Matched comparison of decellularized homografts and bovine jugular vein conduits for pulmonary valve replacement in congenital heart disease.

For decades, bovine jugular vein conduits (BJV) and classic cryopreserved homografts have been the two most widely used options for pulmonary valve replacement (PVR) in congenital heart disease. More recently, decellularized pulmonary homografts (DPH) have provided an alternative avenue for PVR. Matched comparison of patients who received DPH for PVR with patients who received bovine jugular vein conduits (BJV) considering patient age group, type of heart defect, and previous procedures. 319 DPH patients were matched to 319 BJV patients; the mean age of BJV patients was 15.3 (SD 9.5) years versus 19.1 (12.4) years in DPH patients (p = 0.001). The mean conduit diameter was 24.5 (3.5) mm for DPH and 20.3 (2.5) mm for BJV (p < 0.001). There was no difference in survival rates between the two groups after 10 years (97.0 vs. 98.1%, p = 0.45). The rate of freedom from endocarditis was significantly lower for BJV patients (87.1 vs. 96.5%, p = 0.006). Freedom from explantation was significantly lower for BJV at 10 years (81.7 vs. 95.5%, p = 0.001) as well as freedom from any significant degeneration at 10 years (39.6 vs. 65.4%, p < 0.001). 140 Patients, matched for age, heart defect type, prior procedures, and conduit sizes of 20-22 mm (± 2 mm), were compared separately; mean age BJV 8.7 (4.9) and DPH 9.5 (7.3) years (p = n.s.). DPH showed 20% higher freedom from explantation and degeneration in this subgroup (p = 0.232). Decellularized pulmonary homografts exhibit superior 10-year results to bovine jugular vein conduits in PVR.

Optimal treatment of tannic acid for the anti-calcification of bovine jugular veins and the underlying mechanism.

OBJECTIVES: To evaluate the effects of combined treatment with tannic acid and ferric ions on the biomechanical and anti-calcification properties of glutaraldehyde-fixed bovine jugular veins after xenografting. METHODS: Two-point bending test and uniaxial tensile test were used to evaluate the flexural and biomechanical properties; Subcutaneous implantation in rat and right ventricular outflow tract reconstruction of sheep were used to evaluate the anti-calcification effects; The performance of the graft in sheep models was evaluated every month after the surgery with echocardiography examination. Markers of macrophages, T lymphocytes, smooth muscle cell osteogenic differentiation and matrix metalloproteinases in sheep explants were detected by immunohistochemistry. RESULTS: The flexibility of the bovine jugular veins cotreated with ferric ions-tannic acid was improved while maintaining biomechanical properties and excellent anti-calcification effects. Echocardiography results showed that the grafts functioned well in the animals without stenosis or reflux of the valve. Immunohistochemical studies showed that the osteogenic differentiation marker (Runx2) was detected in calcified regions and colocalised with the SMC marker (α-SMA). Compared to the glutaraldehyde-treated samples, T-cell marker (CD3), matrix metalloproteinase-2 and 9 expressions were reduced in the ferric ions-tannic acid treated group. CONCLUSION: Ferric ions-tannic acid treatment can give the conduits better flexibility with excellent biomechanical properties and anti-calcification effects, making it a promising bovine jugular veins processing method.

20-year follow-up and comparison of homografts with bovine jugular vein conduits in children less than 2 years of age.

OBJECTIVES:  Repair of congenital heart defects involving right ventricular outflow tract (RVOT) may require pulmonary valve replacement at time of primary repair or reoperation. This study compares the outcomes of cryopreserved homografts with bovine jugular vein conduits (BJVC) in children < 2 years of age with RVOT reconstruction. METHODS:  Retrospective, single-center review of 70 conduits implanted in 63 patients undergoing right ventricle-to-pulmonary artery reconstruction with valved conduit from 2002 to 2022. RESULTS: A total of 70 conduits were implanted in 63 patients, with mean age of 4.5 ± 6.9 months (range 1 day ‒ 23.5 months). The following conduits were used; homografts 38 (54.2 %), BJVC 32 (45.8 %). During mean follow-up of 6.2 ± 5.6 years, there were 12 deaths, 24 conduit reoperations, and 25 catheter reinterventions. Overall survival, reoperation-free, and catheter reintervention-free survival at 15 years was 82.7 %, 31.2 %, and 25.7 %, respectively. Multivariate analysis revealed that low patient weight, age < 30 days at repair, ventilation time, and ICU length of stay were associated with increased risk of death. CONCLUSION: The performance of homografts and BJVC is comparable in patients ent between the two groups (Tab. 3, Fig. 3, Ref. 16).

