artery wall. This article reviews the current literature concerning the relative oxidizability of HDL, the structural changes induced in HDL by oxidation in vitro, and the potential consequences of oxidative modification on the protective actions of HDL in vivo.     

Tocopherol-mediated peroxidation of lipoproteins: implications for vitamin E as a potential antiatherogenic supplement.

The 'oxidation theory' of atherosclerosis proposes that oxidation of low density lipoprotein (LDL) contributes to atherogenesis. Although little direct evidence for a causative role of 'oxidized LDL' in atherogenesis exists, several studies show that, in vitro, oxidized LDL exhibits potentially proatherogenic activities and lipoproteins isolated from atherosclerotic lesions are oxidized. As a consequence, the molecular mechanisms of LDL oxidation and the actions of alpha-tocopherol (alpha-TOH, vitamin E), the major lipid-soluble lipoprotein antioxidant, have been studied in detail. Based on the known antioxidant action of alpha-TOH and epidemiological evidence, vitamin E is generally considered to be beneficial in coronary artery disease. However, intervention studies overall show a null effect of vitamin E on atherosclerosis. This confounding outcome can be rationalized by the recently discovered diverse role for alpha-TOH in lipoprotein oxidation; that is, alpha-TOH displays neutral, anti-, or, indeed, pro-oxidant activity under various conditions. This review describes the latter, novel action of alpha-TOH, termed tocopherol-mediated peroxidation, and discusses the benefits of vitamin E supplementation alone or together with other antioxidants that work in concert with alpha-TOH in ameliorating lipoprotein lipid peroxidation in the artery wall and, hence, atherosclerosis.     

Smoothelin and intermediate filament proteins in human aortocoronary saphenous vein by-pass grafts

The aim of this immunohistochemical investigation was to study the distribution of the novel cytoskeletal protein smoothelin and the intermediate filament proteins vimentin and desmin in normal human great saphenous vein and in human aortocoronary by-pass vein grafts. Smoothelin was present in most smooth muscle cells in the media of the native vein. In the neointima of the vein grafts that had been in situ for three months or more, smoothelin was, in general, present only in few smooth muscle cells. Desmin was distributed in the same pattern as smoothelin in the native great saphenous vein. When desmin and smoothelin were present in the neointima, smoothelin was detected in more cells than desmin. Vimentin was present in most cells in all wall layers of both the native saphenous vein and the vein grafts. Vascular smooth muscle cells containing vimentin but not desmin or smoothelin are the principal cells in the neointima of human aortocoronary vein grafts. In some grafts, however, all three cytoskeletal proteins were detected in the neointima. The distribution of smoothelin and desmin in aortocoronary vein grafts support the postulate that these proteins are expressed mainly in the contractile smooth muscle cell phenotype.     

Smoothelin and Intermediate Filament Proteins in Humanaortocoronary Saphenous Vein By-pass Grafts

The aim of this immunohistochemical investigation was to study the distribution of the novel cytoskeletal protein smoothelin and the intermediate filament proteins vimentin and desmin in normal human great saphenous vein and in human aortocoronary by-pass vein grafts. Smoothelin was present in most smooth muscle cells in the media of the native vein. In the neointima of the vein grafts that had been in situ for three months or more, smoothelin was, in general, present only in few smooth muscle cells. Desmin was distributed in the same pattern as smoothelin in the native great saphenous vein. When desmin and smoothelin were present in the neointima, smoothelin was detected in more cells than desmin. Vimentin was present in most cells in all wall layers of both the native saphenous vein and the vein grafts. Vascular smooth muscle cells containing vimentin but not desmin or smoothelin are the principal cells in the neointima of human aortocoronary vein grafts. In some grafts, however, all three cytoskeletal proteins were detected in the neointima. The distribution of smoothelin and desmin in aortocoronary vein grafts support the postulate that these proteins are expressed mainly in the contractile smooth muscle cell phenotype.     

Endoscopic Vascular Harvest in Coronary Artery Bypass Grafting Surgery: A Consensus Statement of the International Society of Minimally Invasive Cardiothoracic Surgery (ISMICS) 2005

OBJECTIVE:: This purpose of this consensus statement was to compare endoscopic vascular graft harvesting (EVH) with conventional open vascular harvesting (OVH) in adults undergoing coronary artery bypass grafting (CABG) surgery and to determine which resulted in improved clinical and resource outcomes. METHODS:: Before the consensus conference, the consensus panel reviewed the best available evidence, whereby systematic reviews, randomized trials, and nonrandomized trials were considered in descending order of importance. Evidence-based statements were created, and consensus processes were used to determine the ensuing statements. The AHA/ACC system was used to label the level of evidence and class of recommendation. RESULTS:: The consensus panel agreed upon the following statements: CONCLUSIONS:: Given these evidence-based statements, the consensus panel stated that EVH should be the standard of care for patients who require saphenous vein grafts for coronary revascularization (Class I, Level B). Future research should address long-term safety, cost-effectiveness, and endoarterial harvest.     

