Arteriovenous Fistula Maturation Research Articles

Nitinol stent-assisted maturation of the dysfunctional cannulation zone in the immature arteriovenous fistula.

The native arteriovenous fistula may remain immature despite adequate arterial inflow after formation. This may occur when the puncturable vein segment (cannulation zone) is too small to be reliably punctured, occluded or too deep under the skin for needle access. We performed stenting (stent-assisted maturation) of arteriovenous fistulas with an immature cannulation zone, allowing for a large subcutaneous channel which could then be immediately punctured for dialysis. We performed a retrospective review of 49 patients (mean age was 58.7 ± 16.09 (12-83) years, mean arteriovenous fistula age of 162.6 ± 27.28 days) with end-stage renal failure who underwent balloon dilatation and bare-metal stent implantation (1.6 ± 0.67 (1-3) stents, median diameter and length of 8 (5-14) mm and 80 (40-150) mm, respectively) through their cannulation zone (forced maturation). Radiocephalic (35 arteriovenous fistulas), brachiocephalic (10 arteriovenous fistulas) and autogenous loop arteriovenous fistulas (4 arteriovenous fistulas) were included with 30 patients (61.2%) having an inadequate cannulation zone venous diameter, 9 patients (18.4%) having an absent cannulation zone and 10 patients (20.4%) having a patent cannulation zone deeper than 1 cm which was not reliably puncturable. The study was conducted over 9 years (January 2008-December 2016) with implantation of the SMART® stent and Absolute Pro® stent in 61.2% and 38.8%, respectively. Long-term outcomes including primary useable segmental and access circuit patency as well as assisted primary access circuit patency, rate of re-intervention, technical success and complications were analysed. At 6 months, 12 months and 4 years, respectively, cannulation zone primary patency was 84.4%, 74.4% and 56.1% and access circuit primary patency was 62.2%, 45.3% and 23.2%; however, assisted primary access circuit patency was 95.6%, 91.1% and 83.8%, achieved with an endovascular re-intervention rate of 0.53 procedures/year with only four thrombosed circuits occurring. Forced maturation using nitinol stents allows for long-term haemodialysis access with a low rate of re-intervention.

The role of echocardiography in prognosis for dysfunction and abandonment of radiocephalic arteriovenous fistula in elderly Chinese patients on hemodialysis.

The objective of this study was to examine the impact of cardiac structure and function at baseline on the outcomes associated with arteriovenous fistula (AVF) in patients on hemodialysis (HD). Patients who initiated HD aged ≥70years and received a mature AVF creation were included retrospectively. Echocardiographic parameters measured within 1week before AVF creation were acquired. The observational period for each patient was from the point of AVF creation to the last time of follow-up unless AVF abandonment or death occurred. Kaplan-Meier and Cox proportional hazard regression analyses were conducted. A total of 82 elderly Chinese HD patients with mature radiocephalic AVF (RCAVF) and EF ≥50% were analyzed. During the median study period of 26.8 (12-40) months, 42 (51.2%) experienced RCAVF dysfunction and 34 (41.5%) progressed to abandonment. Primary and cumulative patencies at 6, 12, 24, and 36months were 81%, 73%, 48%, 38%, and 84%, 81%, 68%, 55%, respectively. Left ventricle end-diastolic volume (LVEDV) ≤103.5mL (HR=2.5, P=.019) and the right side of RCAVF (HR=3.59, P=.003) significantly predicted RCAVF dysfunction. The main pulmonary artery internal diameter (MPAID) ≤21.5mm (HR=4.3, P=.001) as well as the right side (HR=2.95, P=.047) were the independent predictors for RCAVF abandonment. In conclusion, LVEDV, MPAID assessed by echocardiography and the right side of RCAVF, showed significant predictive implications for the outcomes of RCAVF. Disparities among nationalities in the areas of utilization and patency of AVFs necessitate additional studies.

Atorvastatin Reduces In Vivo Fibrin Deposition and Macrophage Accumulation, and Improves Primary Patency Duration and Maturation of Murine Arteriovenous Fistula.

