Vein Bypass Grafts Research Articles

Surgical treatment for chronic lower limb ischemia: A report of 60 cases

Objective To explore the clinical characteristics and treatment strategy of chronic lower limb arterial ischemic. Methods The clinical data of 60 patients with chronic lower limb arterial ischemic-treated from January 2017 to May 2017 were analyzed retrospectively (63 affected limbs). According to the patient's physical condition, clinical symptoms and pathological features, individualized surgical treatment was selected, including autogenous great saphenous vein or artificial blood vessel bypass grafting, artery intima stripped, balloon dilatation, stenting, intracavity volume reduction, or hybrid procedures. The ankle brachial index of preoperative and postoperative 3 months was monitored, and patients were classified according to the Rutherford classification standard. Results Sixty cases were underwent surgery treatment, three patients were treated with bilateral lower limbs in the same period, successfully 58 cases and success rate reached 96.67%. One case was subjected to amputation, and 1 case died (cardiovascular disease). Postoperative 3 month follow-up, the Rutherford grading of 59 affected limbs was improved markedly, average ankle brachial index of postoperative was higher than preoperative (P<0.05). Six cases of patients with ulcer were cured, the ulcer surface of 2 cases were significantly narrowed. Conclusions The incidence of chronic lower limb arterial ischemic is increasing year by year, the treatment ideas are constantly updated. It is safe and effective to select individualized treatment according to the patients' physical condition, clinical symptoms and pathological feature. However it still needs to enlarge the sample and extend the time of follow-up to verify this point. Key words: Ischemia/SU; Lower extremity/PA

Invited commentary

Autogenous vein bypass grafting remains an important therapeutic option for patients with peripheral vascular disease. These vein grafts are durable; however, the development of de novo stenosis within the graft occurs in 30% to 50% of patients within the first several years. Despite multiple therapeutic interventions and vein graft manipulations, the incidence of vein graft disease has not changed over the last 30 years. Basic research has focused on endothelial cells, smooth muscle cells, and extracellular matrix as the responsible culprits for the intimal hyperplastic lesion. However, studies have now shown that the adventitial layer may have a more dynamic role in the intimal hyperplastic lesion. Furthermore, recent studies have demonstrated the potential role of genetic variability in the p27 Kip1 gene as a determinant of clinical outcomes in patients with cardiovascular disease and after clinical interventions. The authors present a provocative in vitro study of human venous adventitial and smooth muscle cells that shows that the p27 single nucleotide polymorphism (p27 KIP1-838C>A) is functional and that the levels of p27 messenger RNA and protein were higher in the cells with the AA genotype compared with the CC genotype. Knockdown of p27 increases growth of both cell types with the AA genotype but not those with the CC genotype. What, however, is groundbreaking in their study is the differential effect of the p27 single nucleotide polymorphism on adventitial cell growth. They noted that adventitial cells of the AA genotype grew significantly more slowly than those with the CC genotype. In this study, only the adventitial cells, and not the smooth muscle cells, are responsible to the inhibitory effects of the protective AA genotype in cell growth. The adventitial layer has been noted to have vascular fibroblasts, perivascular adipocytes, and progenitor cells, which have been shown to affect vascular smooth muscle cell phenotype and growth. How these components interact to achieve the complex intimal hyperplastic lesion is still not known. However, using mouse model technology and lineage tracing technology to discover the cells or cells that are really responsible for the intimal hyperplastic lesion and, therefore, more precisely targeting treatment, could one day allow for the treatment of this disease that has been plaguing long-term vascular surgical outcomes for the last 40 years. The opinions or views expressed in this commentary are those of the authors and do not necessarily reflect the opinions or recommendations of the Journal of Vascular Surgery or the Society for Vascular Surgery. A single nucleotide polymorphism of cyclin-dependent kinase inhibitor 1B (p27Kip1) associated with human vein graft failure affects growth of human venous adventitial cells but not smooth muscle cellsJournal of Vascular SurgeryVol. 67Issue 1PreviewCyclin-dependent kinase inhibitor 1B (p27Kip1) is a cell-cycle inhibitor whose -838C>A single nucleotide polymorphism (rs36228499; hereafter called p27 SNP) has been associated with the clinical failure of peripheral vein grafts, but the functional effects of this SNP have not been demonstrated. Full-Text PDF Open Archive

Linking gene dynamics to vascular hyperplasia - Toward a predictive model of vein graft adaptation.