选择性冠状静脉动脉化搭桥术中不同移植物的应用疗效比较

目的:对比选择性冠状静脉动脉化(SCVBG)搭桥治疗弥漫性右冠状动脉狭窄病变中选择乳内动脉和大隐静脉作为桥血管的治疗效果。方法:选择2008年10月到2014年10月在我院行SCVBG搭桥的84例患者资料,其中选择大隐静脉作为桥血管进行冠状静脉动脉化搭桥患者46例(大隐静脉桥组),选择乳内动脉作为桥血管进行冠状静脉动脉化搭桥患者38例(乳内动脉桥组)。随访记录两组患者的生存情况、近期复查超声心动图、冠状动脉CTA及心绞痛复发率。结果:乳内动脉桥组患者总生存率(100%)明显高于大隐静脉桥组(82.6%)(P0.05)。乳内动脉桥组患者桥血管和心中静脉通畅率(100%)明显大于大隐静脉桥组(54.35%)(P0.05)。两组患者左心室射血分数(LVEF)较治疗前明显增加,左心室舒张期末内径(LVEDD)较治疗前明显减小(P0.05)。治疗后,乳内动脉桥组患者心绞痛复发率明显小于大隐静脉桥组(P0.05)。结论:SCVBG搭桥治疗弥漫性右冠状动脉狭窄病变中,选择乳内动脉桥效果优于大隐静脉桥,能明显提高桥血管和心中静脉通畅率,降低心绞痛复发率。     

Gore-Tex small-vessel angioplasty: A suitable substitute for the use of autogenous saphenous vein grafts

Autogenous saphenous vein has been the material of choice for small-vessel angioplasty and for circulatory access graft reconstruction. In an effort to conserve autogenous saphenous vein, we used expanded polytetrafluoroethylene (PTFE) grafts in 45 patients over a 12-month period. We used Gore-Tex(*) to reconstruct 17 circulatory access grafts, 16 carotid arteries, two brachial arteries, seven femoral arteries, and three popliteal anterior or posterior tibial arteries. The indications for reconstruction were chronic occlusion of the access grafts, trauma to the brachial and anterior tibial arteries, and atherosclerotic disease of the carotid, femoral, and popliteal-tibial arteries. Of the reconstructed circulatory access grafts, one failed immediately because of technical problems in the conduit, and one failed 11 months after reconstruction. All other grafts have functioned well and have produced a marked improvement in flow. Of the 28 patients who underwent reconstruction of arteries measuring 3 mm or less, two had patent arteries but died shortly after operation. The remaining 26 have been followed for one to 43 months. All reconstructed arteries are patent, and there have been no instances of distal embolization or false aneurysm formation. From this brief experience, we conclude that Gore-Tex is a suitable short-term alternative to saphenous vein for small vessel arterioplasty; it also may be the material of choice for reconstructing the outflow tract of occluded access grafts.     

Evidence for lipid peroxidation in atherosclerosis

Lipid peroxidation may play a significant role in the initiation and progression of atherosclerotic plaque. Freshly harvested normal and atherosclerotic human aortic tissue, coronary arteries and explanted vein grafts were snap frozen at -70 degrees C. Folch reagent (chloroform-methanol 2:1, v/v) was used to extract lipids from the homogenates. These extracts were assayed for cholesterol, phospholipid and triglyceride content. Lipid peroxide complexes in vessels were measured fluorometrically. Atherosclerotic plaque from patients with aortic aneurysmal and occlusive disease and coronary artery disease contained significantly greater amounts of cholesterol (15.54 +/- 9.71 vs 3.39 +/- 1.14 mg/g tissue) than controls (p less than 0.01). Lipid peroxide fluorochromes were similarly elevated in all atherosclerotic tissue (4.159 +/- 1.065 vs 3.087 +/- 0.497 fluoro units/g tissue) compared to control (p less than 0.01) with significant elevations in saphenous vein grafts and occlusive aortic disease. Although lipid peroxidation and lipid accumulation occur in close association in atherosclerotic plaque, the role of lipid peroxides in the pathogenesis of atherosclerosis remains to be determined.     

