Pre-clinical Evolution of a Novel Transcatheter Bioabsorbable ASD/PFO Occluder Device.

To date, there has been limited investigation of bioabsorbable atrial septal defect (ASD) or patent foramen ovale (PFO) closure devices using clinically relevant large animal models. The purpose of this study is to explore the function and safety of a bioabsorbable ASD occluder (BAO) system for PFO and/or secundum ASD transcatheter closure. Using a sheep model, the intra-atrial septum was evaluated by intracardiac echo (ICE). If a PFO was not present, atrial communication was created via transseptal puncture. Device implantation across the intra-atrial communication was performed with fluoroscopic and ICE guidance. Our 1st generation device consisted of a main structure of thin Poly(L-lactide-co-epsilon-caprolactone) (PLCL) fibers, and an internal Poly glycolic acid (PGA) fabric. Four procedures validated procedure feasibility. Subsequently, device design was modified for improved transcatheter delivery. The 2nd generation device has a two-layered structure and was implanted in six sheep. Results showed procedural success in 9/10 (90%) animals. With deployment, the 1st generation device did not reform into its original disk shape and did not conform nicely along the atrial septum. The 2nd generation device was implanted in six animals, 3 out of 6 survived out to 1 year. At 1 year post implantation, ICE confirmed no residual shunting. By necropsy, biomaterials had partially degraded, and histology of explanted samples revealed significant device endothelialization and biomaterial replacement with a collagen layer. Our results demonstrate that our modified 2nd generation BAO can be deployed via minimally invasive percutaneous transcatheter techniques. The BAO partially degrades over 1 year and is replaced by host native tissues. Future studies are needed prior to clinical trials.

Unique Angiogenesis From Cardiac Arterioles During Pericardial Adhesion Formation.

OBJECTIVES: The molecular mechanisms underlying post-operative pericardial adhesions remain poorly understood. We aimed to unveil the temporal molecular and cellular mechanisms underlying tissue dynamics during adhesion formation, including inflammation, angiogenesis, and fibrosis. METHODS AND RESULTS: We visualized cell-based tissue dynamics during pericardial adhesion using histological evaluations. To determine the molecular mechanism, RNA-seq was performed. Chemical inhibitors were administered to confirm the molecular mechanism underlying adhesion formation. A high degree of adhesion formation was observed during the stages in which collagen production was promoted. Histological analyses showed that arterioles excessively sprouted from pericardial tissues after the accumulation of neutrophils on the heart surface in mice as well as humans. The combination of RNA-seq and histological analyses revealed that hyperproliferative endothelial and smooth muscle cells with dedifferentiation appeared in cytokine-exposed sprouting vessels and adhesion tissue but not in quiescent vessels in the heart. SMAD2/3 and ERK activation was observed in sprouting vessels. The simultaneous abrogation of PI3K/ERK or TGF-ß/MMP9 signaling significantly decreased angiogenic sprouting, followed by inhibition of adhesion formation. Depleting MMP9-positive neutrophils shortened mice survival and decreased angiogenic sprouting and fibrosis in the adhesion. Our data suggest that TGF-ß/matrix metalloproteinase-dependent tissue remodeling and PI3K/ERK signaling activation might contribute to unique angiogenesis with dedifferentiation of vascular smooth muscle cells from the contractile to the synthetic phenotype for fibrosis in the pericardial cavity. CONCLUSIONS: Our findings provide new insights in developing prevention strategies for pericardial adhesions by targeting the recruitment of vascular cells from heart tissues.

Appropriate Surgical Treatment of Symptomatic Primary Varicose Veins Decreases Systemic Inflammatory Biomarkers.