Reductionist approaches, where individual pieces of a process are examined in isolation, have been the mainstay of biomedical research. While these methods are effective in highly compartmentalized systems, they fail to account for the inherent plasticity and non-linearity within the signaling structure. In the current manuscript, we present the computational architecture for tracking an acute perturbation in a biologic system through a multiscale model that links gene dynamics to cell kinetics, with the overall goal of predicting tissue adaptation. Given the complexity of the genome, the problem is made tractable by clustering temporal changes in gene expression into unique patterns. These cluster elements form the core of an integrated network that serves as the driving force for the response of the biologic system. This modeling approach is illustrated using the clinical scenario of vein bypass graft adaptation. Vein segments placed in the arterial circulation for treatment of advanced occlusive disease can develop an aggressive hyperplastic response that narrows the lumen, reduces blood flow, and induces in situ thrombosis. Reducing this hyperplastic response has been a long-standing but unrealized goal of biologic researchers in the field. With repeated failures of single target therapies, the redundant response pathways are thought to be a fundamental issue preventing progress towards a solution. Using the current framework, we demonstrate how theoretical genomic manipulations can be introduced into the system to shift the adaptation to a more beneficial phenotype, where the hyperplastic response is mitigated and the risk of thrombosis reduced. Utilizing our previously published rabbit vein graft genomic data, where grafts were harvested at time points ranging from 2 hours to 28 days and under differential flow conditions, and a customized clustering algorithm, five gene clusters that differentiated the low flow (i.e., pro-hyperplastic) from high flow (i.e., anti-hyperplastic) response were identified. The current analysis advances these general associations to create a model that identifies those genes sets most likely to be of therapeutic benefit. Using this approach, we examine the range of potential opportunities for intervention via gene cluster over-expression or inhibition, delivered in isolation or combination, at the time of vein graft implantation.

Lesion Complexity and Outcomes of Extended Dual Antiplatelet Therapy After Percutaneous Coronary Intervention

BackgroundSubjects undergoing coronary stenting with complex lesion anatomy may experience different risks and benefits with prolonged dual antiplatelet therapy. ObjectivesThe authors assessed the effect of 30 months versus 12 months of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) based on the presence or absence of anatomically-complex target lesions. MethodsIn the DAPT Study, combined myocardial infarction (MI) or stent thrombosis and moderate/severe bleeding were assessed in enrolled (n = 25,416) and randomized (n = 11,554) subjects. Complex lesions had any of the following characteristics: unprotected left main, >2 lesions/vessel, length ≥30 mm, bifurcation with side branch ≥2.5 mm, vein bypass graft, or thrombus-containing lesion. Events were evaluated according to increasing number of complexity characteristics and compared according to DAPT score. ResultsEnrolled subjects with more complex target lesions had higher rates of MI or stent thrombosis in the first 12 months after PCI (3.9% vs. 2.4%; p < 0.001). Among those who were event-free at 12 months, rates of MI or stent thrombosis between 12 and 30 months were similar between those with versus without complex anatomy (3.5% vs. 2.9%; p = 0.07). Reduction of MI or stent thrombosis with continued thienopyridine beyond 12 months versus placebo was similar for subjects with (2.5% vs. 4.5%; hazard ratio: 0.55; 95% confidence interval: 0.38 to 0.79; p = 0.001) and without (2.0% vs. 3.8%; hazard ratio: 0.52; 95% confidence interval: 0.39 to 0.69; p < 0.001) anatomic complexity (pinteraction = 0.81), as was increase in moderate/severe bleeding (pinteraction = 0.44). Among subjects with anatomic complexity, those with DAPT scores ≥2 randomized to continued thienopyridine had greater reductions in MI or stent thrombosis (3.0% vs. 6.1%; p < 0.001) compared with subjects with scores <2 (1.7% vs. 2.3%; p = 0.42; p value comparing risk differences = 0.03). ConclusionsComplex target-lesion anatomy is associated with increased ischemic events, particularly within the first year after PCI. Among those without events in the first 12 months, the benefits of extending DAPT were similar in subjects with and without complex lesions. A high DAPT score identified those experiencing the most benefit from extended treatment among patients with and without complex anatomy. (The Dual Antiplatelet Therapy Study [DAPT Study]; NCT00977938)

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.

Is the Endovascular Treatment of Mild Iliac Stenoses Worthwhile to Improve Wound Healing in Patients Undergoing Femorotibial Bypass?

