A case of endovascular treatment for iatrogenic left vertebral artery injury due to central line catheter placement.

We describe a case of endovascular treatment for an iatrogenic left vertebral artery injury after central line catheter placement in a 68-year-old male patient. The patient had a massive pulmonary embolism, and a Swan-Ganz catheter was required to monitor the patient's circulatory condition. However, the catheter was inserted into the left vertebral artery and passed through the left internal jugular vein. Endovascular treatment was indicated due to the patient's poor general health. Complete hemostasis was achieved, and the postoperative course was uneventful without neurologic deficits.

A central arteriovenous fistula reduces systemic hypertension in a mouse model.

Objective: A central arteriovenous fistula (AVF) has been proposed as a potential novel solution to treat patients with refractory hypertension. We hypothesized that venous remodeling after AVF creation in the hypertensive environment reduces systemic blood pressure but results in increased AVF wall thickness compared with remodeling in the normotensive environment. Methods: A central AVF was performed in C57BL6/J mice previously made hypertensive with angiotensin II (Ang II); mice were sacrificed on postoperative day 7 or 21. Results: In mice treated with Ang II alone, the mean systolic blood pressure increased from 90 ± 5 mmHg to 160 ± 5 mmHg at day 21; however, in mice treated with both Ang II and an AVF, the blood pressure decreased with creation of an AVF. There were significantly more PCNA-positive cells, SM22α/PCNA-positive cells, collagen I deposition, and increased Krüppel-like Factor 2 immunoreactivity in hypertensive mice with an AVF compared with normotensive mice with an AVF. Conclusions: These data show that a central AVF decreases systemic hypertension as well as induces local alterations in venous remodeling.

Poor Limb Prognosis of Patients with Chronic Limb-Threatening Ischemia on Hemodialysis: A Retrospective Observational Study Based on the Global Limb Anatomic Staging System.

BACKGROUND: The Global Limb Anatomic Staging System (GLASS) has been widely used to evaluate patients with chronic limb-threatening ischemia (CLTI). As end-stage kidney disease (ESKD) is a well-known CLTI risk factor, we aimed to determine whether patients on hemodialysis (HD) have a worse limb prognosis than those without ESKD, considering the same GLASS background. METHODS: The data of 445 patients who underwent surgical and/or endovascular revascularization procedures for lower extremity ischemia were retrospectively collected in our division between 2005 and 2018. The major amputation rate and amputation-free survival (AFS) were compared between HD and non-HD patients. RESULTS: Among the 215 (48%) patients receiving HD, 58 limbs required major amputation (27% limb loss rate). Among the non-HD group, the limb loss rate was 13% (P < 0.0001). The overall AFS was significantly worse in patients receiving HD than those not (P < 0.0001). The AFS was significantly worse in HD patients when comparing GLASS-standardized subgroups. CONCLUSIONS: Patients with CLTI who were receiving HD had a worse limb prognosis than those not receiving, even when considering the same GLASS classification. Furthermore, there is a need for an ideal guideline focused on ESKD-directed peripheral artery disease.

Motion capture device reveals a quick learning curve in vascular anastomosis training.

PURPOSE: Surgical procedures are often evaluated subjectively, and an objective evaluation has been considered difficult to make and rarely reported, especially in open surgery, where the range of motion is wide. This study evaluated the effectiveness of surgical suturing training as an educational tool using the Leap Motion Controller (LMC), which can capture hand movements and reproduce them as data comprising parametric elements. METHODS: We developed an off-the-job training system (Off-JT) in our department, mainly using prosthetic grafts and various anastomotic methodologies with graded difficulty levels. We recruited 50 medical students (novice group) and 6 vascular surgeons (expert group) for the study. We evaluated four parameters for intraoperative skills: suturing time, slope of the roll, smoothness, and rate of excess motion. RESULTS: All 4 parameters distinguished the skill of the novice group at 1 and 10 h off-JT. After 10 h of off-JT, all 4 parameters of the novices were comparable to those of the expert group. CONCLUSION: Our education system using the LMC is relatively inexpensive and easy to set up, with a free application for analyses, serving as an effective and ubiquitous educational tool for young surgeons.

Giant Coeliac Artery Aneurysm Treated with a Hybrid Approach: A Case Report.