Objective: To evaluate the relationship between systemic inflammatory biomarkers and efficacy of surgical treatment of primary varicose veins of the lower extremities. Methods: Total 12 patients who underwent endovenous laser ablation or stripping of varicose veins and six healthy subjects were enrolled. Structural and molecular changes of varices were assessed by immunohistochemical staining with anti-monocyte chemotactic protein-1 (MCP-1). MCP-1 and interleukin-6 (IL-6) levels in systemic antecubital blood were measured before and at 12 weeks after treatment. Results: Immunohistochemical staining revealed prominent manifestation of MCP-1-positive endothelial cells in the walls of varices. Preoperative serum MCP-1 and IL-6 levels in the patients were significantly higher than those in the control (166±12 pg/mL vs 99±10 pg/mL, p=0.003; 5.1±0.95 pg/mL vs 0.0±0.0 pg/mL, p=0.001, respectively). The values were significantly correlated with the severity of chronic venous insufficiency (CVI). Postoperative serum MCP-1 level significantly decreased compared with the preoperative level (152±10 pg/mL vs 166±12 pg/mL, p=0.048). The values after endovenous laser ablation did not significantly decrease compared with those after stripping. Conclusion: Varicose veins with CVI increase inflammatory biomarker levels in the local tissue and systemic blood. Appropriate treatment of symptomatic varicose veins decreases inflammatory biomarker levels.

Differential outcomes of venous and arterial tissue engineered vascular grafts highlight the importance of coupling long-term implantation studies with computational modeling.

Electrospinning is commonly used to generate polymeric scaffolds for tissue engineering. Using this approach, we developed a small-diameter tissue engineered vascular graft (TEVG) composed of poly-ε-caprolactone-co-l-lactic acid (PCLA) fibers and longitudinally assessed its performance within both the venous and arterial circulations of immunodeficient (SCID/bg) mice. Based on in vitro analysis demonstrating complete loss of graft strength by 12 weeks, we evaluated neovessel formation in vivo over 6-, 12- and 24-week periods. Mid-term observations indicated physiologic graft function, characterized by 100% patency and luminal matching with adjoining native vessel in both the venous and arterial circulations. An active and robust remodeling process was characterized by a confluent endothelial cell monolayer, macrophage infiltrate, and extracellular matrix deposition and remodeling. Long-term follow-up of venous TEVGs at 24 weeks revealed viable neovessel formation beyond graft degradation when implanted in this high flow, low-pressure environment. Arterial TEVGs experienced catastrophic graft failure due to aneurysmal dilatation and rupture after 14 weeks. Scaffold parameters such as porosity, fiber diameter, and degradation rate informed a previously described computational model of vascular growth and remodeling, and simulations predicted the gross differential performance of the venous and arterial TEVGs over the 24-week time course. Taken together, these results highlight the requirement for in vivo implantation studies to extend past the critical time period of polymer degradation, the importance of differential neotissue deposition relative to the mechanical (pressure) environment, and further support the utility of predictive modeling in the design, use, and evaluation of TEVGs in vivo. STATEMENT OF SIGNIFICANCE: Herein, we apply a biodegradable electrospun vascular graft to the arterial and venous circulations of the mouse and follow recipients beyond the point of polymer degradation. While venous implants formed viable neovessels, arterial grafts experienced catastrophic rupture due to aneurysmal dilation. We then inform a previously developed computational model of tissue engineered vascular graft growth and remodeling with parameters specific to the electrospun scaffolds utilized in this study. Remarkably, model simulations predict the differential performance of the venous and arterial constructs over 24 weeks. We conclude that computational simulations should inform the rational selection of scaffold parameters to fabricate tissue engineered vascular grafts that must be followed in vivo over time courses extending beyond polymer degradation.

A case of nickel allergy after endovascular aortic repair.

A 78-year-old man with no history of allergy, underwent endovascular aortic repair for abdominal aortic aneurysm rupture. Postoperatively, he had low-grade fever and persistently raised white blood cell counts, but tests showed no infection. A skin rash appeared on the trunk and upper arms; we suspected a drug allergy. Despite withdrawal and/or change of medications, the symptoms remained. Finally, a patch test for nickel showed a strongly positive result. Oral prednisone 5 mg·day-1 was started, and the clinical findings resolved thereafter. No recurrence of allergy, infection, or exacerbation of the treated abdominal aortic aneurysm was noted at the 2-year follow-up.

Inhibition of Atherosclerotic Plaque Development by Oral Administration of α-Glucosyl Hesperidin and Water-Dispersible Hesperetin in Apolipoprotein E Knockout Mice.