After an infrapopliteal reconstruction, minor amputations are frequently required, but even in the case of successful revascularization, wound healing is a major concern. We studied the role of iliac artery inflow correction in patients undergoing infrapopliteal vein grafts to improve the heal of midfoot amputation. Thirty-eight patients affected with Rutherford grade III category 5 peripheral arterial disease, who underwent successful simultaneous iliac endovascular procedure, infrapopliteal reversed vein bypass graft, and minor amputation, were enrolled in this retrospective study. The population was divided in group 1 (20 patients) with inflow vessels Trans-Atlantic Inter-Society Consensus Document on Management of Peripheral Arterial Disease (TASC) II type B atherosclerotic lesions and group 2 (18 patients) with TASC II type A atherosclerotic lesions determining an invasive pressure drop greater than 15mm Hg. Fifteen patients (group 3) undergoing infrapopliteal reversed vein bypass graft without associated inflow procedures (TASC II type A and invasive pressure drop greater than 15mm Hg) were matched with group 2 based on propensity score. Healing was calculated by subtracting the final ulcer area from the initial ulcer area and dividing by the number of follow-up months to obtain the total area healed per month (cm2/month). Stepwise logistic regression analysis adjusted for demographics and medical comorbid conditions was used to test the association between wound healing and treatment modalities. Forty-three patients were available for further analysis. Ten patients were excluded because of graft occlusion with consequent impairment of wound healing. After midfoot amputations, mean wound diameter was 20±8cm2, and mean healing time was 10±4months (range 3-20 months; median 9months). Wounds of groups 1 and 2 healed faster than those of group 3 at 4 and 8months (P<0.02 and P<0.001, respectively; P<0.04 and P<0.001, respectively). Multivariate analysis demonstrated the association between wound healing and inflow correction (P<0.001). An aggressive treatment is necessary to obtain the heal of the ischemic wounds. The most important predictive factor for nonhealing wounds is the absence of inflow correction. We demonstrated that the inflow should be also corrected in the presence of subclinical lesions.

Surgical Treatment of Cervical Carotid Artery Aneurysm

Cervical carotid aneurysms are rare, and surgical treatment should be planned for each patient. The authors report 9 cases of cervical carotid aneurysm in 9 patients(mean age, 53.7 years;5 men)who were treated surgically between 2005 and 2014. The aneurysm was located in the internal carotid artery in 6 patients, the common carotid artery in 2 patients, and the carotid bifurcation in 1 patient. Four aneurysms were recurrences after a previous endovascular intervention(parent artery coil embolization, covered stent placement, or stent with coil embolization). The mean interval between the endovascular therapy and the onset of the present illness was 6 years. All the patients presented a mass effect at the neck, including lower cranial nerve dysfunction in 1 patient. Two patients presented with ischemic events presumably due to thromboembolism from the target aneurysms. Surgical treatments included local vascular reconstruction procedures in 6 patients(interposition vein or artificial graft bypass in 5 patients and in situ bypass in 1 patient). Four aneurysms were then resected. Two patients with rich collateral blood flow were treated with ligation of the parent artery proximal to the aneurysm. Surgical complications included embolic stroke and cranial nerve dysfunction in 2 patients, respectively, both presumably due to surgical manipulation. The modified Rankin scale(mRS)score at discharge was 0 in 5 patients, 1 in 1 patient, 2 in 2 patients, and 6 in 1 patient(vascular tumor). Surgical treatment of cervical carotid aneurysms seems a reasonable treatment of choice, but lower nerve dysfunction and embolism from the aneurysm should be avoided.

Abstract 475: Human Saphenous Vein Progenitor Cells Are Susceptible to Mechanical Stimulation. Novel Insights in Pathologic Programming of Saphenous Vein Bypass Graft Disease