Introduction: Coeliac artery aneurysms are rare and have a high mortality rate when ruptured. Although they are often asymptomatic, treatment is recommended for patients with true coeliac aneurysms >2.5 cm, noted enlargement, or associated symptoms. Less invasive endovascular treatment is predominantly performed for coeliac artery aneurysms, while open surgery is preferred for patients with compression symptoms. Here, a case of symptomatic giant coeliac artery aneurysm that was successfully treated with hybrid surgery is reported. Report: A 73 year old man was referred with continuous epigastric discomfort and loss of appetite for two weeks. Abdominal ultrasound and computed tomography revealed a 12 cm aneurysm of the coeliac artery. The splenic and common hepatic arteries were severely distorted and compressed by the aneurysm, making their origins unclear. Considering the risk of rupture, semi-urgent surgery was performed with interruption of the inflow and outflow arteries using open and endovascular techniques together with aneurysmorrhaphy. Vascular reconstruction was omitted because abundant collateral flow to the liver and spleen was confirmed on angiography. Discussion: With the hybrid approach, aneurysmorrhaphy was performed safely with minimal incision and dissection. Short term outcomes were satisfactory, with complete resolution of compression symptoms and remarkable sac shrinkage at 12 months. Owing to the possibility of the pancreaticoduodenal arcade developing as a collateral pathway, periodic surveillance for de novo aneurysms is warranted.

Risk Factors for Incisional Hernia After Open Abdominal Aortic Aneurysm Repair.

BACKGROUND/AIM: Incisional hernia is among the most prevalent complications associated with open abdominal aortic aneurysm repair. However, risk factors for incisional hernias in patients with abdominal aortic aneurysm are multifactorial. Therefore, this study evaluated the risk factors of incisional hernia after open abdominal aortic aneurysm repair, including surgical factors. PATIENTS AND METHODS: We retrospectively extracted data from patients with incisional hernias after abdominal aortic aneurysm repair between 2012 and 2019 and investigated their perioperative characteristics and wound closure techniques. RESULTS: The mean follow-up periods were 41.5±30.3 months, and 30 of 131 (22.9%) patients suffered an incisional hernia. Regarding the underlying disease, only diabetes mellitus was significantly more common in the incisional hernia group (11 of 30 patients, 36.6%), and no significant differences were found in the patients' perioperative data. Interrupted sutures were used in all 30 patients in the hernia group. Moreover, in 8 of the 101 remaining cases, barbed sutures were used, and no incisional hernia occurred in any of these cases. CONCLUSION: In addition to diabetes mellitus, abdominal aortic aneurysm is a significant risk factor for incisional hernia after abdominal aortic aneurysm repair. Therefore, employing the barbed suture technique may effectively prevent incisional hernias after abdominal aortic aneurysm repair.

Area reduction of perforation with a small-size sheath technique for iatrogenic femoral artery pseudoaneurysm with a large perforation.

Open surgery for femoral artery pseudoaneurysms is invasive, and complications can be detrimental. Several cases of treatment of iatrogenic femoral artery pseudoaneurysms using percutaneous suture-mediated closure devices have been reported. However, it is difficult to properly deploy the foot of the device to the arterial wall when the perforation area is large. We developed a technique using a double guidewire to partially occupy the perforation with a small-size sheath, which reduces the area of the perforation. This AREPAS (area reduction of perforation with a small-sized sheath) technique might allow for minimally invasive closure of perforations even in patients with large perforation areas.

EphB4 monomer inhibits chronic graft vasculopathy in an aortic transplant model.

T cells and macrophages play an important role in the formation of allograft vasculopathy, which is the predominant form of chronic rejection in cardiac transplants. Arteries express Ephrin-B2 as a marker of arterial identity, whereas circulating monocytes express the cognate receptor EphB4, which facilitates monocyte adhesion to the endothelial surface. Adherent monocytes transmigrate and differentiate into macrophages that activate T cells and are a main source of tissue damage during rejection. We hypothesized that inhibition of Ephrin-B2-EphB4 binding would decrease immune cell accumulation within a transplanted graft and prevent allograft vasculopathy. We used EphB4 monomer to inhibit Ephrin-B2-EphB4 binding in a rat infrarenal aortic transplant model. Rats treated with EphB4 monomer had fewer macrophages and T cells in the aortic allografts at 28 days, as well as significantly less neointima formation. These data show that the Ephin-B2-EphB4 axis may be an important target for prevention or treatment of allograft vasculopathy.

A case of popliteal artery rupture in an 11-year-old patient with vascular Ehlers-Danlos syndrome.