Manual pressure distension of the human saphenous vein changes its biomechanical properties-implication for coronary artery bypass grafting

Patency rates of saphenous vein grafts following coronary artery bypass grafting (CABG) depend on multiple factors. Information regarding the impact of biomechanical properties of vein grafts on patency rates is not available. The objective of the present study was to evaluate whether uncontrolled manual pressure distension during routine preparation of the saphenous vein in CABG-induced changes in the biomechanical properties of the vein. The morphometric and stress-strain properties were studied in isolated segments of the saphenous vein from 12 patients undergoing elective CABG. Six segments were manually distended without pressure control and six were not distended. The mechanical test was performed as a ramp inflation using syringe pump. The vein dimensions were obtained from digitised images at different pressures as well as at the no-load and zero-stress states. The circumferences, the wall and lumen area, the wall thickness, and the outer diameter as function of the applied pressure were largest in the segments with uncontrolled manual distension compared to those without distension (P<0.05). The opening angle and the absolute value of the residual strains were lower (P<0.01) and the circumferential stress-strain curve shifted to the left, indicating the wall became stiffer with uncontrolled manual distension compared to those without distension (P<0.05). In conclusion, manual pressure distension changed the morphometric and biomechanical properties of the saphenous vein. The perspective is that studies on biomechanical properties on the saphenous vein may guide surgeons how to handle graft material without causing major changes of the biomechanical properties during harvesting and preparation.     

Percutaneous intervention of old degenerated saphenous vein grafts

The treatment of failing bypass grafts is difficult because repeat surgery carries a higher mortality rate than a first operation. Percutaneous intervention is more difficult because mechanical manipulation of these soft, friable atherosclerotic plaques have been associated with a significant rate of distal embolization, myocardial infarction, late restenosis and death. Balloon angioplasty alone has proven to have serious limitations in the treatment of older degenerated saphenous vein grafts (SVG). Although directional atherectomy yielded a higher angiographic success in a randomized trial, the restenosis rate was similar, and the procedural complications higher. The transluminal extraction catheter (TEC) has also shown significant limitations for the treatment of degenerated or thrombotic vein grafts with a significant procedural complication rate. A randomized trial comparing stenting versus balloon angioplasty in focal SVG lesions showed a higher freedom from major adverse cardiovascular events in the stent group, but there was no significant difference in the angiographic restenosis rates. More recently, rheolytic thrombectomy and mechanical thrombolysis have proven useful in treating thrombotic lesions in SVG. In addition, the recent development of distal protection devices appears very promising and will probably contribute to decreased distal embolization during percutaneous revascularization of these conduits.     

Human saphenous vein and coronary bypass surgery: ultrastructural aspects of conventional and "no-touch" vein graft preparations

Coronary artery bypass graft surgery (CABG) is routinely used to restore blood flow to diseased cardiac muscle due to coronary artery disease. The patency of conventional grafts decreases with time, which is due to thrombosis and formation of neointima. A primary cause of graft failure is the mechanical damage inflicted to the graft during harvesting, including removal of surrounding tissue accompanied by high pressure saline distension to overcome vasospasm (both causing considerable mechanical trauma). The aim of this study was to compare the ultrastructural features of human saphenous vein (SV) grafts harvested conventionally and grafts prepared using an atraumatic 'no-touch' harvesting technique introduced by Souza (1996). The results of this study showed a better preservation of the lumenal endothelium and medial vascular smooth muscle (SM) in 'no-touch' versus conventional grafts. A 'fast' (within 30 min) response of SM cells to conventional harvesting was noted where features of both SM cell division and apoptosis were observed. It is concluded that the 'preserved' nature of the 'no-touch' aortocoronary SV grafts renders them less susceptible to thrombotic and atherosclerotic factors than grafts harvested conventionally. These features are suggested to contribute to the improved early patency rate described using the no-touch technique of SV harvesting.     