Background: Implantation of saphenous vein (SV) grafts into coronary position determines structural vessel wall remodeling and intimal hyperplasia. The role of the altered wall mechanics and cell-based mechanosensing has been recently implicated in the priming of this pathologic process. We investigated the effects of cyclic uniaxial strain on human saphenous vein progenitor cells (SVPs), a cell type endowed with pericyte stem cell characteristics resident in the adventitia. Methods: CD34 + CD31 - SVPs were isolated with immuno-magnetic sorting (MACS) from SVs of patients (age 58±12.6, Mean±SD) undergoing saphenectomy. Cells were subject to uniaxial strain (10% elongation; 1Hz) for 24 and 72 hrs using the FlexCell system. Cell orientation, immunofluorescence and western analyses were performed to assess the effects of strain on cell orientation/shape, cell cycle and activity of the YAP/Hippo-dependent mechanotransduction machinery. RNA-sequencing from control vs. strained SVPs was performed at both time points using RNA from cells of 5 independent donors. Results: Results indicated an increase in the expression of the cell cycle-associated markers Ki67 and pHH3 in mechanically stimulated vs. control SVPs at 24 hrs, followed by a significant reduction at 72 hrs of stimulation. Variations in cell shape was observed as verified by a significant change in the nuclei orientation in the strain field as well as in the cell shape index/spread areas at both time points. Immunofluorescence revealed a significant increase in cells showing a nuclear localization of the YAP transcription factor at 72hrs. In line with these findings Western analyses indicated a significant decrease in the ratio between phosphorylated/total YAP and its upstream kinase LATS in mechanically stimulated vs. control SVPs, suggesting an inhibition of the HIPPO kinase pathway by mechanosensing. RNASeq gene expression analyses showed a coherent modification of gene expression pathways and the upregulation of a specific HIPPO/YAP/TEAD gene expression signature in SVPs mechanically stimulated for 72hrs. Conclusions: These findings demonstrate the direct susceptibility of human SVPs to pathologic strain and identifies this cell population as mechano-perceptors in the vein wall.

Superior Lower Extremity Vein Graft Bypass Patency among Married Patients with Peripheral Artery Disease

Outcome disparities associated with lower extremity bypass (LEB) for peripheral artery disease (PAD) have been identified but are poorly understood. Marital status may affect outcomes through factors related to health risk behaviors, adherence, and access to care but has not been characterized as a predictor of surgical outcomes and is often omitted from administrative data sets. We evaluated associations between marital status and vein graft patency following LEB using multivariable models adjusting for established risk factors. Consecutive patients undergoing autogenous LEB for PAD were identified and analyzed. Survival analysis and Cox proportional hazards models were used to evaluate patency stratified by marital status (married versus single, divorced, or widow[er]) adjusting for demographic, comorbidity, and anatomic factors in multivariable models. Seventy-three participants who underwent 79 autogenous vein LEB had complete data and were analyzed. Forty-three patients (58.9%) were married, and 30 (41.1%) were unmarried. Compared with unmarried patients, married patients were older at the time of their bypass procedure (67.3±10.8years vs. 62.2±10.6years; P=0.05). Married patients also had a lower prevalence of female gender (11.6% vs. 33.3%; P=0.02). Diabetes, hypertension, hyperlipidemia, and smoking were common among both married and unmarried patients. Minimum great saphenous vein conduit diameters were larger in married versus unmarried patients (2.82±0.57mm vs. 2.52±0.65mm; P=0.04). Twenty-four-month primary patency was 66% for married versus 38% for unmarried patients. In a multivariable proportional hazards model adjusting for proximal and distal graft inflow/outflow, medications, gender, age, race, smoking, diabetes, and minimum vein graft diameter, married status was associated with superior primary patency (hazard ratio [HR] = 0.33; 95% confidence limits [0.11, 0.99]; P=0.05); other predictive covariates included preoperative antiplatelet therapy (HR=0.27; 95% confidence limits [0.10,0.74]; P=0.01) and diabetes (HR = 2.56; 95% confidence limits [0.93-7.04]; P=0.07). Marital status is associated with vein graft patency following LEB. Further investigation into the mechanistic explanation for improved patency among married patients may provide insight into social or behavioral factors influencing other disparities associated with LEB outcomes.

Variation of the cephalic and basilic veins: A case report

Cephalic and basilic veins begin their path from around the wrist and continue towards the area above the forearm. The basilic vein becomes deep around the mid-arm, while the cephalic vein becomes deep around the upper forearm, in deltopectoral groove. The superficial veins are most commonly used for vein puncture, transfusion, bypass graft, and cardiac catheterization. In renal patients, the basilic vein use as an arteriovenous graft or fistula for haemodialysis access. During a routine dissection in the department of anatomy in Isfahan, we observed a variation in the left arm of an infant boy (six months old). The cephalic and basilic veins directly joined together in the middle of the cubital fossa. The brachial vein began from this point and, unlike the normal anatomy location, there was no paired brachial vein; rather, it was one unpaired brachial vein.