We have described a case of multiple surgeries for a ruptured popliteal artery in an 11-year-old female patient with vascular Ehlers-Danlos syndrome. She underwent emergency hematoma evacuation and ruptured popliteal artery interposition with the great saphenous vein graft, which was notably fragile during surgery and had ruptured on the seventh postoperative day. We performed another emergency hematoma evacuation and popliteal artery interposition with an expanded polytetrafluoroethylene vascular graft. Despite the early occlusion of the expanded polytetrafluoroethylene graft, she recovered with mild intermittent claudication in the left lower extremity and was discharged on postoperative day 20 after the first surgery.

Midterm outcomes of AFX2 endografts used in combination with aortic cuffs.

OBJECTIVE: Type III endoleaks after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs) with the Endologix unibody endograft remain a major concern, despite fabric, system, and instructional updates. The purpose of this study was to examine real-world outcomes of repairing AAAs using the current version of the AFX2 main body in combination with an aortic cuff, specifically focusing on type III endoleaks and morphological changes of the endograft. METHODS: We recruited facilities in Japan that used AFX2 combined with an aortic cuff for at least five cases between April 2017 and March 2018. A total of 175 cases in 24 facilities were analyzed. Patients' background information, including anatomic factors, operative findings, device component variations, and midterm outcomes at 3 years after the EVAR were collected. The data on computed tomography scans from cases registered as types I and III endoleaks and migration from each institute were sent to our department for verification. RESULTS: The mean patient age was 74.6 ± 8.1 years, and 48 cases (27%) were saccular aneurysms. The mean fusiform and saccular AAA diameters were 50.5 ± 5.8 mm and 43.5 ± 8.9 mm, respectively. No in-hospital deaths occurred. Data at 3 years, including computed tomography images, of 128 cases were analyzed. Overall survival, freedom from aneurysm-related mortality, and freedom from reintervention rates at 3 years were 85.8%, 99.3%, and 87.3%, respectively. There were three, one, and three cases of types I, IIIa, and IIIb endoleaks without sac dilatations, respectively. Among five migration cases, one case of aortic cuff migration presented as a type Ia endoleak, and four cases demonstrated sideways displacement, one of which presented as a type IIIa endoleak. The sac regression and enlargement rates at 3 years were 41.4% and 20.5% in the fusiform group and 44.2% and 16.7% in the saccular group, respectively. The proximal neck diameter slightly increased from 20.8 ± 2.7 mm before the EVAR to 22.2 ± 4.6 mm after the repair. CONCLUSIONS: Midterm outcomes of the AFX2 used in combination with an aortic cuff were acceptable, considering the rates of types I and III endoleaks. However, there were cases of sideways displacement that could cause future type IIIa endoleaks. When the AFX2 is used in combination with an aortic cuff, close surveillance for endograft deformations and subsequent adverse events, including type III endoleaks, is needed.

Sex differences in arterial identity correlate with neointimal hyperplasia after balloon injury.

BACKGROUND: Endovascular treatment of atherosclerotic arterial disease exhibits sex differences in clinical outcomes including restenosis. However, sex-specific differences in arterial identity during arterial remodeling have not been described. We hypothesized that sex differences in expression of the arterial determinant erythropoietin-producing hepatocellular receptor interacting protein (Ephrin)-B2 occur during neointimal proliferation and arterial remodeling. METHODS AND RESULTS: Carotid balloon injury was performed in female and male Sprague-Dawley rats without or 14 days after gonadectomy; the left common carotid artery was injured and the right carotid artery in the same animal was used as an uninjured control. Arterial hemodynamics were evaluated in vivo using ultrasonography pre-procedure and post-procedure at 7 and 14 days and wall composition examined using histology, immunofluorescence and Western blot at 14 days after balloon injury. There were no significant baseline sex differences. 14 days after balloon injury, there was decreased neointimal thickness in female rats with decreased smooth muscle cell proliferation and decreased type I and III collagen deposition, as well as decreased TNFα- or iNOS-positive CD68+ cells and increased CD206- or TGM2-positive CD68+ cells. Female rats also showed less immunoreactivity of VEGF-A, NRP1, phosphorylated EphrinB2, and increased Notch1, as well as decreased phosphorylated Akt1, p38 and ERK1/2. These differences were not present in rats pretreated with gonadectomy. CONCLUSIONS: Decreased neointimal thickness in female rats after carotid balloon injury is associated with altered arterial identity that is dependent on intact sex hormones. Alteration of arterial identity may be a mechanism of sex differences in neointimal proliferation after arterial injury.