Plasma adrenomedullin concentration is increased in patients with peripheral arterial occlusive disease associated with vascular inflammation

Adrenomedullin (AM), a potent vasodepressor, is known to have anti-atherosclerotic and anti-inflammatory effects. However, there is no information about its level in severe atherosclerotic diseases, such as peripheral arterial occlusive disease (PAOD). The present study investigated the plasma concentration of AM and several inflammatory parameters in 72 patients with and without PAOD. The plasma AM concentration in patients with PAOD was significantly higher than in those without PAOD. Its concentration had significant correlations with ankle-brachial index and Fontaine's stage. The plasma AM level also correlated with high sensitive C-reactive protein and interleukin-6. As an additional study, plasma levels of two forms of AM drawn from the femoral artery and saphenous vein were measured in 27 other subjects. Both mature and intermediate forms of plasma AM in the femoral artery and saphenous vein were higher in patients with PAOD than in those without PAOD. A significant step-up of the mature form of AM from the femoral artery to the saphenous vein was observed. Our findings indicate that the plasma AM concentration was elevated in patients with PAOD in proportion to the severity of the disease and associated with vascular inflammation. An increased production of AM in PAOD may play a protective role against advanced atherosclerosis with an inflammatory signature.     

CD68 expression in aortocoronary saphenous vein bypass grafts

Atherosclerosis commonly affects the arteries harvested from patients 70 years of age or older. Saphenous vein grafts appear to maintain a higher patency rate after coronary artery bypass grafting in these subjects. The infiltration of macrophages is an early step in saphenous vein graft atherosclerosis; however, little is known regarding the underlying mechanisms of infiltration. The objective of the present report is to evaluate the presence of CD68-positive cells in the saphenous vein wall and correlate initial CD68-positive infiltration to specific clinical and biochemical parameters and the graft patency rate as estimated in patients undergoing coronary artery bypass grafting. A total of 309 patients were allocated into two groups: A1 patients, who were between 50 and 70 years of age, and A2 patients, who were 70 years or older at the time of vein harvesting. CD68 expression was evaluated by immunohistochemistry. There were no significant differences between A1 and A2 patients regarding macrophage expression within any of the analyzed vascular regions. Saphenous vein macrophages were never present in the tunica intima unless they were also expressed in the media or the adventitia. The patients with CD68-positive cells in the tunica intima had a significantly higher number of bypass stenoses when compared with the subjects who did not have CD68-positive cells in this layer. These findings suggest that the CD68-positive cells (those that have not yet developed into foam cells) present in the intima of saphenous vein grafts might serve as a very early marker of graft occlusion.     

The geometry of unstented and stented pig common carotid artery bypass grafts

The long-term success of arterial bypass grafting with autologous saphenous veins is limited by neointimal hyperplasia (NIH), which seemingly develops preferentially at sites where hydrodynamic wall shear is low. Placement of a loose-fitting, porous stent around end-to-end, or end-to-side, autologous saphenous vein grafts on the porcine common carotid artery has been found significantly to reduce NIH, but the mechanism is unclear. In a preliminary study, we implanted autologous saphenous vein grafts bilaterally on the common carotid arteries of pigs, placing a stent around one graft and leaving the contralateral graft unstented. At sacrifice 1 month post implantation, the grafts were pressure fixed in situ and resin casts were made. Unstented graft geometry was highly irregular, with non-uniform dilatation, substantial axial lengthening, curvature, kinking, and possible long-pitch helical distortion. In contrast, stented grafts showed no major dilatation, lengthening or curvature, but there was commonly fine corrugation, occasional slight kinking or narrowing of segments, and possible long-pitch helical distortion. Axial growth of grafts against effectively tethered anastomoses could account for these changes. CFD studies are planned, using 3D MR reconstructions, on the effects of graft geometry on the flow. Abnormality of the flow could favour the development of vascular pathology, including NIH.     

Influence of smoking and plasma factors on patency of femoropopliteal vein grafts.

OBJECTIVE--To determine the effects of smoking, plasma lipids, lipoproteins, apolipoproteins, and fibrinogen on the patency of saphenous vein femoropopliteal bypass grafts at one year. DESIGN--Prospective study of patients with saphenous vein femoropopliteal bypass grafts entered into a multicentre trial. SETTING--Surgical wards, outpatient clinics, and home visits coordinated by two tertiary referral centres in London and Birmingham. PATIENTS--157 Patients (mean age 66.6 (SD 8.2) years), 113 with patent grafts and 44 with occluded grafts one year after bypass. MAIN OUTCOME MEASURE--Cumulative percentage patency at one year. RESULTS--Markers for smoking (blood carboxyhaemoglobin concentration (p less than 0.05) and plasma thiocyanate concentration (p less than 0.01) and plasma concentrations of fibrinogen (p less than 0.001) and apolipoproteins AI (p less than 0.04) and (a) (p less than 0.05) were significantly higher in patients with occluded grafts. Serum cholesterol concentrations were significantly higher in patients with grafts that remained patent one year after bypass (p less than 0.005). Analysis of the smoking markers indicated that a quarter of patients (40) were untruthful in their claims to have stopped smoking. Based on smoking markers, patency of grafts in smokers was significantly lower at one year by life table analysis than in non-smokers (63% v 84%, p less than 0.02). Patency was significantly higher by life table analysis in patients with a plasma fibrinogen concentration below the median than in those with a concentration above (90% v 57%, p less than 0.0002). Surprisingly, increased plasma low density lipoprotein cholesterol concentration was significantly associated with improved patency at one year (85%) at values above the median compared with patency (only 68%) at values in the lower half of the range (p less than 0.02). CONCLUSIONS--Plasma fibrinogen concentration was the most important variable predicting graft occlusion, followed by smoking markers. A more forceful approach is needed to stop patients smoking; therapeutic measures to improve patency of vein grafts should focus on decreasing plasma fibrinogen concentration rather than serum cholesterol concentration.     

