Venous External Support in Coronary Artery Bypass Surgery: A Systematic Review and Meta-Analysis.

Neointimal hyperplasia and lumen irregularities are major contributors to vein graft failure and the use of VEST(R) should prevent this. In this review, we aim to evaluate the angiographic outcomes of externally supported vein grafts. Medline, Embase and Cochrane Library were systematically reviewed for randomized clinical trials published by August 2022. The primary outcome was graft failure. Secondary outcomes included graft ectasia, intimal hyperplasia area and thickness, and graft nonuniformity. Odds ratios (OR) for dichotomous variables and mean difference (MD) for continuous variables with 95% confidence intervals (CI) were pooled using a fixed-effects model. Three randomized controlled trials with a total of 437 patients were included with follow-up ranging from 1 to 2 years. The odds of graft failure were similar in the 2 groups (OR 1.22; 95%CI 0.88-1.71; I²â€¯= 0%). Intimal hyperplasia area [MD -0.77 mm2; 95%CI -1.10 to -0.45; I2 = 0%] and thickness [MD -0.06 mm; 95% CI -0.08 to -0.04; I2=0%] were significantly lower in the VEST group. Fitzgibbon Patency Scale of II or III (representing angiographic conduit nonuniformity; OR 0.67; 95%CI 0.48-0.94; I2 = 0%) and graft ectasia (OR 0.53; 95%CI 0.32-0.88; I2 = 33%) were also significantly lower in the VEST group. At short-term follow-up, VEST does not seem to reduce the incidence of graft failure, although it is associated with attenuation of intimal hyperplasia and nonuniformity. Longer angiographic follow-up is warranted to determine whether these positive effects might translate into a positive effect in graft failure and in long-term clinical outcomes.

External Support for Saphenous Vein Grafts in Coronary Artery Bypass Surgery: A Randomized Clinical Trial.

Importance: Intimal hyperplasia and subsequent saphenous vein graft failure may have significant adverse clinical effects in patients undergoing coronary artery bypass surgery. External support of saphenous vein grafts has the potential to prevent vein graft dilation and hence slow the rate of intimal hyperplasia and increase long-term vein patency. Objective: To determine efficacy, as measured by intimal hyperplasia, and safety of an external saphenous vein graft support device in patients undergoing a coronary bypass graft procedure. Design, Setting, and Participants: This within-patient randomized, open-label, multicenter study was conducted at 17 Cardiothoracic Surgical Trials Network centers in North America. Between January 2018 and February 2019, 224 patients with multivessel coronary artery disease undergoing isolated bypass surgery were enrolled. For each patient, 1 of 2 vein grafts was randomized to receive external support or no support. Interventions: External vein graft support or no support. Main Outcomes and Measures: The primary efficacy end point was intimal hyperplasia area assessed by intravascular ultrasound at 12 months postrandomization for each study graft. Secondary confirmatory end points were lumen diameter uniformity assessed by angiography and graft failure (≥50% stenosis) by quantitative coronary angiography. Major cardiac and cerebrovascular events were collected through month 12. Results: Among 224 patients (mean [SD] age, 65.8 [8.3] years; 178 [79.5%] male), 203 (90.6%) were eligible for intravascular ultrasound, of which 85 (41.9%) had at least 1 study graft occluded or severely diseased at 12 months (55 supported, 56 unsupported). After imputation of data missing because of graft occlusion or severe disease, the estimated mean (SE) intimal hyperplasia area was 5.11 (0.16) mm2 in supported grafts and 5.79 (0.20) mm2 in unsupported grafts (P = .07). In a sensitivity analysis of 113 patients with both grafts imaged, the mean intimal hyperplasia area was 4.58 (0.18) mm2 and 5.12 (0.23) mm2 in supported and unsupported grafts, respectively (P = .04). By 12 months, 5 patients (2.2%) died and 16 patients (7.1%) experienced a major cardiac or cerebrovascular event. Conclusions and Relevance: The 12-month difference in intimal hyperplasia area between supported and unsupported grafts did not achieve statistical significance. Cumulative mortality and major cardiac or cerebrovascular events rates were similar to those in other randomized coronary artery bypass trials. Further investigation to assess the effect of external graft support devices on long-term graft patency and clinical outcomes is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT03209609.