Use of Embolic Protection Devices in Peripheral Interventions.

The use of embolic protection devices (EPDs) when treating coronary saphenous vein bypass grafts, performing carotid arterial stenting and treating acute coronary syndromes is well accepted. We will review currently available devices and approaches to reduce distal embolisation, first discussing their uses in carotid interventions and then in vertebral and peripheral vascular interventions.

Follow-up and surveillance of vein grafts: when and how to intervene to prevent complications.

Despite advances in endovascular strategies, surgical infrainguinal lower limb revascularization remains the gold standard treatment for critical lower limb ischemia and disabling claudication. Maintaining patency of infrainguinal vein bypass grafts has been a challenging task for vascular surgeons as they are prone to developing stenoses which may precipitate failure of the bypass. Duplex ultrasound scanning has evolved as the investigation of choice to identify vein graft lesions but graft surveillance programs using this technique remain controversial. The rationale for graft surveillance is that intervention in a patent but failing graft results in improved long-term patency and limb salvage rates compared to rescue of an occluded graft. The six-week postoperative Duplex ultrasound scan is important in identifying flow abnormalities that can predict the natural history of a vein graft and the outlook for the limb in the medium term. There are multiple factors influencing vein graft failure, which means guidelines should be flexible in terms of when and which type of intervention to the graft is optimum. Patency and durability favour open surgical revision over endovascular intervention but this must be counter balanced by the increased morbidity associated with surgical revision.

Smooth muscle cell-specific Tgfbr1 deficiency attenuates neointimal hyperplasia but promotes an undesired vascular phenotype for injured arteries.

Neointimal hyperplasia (NIH) and inward wall remodeling cause arterial restenosis and failure of bypass vein grafts. Previous studies from our group suggest that transforming growth factor (TGF) β promotes these pathologies via regulating cell kinetics at the early stage and matrix metabolism at the late stage. Although these temporal TGF β effects may result from its signaling in different cell groups, the responsible cell type has not been identified. In the current study, we evaluated the effect of smooth muscle cell (SMC)‐specific TGF β signaling through its type I receptor TGFBR1 on NIH and wall remodeling of the injured femoral arteries (FAs). An inducible Cre/loxP system was employed to delete SMC Tgfbr1 (Tgfbr1 iko). Mice not carrying the Cre allele (Tgfbr1 f/f) served as controls. The injured FAs were evaluated on d3, d7, and d28 postoperatively. Tgfbr1 iko attenuated NIH by 92%, but had insignificant influence on arterial caliber when compared with Tgfbr1 f/f controls on d28. This attenuation correlated with greater cellularity and reduced collagen content. Compared with Tgfbr1 f/f FAs, however, Tgfbr1 iko FAs exhibited persistent neointimal cell proliferation and cell apoptosis, with both events at a greater rate on d28. Tgfbr1 iko FAs additionally contained fewer SMCs and more inflammatory infiltrates in the neointima and displayed a thicker adventitia than did Tgfbr1 f/f FAs. More MMP9 proteins were detected in the adventitia of Tgfbr1 iko FAs than in that of Tgfbr1 f/f controls. Our results suggest that disruption of SMC Tgfbr1 inhibits arterial NIH in the short term, but the overall vascular phenotype may not favor long‐term performance of the injured arteries.

Validation of a Decision Tree to Streamline Infrainguinal Vein Graft Surveillance

Duplex ultrasound (DU)-based graft surveillance remains controversial. The aim of this study was to assess the ability of a recently proposed decision tree in identifying high-risk grafts which would benefit from DU-based surveillance. Consecutive patients undergoing infrainguinal vein graft bypass from January 2008 to December 2015 were identified from the National Vascular registry and enrolled in a duplex surveillance program. An early postoperative DU was performed at a median of 6weeks (range: 4-9 weeks). Grafts were classified into high risk or low risk based on the findings of the earliest postoperative scan and 4 established risk factors for graft failure (diabetes, smoking, infragenicular distal anastomosis, and revision bypass surgery) using a classification and regression tree (CRT). The accuracy of the CRT model was evaluated using area under receiver operator characteristic (AROC) curve. About 278 vein graft bypasses were performed; 29 grafts had occluded by the first surveillance visit; 249 vein grafts were entered into surveillance. Sixty-four (23%) developed critical stenosis. Overall 30-month primary patency, primary-assisted patency, and secondary patency rates were 71.2%, 77.2%, and 80.1%, respectively. AROC for prediction of graft stenosis or occlusion was 83% (95% confidence interval [CI]: 78-87%). The sensitivity and specificity of the CRT model for prediction of graft stenosis or occlusion were 95% (95% CI: 88-98%) and 52.2% (95% CI: 45-60%). A prediction model based on commonly recorded clinical variables and early postoperative DU scan is accurate at identifying grafts which are at high risk of failure. These high-risk grafts may benefit from DU-based surveillance.

