Coronary Artery Bypass Vein Graft Research Articles

FGL2/FcγRIIB Signalling Mediates Arterial Shear Stress-Mediated Endothelial Cell Apoptosis: Implications for Coronary Artery Bypass Vein Graft Pathogenesis.

The sudden exposure of venous endothelial cells (vECs) to arterial fluid shear stress (FSS) is thought to be a major contributor to coronary artery bypass vein graft failure (VGF). However, the effects of arterial FSS on the vEC secretome are poorly characterised. We propose that analysis of the vEC secretome may reveal potential therapeutic approaches to suppress VGF. Human umbilical vein endothelial cells (HUVECs) pre-conditioned to venous FSS (18 h; 1.5 dynes/cm2) were exposed to venous or arterial FSS (15 dynes/cm2) for 24 h. Tandem Mass Tagging proteomic analysis of the vEC secretome identified significantly increased fibroleukin (FGL2) in conditioned media from HUVECs exposed to arterial FSS. This increase was validated by Western blotting. Application of the NFκB inhibitor BAY 11-7085 (1 µM) following pre-conditioning reduced FGL2 release from vECs exposed to arterial FSS. Exposure of vECs to arterial FSS increased apoptosis, measured by active cleaved caspase-3 (CC3) immunocytochemistry, which was likewise elevated in HUVECs treated with recombinant FGL2 (20 ng/mL) for 24 h under static conditions. To determine the mechanism of FGL2-induced apoptosis, HUVECs were pre-treated with a blocking antibody to FcγRIIB, a receptor FGL2 is proposed to interact with, which reduced CC3 levels. In conclusion, our findings indicate that the exposure of vECs to arterial FSS results in increased release of FGL2 via NFκB signalling, which promotes endothelial apoptosis via FcγRIIB signalling. Therefore, the inhibition of FGL2/FcγRIIB signalling may provide a novel approach to reduce arterial FSS-induced vEC apoptosis in vein grafts and suppress VGF.

The role of FGL2 in vascular smooth muscle cell dysfunction in coronary artery bypass vein graft failure

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): British Heart Foundation Rationale The sudden exposure of venous endothelial cells (vECs) to arterial fluid shear stress (FSS) is thought to be a major contributor to coronary artery bypass vein graft failure (VGF). However, the acute effects of arterial FSS on the vEC secretome and the corresponding effects on underlying vascular smooth muscle cells (VSMCs) remains poorly characterised. Methods & Results Human umbilical vein endothelial cells (HUVECs; n=6) pre-conditioned to venous FSS (18h; 1.5 dynes/cm2) were further exposed to venous or arterial FSS (24h; 15 dynes/cm2) using an Ibidi pump system. Analysis of the EC secretome using Tandem Mass Tagging proteomics detected significantly increased fibroleukin (FGL2) in conditioned media from ECs exposed to arterial FSS compared to venous FSS (fold-change 1.97±0.72; P=0.0078). In addition, RT-qPCR analysis of FGL2 production showed a significant increase in vECs exposed to arterial FSS (2.11±0.27 vs. 0.05±0.04 log(copy number/mg); P=0.0312). Subsequently, pooled human saphenous vein VSMCs (3 donors per pool) were treated with conditioned media from ECs exposed to arterial FSS (n=6) which showed a significant increase in apoptosis, measured by active cleaved caspase-3 (CC3) immunocytochemistry (27±1% vs 22±1%; P=0.0391), and a significant decrease in the contractile markers smoothelin and desmin quantified by Western blotting (fold-change 0.76±0.06 and 0.44±0.11; P=0.004 and P=0.0421, respectively), in comparison to VSMCs treated with conditioned media from ECs exposed to venous FSS. Treatment of VSMCs (n=6) with recombinant FGL2 (20 ng/mL) for 72h likewise resulted in increased apoptosis (27±4% vs. 16±3%; P=0.0169) and decreased desmin and smoothelin (fold-change 0.68±0.03 and 0.61±0.07; P=0.0322 and P=0.0479, respectively). Conclusions The exposure of vECs to arterial FSS results in increased production and release of FGL2 which induced VSMC apoptosis and de-differentiation and therefore potentially contributes to VGF. Consequently, targeting FGL2 production or release may provide a therapeutic target to improve vein graft patency.