Poly (ɛ-Caprolactone-co-l,l-Lactide) Vascular External Sheath Carrying Prednisone for Improving Patency Rate of the Vein Graft.

Coronary artery bypass graft (CABG) surgery is an impactful treatment for coronary heart disease. Intimal hyperplasia is the central reason for the restenosis of vein grafts (VGs) after CABG. The introduction of external vascular sheaths around VGs can effectively inhibit intimal hyperplasia and ensure the patency of VGs. In this study, the well-known biodegradable copolymer poly (ɛ-caprolactone-co-l,l-lactide) (PLCL) was electrospun into high porosity external sheaths. The prednisone loaded in the PLCL sheath was slowly released during the degradation process of PLCL. Under the combined effects of sheath and prednisone, intimal hyperplasia was inhibited. For the cell experiments, all sheaths show low cytotoxicity to L929 cells at different concentrations at different time intervals. The ultrasonography and histological results showed prominent dilation and intimal hyperplasia of VG without sheath after 2 months of surgery. But there was no dilation in PLCL and PLCLPrednisone groups. Of note, the prednisone-loaded sheath group exhibited efficacy in inhibiting intimal hyperplasia and ensured graft patency. Impact statement To inhibit intimal hyperplasia after coronary artery bypass graft, the use of external vascular sheaths can prevent vein graft (VG) dilatation, then reduce turbulent blood flow shear stress to vessel wall, and lower the stimulation of shear stress to smooth muscle cells (SMCs), so as to prevent the proliferation and migration of vascular SMC. We provide a biodegradable sheath electrospun by poly (ɛ-caprolactone-co-l,l-lactide) (PLCL) loading prednisone and utilize it around VG in animal models. Vascular ultrasound examinations show strong evidence of vascular patency. The histological alterations of VGs in PLCLPrednisone group gave a narrower intima layer owing to the inhibition effect of prednisone.

Effect of Rivaroxaban and Clopidogrel Combination Therapy on In-Stent Responses After Everolimus-Eluting Stent Implantation in a Porcine Coronary Model.

AIM: According to recent clinical trials, a combination of direct oral anticoagulants with antiplatelet drugs is often recommended for atrial fibrillation patients who receive drug-eluting stents (DESs). Although the optimal combination comprises direct factor Xa inhibitors and a P2Y12 receptor antagonist (or aspirin), their influence on vascular responses to DESs remains unclear. METHODS: Pigs were given either aspirin and clopidogrel (dual antiplatelet therapy [DAPT] group), aspirin and rivaroxaban (AR group), or clopidogrel and rivaroxaban (CR group), followed by everolimus-eluting stent (Promus Element) implantation into the coronary artery. Stented coronary arteries were evaluated via intravascular optical coherence tomography (OCT) and histological analysis at 1 and 3 months. RESULTS: OCT revealed lower neointimal thickness in the DAPT group and comparable thickness among all groups at 1 and 3 months, respectively. Histological analyses revealed comparable neointimal area among all groups and the smallest neointimal area in the CR group at 1 and 3 months, respectively. In the DAPT and AR groups, the neointima continued to grow from 1 to 3 months. A shortened time course for neointima growth was observed in the CR group, with rapid growth within a month (maintained for 3 months). A higher incidence of in-stent thrombi was observed in the AR group at 1 month; no thrombi were found in either group at 3 months. More smooth muscle cells with contractile features were found in the CR group at both 1 and 3 months. CONCLUSIONS: Our results proved the noninferiority of the combination of rivaroxaban with an antiplatelet drug, particularly the dual therapy using rivaroxaban and clopidogrel, compared to DAPT after DES implantation.