[Transcriptome sequencing for identification of the genes associated with restenosis of venous grafts in rabbits].

OBJECTIVE: To identify the genes associated with venous graft restenosis in rabbits using transcriptome sequencing. METHODS: Forty New Zealand rabbits were randomly divided into experimental group and control group, and in the experimental group, the left external jugular veins of the rabbits were engrafted to the left common carotid artery with continuous running suture; the rabbits in the control group received no operation. At 2 and 4 weeks after the operation, 10 rabbits from each group were euthanized and the venous grafts (in experimental group) or left external jugular vein (in control group) were harvested for measurement of the intima-media thickness using HE staining. RNA high-throughput sequencing (RNA-seq) was performed to identify the differentially expressed genes (DEGs) between the venous grafts and the control veins, and the biological functions of the DEGs were analyzed using GO and KEEG databases. RESULTS: In the experimental group, intima-media thickening with increased extracellular matrix and vascular smooth muscle cell proliferation occurred in the venous grafts at 2 weeks and aggravated at 4 weeks after the operation. RNA high-throughput sequencing identified 1583 up-regulated genes and 608 down-regulated genes in the venous grafts in the experimental group, and GO and KEGG analysis of the DEGs pinpointed 10 hub genes, namely CD4, ZAP70, SYK, CD28, PIK3CD, CXCR4, CCR5, ITK, CCL5 and BTK. CONCLUSION: CD4, ZAP70, SYK, CD28, PIK3CD, CXCR4, CCR5, ITK, CCL5 and BTK are probably the key genes associated with vein graft restenosis in rabbits.

Right Ventricular Outflow Tract Reconstruction in Truncus Arteriosus: A 30-Year Two-Center Comparison between Homografts and Bovine Jugular Vein.

INTRODUCTION: Homografts and bovine jugular vein are the most commonly used conduits for right ventricular outflow tract reconstruction at the time of primary repair of truncus arteriosus. METHODS: We reviewed all truncus patients from 1990 to 2020 in two mid-volume centers. Inclusion criteria were primary repair, age under one year, and implantation of either homograft or bovine jugular vein. Kaplan-Meier analysis was used to estimate survival, freedom from reoperation on right ventricular outflow tract, and freedom from right ventricular outflow tract reoperation or catheter intervention. RESULTS: Seventy-three patients met the inclusion criteria, homografts were implanted in 31, and bovine jugular vein in 42. There was no difference in preoperative characteristics between the two groups. There were 25/73 (34%) early postoperative deaths and no late deaths. Follow-up for survivals was 17.5 (interquartile range 13.5) years for homograft group, and 11.5 (interquartile range 8.5) years for bovine jugular vein group (P=0.002). Freedom from reoperation on right ventricular outflow tract at one, five, and 10 years in the homograft group were 100%, 83%, and 53%; and in bovine jugular vein group, it was 100%, 85%, and 50% (P=0.79). There was no difference in freedom from reoperation or catheter intervention (P=0.32). CONCLUSION: Bovine jugular vein was equivalent to homografts up to 10 years in terms of survival and freedom from right ventricular outflow tract reoperation or catheter intervention. The choice of either valved conduit did not influence the durability of the right ventricle-pulmonary artery conduit in truncus arteriosus.

Comparison of homografts and bovine jugular vein conduits in the pulmonary position in patients <20 years of age.