A Rabbit Model for Testing Helper-Dependent Adenovirus-Mediated Gene Therapy for Vein Graft Atherosclerosis

Coronary artery bypass vein grafts are a mainstay of therapy for human atherosclerosis. Unfortunately, the long-term patency of vein grafts is limited by accelerated atherosclerosis. Gene therapy, directed at the vein graft wall, is a promising approach for preventing vein graft atherosclerosis. Because helper-dependent adenovirus (HDAd) efficiently transduces grafted veins and confers long-term transgene expression, HDAd is an excellent candidate for delivery of vein graft-targeted gene therapy. We developed a model of vein graft atherosclerosis in fat-fed rabbits and demonstrated long-term (≥20 weeks) persistence of HDAd genomes after graft transduction. This model enables quantitation of vein graft hemodynamics, wall structure, lipid accumulation, cellularity, vector persistence, and inflammatory markers on a single graft. Time-course experiments identified 12 weeks after transduction as an optimal time to measure efficacy of gene therapy on the critical variables of lipid and macrophage accumulation. We also used chow-fed rabbits to test whether HDAd infusion in vein grafts promotes intimal growth and inflammation. HDAd did not increase intimal growth, but had moderate—yet significant—pro-inflammatory effects. The vein graft atherosclerosis model will be useful for testing HDAd-mediated gene therapy; however, pro-inflammatory effects of HdAd remain a concern in developing HDAd as a therapy for vein graft disease.

Repeat Percutaneous Treatment of a Large Vein Graft Aneurysm with Covered Stents

We present a case of repeat percutaneous intervention on a coronary artery bypass vein graft using polytetrafluoroethylene (PTFE) covered stents. The original intervention was performed using a combination of PTFE covered stents and bare metal stents for a large vein graft aneurysm. Successful exclusion of the aneurysm was demonstrated on follow up angiography. The patient represented six years after the original intervention with a non ST-segment elevation myocardial infarction. Further angiography demonstrated a recurrence of the aneurysm which we presumed to be due to late malapposition and required repeat PTFE covered stent deployment.

Relationship of lipoprotein-associated phospholipase A2 and oxidized low density lipoprotein in carotid atherosclerosis

Plasma levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and oxidized low density lipoprotein (oxLDL) have been identified as risk factors for cardiovascular disease. Lp-PLA(2) is the sole enzyme responsible for the hydrolysis of oxidized phospholipids on LDL particles in atherosclerotic plaques. We have studied the relationship between Lp-PLA(2) and oxLDL in carotid endarterectomy (CEA) tissues and in matched plasmas. In extracts from CEA anatomical segments, the levels of oxLDL were significantly associated with the levels of Lp-PLA(2) protein (r = 0.497) and activity (r = 0.615). OxLDL and Lp-PLA(2) mass/activity were most abundant in the carotid bifurcation and internal segments where plaque was most abundant. In extracts from CEA atheroma, the levels of oxLDL and Lp-PLA(2) were significantly correlated (r = 0.634). In matched plasma and atheroma extracts, the levels of Lp-PLA(2) were negatively correlated (r = - 0.578). The ratio of Lp-PLA(2) to oxLDL was higher in atheromatous tissue (277:1) than in normal tissue (135:1) and plasma (13:1). Immunohistochemical experiments indicated that in plaques, oxLDL and Lp-PLA(2) existed in overlapping but distinctly different distribution. Fluorescence microscopy showed both oxLDL and Lp-PLA(2) epitopes on the same LDL particle in plasma but not in plaque. These results suggest that the relationship between Lp-PLA(2) and oxLDL in the atherosclerotic plaque is different from that in the plasma compartment.