Computationally guided in-vitro vascular growth model reveals causal link between flow oscillations and disorganized neotissue.

Disturbed shear stress is thought to be the driving factor of neointimal hyperplasia in blood vessels and grafts, for example in hemodialysis conduits. Despite the common occurrence of neointimal hyperplasia, however, the mechanistic role of shear stress is unclear. This is especially problematic in the context of in situ scaffold-guided vascular regeneration, a process strongly driven by the scaffold mechanical environment. To address this issue, we herein introduce an integrated numerical-experimental approach to reconstruct the graft-host response and interrogate the mechanoregulation in dialysis grafts. Starting from patient data, we numerically analyze the biomechanics at the vein-graft anastomosis of a hemodialysis conduit. Using this biomechanical data, we show in an in vitro vascular growth model that oscillatory shear stress, in the presence of cyclic strain, favors neotissue development by reducing the secretion of remodeling markers by vascular cells and promoting the formation of a dense and disorganized collagen network. These findings identify scaffold-based shielding of cells from oscillatory shear stress as a potential handle to inhibit neointimal hyperplasia in grafts.

Revascularisation of type 2 diabetics with coronary artery disease: Insights and therapeutic targeting of O-GlcNAcylation.

AIM: Coronary artery bypass graft (CABG) using autologous saphenous vein continues to be a gold standard procedure to restore the supply of oxygen-rich blood to the heart muscles in coronary artery disease (CAD) patients with or without type 2 diabetes mellitus (T2DM). However, CAD patients with T2DM are at higher risk of graft failure. While failure rates have been reduced through improvements in procedure-related factors, much less is known about the molecular and cellular mechanisms by which T2DM initiates vein graft failure. This review gives novel insights into these cellular and molecular mechanisms and identifies potential therapeutic targets for development of new medicines to improve vein graft patency. DATA SYNTHESIS: One important cellular process that has been implicated in the pathogenesis of T2DM is protein O-GlcNAcylation, a dynamic, reversible post-translational modification of serine and threonine residues on target proteins that is controlled by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Protein O-GlcNAcylation impacts a range of cellular processes, including trafficking, metabolism, inflammation and cytoskeletal organisation. Altered O-GlcNAcylation homeostasis have, therefore, been linked to a range of human pathologies with a metabolic component, including T2DM. CONCLUSION: We propose that protein O-GlcNAcylation alters vascular smooth muscle and endothelial cell function through modification of specific protein targets which contribute to the vascular re-modelling responsible for saphenous vein graft failure in T2DM.

First Reported Case of Neointimal Hyperplasia in the Midportion of a Polytetrafluoroethylene Dialysis Graft.

We report a case of stenosis involving the midportion of a polytetrafluoroethylene graft caused by the infiltration of fibroblasts into the lumen of the graft with the development of fibrovascular tissue.

Reactive Oxygen Species: Modulators of Phenotypic Switch of Vascular Smooth Muscle Cells.

Reactive oxygen species (ROS) are natural byproducts of oxygen metabolism in the cell. At physiological levels, they play a vital role in cell signaling. However, high ROS levels cause oxidative stress, which is implicated in cardiovascular diseases (CVD) such as atherosclerosis, hypertension, and restenosis after angioplasty. Despite the great amount of research conducted to identify the role of ROS in CVD, the image is still far from being complete. A common event in CVD pathophysiology is the switch of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic phenotype. Interestingly, oxidative stress is a major contributor to this phenotypic switch. In this review, we focus on the effect of ROS on the hallmarks of VSMC phenotypic switch, particularly proliferation and migration. In addition, we speculate on the underlying molecular mechanisms of these cellular events. Along these lines, the impact of ROS on the expression of contractile markers of VSMCs is discussed in depth. We conclude by commenting on the efficiency of antioxidants as CVD therapies.