OBJECTIVE: To compare the performance of homografts and bovine jugular vein (BJV) conduits in the pulmonary position. METHODS: All patients with congenital heart disease up to age 20 years who underwent pulmonary valve replacement with homografts or BJV at 3 centers in Australia were evaluated. There were 674 conduits, with 305 (45%) pulmonary homografts (PHs), 303 (45%) BJV conduits, and 66 (10%) aortic homografts (AHs). Endpoints were freedom from reintervention, structural valve degeneration (SVD), and infective endocarditis (IE). Propensity score matching was used to balance the comparison of PH and BJV conduits. RESULTS: The median follow-up was 6.4 years (interquartile range, IQR, 3.1-10.7 years). Freedom from reintervention at 5 and 10 years was 92% and 80%, respectively, for PH, 74% and 37% for BJV, and 75% and 47% for AH. BJV conduits had a higher risk of reintervention (P < .001) and SVD (P < .001) compared with PHs. These findings were confirmed with propensity score matching valid for conduit size >15 mm. AHs >15 mm had a higher risk of reintervention (P < .001) and SVD (P < .001) compared with PHs >15 mm. The performance of AHs and BJV conduits was similar across all sizes (reintervention, P = .94; SVD, P = .72). The incidence of IE was 1% for PH, 10% for BJV, and 1.5% for AH. CONCLUSIONS: In patients age <20 years with a conduit >15 mm, PHs outperformed BJV conduits and AHs in the pulmonary position. The performance of AH and BJV was comparable. Small conduits (≤15 mm) had similar performance across all conduit types.

Adiponectin Prevents Restenosis Through Inhibiting Cell Proliferation in a Rat Vein Graft Model. / A Adiponectina Previne a Reestenose pela Inibição da Proliferação Celular em um Modelo de Enxerto Venoso em Ratos.

BACKGROUND: Coronary artery bypass grafting (CABG) continues to be an effective therapy for coronary artery disease patients, but the vein graft is prone to restenosis or occlude. Adiponectin (ADP) is a plasma hormone protein with the function of regulating cell proliferation. OBJECTIVE: This study used two different doses of ADP protein in a rat vein graft model to stimulate vein graft change. The aim of our study was to investigate the effect of ADP on vein graft restenosis. METHODS: Autologous jugular veins were implanted as carotid interposition grafts through the anastomotic cuff technique in Sprague Dawley rats. Adiponectin (2.5 µg and 7.5 µg) was delivered to the vein bypass grafts in a perivascular fashion, suspended in a 30% Pluronic-F127 gel. No treatment (bypass only) and vehicle loaded Pluronic gel served as controls. Comparisons were made with one-way analysis of variance and a post-hoc test, with p < 0.05 considered significant. RESULTS: Cell proliferation (PCNA index) was significantly low in adiponectin-treated versus control and vehicle-gel-treated grafts, both in intima and adventitia, as of day 3 (p < 0.01). VCAM-1 and ICAM-1 evaluated by immunohistochemistry significantly down-regulated in the adiponectin-treated vein grafts in the fourth week (p <0.01). Treatment of vein grafts with adiponectin-loaded gels reduced intimal, media, and adventitia thickness when compared with the control and vehicle-gel-treated vein grafts at day 28 (p < 0.01). CONCLUSIONS: Our studies provide further support for the potential therapeutic role of adiponectin in modulating vascular injury and repair.