Abstract 12889: Drug-Eluting Stents in the Treatment of Saphenous Vein Graft Disease: Disappointing Outcome During Long-term Follow-up

Introduction: Drug-eluting stents (DES) have been shown to have superior short term outcomes in the treatment of saphenous vein graft (SVG) disease compared to bare metal stents. Hypothesis: The goal of this study was to assess the long term clinical outcome of all patients with SVG disease treated with DES. Methods: 183 consecutive patients undergoing SVG intervention with DES were evaluated. Post-procedure, antiplatelet therapy included aspirin indefinitely and dual antiplatelet therapy for a minimum of 1 year. Major adverse cardiac events (MACE) were assessed at a mean follow-up of 5 years. MACE was defined as any of the following: death, stroke, myocardial infarction, repeat bypass surgery, repeat target vessel revascularization, or stent thrombosis. Results: The study population consisted of 149 men and 34 women with a mean age of 69 ± 10 years. Diabetes was present in 83 (45%) and acute coronary syndromes were present in 116 (63%). Mean SVG age was 12 ± 6 years. Diffuse disease (≥ 30 mm of treated disease and/or 3 or more lesions in a single vessel) was present in 37%. A total of 243 lesions were treated with 395 DES. Procedural techniques during DES deployment included direct stenting in 50%, pretreatment with intracoronary nicardipine in 49%, and use of a distal protection device in 38%. Kaplan Meier analysis of long-term MACE free survival is shown in the Figure. Although only 18% of patients had a MACE at one year, continued events were common after the first year. At 49 months, 50% of the patients had one or more MACE. Event free survival which was 82% at 1 year was only 41% at 5 years. MACE free survival after first and second generation DES were similar. Conclusions: The long-term outcome after percutaneous intervention of aortocoronary bypass vein grafts continues to present a clinical challenge. Within 5 years after DES placement for SVG disease, fewer than half of the patients remain event free.

P11 Role of MIR-145 as a mediator of DNA damage and senescence in vascular smooth muscle cells from type 2 diabetes patients

Introduction Type 2 diabetes (T2DM) confers a significant risk of premature coronary heart disease and poor outcomes after saphenous vein (SV) bypass grafting. We previously reported an aberrant phenotype in smooth muscle cells (SMC) cultured from T2DM patients, and elevated expression levels of a small non-coding RNA, microRNA (miR)-145. Here we explored the ?relationship between miR-145 overexpression and the senescence- associated secretory phenotype (SASP). Methods Cultured SMC from non-diabetic (ND) and T2DM patients were investigated for markers of senescence (SA β-gal), DNA damage (γH2AX immunofluorescence) and expression of SASP molecules (real time RT-PCR). In some experiments, ND-SMC were exposed to a DNA damaging stimulus, (etoposide 5?µM) and in others, miR-145 expression was manipulated via transfection of pre-miR- or anti-miR-145, as appropriate. Results Native T2DM-SMC displayed increased levels of senescence (n = 7, p Conclusion T2DM SV-SMC are aberrant in terms of senescence, DNA damage and expression of miR-145. Overexpression of miR-145 in ND-SMC increases senescence, DNA damage and secretion of SASP molecules, particularly MCP-1. Delineation of the role of miR-145 as a cause or effect of DNA damage is an important aim.

Inhibitory Effect of TLR4 Gene Silencing on Intimal Hyperplasia of Vein Grafting.