A novel biodegradable external stent regulates vein graft remodeling via the Hippo-YAP and mTOR signaling pathways.

Coronary artery bypass graft (CABG) has been confirmed to effectively improve the prognosis of coronary artery disease, which is a major public health concern worldwide. As the most frequently used conduits in CABG, saphenous vein grafts have the disadvantage of being susceptible to restenosis due to intimal hyperplasia. To meet the urgent clinical demand, adopting external stents (eStents) and illuminating the potential mechanisms underlying their function are important for preventing vein graft failure. Here, using 4-axis printing technology, we fabricated a novel biodegradable and flexible braided eStent, which exerts excellent inhibitory effect on intimal hyperplasia. The stented grafts downregulate Yes-associated protein (YAP), indicating that the eStent regulates vein graft remodeling via the Hippo-YAP signaling pathway. Further, as a drug-delivery vehicle, a rapamycin (RM)-coated eStent was designed to amplify the inhibitory effect of eStent on intimal hyperplasia through the synergistic effects of the Hippo and mammalian target of rapamycin (mTOR) signaling pathways. Overall, this study uncovers the underlying mechanisms of eStent function and identifies a new therapeutic target for the prevention of vein graft restenosis.

Surgical treatment of outflow graft kinking complicated by external obstruction with a fibrin mass in a patient with LVAD.

BACKGROUND: Outflow graft (OG) obstruction is a dangerous complication that may occur for various reasons after left ventricular assist device (LVAD) implantation. CASE SUMMARY: We describe the case of a 51-year-old patient on LVAD support who developed significant OG kinking and external OG obstruction due to a fibrin mass causing severe stenosis. Both the OG kinking and external obstruction were eliminated via a left lateral thoracotomy.

Oral Charcoal Adsorbents Attenuate Neointima Formation of Arteriovenous Fistulas.

Chronic kidney disease (CKD) accelerates the development of neointima formation at the anastomosis site of arteriovenous (AV) fistulas. Accumulation of certain uremic toxins has a deleterious effect on the cardiovascular system. The oral charcoal adsorbent, AST-120, reduces circulating and tissue uremic toxins, but its effect on neointima formation at an AV fistula is unknown. To understand the effect of CKD and AST-120 on neointima formation, we created AV fistulas (common carotid artery to the external jugular vein in an end-to-side anastomosis) in mice with and without CKD. AST-120 was administered in chow before and after AV fistula creation. Administration of AST-120 significantly decreased serum indoxyl sulfate levels in CKD mice. CKD mice had a larger neointima area than non-CKD mice, and administration of AST-120 in CKD mice attenuated neointima formation. Both smooth muscle cell and fibrin components were increased in CKD mice, and AST-120 decreased both. RNA expression of MMP-2, MMP-9, TNFα, and TGFß was increased in neointima tissue of CKD mice, and AST-120 administration neutralized the expression. Our results provided in vivo evidence to support the role of uremic toxin-binding therapy on the prevention of neointima formation. Peri-operative AST-120 administration deserves further investigation as a potential therapy to improve AV fistula patency.

Endothelin-1, endothelin receptor antagonists, and vein graft occlusion in coronary artery bypass surgery: 20 years on and still no journey from bench to bedside.

The saphenous vein is the most commonly used bypass graft in patients with coronary artery disease. During routine coronary artery bypass, grafting the vascular damage inflicted on the vein is likely to stimulate the release of endothelin-1, a potent endothelium-derived vasoconstrictor that also possesses cell proliferation and inflammatory properties, conditions associated with vein graft failure. In both in vitro and in vivo studies, endothelin receptor antagonists reduce neointimal thickening. The mechanisms underlying these observations are multifactorial and include an effect on cell proliferation and cell/tissue damage. Much of the data supporting the beneficial action of endothelin-1 receptor antagonism at reducing intimal thickening and occlusion in experimental vein grafts were published over 20 years ago. The theme of the recent ET-16 conference in Kobe was "Visiting Old and Learning New". This short review article provides an overview of studies showing the potential of endothelin receptor antagonists to offer an adjuvant therapeutic approach for reducing saphenous vein graft failure and poses the question why this important area of research has not been translated from bench to bedside given the potential benefit for coronary artery bypass patients.