FUNDAMENTO: O enxerto de bypass na artéria coronária (CABG) continua a ser eficiente como tratamento para pacientes portadores de doença arterial coronariana; entretanto, o enxerto venoso tende a apresentar reestenose ou oclusão. A adiponectina (ADP) é uma proteína hormonal plasmática com a função de regular a proliferação celular. OBJETIVO: Foram utilizadas duas doses diferentes da proteína ADP em um modelo de enxerto venoso em ratos para estimular a alteração do enxerto venoso. O objetivo deste estudo foi investigar o efeito da ADP sobre a reestenose em enxerto venoso. MÉTODOS: Veias jugulares autólogas foram implantadas como enxertos interposicionais de carótida pela técnica de anastomose de manga em ratos Sprague Dawley. A adiponectina (2,5 µg e 7,5 µg) foi entregue ao enxerto venoso por bypass de forma perivascular, suspensa em gel Pluronic-F127 a 30%. O grupo tratado apenas com bypass e o grupo tratado com gel veículo carregado apenas com Pluronic funcionaram como controle. Foram feitas comparações com análise de via única de variância e teste post-hoc, com p <0,05 sendo considerado significativo. RESULTADOS: A proliferação celular (índice de PCNA) foi significativamente baixa no grupo tratado com adiponectina em comparação com o grupo de controle e o grupo tratado com o gel veículo na íntima e na adventícia dos enxertos a partir do dia 3 (p <0,01). VCAM-1 e ICAM-1 avaliados por imuno-histoquímica diminuíram significativamente em enxertos venosos tratados com adiponectina na quarta semana (p <0,01). O tratamento de enxertos venosos com gel carregado com adiponectina reduziu a espessura da íntima, da média e da adventícia, em comparação com os enxertos de controle e tratados com gel veículo no dia 28 (p <0,01). CONCLUSÕES: Este estudo oferece evidências adicionais do possível papel terapêutico da adiponectina na modulação de lesão vascular e seu reparo.

Outcomes of Right Ventricular Outflow Tract Reconstruction in Children: Retrospective Comparison Between Bovine Jugular Vein and Expanded Polytetrafluoroethylene Conduits.

Bovine jugular vein (BJV) and expanded polytetrafluoroethylene (ePTFE) conduits have been described as alternatives to the homograft for right ventricular outflow tract (RVOT) reconstruction. This study compared RVOT reconstructions using BJV and ePTFE conduits performed in a single institution. The valve functions and outcomes of patients aged < 18 years who underwent primary RVOT reconstruction with a BJV or ePTFE conduit between 2013 and 2017 were retrospectively investigated. 44 patients (20 and 24 with BJV and ePTFE conduits, respectively) met the inclusion criteria. The mean follow-up time was 4.5 ± 1.5 years. No significant differences in peak RVOT velocity (1.8 ± 0.9 m/s vs 2.1 ± 0.9 m/s, P = 0.27), branch pulmonary stenosis (P = 0.50), or pulmonary regurgitation (P = 0.44) were found between the BJV and ePTFE conduit groups, respectively. Aneurysmal dilatation of the conduit was observed in 25.0% of the patients in the BJV conduit group but not in the ePTFE conduit group (P = 0.011). All the cases with aneurysmal dilatation of the BJV conduit were complicated with branch pulmonary stenosis up to 3.0 m/s (P = 0.004). No conduit infections occurred during the follow-up period, and no significant difference in conduit replacement (20.0% vs 8.3%, P = 0.43) was found between the BJV and ePTFE conduit groups, respectively. The outcomes of the RVOT reconstructions with BJV and ePTFE conduits were clinically satisfactory. Aneurysmal dilatation was found in the BJV conduit cases, with branch pulmonary stenosis as the risk factor.

Comparison of diameter and length of subclavian arteries to external jugular veins in variably sized dogs: A cadaveric study.

OBJECTIVE: To evaluate the length and diameter of a left external jugular vein graft as a substitute for the left subclavian artery in the modified Blalock-Thomas-Taussig shunt (mBTTS) in differently sized dogs. STUDY DESIGN: Cadaveric study. ANIMALS: Dog cadavers of three weight categories (10/group): <9.5 kg, 9.5 to 27 kg, and > 27 kg. METHODS: The length and infused external diameters of harvested vessels were measured with vernier calipers and recorded. A matched-pairs t test was used to test the difference in vessel lengths. The agreement in vessel diameters was assessed by using Lin's concordance correlation coefficient (CCC). Pearson's correlation coefficients (CC) were determined for vessel diameter to weight category and vessel length to weight category. RESULTS: The external jugular vein measured longer than the subclavian artery in all dogs (52.0 ± 20.8 mm and 23.0 ± 8.9 mm, respectively), with a mean difference of 28 ± 14.3 mm (P < .001). The mean external infused subclavian and external jugular diameters measured 7.8 ± 2.2 mm and 8.0 ± 2.5 mm, respectively (P = .32). Lin's CCC was 0.87. Pearson's CC were 0.74 in both vessel diameters (P < .001); they were 0.36 and 0.43, respectively, for subclavian artery and external juglar vein length (P < .001). CONCLUSION: Autologous external jugular vein grafts had an external diameter similar to subclavian artery and a significantly longer length in variably sized dogs. CLINICAL SIGNIFICANCE: External jugular vein grafts may be an acceptable graft choice for mBTTS.