Endothelial Cell TGF-ß (Transforming Growth Factor-Beta) Signaling Regulates Venous Adaptive Remodeling to Improve Arteriovenous Fistula Patency.

BACKGROUND: Arteriovenous fistulae (AVF) are the gold standard for vascular access for hemodialysis. Although the vein must thicken and dilate for successful hemodialysis, excessive wall thickness leads to stenosis causing AVF failure. Since TGF-ß (transforming growth factor-beta) regulates ECM (extracellular matrix) deposition and smooth muscle cell (SMC) proliferation-critical components of wall thickness-we hypothesized that disruption of TGF-ß signaling prevents excessive wall thickening during venous remodeling. METHODS: A mouse aortocaval fistula model was used. SB431542-an inhibitor of TGF-ß receptor I-was encapsulated in nanoparticles and applied to the AVF adventitia in C57BL/6J mice. Alternatively, AVFs were created in mice with conditional disruption of TGF-ß receptors in either SMCs or endothelial cells. Doppler ultrasound was performed serially to confirm patency and to measure vessel diameters. AVFs were harvested at predetermined time points for histological and immunofluorescence analyses. RESULTS: Inhibition of TGF-ß signaling with SB431542-containing nanoparticles significantly reduced p-Smad2-positive cells in the AVF wall during the early maturation phase (days 7-21) and was associated with decreased AVF wall thickness that showed both decreased collagen density and decreased SMC proliferation. SMC-specific TGF-ß signaling disruption decreased collagen density but not SMC proliferation or wall thickness. Endothelial cell-specific TGF-ß signaling disruption decreased both collagen density and SMC proliferation in the AVF wall and was associated with reduced wall thickness, increased outward remodeling, and improved AVF patency. CONCLUSIONS: Endothelial cell-targeted TGF-ß inhibition may be a translational strategy to improve AVF patency.

Specific Features of Patients Under 40 Years Old With Small-to-Medium-Sized Arterial Deterioration.

Background: Arterial deterioration is mostly caused by atherosclerosis, which progresses with age. However, we have observed serious backgrounds or etiologies in younger patients with non-atherosclerotic diseases and deterioration of small-to-medium-sized arterial lesions. Therefore, we aimed to identify the specific features of patients aged <40 years with deterioration of small-to-medium-sized arteries. Methods: We selected patients who were admitted to our department from 1995 to 2019 with deterioration of small-to-medium-sized arteries (aneurysms, dissection, rupture, or arterial injury/damage) and focused on the cohort aged <40 years. We examined the backgrounds or etiologies of the patients including genetic and inflammatory diseases, which might have caused the arterial deterioration. Results: Consequently, more than half (54.1%) of the patients aged <40 years had non-atherosclerotic comorbid diseases. However, the number of deteriorated arterial lesions was higher in patients aged <40 years than in patients aged ≥40 years (3.13 vs. 1.33 lesion/patient; P = 0.011). Furthermore, the data analysis of patients with multiple arterial lesions (≥3) revealed that the younger population tended to have more specific backgrounds or etiologies, notably Ehlers-Danlos syndrome and Behçet's disease. There were no differences in the all-cause mortality and cardiovascular disease-related mortality between patients aged <40 and ≥40 years (P = 0.89 and 0.29, respectively). Conclusions: Over 50% of patients aged <40 years with deterioration of small-to-medium-sized arteries had non-atherosclerotic, specific clinical backgrounds or etiologies, including genetic and inflammatory diseases. In addition, they exhibited more arterial lesions than older patients.

Sac enlargement due to perigraft seroma and back-bleeding from the remnant wall 11 years after open surgical repair of an infected abdominal aortic aneurysm.

We describe a case of sac enlargement that occurred 11 years after emergent open surgical repair of an infected abdominal aortic aneurysm. The diameter of the sac covering the Dacron graft had gradually expanded to 80 mm, and the flow of contrast medium into the sac was suspected. Elective surgery revealed a perigraft seroma and back-bleeding from the remnant wall. After attaining hemostasis, fibrin glue and oxidized cellulose were applied, and sac plication was performed. Thereafter, the sac has not expanded. Open diagnostic treatment should be a good option for cases of postoperative sac enlargement with an unknown origin.

Arteriovenous Fistula-induced Cardiac Remodeling Shows Cardioprotective Features in Mice.