Evaluation of a Novel Spun Polytetrafluoroethylene Stent Graft in an Ovine External Iliac Artery Model.

PURPOSE: To evaluate the patency, cellular response, and thrombogenicity of a novel vascular stent graft. MATERIALS AND METHODS: Test stent grafts, incorporating luminal spun polytetrafluoroethylene and a nonpermeable fluoropolymer layer, and control stent grafts, constructed of permeable expanded polytetrafluoroethylene, were implanted in the external iliac arteries of 14 adult sheep with a median weight of 73.4 kg ranging from 60.6-86.8 kg for 30 (n = 4), 90 (n = 4), and 180 (n = 6) days. Angiographic patency and percent diameter stenosis (%DS) were assessed at termination. Excised stent grafts were fixed and stained for histopathologic analysis, including neointimal coverage (NC) assessment. RESULTS: Test and control device migration occurred in 1 animal, resulting in test device thrombosis. Both devices were excluded from analysis. Mean %DS in test and control implants was 4.6% and 8.2% (P = .563), 2.0% and 10.9% (P = .363), and 2.1% and 10.3% (P = .009) at 30, 90, and 180 days, respectively. Median NC scores at 30, 90, and 180 days were significantly lower in middle test device sections (P < .05). Proximal and distal test and control sections exhibited similar median NC scores at all time periods (P > .05). When present, test and control devices exhibited no neointimal detachment from the graft surface. Except for the migrated test device, no thrombus was observed. Transgraft cellular migration was absent in test devices but present in control devices with tissue accumulation around the stent struts. CONCLUSIONS: Test and control devices demonstrated excellent patency in an ovine model. Compared to the control, test devices exhibited significantly lower %DS values at 180 days and significantly lower mid-device NC scores at 30, 90, and 180 days.

Short-term preoperative protein restriction attenuates vein graft disease via induction of cystathionine γ-lyase.

AIMS: Therapies to prevent vein graft disease, a major problem in cardiovascular and lower extremity bypass surgeries, are currently lacking. Short-term preoperative protein restriction holds promise as an effective preconditioning method against surgical stress in rodent models, but whether it can improve vein graft patency after bypass surgery is undetermined. Here, we hypothesized that short-term protein restriction would limit vein graft disease via up-regulation of cystathionine γ-lyase and increased endogenous production of the cytoprotective gaseous signalling molecule hydrogen sulfide. METHODS AND RESULTS: Low-density lipoprotein receptor knockout mice were preconditioned for 1 week on a high-fat high-cholesterol (HFHC) diet with or without protein prior to left common carotid interposition vein graft surgery with caval veins from donor mice on corresponding diets. Both groups were returned to a complete HFHC diet post-operatively, and vein grafts analysed 4 or 28 days later. A novel global transgenic cystathionine γ-lyase overexpressing mouse model was also employed to study effects of genetic overexpression on graft patency. Protein restriction decreased vein graft intimal/media+adventitia area and thickness ratios and intimal smooth muscle cell infiltration 28 days post-operatively, and neutrophil transmigration 4 days post-operatively. Protein restriction increased cystathionine γ-lyase protein expression in aortic and caval vein endothelial cells (ECs) and frequency of lung EC producing hydrogen sulfide. The cystathionine γ-lyase inhibitor propargylglycine abrogated protein restriction-mediated protection from graft failure and the increase in hydrogen sulfide-producing ECs, while cystathionine γ-lyase transgenic mice displayed increased hydrogen sulfide production capacity and were protected from vein graft disease independent of diet. CONCLUSION: One week of protein restriction attenuates vein graft disease via increased cystathionine γ-lyase expression and hydrogen sulfide production, and decreased early inflammation. Dietary or pharmacological interventions to increase cystathionine γ-lyase or hydrogen sulfide may thus serve as new and practical strategies to improve vein graft durability.