Acute Internal Carotid Artery Occlusion Long after Carotid Revascularization by Vein Graft.

We report the case of a 27-year-old woman with acute internal carotid artery occlusion long after carotid artery revascularization by vein graft. She presented with sudden unconsciousness and left hemiparesis. Her right carotid artery was revascularized with an ipsilateral internal jugular vein graft during a carotid body tumor resection 10 years ago. Computed tomography angiography revealed a right internal carotid artery terminus occlusion. Intravenous rt-PA and mechanical thrombectomy were performed, resulting in successful recanalization. Her neurological symptoms gradually recovered. When examining the embolic source, carotid ultrasonography for the vein graft showed intimal thickening, some high-echoic plaques, and lumen dilation, but no thrombus was observed. Color Doppler imaging showed laminar flow at the graft. Angiography after thrombectomy also showed pooling of contrast at the vein graft. We suspected that the blood flow stagnation at the vein graft induced thrombus formation; therefore, anticoagulation therapy was initiated. One year later, she was independent without recurrence of stroke, and anticoagulation therapy was replaced with aspirin because she went abroad. However, a carotid ultrasonography exam the following year revealed a huge thrombus at the graft. Anticoagulation therapy was resumed; subsequently, the thrombus decreased. In conclusion, we could monitor the long-term change in the vein graft by ultrasonography. Moreover, anticoagulation therapy was more effective.

Mature Vascular Smooth Muscle Cells, but Not Endothelial Cells, Serve as the Major Cellular Source of Intimal Hyperplasia in Vein Grafts.

OBJECTIVE: Neointima formation is a primary cause of intermediate to late vein graft (VG) failure. However, the precise source of neointima cells in VGs remains unclear. Approach and Results: Herein we clarify the relative contributions of mature vascular smooth muscle cells (SMCs) and endothelial cells (ECs) to neointima formation in a mouse model of VG remodeling via the genetic-inducible fate mapping approaches. Regardless of the magnitude of neointima formation, the recipient arterial and the donor venous SMCs contributed ≈55% of the neointima cells at the anastomotic regions, whereas only donor venous SMCs donated ≈68% of the neointima cells at the middle bodies. A small portion of the SMC-derived cells became non-SMC cells, most likely vascular stem cells, and constituted 2% to 11% of the cells in each major layer of VGs. In addition, the recipient arterial ECs were the major cellular source of re-endothelialization but did not contribute to neointima formation. The donor venous ECs donated ≈17% neointima cells in the VGs with mild neointima formation and conditional media from ECs after endothelial-to-mesenchymal transition suppressed vascular SMC dedifferentiation. CONCLUSIONS: The recipient arterial and donor venous mature SMCs dominate but contribute distinctly to intimal hyperplasia at the anastomosis and the middle body regions of VGs. The recipient arterial ECs are the major cellular source of re-endothelialization but do not donate neointima formation in VGs. Only the donor venous ECs undergo endothelial-to-mesenchymal transition. Endothelial-to-mesenchymal transition is marginal for generating neointima cells but is likely required for controlling the quality of VG remodeling.

A rat arteriovenous graft model using decellularized vein.

BACKGROUND: The high rate of clinical failure of prosthetic arteriovenous grafts continues to suggest the need for novel tissue-engineered vascular grafts. We tested the hypothesis that the decellularized rat jugular vein could be successfully used as a conduit and that it would support reendothelialization as well as adaptation to the arterial environment. MATERIALS AND METHODS: Autologous (control) or heterologous decellularized jugular vein (1 cm length, 1 mm diameter) was sewn between the inferior vena cava and aorta as an arteriovenous graft in Wistar rats. Rats were sacrificed on postoperative day 21 for examination. RESULTS: All rats survived, and grafts had 100% patency in both the control and decellularized groups. Both control and decellularized jugular vein grafts showed similar rates of reendothelialization, smooth muscle cell deposition, macrophage infiltration, and cell turnover. The outflow veins distal to the grafts showed similar adaptation to the arteriovenous flow. Both CD34, CD90 and nestin positive cells, as well as M1-type and M2-type macrophages accumulated around the graft. CONCLUSIONS: This model shows that decellularized vein can be successfully used as an arteriovenous graft between the rat aorta and the inferior vena cava. Several types of cells, including progenitor cells and macrophages, are present in the host response to these grafts in this model. This model can be used to test the application of arteriovenous grafts before conducting large animal experiments.