CT of a Ruptured Vein Graft Pseudoaneurysm: An Unusual Cause of Superior Vena Cava Obstruction

presentation. The coronary artery bypass surgery had been an uncomplicated procedure, and the patient had been free of symptoms of coronary disease in the interim. The patient had recently undergone multiple diagnostic evaluations for investigation of lethargy and weight loss that had included CT of the thorax and abdomen. This examination had failed to reveal any cause for the symptoms. When the patient presented with signs and symptoms of superior vena cava obstruction, the previously obtained CT scan was reviewed to see whether a potential cause could be found. A pseudoaneurysm of the right coronary artery bypass vein graft was identified (Fig. 1A). This dilated vascular structure was deemed a pseudoaneurysm because of its proximity to the anastomosis of the vein graft and the right coronary artery. This finding had not been noted at the time of the previous examination. A repeat CT scan of the thorax showed a large ruptured pseudoaneurysm of the right coronary artery bypass vein graft with a hematoma that was compressing the right atrium and superior vena cava (Fig. 1B). Although an arterial phase CT scan was acquired, the ruptured pseudoaneurysm was more clearly defined on the delayed phase scan (Fig. 1C). The findings were consistent with the rupture of a pseudoaneurysm of the coronary artery bypass vein graft, resulting in acute superior vena cava obstruction. The patient developed a fatal arrhythmia while being transferred to the operating room for surgical repair, and subsequent resuscitation attempts were unsuccessful.

Coronary in-stent restenosis following beta brachytherapy A histopathological examination

Two cases of in-stent restenosis of a coronary artery bypass vein graft following beta (β) brachytheraphy are presented. Previously unreported histopathology of directed atherectomy specimens of such restenotic lesions and a discussion of their proposed significance form the basis of this report.

Passive leg elevation and head-down tilt: effects and duration of changes.

I am intrigued by the recent further evaluation of passive leg elevation (PLE) in the perioperative period for patients undergoing cardiac surgery [1]. Following prior involvement with somewhat similar evaluations [2], I am left wondering what conclusions may have been reached if the experimental protocol had been expanded to include a penultimate assessment with the legs still elevated (i.e. between time point 3 and time point 4), and also to examine the effects of head-down tilt (HDT) as used during central venous cannulation. On the one hand, the autonomic [2] and haemodynamic effects [3-5] of postural manipulation have been shown to be both minimal and short lived. I surmise that the adverse effects observed may have been self-correcting during the course of PLE, rather than only after resumption of the supine position (i.e. before time point 4). This perhaps thereby minimises the clinical importance of these effects. On the other hand, the patterns of changes seen with HDT are very similar to those induced by PLE [2,3]. It follows that any caution advised regarding PLE for patients known to have reduced right ventricular ejection fraction should be extrapolated to the use of HDT for central venous catheter placement. The data provided could justifiably be added to a list of reasons for avoiding the indiscriminate use of PLE as a therapeutic manoeuvre in hypotensive conditions. As for other applications, it is difficult to think of an immediate alternative to PLE for the preparation of the sterile field required for a coronary artery bypass vein graft requiring use of harvested saphenous veins (or to HDT in central venous catheter placement). The advised caution deserves due consideration for both PLE and HDT.

Influence of Procedural Success on Immediate and Long-Term Clinical Outcome of Patients Undergoing Percutaneous Revascularization of Occluded Coronary Artery Bypass Vein Grafts