Vascularization of the arteriovenous fistula wall and association with maturation outcomes.

BACKGROUND AND OBJECTIVES: The venous vasa vasorum is the mesh of microvessels that provide oxygen and nutrients to the walls of large veins. Whether changes to the vasa vasorum have any effects on human arteriovenous fistula outcomes remains undetermined. In this study, we challenged the hypothesis that inadequate vascularization of the arteriovenous fistula wall is associated with maturation failure. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This case-control pilot study includes pre-access veins and arteriovenous fistula venous samples (i.e. tissue pairs) from 30 patients undergoing two-stage arteriovenous fistula creation (15 matured and 15 failed to mature). Using anti-CD31 immunohistochemistry, we quantified vasa vasorum density and luminal area (vasa vasorum area) in the intima, media, and adventitia of pre-access veins and fistulas. We evaluated the association of pre-existing and postoperative arteriovenous fistula vascularization with maturation failure and with postoperative morphometry. RESULTS: Vascularization of veins and arteriovenous fistulas was predominantly observed in the outer media and adventitia. Only the size of the microvasculature (vasa vasorum area), but not the number of vessels (vasa vasorum density), increased after arteriovenous fistula creation in the adventitia (median vasa vasorum area 1366 µm2/mm2 (interquartile range 495-2582) in veins versus 3077 µm2/mm2 (1812-5323) in arteriovenous fistulas, p < 0.001), while no changes were observed in the intima and media. Postoperative intimal thickness correlated with lower vascularization of the media (r 0.53, p = 0.003 for vasa vasorum density and r 0.37, p = 0.045 for vasa vasorum area). However, there were no significant differences in pre-existing, postoperative, or longitudinal change in vascularization between arteriovenous fistulas with distinct maturation outcomes. CONCLUSION: The lack of change in intimal and medial vascularization after arteriovenous fistula creation argues against higher oxygen demand in the inner walls of the fistula during the vein to arteriovenous fistula transformation. Postoperative intimal hyperplasia in the arteriovenous fistula wall appears to thrive under hypoxic conditions. Vasa vasorum density and area by themselves are not predictive of maturation outcomes.

Preventing treatment failures in coronary artery disease: what can we learn from the biology of in-stent restenosis, vein graft failure, and internal thoracic arteries?

Coronary artery disease (CAD) remains one of the most important causes of morbidity and mortality worldwide, and the availability of percutaneous or surgical revascularization procedures significantly improves survival. However, both strategies are daunted by complications which limit long-term effectiveness. In-stent restenosis (ISR) is a major drawback for intracoronary stenting, while graft failure is the limiting factor for coronary artery bypass graft surgery (CABG), especially using veins. Conversely, internal thoracic artery (ITA) is known to maintain long-term patency in CABG. Understanding the biology and pathophysiology of ISR and vein graft failure (VGF) and mechanisms behind ITA resistance to failure is crucial to combat these complications in CAD treatment. This review intends to provide an overview of the biological mechanisms underlying stent and VGF and of the potential therapeutic strategy to prevent these complications. Interestingly, despite being different modalities of revascularization, mechanisms of failure of stent and saphenous vein grafts are very similar from the biological standpoint.

The placental growth factor attenuates intimal hyperplasia in vein grafts by improving endothelial dysfunction.