Vein conduits used to enhance arterial microsurgical end-to-end suture repair: A randomized comparative study.

Wrapping microsurgical sutures with a vein conduit is a well-described procedure for microsurgical nerve repair. While this has rarely been described in the context of vascular repair, this technique could increase the permeability of the sutured vessels. As part of a University Diploma in Microsurgery, 9 junior surgeons performed a comparative study of 18 microsurgical repairs on rats with and without vein sleeve. The vessels used were an external jugular vein sleeve on the end-to-end anastomosis of the common carotid artery and comparing it to this same anastomosis without a sleeve. The data analyzed were rat weight, suture time with carotid clamping time, number of stitches used, complications as well as vascular leakage and permeability of the repair at 0 and 5minutes evaluated with a patency test. The average rat body weight was 255g. Mean suture time was 52minutes in group A (sleeved repairs) and 41minutes in group B (standard repairs). The number of stitches placed was 5.1 points on average in group A and 5.6 points in group B. The time to perform the repair and the number of stitches was not statistically different between groups. The patency test was positive in 100% of cases in group A and in 78% of cases in group B. There was a significant difference between the permeability rate of the repairs, with better results in group A (p=0.03). There were two anastomotic leaks after declamping in the sleeve group and five in the standard suture group, thus 2.5 times more leaks in the group without a sleeve (p<0.01). The addition of a vein sleeve around an end-to-end arterial suture repair seems to improve its permeability and therefore its reliability.

Surgical Procedures of Portal Vein Reconstruction for Recipients With Portal Vein Thrombosis in Adult-to-Adult Living Donor Liver Transplantation.

BACKGROUND: Portal vein (PV) reconstruction is an important surgical skill for living donor liver transplantation (LDLT), especially for patients with portal vein thrombosis (PVT). However, this technique remains a critical problem in LDLT because of technical demands and requirements for appropriate venous graft harvesting. This study aimed to evaluate the surgical procedure used for PV reconstruction and outcomes in LDLT recipients with PVT. METHODS: Between March 2002 and December 2018, 128 adult LDLTs were performed. Fourteen recipients (10.8%) had PVT at the time of LDLT, classified as grade I in 2, grade II in 5, grade III in 6, and grade IV in 1, according to the Yerdel classification. We retrospectively analyzed the surgical procedure and postoperative complications associated with PV reconstruction of recipients with PVT. RESULTS: Surgical treatments for 14 recipients with PVT were as follows: thrombectomies in 2 recipients, replacement of interpositional venous grafts using the internal jugular vein (IJV) in 3 recipients and the external iliac vein (EIV) in 6 recipients, mesoportal jump grafts using the IJV in 1 recipient and the IJV + EIV in 1 recipient, and renoportal anastomosis using the EIV in 1 recipient. Among interpositional venous grafts, 5 venous grafts (IJV: 2, EIV: 3) passed the dorsal side of the pancreas without using the jump graft. Postoperative complications associated with PV anastomosis occurred in 1 of 14 (7.1%) recipients, who developed anastomosis bleeding caused by coagulation disorders at 27 days after LDLT, without any strictures of PV anastomoses. The overall survival rate at 5 years posttransplant was not statistically different between recipients with and without PVT (50.0% vs 65.0%, P = .163). CONCLUSION: Our techniques of PV reconstruction, using the appropriate venous grafts and route, are feasible, resulting in a prognosis comparable to that of recipients without PVT.

Bovine jugular vein valved xenograft for extracardiac total cavo-pulmonary connection: The risk of thrombosis and the potential liver protection effect.