Arteriovenous fistulas placed surgically for dialysis vascular access have a high primary failure rate resulting from excessive inward remodeling, medial fibrosis, and thrombosis. No clinically established pharmacologic or perisurgical therapies currently address this unmet need. Statins' induction of multiple anti-inflammatory and antithrombotic effects suggests that these drugs might reduce arteriovenous fistula failure. Yet, the in vivo physiologic and molecular effects of statins on fistula patency and maturation remain poorly understood. We randomized 108 C57Bl/6J mice to receive daily atorvastatin 1.14 mg/kg or PBS (control) starting 7 days before end-to-side carotid artery-jugular vein fistula creation and for up to 42 days after fistula creation. We then assessed longitudinally the effects of statin therapy on primary murine fistula patency and maturation. We concomitantly analyzed the in vivo arteriovenous fistula thrombogenic and inflammatory macrophage response to statin therapy, using the fibrin-targeted, near-infrared fluorescence molecular imaging agent FTP11-CyAm7 and dextranated, macrophage-avid nanoparticles CLIO-VT680. In vivo molecular-structural imaging demonstrated that atorvastatin significantly reduced fibrin deposition at day 7 and macrophage accumulation at days 7 and 14, findings supported by histopathologic and gene-expression analyses. Structurally, atorvastatin promoted favorable venous limb outward remodeling, preserved arteriovenous fistula blood flow, and prolonged primary arteriovenous fistula patency through day 42 (P<0.05 versus control for all measures). These findings provide new in vivo evidence that statins improve experimental arteriovenous fistula patency and maturation, indicating that additional clinical evaluation of statin therapy in patients on dialysis undergoing arteriovenous fistula placement is warranted.

Role of peribrachial fat as a key determinant of brachial artery dilatation for successful arteriovenous fistula maturation in hemodialysis patients

The functional quality of the inflow artery is one of the most important determinants of arteriovenous fistula (AVF) success. We evaluated the association of early optimal brachial arterial dilatation with a successful AVF maturation and assessed the role of peribrachial adipose tissue in determining brachial arterial distensibility. All patients underwent a preoperative vascular mapping with Doppler ultrasound (US), and only patients who had suitable vessels for AVF creation were enrolled (n = 162). Peribrachial fat thickness was measured using US. To evaluate the degree of brachial dilatation, follow-up US was performed at 1 month after surgery, and early brachial artery dilation was defined as the change in postoperative arterial diameter compared to the preoperative value. The primary outcome was failure to achieve a clinically functional AVF within 8 weeks. Nonfunctional AVF occurred in 21 (13.0%) patients, and they had a significantly lower brachial dilatation than patients with successful AVF during early period after surgery (0.85 vs. 0.43 mm, p = 0.003). Patients with a brachial dilatation greater than median level showed a 1.8-times higher rate of achieving a successful AVF than those without. Interestingly, the early brachial dilatation showed significant correlations with diabetes (r = −0.260, p = 0.001), peribrachial fat thickness (r = −0.301, p = 0.008), and the presence of brachial artery calcification (r = −0.178, p = 0.036). Even after adjustments for demographic factors, comorbidities, and baseline brachial flow volume, peribrachial fat thickness was an independent determinant for early brachial dilatation (β = −0.286, p = 0.013). A close interplay between the peri-brachial fat and brachial dilatation can be translated into novel clinical tools to predict successful AVF maturation.

Selecting important predictors for arteriovenous fistula maturation in older hemodialysis patients by using random survival forests.

Placing an arteriovenous fistula (AVF) in older hemodialysis patients at great risk of primary failure leads to prolonged dependency on central venous catheter (CVC). A model which accurately predicts AVF maturation can facilitate better clinical determination for AVF placement. We assembled a retrospective cohort of 14 892 patients aged 67years and older who started hemodialysis with a CVC between 7/1/2010 and 6/30/2012 and had a subsequent, incident AVF placement from the United States Renal Data System (USRDS). We used random survival forests (RSF) with competing risks to identify important predictors for AVF maturation. Approximately 49.7% patients achieved AVF maturation and 13.6% had a competing event. The median time to maturation was 4 (IQR: 3-5) months. Patient's gender had the highest variable importance (VIMP, 0.0027), followed by race, being institutionalized, days on hemodialysis without an AVF, estimated glomerular filtration rate, and body mass index with borderline importance (VIMP ≥0.0005). The out-of-bag (OOB) error rate of the RSF was 45.3% and 45.8% for AVF maturation in the training and validation data sets, respectively. Predictors in USRDS data have limited ability to predict AVF maturation. Patient's gender might be considered as the most important predictor for AVF maturation.