ObjectivesThis study sought to determine whether successful recanalization of an occluded vein graft is associated with improvement in long-term clinical outcome. BackgroundCoronary angioplasty of occluded vein grafts is associated with a lower initial success rate and a higher complication rate than angioplasty of vein grafts with subtotal stenoses and native coronary arteries. Whether successful angioplasty improves clinical outcome is unknown. MethodsWe analyzed 77 consecutive patients who underwent angioplasty of an occluded saphenous vein coronary artery bypass graft between August 1983 and June 1994. Patients with a myocardial infarction in the previous 24 h were excluded from the study. ResultsThe mean age of the study cohort was 65 years; the mean (±SD) age of the treated grafts was 7.5 ± 3.9 years. As an adjunct to balloon angioplasty, stents were used in 9% of procedures, laser in 30%, and atherectomy in 16%, and thrombolytic therapy was administered in 23% of patients. The angioplasty success rate was 71%. Major complications within 30 days of the procedure included death in 5.2% of patients, Q wave myocardial infarction in 1.3% and repeat bypass surgery in 7.8%; these events occurred with similar frequency in patients in whom angiographic success was and was not achieved. Kaplan-Meier analysis comparing patients in whom angioplasty was successful (n = 55) and not successful (n = 22) revealed no differences in survival or occurrence of myocardial infarction or recurrent severe angina between the two groups in the 3 years after the procedure. Univariate analysis identified the age of the graft and use of newer interventional devices as predictors of death or myocardial infarction during this time period; procedural success was not associated with freedom from these adverse events after adjusting for these variables. ConclusionsAngioplasty of occluded vein grafts is associated with a low initial success rate and a high complication rate. Successful angioplasty does not appear to reduce the occurrence of adverse events in the 3 years after the procedure.

Metabolic and physical factors in early coronary artery bypass vein graft occlusion

Metabolic and physical factors in early coronary artery bypass vein graft occlusion

Metabolic and Technical Factors in Early Coronary Artery bypass Vein Graft Occlusion

Metabolic and Technical Factors in Early Coronary Artery bypass Vein Graft Occlusion

Percutaneous Angioplasty of Totally Occluded Coronary Vein Bypass Grafts: Case Histories

Seven patients with totally occluded coronary artery bypass vein grafts underwent percutaneous transluminal angioplasty. All patients had either acute or recent occlusion of the graft itself. In 2 patients the proximal and in 3 the distal anastomosis were also narrowed. The vein graft was successfully dilated in all the patients. Six patients also received direct intragraft thrombolytic therapy during the procedure. Five uncomplicated patients improved clinically. One patient was studied routinely as part of a myocardial infarction-streptokinase protocol and had no symptoms. This patient had a no-reflow phenomenon. One patient did not receive intragraft thrombolytic therapy and the procedure was complicated by embolization with myocardial infarction and a cerebral embolus. In 2 patients, a routine angiogram was performed two to six months after graft dilatation and in both the grafts were patent. Another patient, initially successfully dilated, had recurrent angina and restenosis of the proximal anastomosis ten months after angioplasty; this was successfully redilated. Angioplasty of acutely or recently totally occluded coronary vein grafts is feasible and improves angina when present. Additional thrombolytic therapy prevents embolization.

Quantitation and localization of apolipoproteins [a] and B in coronary artery bypass vein grafts resected at re-operation.

Lp[a] is a lipoprotein whose plasma concentration is highly correlated with cardiovascular disease. Its protein moiety, apoLp[a], consists of two large polypeptides, apo[a] and apo B. The possible contribution of Lp[a] to atherosclerosis in saphenous vein aortocoronary bypass grafts was studied in a population of patients undergoing coronary re-bypass surgery. The vein graft tissue levels of apoLp[a] were compared with graft duration, gross and light microscopic pathology, as well as plasma levels of apoLp[a]. The localization pattern of apo[a] and apo B in vein graft tissue was determined. In addition, the plasma levels of cholesterol, triglycerides, apoproteins (apo) A-I, A-II, and E were measured. In a representative subpopulation of 17 patients with a mean age of 63 years from whom grafts with a mean duration of 112 months were resected, the mean total plasma cholesterol level was 221 mg/dl, the mean high density lipoprotein cholesterol level was 31 mg/dl, and the mean plasma triglyceride level was 228 mg/dl. In normal saphenous veins, the level of apoLp[a] was below measurable limits (less than 2 ng/mg), and the level of apo B was very low (3.3 ng/mg). In resected grafts, the mean tissue level of apoLp[a] was 32 ng/mg, and that of apo B was 70 ng/mg, demonstrating the net accumulation of these apoproteins in veins from the time of their grafting into the arterial bed. The apoLp[a]/apo B ratio was determined in 77 tissue segments from 59 grafts (28 patients) and was found to be 0.313. This tissue ratio was significantly higher (p = 0.02) than the plasma apoLp[a]/apo B ratio from these patients, which was 0.132. Immunostaining showed co-localization of apo[a] and apo B in the neointima of grafts. The most abundant pathologic features observed in resected grafts were proliferated intima (43/52), thrombus (28/52), and atherosclerotic core regions (21/52). The level of tissue apo B correlated well with the abundance of core regions (r = 0.501), whereas the level of tissue apoLp[a] did not correlate as well with this feature (r = 0.233). Although apo[a] and apo B are almost absent from normal saphenous vein, these apoproteins (and presumably the lipoproteins Lp[a] and low density lipoprotein) accumulate in bypass vein grafts. The data support the view that these lipoproteins play a significant role in vein graft atherosclerosis.