OBJECTIVE---: Arteriovenous fistulae (AVF) placed for hemodialysis have high flow rates that can stimulate left ventricular (LV) hypertrophy. LV hypertrophy generally portends poor cardiac outcomes, yet clinical studies point to superior cardiac-specific outcomes for patients with AVF when compared to other dialysis modalities. We hypothesize that AVF induce physiologic cardiac hypertrophy with cardioprotective features. METHODS---: 9-11 week C57Bl/6 male and female mice were treated with sham laparotomy or an aortocaval fistula via a 25Ga needle. Cardiac chamber size and function were assessed with serial echocardiography, and cardiac CTA. Hearts were harvested at 5 weeks post-operatively, and collagen content assessed with Masson's trichrome. Bulk mRNA sequencing was performed from LV of sham and AVF mice at 10 days. Differentially expressed genes were analyzed using Ingenuity Pathway Analysis (Qiagen) to identify affected pathways and predict downstream biological effects. RESULTS---: Mice with AVF had similar body weight and wet lung mass, but increased cardiac mass compared to sham-operated mice. AVF increased cardiac output while preserving LV systolic and diastolic function, as well as indices of right heart function; all 4 cardiac chambers were enlarged, with slight decrement in relative LV wall thickness. Histology showed preserved collagen density within each of the 4 chambers without areas of fibrosis. RNA sequencing captured 19,384 genes, of which 857 were significantly differentially expressed, including transcripts from extracellular matrix-related genes, ion channels, metabolism, and cardiac fetal genes. Top upstream regulatory molecules predicted include activation of angiogenic (Vegf, Akt1), pro-cardiomyocyte survival (Hgf, Foxm1, Erbb2, Lin9, Areg), and inflammation-related (CSF2, Tgfb1, TNF, Ifng, Ccr2, IL6) genes, as well as the inactivation of cardiomyocyte antiproliferative factors (Cdkn1a, FoxO3, α-catenin). Predicted downstream effects include reduction to heart damage, and increased arrhythmia, angiogenesis, and cardiogenesis. There were no significant sex-dependent differences in the AVF-stimulated cardiac adaptation. CONCLUSIONS---: AVF stimulate adaptive cardiac hypertrophy in wild-type mice without heart failure or pathological fibrosis. Transcriptional correlates suggest AVF-induced cardiac remodeling has some cardioprotective, although also arrhythmogenic features.

Human-Induced Pluripotent Stem-Cell-Derived Smooth Muscle Cells Increase Angiogenesis to Treat Hindlimb Ischemia.

Induced pluripotent stem cells (iPSC) represent an innovative, somatic cell-derived, easily obtained and renewable stem cell source without considerable ethical issues. iPSC and their derived cells may have enhanced therapeutic and translational potential compared with other stem cells. We previously showed that human iPSC-derived smooth muscle cells (hiPSC-SMC) promote angiogenesis and wound healing. Accordingly, we hypothesized that hiPSC-SMC may be a novel treatment for human patients with chronic limb-threatening ischemia who have no standard options for therapy. We determined the angiogenic potential of hiPSC-SMC in a murine hindlimb ischemia model. hiPSC-SMC were injected intramuscularly into nude mice after creation of hindlimb ischemia. Functional outcomes and perfusion were measured using standardized scores, laser Doppler imaging, microCT, histology and immunofluorescence. Functional outcomes and blood flow were improved in hiPSC-SMC-treated mice compared with controls (Tarlov score, p < 0.05; Faber score, p < 0.05; flow, p = 0.054). hiPSC-SMC-treated mice showed fewer gastrocnemius fibers (p < 0.0001), increased fiber area (p < 0.0001), and enhanced capillary density (p < 0.01); microCT showed more arterioles (<96 µm). hiPSC-SMC treatment was associated with fewer numbers of macrophages, decreased numbers of M1-type (p < 0.05) and increased numbers of M2-type macrophages (p < 0.0001). Vascular endothelial growth factor (VEGF) expression in ischemic limbs was significantly elevated with hiPSC-SMC treatment (p < 0.05), and inhibition of VEGFR-2 with SU5416 was associated with fewer capillaries in hiPSC-SMC-treated limbs (p < 0.0001). hiPSC-SMC promote VEGF-mediated angiogenesis, leading to improved hindlimb ischemia. Stem cell therapy using iPSC-derived cells may represent a novel and potentially translatable therapy for limb-threatening ischemia.