WEARABLE DEVICE FOR CONTINUOUS, NONINVASIVE MONITORING OF VASCULAR ACCESS HEALTH AND FLUID STATUS IN HEMODIALYSIS PATIENTS

Over 1 million patients are undergoing hemodialysis in the United States. A healthy, mature arteriovenous fistula (AVF) is critical for these patients, for whom maintenance of euvolemia is also a major challenge. Clinical outcomes could be improved, and healthcare costs lowered, by preventing fluid

Role of Balloon Assisted Maturation Technique in the Rate of AVF Maturation in Chronic Renal Failure Patients

Abstract Background the current recommendations from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKFDOQI) favors the use of arteriovenous fistulas (AVF) over grafts and central catheters, in an effort to decrease cost, increase long term patency, reduce interventions and decrease patient morbidity. Purpose this study was designed to determine the rate of AVF maturation using the (BAM) technique; the primary and secondary patency rate and to evaluate the feasibility and safety of the (BAM) technique for the immature or failed AVF. Patients and Methods 30 chronic renal failure patients were selected for the purpose of this study from patients presented to vascular surgery clinic, Ain Shams University Hospital and Nasr City Hospital. Results this study included 30 arteriovenous fistula, belonging to 30 chronic renal failure patient. Their mean age was 57.6 years (±14.6). The demographic characteristics and risk factor distribution are shown below. Conclusion endovascular techniques have an important role to play in helping the dialysis community meet the goals of the Fistula First Initiative. To meet these goals, the previously mentioned techniques need to be used in varying degrees to salvage &amp;gt; 95% of the nearly 60% of AVFs that fail to mature. When prolonged catheter time is taken into account, it is imperative to have a systematic method for salvaging these failing accesses before catheter-related complications are encountered.

The Predictive Factors of Arteriovenous Fistula Maturation in Patients with End-Stage Renal Disease

Highlights Arterial diameter above 2 mm had an almost 5 times better AVF maturation outcome. Average age of ESRD patients who underwent the AVF procedure was above 50 years. Percentage of AVF maturation was higher in men. Hypertension was the most common comorbid factor in ESRD patients.

Abstract No. 439 The favorable impacts of resolvin D1 in arteriovenous fistula maturation in mice disappears in a uremic environment

Abstract No. 439 The favorable impacts of resolvin D1 in arteriovenous fistula maturation in mice disappears in a uremic environment

Outcomes for Antecubital Arteriovenous Fistulas in Patients With High Brachial Artery Bifurcation

Preoperative ultrasound vessel mapping is a crucial step in operative planning for permanent hemodialysis access creation. Whereas the majority of the focus remains on vein caliber, anatomic arterial variants are often overlooked. Despite being a relatively common variation, little is known about the impact of a high brachial bifurcation on hemodialysis access outcomes. Our goal was to examine the relationship between a high brachial bifurcation and arteriovenous fistula (AVF) maturation and patency in patients undergoing upper arm hemodialysis access placement.

Co-culture of human fibroblasts, smooth muscle and endothelial cells promotes osteopontin induction in hypoxia.

Arteriovenous fistulas (AVFs) are the preferred vascular access for haemodialysis of patients suffering from end‐stage renal disease, a worldwide public health problem. However, they are prone to a high rate of failure due to neointimal hyperplasia and stenosis. This study aimed to determine if osteopontin (OPN) was induced in hypoxia and if OPN could be responsible for driving AVF failure. Identification of new factors that participate in remodelling of AVFs is a challenge. Three cell lines representing the cells of the three layers of the walls of arteries and veins, fibroblasts, smooth muscle cells and endothelial cells, were tested in mono‐ and co‐culture in vitro for OPN expression and secretion in normoxia compared to hypoxia after silencing the hypoxia‐inducible factors (HIF‐1α, HIF‐2α and HIF‐1/2α) with siRNA or after treatment with an inhibitor of NF‐kB. None of the cells in mono‐culture showed OPN induction in hypoxia, whereas cells in co‐culture secreted OPN in hypoxia. The changes in oxygenation that occur during AVF maturation up‐regulate secretion of OPN through cell‐cell interactions between the different cell layers that form AVF, and in turn, these promote endothelial cell proliferation and could participate in neointimal hyperplasia.