BACKGROUND: Currently, non-valved conduits are preferred for extracardiac total cavo-pulmonary connection (TCPC). However, previous work has failed to provide objective data comparing the postoperative outcome between non-valved TCPCs and bovine jugular vein valved xenograft (BJV) TCPCs. Hence, the objective of this study is to compare the postoperative outcomes in extracardiac TCPC patients who received BJV vs synthetic non-valved conduits and evaluate the effect of BJV on liver fibrosis. METHODS: Of 206 patients who had extracardiac TCPC from 2002 to 2017 were divided into three groups. Group A (n = 66) received BJV, group B (n = 37) received PET conduits and group C (n = 103) received polytetrafluoroethylene (PTFE) tube. Study endpoints were hospital outcomes, conduits thrombosis, reinterventions, and survival. Liver stiffness and fibrosis were assessed in eight patients with BJV. RESULTS: Preoperative parameters were comparable among groups. Thrombosis was significantly lower in group C (P < .0003) but no difference between groups A and B (P = .951). Reinterventions did not differ significantly among groups (Log-rank P = .598). Hospital deaths occurred in seven patients (3.4%). There was no difference in survival between groups (Log-rank P = .221). The median liver stiffness score was 18.65 kPa and the eight patients had advanced liver fibrosis (grade F3-4) in group A. CONCLUSION: PTFE is the recommended conduit for TCPC with a lower risk of thrombosis compared to BJV and PET. BJV conduits in TCPC circuits may not protect against liver fibrosis. BJV should not be considered as an option for TCPC.

Sirtuin 3 Therapy Attenuates Aging Expression, Oxidative Stress Parameters, and Neointimal Hyperplasia Formation in Vein Grafts.

BACKGROUND: Vein graft (VG) failure due to neointimal hyperplasia remains an important and unresolved problem in cardiovascular surgery. Sirtuin3 (SIRT3) is associated with oxidative stress and lifespan. We aimed to measure SIRT3 expression in the veins of humans and rats during aging, explore the inhibitory effects of SIRT3 on vascular smooth muscle cell (VSMC) proliferation and neointimal hyperplasia in VGs, and investigate the underlying mechanisms. METHODS: SIRT3 mRNA and protein levels in saphenous veins of young and older humans and in veins of young and old rats were measured by quantitative real-time polymerized chain reaction (PCR) and Western blot analysis. Young and old male rats were randomized to the control (control), graft (graft), adenovirus-encoding green fluorescent protein (Ad-GFP), and adenovirus encoding SIRT3 (Ad-SIRT3) groups. At 7 days after operation, the mRNA and protein levels of SIRT3 and endothelial nitric oxide synthase (eNOS) were measured by quantitative real-time PCR and Western blot analysis. The mRNA levels and enzyme activity of manganese superoxide dismutase (MnSOD) and catalase (CAT) were measured by quantitative real-time PCR and enzymatic activity assay kits, and total nitric oxide (NO) levels were measured by biochemical assay kits. Histomorphometric analysis of VGs and immunohistochemical staining for proliferative activity were performed at 4 weeks after operation. The hemodynamic parameters of the VGs were also measured by ultrasonic examination. RESULTS: SIRT3 mRNA and protein levels were lower in older human and rat veins than in younger human and rat veins. Ad-SIRT3 treatment significantly increased the expression and concentration of SIRT3, MnSOD, CAT, eNOS, and NO in VGs at 7 days after operation. Ad-SIRT3 gene transfer reduced the neointimal thickness and neointimal area/media area ratio in the VGs of the Ad-SIRT3 groups compared with the graft and Ad-GFP groups, especially in old rats. Proliferative activity was lower in the Ad-SIRT3 groups than in the other groups. The hemodynamic parameters of VGs were obviously improved in the Ad-SIRT3 groups. CONCLUSIONS: SIRT3 expression decreases in the veins of humans and rats during aging. Furthermore, SIRT3 overexpression can significantly reduce VSMC proliferation and neointimal hyperplasia in VGs. Local intravenous delivery of adenovirus encoding SIRT3 may be a promising gene therapy for preventing VG failure.