Saphenous vein grafts (SVG) patency is limited by intimal hyperplasia (IH) caused by endothelial dysfunction. This study aimed to explore the effect of placental growth factor (PlGF) on the endothelial function of SVG. In rat models of external jugular vein-carotid artery graft treated with PlGF or saline hydrogel, PlGF inhibited vein graft IH (day 28: 12.0 ± 1.9 vs. 61.7 ± 13.1 µm, P < 0.001), promoted microvessel proliferation (day 14: 33.3% 3+ vs. 50.0% 2+, P = 0.03), and increased nitric oxide (NO) production (P < 0.05 on days 1/3/5) and NO synthase (NOS) expression by immunohistochemistry. In human umbilical vein endothelial cells (HUVECs) cultured under hypoxia and treated or not with PlGF, PlGF restored the survival (50 ng/ml PlGF, 48 h: 91.7 ± 0.6% vs. 84.9 ± 0.5%, P < 0.01), migration (by Matrigel assay), and tube formation ability (junctions, tubules, and tubule total length; all P < 0.01) of HUVECs after hypoxia. PlGF increased NO production through increased eNOS expression (P < 0.05), without changes in iNOS expression. The mRNA expression of eNOS decreased after the addition of the PI3K inhibitor LY294002 (P < 0.05). PlGF promoted the protein expression of eNOS by up-regulating AKT, and the AKT and eNOS protein levels were decreased after adding LY294002 (all P < 0.05). In conclusion, PlGF is a candidate for the inhibition of IH in SVG after coronary artery bypass graft. The effects of PlGF are mediated by the upregulation of the eNOS mRNA and protein through the PI3K/AKT signaling pathway. PlGF promotes the secretion of NO by endothelial cells and thereby reduces the occurrence and development of IH.

Reduced patency in left-sided arteriovenous grafts in a porcine model.

OBJECTIVE: The porcine arteriovenous graft model is commonly used to study hemodialysis vascular access failure, with most studies using a bilateral, paired-site approach in either the neck or femoral vessels. In humans, left- and right-sided central veins have different anatomy and diameters, and left-sided central vein catheters have worse outcomes. We assessed the effect of laterality on arteriovenous prosthetic graft patency and hypothesized that left-sided carotid-jugular arteriovenous prosthetic grafts have reduced patency in the porcine model. METHODS: Arteriovenous polytetrafluoroethylene grafts were placed ipsilaterally or bilaterally in 10 Yorkshire male pigs from the common carotid artery to the internal jugular vein. Ultrasound measurements of blood flow velocities and diameters were assessed before graft placement. Animals were sacrificed at 1 week, 2 weeks, or 3 weeks. Patency was determined clinically; grafts and perianastomotic vessels were excised and analyzed with histology and immunostaining. RESULTS: At baseline, left- and right-sided veins and arteries had similar blood flow velocities. Although internal jugular veins had similar diameters at baseline, left-sided carotid arteries had 11% smaller outer diameters (P = .0354). There were 10 left-sided and 8 right-sided polytetrafluoroethylene grafts placed; only 4 of 10 (40%) grafts were patent on the left compared with 7 of 8 (88%) grafts patent on the right (P = .04). Left-sided grafts had increased macrophages at the arterial anastomosis (P = .0007). Left-sided perianastomotic arteries had thicker walls (0.74 vs 0.60 mm; P = .0211) with increased intima-media area (1.14 vs 0.77 mm2; P = .0169) as well as a trend toward 38% smaller luminal diameter (1.6 vs 2.5 mm; P = .0668) and 20% smaller outer diameter (3.0 vs 3.7 mm; P = .0861). Left- and right-sided perianastomotic veins were similar histologically, but left-sided veins had decreased expression of phosphorylated endothelial nitric oxide synthase (P = .0032) and increased numbers of α-actin-positive smooth muscle cells (P = .0022). CONCLUSIONS: Left-sided arteriovenous grafts are associated with reduced short-term patency compared with right-sided grafts in the Yorkshire pig preclinical model of arteriovenous prosthetic grafts. Laterality must be considered in planning and interpreting surgical preclinical models.