Upper limb isometric exercise protocolled programme and arteriovenous fistula maturation process

IntroductionArteriovenous fistula (AVF) is the gold standard for vascular access (VA) for end-stage chronic kidney disease (CKD) patients. Post-operative exercises may help to improve maturation. Nevertheless, scarce scientific evidence has been reported about their utility to date. Our objective was to assess the effect of a post-operative isometric exercise programme on native VA maturation in patients with stage 5–5D CKD.MethodsWe performed a 24-month prospective study. After surgery, patients were randomized to the isometric exercise group (EG) or control group (CG). An isometric exercise protocolled programme was performed in the EG. The CG received usual care. Demographic data, muscle strength using a hand-grip (HG) dynamometer, main Doppler ultrasound (DUS) measurements, clinical and DUS maturation and VA complications were assessed at 4 and 8 weeks post-operatively.ResultsFor 60 sixty patients (30 in the EG), demographic data and HG and DUS measurements at baseline were similar. A significant increase in HG was observed only in the EG at the end of the study (20.7 ± 8.1 versus 25.1 ± 10.3 kg, P = 0.001). The EG obtained the highest clinical maturation at 4 (CG 33.3% versus EG 70%, P = 0.009) and 8 weeks (CG 33.3% versus EG 76.7%, P = 0.002). Similarly, DUS maturation was better in the EG at 4 (CG 40% versus EG 80%, P = 0.003) and 8 weeks (CG 43.3% versus EG 83.3%, P = 0.003) and remained so in the EG for both distal and proximal VA territories for all these periods.ConclusionsThe upper limb isometric exercise protocolled programme improved clinical and DUS maturation in our patients in both the distal and proximal VA territories. Further studies are required to support these results.

Predictors of Primary Functional Maturation of Autogenous Radiocephalic Arteriovenous Fistula in a Cohort of Asian Patients

The aim of this study was to investigate the predictors of autogenous radiocephalic arteriovenous fistula (RCAVF) maturation. This was a retrospective analysis of patients undergoing RCAVF creation from June 2013 to December 2018 at a single medical center. Comparison of the variables between the matured and nonmatured group was performed. A total of 277 patients (men, 173; 62.5%) with a mean age of 56.6±16.9years underwent primary RCAVF creation during the study period. The mean diameter of the cephalic vein and radial artery were 2.4±0.6mm (range 1.5 to 4.3mm) and 2.3±0.5mm (range 1.5 to 4.0mm), respectively. Primary functional maturation was achieved in 236 patients (236/277, 85%). There was no statistical significance between the matured and nonmatured group in terms of age (56.4±14.8 vs. 58.1±15.1, respectively; P=0.498), coronary arterial disease (12% vs. 17%, respectively; P=0.449), diabetes mellitus (42% vs. 39%, respectively; P=0.864), smoking (26% vs. 22%, respectively; P=0.699), or antiplatelet therapy (23% vs. 24%, respectively; P=0.844). However, female gender (35% vs. 54%, respectively; P=0.024), peripheral arterial disease (9% vs. 22%, respectively; P=0.025), and small vein (2.4±0.5mm vs. 2.0±0.5mm, respectively; P<0.01) and artery (2.4±0.5 vs. 2.1±0.4, respectively; P<0.01) diameter were associated with the failure of maturation. The best cutoff diameter for the cephalic vein and radial artery was 1.85mm and 2.05mm, respectively. In this cohort of patients undergoing RCAVF creation, vein and artery diameter on preoperative ultrasound mapping was the predictor of functional maturation. Female gender and presence of peripheral arterial disease were associated with failure of maturation.

Distinct subsets of T cells and macrophages impact venous remodeling during arteriovenous fistula maturation

Patients with end-stage renal failure depend on hemodialysis indefinitely without renal transplantation, requiring a long-term patent vascular access. Although an arteriovenous fistula (AVF) remains the preferred vascular access for hemodialysis because of its longer patency and fewer complications compared with other vascular accesses, the primary patency of AVF is only 50% to 60%, presenting a clinical need for improvement. AVF mature by developing a thickened vascular wall and increased diameter to adapt to arterial blood pressure and flow volume. Inflammation plays a critical role during vascular remodeling and fistula maturation; increased shear stress triggers infiltration of T cells and macrophages that initiate inflammation, with involvement of several different subsets of T cells and macrophages. We review the literature describing distinct roles of the various subsets of T cells and macrophages during vascular remodeling. Immunosuppression with sirolimus or prednisolone decreases neointimal hyperplasia during AVF maturation, suggesting novel approaches to enhance vascular remodeling. However, M2 macrophages and CD4+ T cells play essential roles during AVF maturation, suggesting that total immunosuppression may suppress adaptive vascular remodeling. Therefore, it is likely that regulation of inflammation during fistula maturation will require a balanced approach to coordinate the various inflammatory cell subsets. Advances in immunosuppressive drug development and delivery systems may allow for more targeted regulation of inflammation to improve vascular remodeling and enhance AVF maturation. (JVS–Vascular Science 2020;1:207-18.)