OBJECTIVE: Hesperidin, an abundant flavonoid in citrus fruit, and its aglycone, hesperetin, have been reported to possess various physiological activities, including antioxidant, anti-inflammatory, hypolipidemic, and antihypertensive activities. In this study, we investigated whether α-glucosyl hesperidin and water-dispersible hesperetin have protective effects on atherosclerotic progression in apolipoprotein E knockout (Apo-E KO) mice. METHODS: Ten-week-old male Apo-E KO mice were randomly assigned a regular high-fat diet, a high-fat diet with 0.5% α-glucosyl hesperidin, or a high-fat diet with 0.1% water-dispersible hesperetin for 12 weeks. Measurement of plasma total cholesterol levels, histological staining of aortic root, and immunohistochemistry for macrophages were performed to evaluate atherosclerotic plaque formation. Vascular reactivity of mouse aortic rings was also measured. RESULTS: Both α-glucosyl hesperidin and water-dispersible hesperetin reduced plasma total cholesterol level. They also reduced plaque formation area, adipose deposition, and macrophage infiltration into atherosclerotic lesion. Vascular-endothelium-dependent relaxation in response to acetylcholine was improved in both experimental diet groups compared to the high-fat diet group. CONCLUSIONS: Our study suggests that both α-glucosyl hesperidin and water-dispersible hesperetin exert protective effects on atherosclerotic progression in Apo-E KO mice because they exhibit hypolipidemic activity, reduce inflammation through macrophages, and prevent endothelial dysfunction.

Thoracic Endovascular Aortic Repair for Blunt Thoracic Aortic Injury: A Report of Three Cases in Which Surgeries Were Performed at Different Timings.

INTRODUCTION: Blunt thoracic aortic injury (BTAI) is a critical condition. Thoracic endovascular aortic repair (TEVAR) is considered a surgical treatment for BTAI. Reports reveal that some patients benefit from conservative and delayed operation rather than emergency operative therapy. Here, we present three BTAI cases that were treated with TEVAR using different timings. CASE PRESENTATION: Case 1 involved a 49-year-old man injured in a car accident and who went into shock. After stabilization with Advanced Trauma Life Support in the emergency room, TEVAR was performed immediately. Case 2 involved a 69-year-old man who was injured after falling. His hemodynamic status was stable and enhanced computed tomography revealed intraluminal hematoma. He underwent TEVAR 15 days after the injury occurred, following conservative therapy. Case 3 involved a 60-year-old man who was injured in a car accident and presented BTAI with subarachnoid hemorrhage and diaphragm tear. A pseudoaneurysm was observed in the distal aortic arch. After open abdominal exploration, diaphragm repair, and observation for subarachnoid hemorrhage, TEVAR was performed 8 hours after arrival. All three patients survived. CONCLUSIONS: We treated BTAI successfully. We suggest that TEVAR is useful for BTAI. The timing of the operation and therapeutic option, including conservative therapy, should be decided for each patient.

Magnetic Resonance Imaging of Shear Stress and Wall Thickness in Tissue-Engineered Vascular Grafts.

OBJECTIVES: Tissue-engineered vascular grafts (TEVGs) have demonstrated potential for treating congenital heart disease (CHD); however, quantitative imaging for tracking functional and structural remodeling of TEVGs has not been applied. Therefore, we evaluated the potential of magnetic resonance (MR) imaging for assessing TEVG wall shear stress (WSS) and wall thickness in a large animal model. METHODS: Cell-seeded (n = 3) or unseeded (n = 3) TEVGs were implanted as inferior vena cava interposition grafts in juvenile lambs. Six months following implantation, two-dimensional phase-contrast MR imaging was performed at 3 slice locations (proximal, middle, and distal) to assess normalized WSS (i.e., WSS-to-cross sectional area). T2-weighted MR imaging was performed to assess TEVG wall thickness. Histology was qualitatively assessed, whereas immunohistochemistry was semiquantitatively assessed for smooth muscle cells (αSMA), macrophage lineage cells (CD11b), and matrix metalloproteinase activity (MMP-2 and MMP-9). Picrosirius Red staining was performed to quantify collagen content. RESULTS: TEVG wall thickness was significantly higher for proximal, middle, and distal slices in unseeded versus cell-seeded grafts. Significantly higher WSS values existed for proximal versus distal slice locations for cell-seeded TEVGs, whereas no differences in WSS existed between slices for unseeded TEVGs. Additionally, no differences in WSS existed between cell-seeded and unseeded groups. Both groups demonstrated elastin formation, without vascular calcification. Unseeded TEVGs possessed greater content of smooth muscle cells when compared with cell-seeded TEVGs. No differences in macrophage, MMP activity, or collagen content existed between groups. CONCLUSION: MR imaging allows for in vivo assessment of functional and anatomical characteristics of TEVGs and may provide a nonionizing approach that is clinically translatable to children undergoing treatment for CHD.