Additional improvement of stenosis geometry in human coronary arteries by stenting after balloon dilatation

The purpose of this study was to assess the early changes in stenosis geometry after insertion of intravascular stents in human coronary arteries. Morphologic changes were evaluated by quantitative coronary angiography (using automated edge detection) and by calculation of the theoretical pressure decrease across the dilated and stented stenosis from the Poiseuille and turbulent resistances assuming a coronary blood flow of either 1 or 3 ml/s. Twenty-six patients were studied before and after angioplasty, as well as immediately after stent implantation. The stented coronary artery was the left anterior descending artery in 19 cases, the circumflex artery in 2 cases, the right coronary artery in 2 cases and a coronary artery bypass vein graft in 3 cases. After stent implantation, an additional increase in minimal luminal cross-sectional area of the dilated vessel was observed, suggesting that the self-expanding stainless steel endoprosthesis used in this study has a dilating function in addition to its stenting role.

The factors influencing early patency of coronary artery bypass vein grafts: Correlation of angiographic and ultrastructural findings

To test the hypothesis that suboptimal preparation of saphenous veins may adversely affect early patency of aorta-coronary artery bypass grafts, a nonrandomized prospective study was undertaken comparing two methods of saphenous vein preparation prior to grafting. Forty recatheterizations were performed during the postoperative hospital stay (approximately 10 days) in two groups of asymptomatic patients who had undergone isolated coronary artery bypass grafting. Veins from patients in Group I were bathed in autologous, heparinized blood at 20 degrees C and distended to 80 mm Hg, prior to grafting. The veins from Group II patients were prepared in an identical manner, except that the bathing solution consisted of heparinized electrolyte solution with added papaverine (0.6 mg/lg). Segments of vein from each group were obtained prior to grafting and preserved in 3% glutaraldehyde for subsequent electron microscopic studies. Operative technique in both groups of patients was identical and all procedures were performed by the same surgeons. Comparison of patients in Group I and II revealed no significant difference in the number of diseased vessels per patient (3.1 versus 3.4), number of grafts per patient (2.9 versus 2.9), native vessel diameter (1.9 versus 1.7 mm), and postoperative graft flows (65 versus 68 cc/min). However, early postoperative graft patency in Group II patients was 93% versus 80% in patients in Group I (p less thn 0.01). Electron microscopic analysis revealed severe spasm of venous smooth muscle in the blood-stored veins causing intraluminal smooth muscle cell cytoplasmic protrusions with resultant endothelial separation and desquamation. Formation of fibrin-platelet microaggregates was common. These findings were not present in the solution-treated veins. In view of these ultrastructural findings, and the highly significant difference in patency rates, we have abandoned all blood storage techniques and now prepare saphenous veins by soaking them in a clear bathing medium with added heparin and papaverine. Long-term follow-up of these patients is currently in progress and may reveal even more dramatic results than we have heretofore observed.

Reduction of intimal thickening in canine coronary artery bypass vein grafts with dipyridamole and aspirin

Reduction of intimal thickening in canine coronary artery bypass vein grafts with dipyridamole and aspirin