Influence of cephalic vein dilation on arteriovenous fistula maturation in patients with small cephalic veins.

A substantial limitation of dialysis fistulas is their high primary failure rate due to nonmaturation. Various studies have documented that patients with larger vein diameters exhibit reduced risks for nonmaturation. Nevertheless, some patients have small veins. Few studies have focused on patients with small veins. We hypothesize that sufficient venous dilation contributes to fistula maturation. Therefore, we studied the influence of cephalic vein dilation on fistula maturation in patients with small veins.Patients with small cephalic veins (diameter <2 mm) undergoing initial arteriovenous fistulae (AVF) operation were included. A total of 72 patients were enrolled in this study. A prospective study was performed, and the patients were followed for 6 weeks after surgery. Preoperative and postoperative duplex ultrasound mapping of veins was performed, and dilation of the cephalic vein was evaluated.The fistula maturation rate was 44.44%. Multivariate logistic regression analysis revealed a significant relationship between fistula maturation and preoperative cephalic vein dilation. Based on the results of ROC analysis, the fistula maturation rate in patients with vein dilation greater than or equal to the cut-off was 57.14% in the training data set and 54.55% in the testing data set. The independent influencing factors for fistula maturation were used to establish a combined index with logistic regression analysis. The fistula maturation rate in patients with combined indexes greater than or equal to the cut-off was 80.95% in the training data set and 77.78% in the testing data set.Our results demonstrated that preoperative venous dilation was associated with AVF maturation. For patients with small veins, venous distensibility needs to be carefully assessed before surgery, as it may be a better predictor of AVF maturation than venous diameter.

Programmed Death Ligand-1 Regulates T Cells and M2 Macrophages to Control Wall Thickening During Arteriovenous Fistula Maturation

Programmed Death Ligand-1 Regulates T Cells and M2 Macrophages to Control Wall Thickening During Arteriovenous Fistula Maturation

The Role of Far Infrared Therapy in the Unassisted Maturation of Arterio-venous Fistula in Patients with Chronic Kidney Disease.

Introduction:The goal of arterio-venous fistula (AVF) creation is to achieve a well-functioning access that can be cannulated repetitively and can provide adequate flow for the dialysis. The objective of this study was to assess the role of far infrared (FIR) therapy in the unassisted maturation of newly created AVF in patients with chronic kidney disease (CKD).Materials and Methods:In this prospective open labeled randomised control trial, 107 patients were randomized. Participants in the control arm received oral clopidogrel 75 mg once daily for 30 days along with isometric hand exercise, whereas those in the test arm received FIR therapy twice weekly, 40 min session each, for 4 weeks. A biopsy from venous end was taken during fistula surgery. Doppler study of AVF was done at the end of the 4th and 12th week to assess AVF. Vascular access guidelines proposed by National Kidney Foundation –Kidney Disease Outcomes Quality Initiative (NKF- KDOQI) in 2006 were adapted to define the maturation of AVF.Results:Out of 107 patients, 51 were randomized to the test arm and 56 to the control arm. During follow-up, the blood flow rate through AVF (Qa) and the diameter of the cephalic vein draining (CVd) the AVF were measured. At the end of 3 months, Qa in Radio-Cephalic Fistula (RCF) was high in the test arm (p–0.003). The AVF failures were 5 (10.2%) and 14 (28%) in the test and control arms, respectively (p: 0.025). However, when adjusted for AVF failure within 6 h of surgery (may be related to surgical technique) this difference in AVF patency was statistically insignificant (p: 0.121). The mean Qa was high in patients with an arterial intimal medial thickness (AIMT) <0.5 mm. The IMT of the anastomosed artery had statistically significant correlation with the primary failure rate of AVF (P < 0.001).Conclusion:In patients with CKD, FIR therapy was effective in increasing the AVF blood flow rate at the end of 3 months, though the difference in primary failure rate was statistically insignificant.