Paneled Saphenous Vein Grafts Compared to Internal Jugular Vein Grafts in Venous Reconstruction after Pancreaticoduodenectomy.

BACKGROUND: Venous resection during pancreaticoduodenectomy for the excision of pancreatic cancer allows for a more complete resection with negative margins, which increases survival. When the resected vein is greater than 3 cm, reconstruction with an interposition graft is recommended. However, consensus regarding the optimal venous conduit has not been reached. The objective of this study is to compare outcomes between the paneled saphenous vein graft (SVG) and internal jugular vein graft (IJVG) in portomesenteric venous reconstructions after pancreaticoduodenectomy. METHOD: A retrospective review was performed of patients undergoing pancreaticoduodenectomy requiring an interposition graft for venous reconstruction between 2011 and 2019. Patients were stratified based on the type of conduit used (paneled SVG or IJVG). Preoperative patient characteristics, reconstruction details, and postoperative outcomes including graft patency were recorded. RESULTS: During the study period, 18 patients met inclusion criteria (10 female, mean age: 63 years, age range: 41-82 years). Thirteen patients underwent reconstruction with paneled SVG and five with IJVG. Comparing SVG and IJVG groups, there were no significant differences in venous resection length, venous diameters at the resection margins, or splenic vein ligation rate. For the paneled SVG, the average length of harvested vein was 168 mm which rendered 3-paneled grafts with an average diameter of 12 mm. The time to complete the venous reconstructions did not differ between the two groups (SVG: 263+/-204 min, IJVG: 216+/-77 min, P = 0.63). There were five graft thrombosis, three in the SVG group (mean follow-up time of 17 months) and two in the IJVG group (mean follow-up time of 8 months). All but one of the graft thromboses occurred during the index hospitalization. There was one donor site seroma and wound dehiscence in the SVG group and none in the IJVG group. Hospital length of stay was longer for the IJVG group (IJVG: 15.2 days, SVG: 10.2 days, P = 0.03). However, in-hospital and late mortality did not differ between the groups. CONCLUSIONS: Paneled SVG and IJVG are both versatile and durable conduits for venous reconstruction after pancreaticoduodenectomy, able to accommodate a wide range of venous defects. In this small series, SVG has comparable outcomes to IJVG. Paneled SVG is a suitable alternative to IJVG for portomesenteric reconstruction.

Adventitial Collagen Crosslink Reduces Intimal Hyperplasia in a Rabbit Arteriovenous Graft Model.

BACKGROUND: Intimal hyperplasia (IH) is the initial lesion of vein graft failure after coronary artery bypass grafting. The weak venous wall is likely one of the primary reasons for IH after exposure to the arterial environment. We investigate whether adventitial collagen cross-link by glutaraldehyde (GA) reinforces the venous wall and then reduces IH. MATERIALS AND METHODS: Adventitial collagen cross-link by 0.3% GA was performed on the rabbit jugular veins. The degree of cross-link was accessed by tensile test. The jugular vein with or without cross-link was implanted into the carotid artery of rabbit. Vein dilatation at the immediate anastomosis and pathological remodeling of vein graft after 4 wk was assessed. RESULTS: Tensile test indicated that the mechanical property of 3-min cross-linked veins more closely resembled that of the carotid artery. In rabbit arteriovenous graft models, 3-min adventitial collagen cross-link limited overdistension (diameter: 3.24 mm versus 4.65 mm, P < 0.01) at the immediate anastomosis and reduced IH (intima thickness: 78.83 µm versus 140.19 µm, P < 0.01) of vein grafts 4 wk after implantation in the cross-link group as compared with the graft group (without cross-link). Compared with the cross-link group, the expression of proliferating cell nuclear antigen and vascular cell adhesion molecule-1 increased significantly at both the mRNA and protein levels within the graft group (P < 0.01), but the expression of smooth muscle-22α decreased significantly (P < 0.01). CONCLUSIONS: Adventitial collagen cross-link by GA increased the vessel stiffness and remarkably reduced IH in a rabbit arteriovenous graft model.

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.