The present study aimed to explore the regulating effect of Toll-like receptor 4 (TLR4) on intimal hyperplasia in rat vein grafts. Rat models of external jugular vein carotid artery bypass grafting were established. Afterward, TLR4 small interfering RNA (siRNA) recombinant plasmids were constructed, which were transfected into rat vein graft bypass to study the effect of TLR4 silencing on intimal hyperplasia and to explore the underlying mechanisms. Real-time polymerase chain reaction and Western blot were used to detect the expression levels of TLR4 and inflammatory factors in TLR4 siRNA-transfected vein graft bypass. The intimal thickness was evaluated using hematoxylin-eosin staining. Compared with the scramble siRNA group, the intimal thickness of vein grafting was decreased significantly, while the inflammatory factors including interleukin (IL) 1β, IL-6, and tumor necrosis factor α in grafted vein were dramatically downregulated in the TLR4 siRNA group. These results showed that local silencing of TLR4 in the vein grafts could inhibit intimal hyperplasia by downregulating the expression of inflammatory factors in the vein grafts, suggesting that TLR4 can be used as a new target for therapy of vascular intimal hyperplasia.

Invited commentary

The treatment of chronic venous insufficiency attributed to deep valvular incompetence has been limited because of challenges in correcting the anatomic and physiologic derangements in the lower limb. Our specialty has attempted deep vein valvuloplasty, valvulopexy, valve transposition, vein bypass grafts, and various deep vein endoluminal therapies. Failure modes have primarily been attributed to thrombotic complications, which may worsen the patient's symptoms. None of these therapies have demonstrated reversal of venous hypertension or improvement in venous wound healing. The current article examines a novel therapy, popliteal vein external banding, during a 15-year period. The authors present a robust cohort, 1252 patients, managed with this technique, and their results are better than in any previous report to date. They should be applauded for their ulcer healing rates and wound recurrence rates of only 3.6%. In addition, they experienced a relatively low rate of venous thrombotic complications as a result of popliteal venous banding. This technique is the first intervention that has demonstrated promising results for deep venous insufficiency. I look forward to other centers examining this technique, validating their results, and potentially improving therapies for deep venous insufficiency. Popliteal vein external banding at the valve-free segment to treat severe chronic venous insufficiencyJournal of Vascular SurgeryVol. 64Issue 2PreviewAxial deep venous reflux causes skin changes or ulcers in patients with chronic venous insufficiency (CVI). The study aimed to review the results of correcting axial deep venous reflux using the novel valve-free popliteal vein external banding (PVEB) technique in patients with severe CVI. Full-Text PDF Open Archive

Simulation of Anastomosis in Coronary Artery Bypass Surgery.

Developing cardiac surgical skills and experience takes years of practice. Cardiac trainees need to develop technical proficiency in order to enhance quality of care and patient safety. Simulation-based models are common resources for teaching procedural skills in both undergraduate and postgraduate medical education. Suitable and accessible educational platforms can play a progressively important role in the training process for young surgeons in the area of cardiac surgery. Coronary artery bypass graft (CABG) surgery consists of a wide range of pathologic anatomies and surgical techniques. In this paper we introduce a novel, synthetic, biomimetic platform that allows for the realistic practice of the CABG surgery. The prototype uses a polyvinyl alcohol hydrogel which has been designed to mimic the geometric properties of vasculature. The proposed models look and feel like human tissue and possess somewhat consistent mechanical properties. In this study, we apply the platform to simulate a case of autogenous saphenous vein bypass grafting of a patient. An autogenous saphenous vein graft is placed from the aorta to the left anterior descending coronary artery. The standard procedures of the coronary artery bypass surgery were successfully simulated. Using the proposed technology, other complicated surgeries such as end to end, side to end, and sequential anastomoses can be simulated such that these models lend themselves very well to various types of anastomoses.

Stenting as a bail-out option after failed percutaneous transluminal angioplasty in infrainguinal vein bypass grafts.

To study the safety and efficacy of bare and covered stents in infrainguinal vein grafts after failure of PTA for treating graft stenoses. An analysis of a prospective database of all patients who underwent stenting of infrainguinal vein bypass grafts at this institution between 1 January 2008 and 31 December 2012 was carried out. The main outcome considered was primary patency, which was reported at 1, 6 and 12 months. A total of 18 patients with a mean age of 73 years (range: 56 to 86) were included. The indications for stent placement were significant recoil (7, 39%), graft rupture (6, 33%), residual vein cusps (3, 17%) and aneurysmal degeneration (2, 11%). There was a high overall technical success rate of 94% (17/18) and arrest of haemorrhage was achieved in all cases of graft rupture. The primary patency at 1, 6 and 12 months was 89%, 71% and 59%, respectively. The use of bare and covered stents in infrainguinal vein grafts appears safe and effective. They are an excellent bail-out option for the treatment of graft rupture and give acceptable short-term results.