Altered hemodynamics during arteriovenous fistula remodeling leads to reduced fistula patency in female mice

ObjectiveThe arteriovenous fistula (AVF) is the preferred method of dialysis access because of its proven superior long-term outcomes. However, women have lower rates of AVF patency and utilization than men. We used a novel mouse AVF model that recapitulates human AVF maturation to determine whether there are differences in AVF patency in female and male mice. MethodsAortocaval fistulas were created in female and male C57BL/6 mice (9-10 weeks). At days 0, 3, 7, and 21, infrarenal inferior vena cava (IVC) and aortic diameters and flow velocity were monitored by Doppler ultrasound and used to calculate the vessel diameter, blood flow, and shear stress. AVF were harvested, and expression of proteins was examined by proteomic analysis and immunofluorescence and of messenger RNA by quantitative polymerase chain reaction analysis. ResultsAt baseline, female mice weighed less and had lower IVC velocity and smaller magnitudes of shear stress, but there was no significant difference in IVC diameter and thickness. After AVF creation, both female and male mice had similar IVC dilation and thickening with no significant differences in IVC wall thickness at day 21. However, female mice had diminished AVF patency by day 42 (25.7% vs 64.3%; P = .039). During fistula remodeling, female mice had lower IVC mean velocity and shear stress magnitude and increased spectral broadening (days 0-21). Messenger RNA and protein expression of Krüppel-like factor 2, endothelial nitric oxide synthase, and vascular cell adhesion molecule 1 was similar at baseline in female and male mice but increased in the AVF only in male mice but not in female mice (day 21). Proteomic analysis of female and male mice detected 56 proteins expressed at significantly higher levels in the IVC of female mice and 67 proteins expressed at significantly higher levels in the IVC of male mice (day 7); function-specific analysis showed that the IVC of male mice overexpressed proteins that belong to pathways implicated in the regulation of vascular function, thrombosis, response to flow, and vascular remodeling. ConclusionsAVF in female mice have diminished patency, preceded by lower velocity, reduced magnitudes of shear stress, and less laminar flow during remodeling. There is also sex-specific differential expression of proteins involved in thrombosis, response to laminar flow, inflammation, and proliferation. These findings suggest that hemodynamic changes during fistula maturation may play an important role underlying the diminished rates of AVF utilization in women.

A two-stage model of an arteriovenous fistula maturation process

An arteriovenous fistula has been a widely accepted vascular access for hemodialysis, however, a fistula maturation process is still not fully understood. In the short period of time, right after vein and artery shunting, the physical and biological changes take place mainly in the venous wall. A two-stage modeling method of arteriovenous fistula maturation process was proposed and presented. The first stage of the maturation was modeled with two-way coupled fluid structure interaction computer simulations. Whereas for the second, biological stage, a model was based on the change in the elasticity of the venous wall due to wall shear stress (WSS) modifications. The relation between stress and radial and circumferential strain, based on Lame's theory, makes possible to introduce a mathematical model defining modulus of elasticity, averaged WSS, and venous diameter as time functions. The presented model enables one to predict changes in the monitored parameters in the arteriovenous fistula taking place in the time longer than 90 days. We found that probably the majority of fistulas can be assessed to be mature too early, when the adequate blood flow rate is achieved but mean WSS still remains at the non-physiological level (>10 Pa).

Venous Mechanical Properties After Arteriovenous Fistulae in Mice

BackgroundAn arteriovenous fistula (AVF) exposes the outflow vein to arterial magnitudes and frequencies of blood pressure and flow, triggering molecular pathways that result in venous remodeling and AVF maturation. It is unknown, however, how venous remodeling, that is lumen dilation and wall thickening, affects venous mechanical properties. We hypothesized that a fistula is more compliant compared with a vein because of altered contributions of collagen and elastin to the mechanical properties. MethodsEphb4+/− and littermate wild-type (WT) male mice were treated with sham surgery or needle puncture to create an abdominal aortocaval fistulae. The thoracic inferior vena cava was harvested 3 wk postoperatively for mechanical testing and histological analyses of collagen and elastin. ResultsMechanical testing of the thoracic inferior vena cava from Ephb4+/− and WT mice showed increased distensibility and increased compliance of downstream veins after AVF compared with sham. Although Ephb4+/− veins were thicker than WT veins at the baseline, after AVF, both Ephb4+/− and WT veins showed similar wall thickness as well as similar collagen and elastin area fractions, but increased collagen undulation compared with sham. ConclusionsFistula-induced remodeling of the outflow vein results in circumferentially increased distensibility and compliance, likely due to post-translational modifications to collagen.