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

OBJECTIVE: The arteriovenous fistula (AVF) is the preferred method of dialysis access because of its proven superior long-term outcomes.However, women havelower rates of AVF patency andutilizationthan men.We used a novel mouseAVF model that recapitulates human AVF maturation to determine whether there are differences in AVF patency in female and male mice. METHODS: Aortocaval 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. RESULTS: At 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. CONCLUSIONS: AVF 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. CLINICAL RELEVANCE: Women have lower rates of arteriovenous fistula (AVF) utilization than men. Using a mouse AVF model that recapitulates human AVF maturation, we show that female mice have similar AVF remodeling but diminished patency. AVF remodeling in female mice is associated with reduced shear stress and laminar flow; lack of increased transcription and translation of several anti-inflammatory, antiproliferative, and laminar flow response proteins (endothelial nitric oxide synthase, Krüppel-like factor 2, and vascular cell adhesion molecule 1); and different patterns of expression of pathways that regulate thrombosis and venous remodeling. Identifying downstream targets involved in these mechanisms may improve AVF outcomes in female patients.

Author Correction: Inhibition of the Akt1-mTORC1 Axis Alters Venous Remodeling to Improve Arteriovenous Fistula Patency.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Induced pluripotent stem cell-derived smooth muscle cells increase angiogenesis and accelerate diabetic wound healing.

Aim: To assess the potential of human induced pluripotent stem cell-derived smooth muscle cells (hiPSC-SMC) to accelerate diabetic wound healing. Methods: hiPSC-SMC were embedded in 3D collagen scaffolds and cultured in vitro for 72 h; scaffolds were then applied to diabetic, nude mouse, splinted back wounds to assess in vivo healing. Cultured medium after scaffold incubation was collected and analyzed for expression of pro-angiogenic cytokines. Results: hiPSC-SMC secrete increased concentration of pro-angiogenic cytokines, compared with murine adipose derived stem cells. Delivery of hiPSC-SMC-containing collagen scaffolds accelerates diabetic wound healing and is associated with an increased number of total and M2 type macrophages. Conclusion: hiPSC-SMC promote angiogenesis and accelerate diabetic wound healing, making them a promising new candidate for treatment of diabetic wounds.

A mouse model of stenosis distal to an arteriovenous fistula recapitulates human central venous stenosis.

OBJECTIVE: Central venous stenosis (CVS) is a major cause of arteriovenous fistula (AVF) failure. However, central veins are relatively inaccessible to study with conventional Doppler ultrasound methods. To understand mechanisms underlying AVF failure owing to CVS, an animal model was established that creates a stenosis distal to an AVF. We hypothesized that this mouse model will show comparable morphology and physiology to human CVS. METHODS: An aortocaval fistula was created between the distal aorta and inferior vena cava (IVC); a stenosis was then created distal to the fistula by partial IVC ligation. Sham-operated animals, AVF without venous stenosis, and venous stenosis without AVF were used as controls. Physiologic properties of the IVC, both upstream and downstream of the stenosis, or the corresponding sites in models without stenosis, were assessed with ultrasound examination on days 0 to 21. The spectral broadening index was measured to assess the degree of disturbed shear stress. The IVC was harvested at day 21 and specimens were analyzed with immunofluorescence. RESULTS: The IVC diameter of mice with an AVF and stenosis showed increased upstream (P = .013), but decreased downstream diameter (P = .001) compared with mice with an AVF but without a stenosis, at all postoperative times (days 3-21). IVC wall thickness increased in mice with an AVF, compared with IVC without an AVF (upstream of stenosis: 13.9 µm vs 11.0 µm vs 4.5 µm vs 3.9 µm; P = .020; downstream of stenosis: 6.0 µm vs 6.6 µm vs µm 4.5 µm vs 3.8 µm; P = .002; AVF with stenosis, AVF, stenosis, sham, respectively). AVF patency significantly decreased in mice with an AVF and stenosis by day 21 (50% vs 90%; P = .048). The IVC of mice with AVF and stenosis showed a venous waveform with pulsatility as well as enhanced velocity at and downstream of the stenosis; similar waveforms were observed in a human case of CVS. Downstream to the stenosis, the spectral broadening index was significantly higher compared with mice with AVF alone (1.06 vs 0.78; P = .011; day 21), and there was a trend towards less immunoreactivity of both Krüppel-like factor 2 and phosphorylated-endothelial nitric oxide synthase compared with mice with an AVF alone. CONCLUSIONS: Partial IVC ligation distal to a mouse aortocaval fistula alters the fistula diameter and wall thickness, decreases patency, and increases distal disturbed flow compared with fistulae without a distal stenosis. Our mouse model of stenosis distal to an AVF may be a faithful representation of human CVS that shows similar morphology and physiology, including disturbed shear stress.