Clinical outcomes of long coronary stents: a single-center experience

BACKGROUND: Coronary artery stenting is particularly useful during percutaneous coronary intervention for long lesions previously associated with a low procedural success rate and a high complication rate of dissection and occlusion. Current treatment options include implantation of a single long stent, multiple contiguous stents, or 'spot' stenting. However, multiple stent implantation may result in sections of overlapping stent or gaps of unstented segments and is an independent predictor of restenosis. The early and intermediate clinical outcome of single and multiple long stent (>/= 30 mm) implantation is not established. METHODS AND RESULTS: The authors retrospectively identified 123 consecutive patients who had undergone stenting using one or more long coronary stents. Baseline clinical data, procedural outcomes and completed clinical follow-up to 52 weeks were obtained by case-note review. The majority (69%) required intervention for stable coronary disease. Seventy-seven per cent of lesions were either type B2 or C and only 2% were in saphenous vein grafts. The procedural success rate was 94%. A total of 15 major events occurred in 13 patients (11%). Ten acute events occurred and five events were during the follow-up period from 30 days to 52 weeks. Two patients died, one from uncontrolled bleeding secondary to the use of antithrombotic agents and one at four weeks due to sudden death. One patient had a postprocedural infarct. Two patients required in-hospital repeat revascularization for acute vessel closure and eight required revascularization during follow-up (three cases of occlusion/thrombosis and five cases of restenosis). CONCLUSIONS: The use of long coronary stents (>/= 30 mm) for the treatment of long diffuse native vessel disease, saphenous vein graft disease and long coronary dissections is associated with a reasonable procedural success rate and acceptable early and intermediate-term clinical outcomes.     

ATHEROSCLEROSIS OF AORTOCORONARY ARTERY SAPHENOUS VEIN BYPASS GRAFTS

Among a series of 109 patients who underwent aortocoronary artery bypass reoperation and received a total of 168 grafts, atherosclerosis was found in 29 saphenous vein grafts. Specimens were obtained at reoperation in 25 patients and at postmortem examination in four. Plaques were found from 3 months to 6 years after operation. The plaques often were combined with old or recent mural thrombi, intimal fibroses, or thickened intima associated with intramural hematomas. Clinical findings did not correlate with risk factors such as hypercholesterolemia, hypertension, or diabetes mellitus. In a well-functioning graft with adequate flow, cellular proliferation generally reflects an adjustment of the venous wall to a higher pressure. Such a vessel retains elastic properties of pulsating structures. In the specimens studied, intimal fibrosis associated with plaques was always poorly cellular, causing the grafts to become rigid. This resulted in irregular flow and, in some patients, dissection. The possible pathogenesis of atheromatosis in vein grafts may include the usual mechanisms of atherogenesis and atheromatous transformation of thrombi. It appears that hemodynamically significant stenosis of vein grafts caused by atherosclerosis is an infrequent complication.     

Lipolytic enzymes in atherosclerosis as the potential target of inhibitors

It is at present generally accepted that three components—modification of lipoproteins, infection and inflammation play an important role in the evaluation of atherosclerotic lesions. Low density lipoprotein (LDL) can undergo modification and accumulate over time in the artery wall. Modified LDL particles share the ability to induce inflammatory functions of cells associated with atheroma. The present review will focus on the multifunction action of lipases and phospholipases in lipid and lipoprotein metabolism, and atherosclerosis. The development of highly specific lipolytic enzyme inhibitors not only for studying their kinetic effects but also for potential pharmacological application is discussed.