The ratio of contrast medium volume to estimated glomerular filtration rate as a predictor of contrast-induced nephropathy after endovascular aortic repair.

OBJECTIVE: This study aimed to determine the perioperative predictors of contrast medium-induced nephropathy (CIN) after endovascular aortic repair (EVAR). MATERIALS AND METHODS: The data of 203 consecutive patients who underwent elective EVAR for thoracic and abdominal aortic aneurysm between January 2014 and September 2014 were retrospectively analyzed. CIN was defined according to the diagnostic criteria of the European Society of Urogenital Radiology. RESULTS: Fourteen patients (6.9%) developed CIN after EVAR. Contrast medium volume (CV), preoperative serum creatinine, estimated glomerular filtration rate (eGFR), and the CV/eGFR ratio were significantly related with CIN development after EVAR. The CV/eGFR ratio was significantly higher in patients with CIN than those without CIN. Receiver operator characteristic curve analysis showed that the area under the curve of the CV/eGFR ratio was 0.782, indicating that it was the most important predictor. The appropriate CV/eGFR ratio cutoff was 1.62. Sensitivity and specificity were 85.7% and 65.6%, respectively. CONCLUSIONS: The CV/eGFR ratio was a useful predictor of contrast medium-induced nephropathy after EVAR. It is possible that the score can be used in patients when managing the EVAR techniques and contrast medium volume. J. Med. Invest. 65:116-121, February, 2018.

Novel application and serial evaluation of tissue-engineered portal vein grafts in a murine model.

AIM: Surgical management of pediatric extrahepatic portal vein obstruction requires meso-Rex bypass using autologous or synthetic grafts. Tissue-engineered vascular grafts (TEVGs) provide an alternative, but no validated animal models using portal TEVGs exist. Herein, we preclinically assess TEVGs as portal vein bypass grafts. MATERIALS & METHODS: TEVGs were implanted as portal vein interposition conduits in SCID-beige mice, monitored by ultrasound and micro-computed tomography, and histologically assessed postmortem at 12 months. RESULTS: TEVGs remained patent for 12 months. Histologic analysis demonstrated formation of neovessels that resembled native portal veins, with similar content of smooth muscle cells, collagen type III and elastin. CONCLUSION: TEVGs are feasible portal vein conduits in a murine model. Further preclinical evaluation of TEVGs may facilitate pediatric clinical translation.

Aortic rupture due to radiation injury successfully treated with thoracic endovascular aortic repair.

Thoracic endovascular aortic repair (TEVAR) has been reported to be an effective treatment option for aortic emergencies. However, there are few reports about TEVAR for aortic rupture due to radiation injury. A 54-year-old man presented with haemoptysis. He had a history of lung cancer, which had been treated with chemotherapy and radiation therapy (72 Gy/16 times) 3 years previously, and the cancer lesion did not progress. On chest radiography, pneumonia was suspected in the radiated lesion. However, after admission, he presented with back pain, progressive anaemia and hypotension. Enhanced computed tomography revealed extravasation of contrast medium in the distal aortic arch. He was diagnosed with aortic rupture due to radiation injury. TEVAR was performed. He was extubated one day after the operation, and the haemoptysis disappeared. He was discharged from the hospital without any complications. He is well 1 year after the surgery, without aortic disease progression or lung cancer recurrence.

Acute pancreatitis caused by pancreatic ischemia after TEVAR combined with intentional celiac artery coverage and embolization of the branches of the celiac artery.

Covering and embolizing the celiac artery has been reported to be a relatively safe procedure, owing to the rich collateral pathway between the celiac artery and superior mesenteric artery. A 69-year-old man presented with an aneurysm on the distal descending aorta. The proximity of the aneurysm to the celiac artery origin necessitated covering the artery with a stent graft. Additionally, the celiac trunk was short, increasing the risk for Type II endoleak. The origin of the celiac artery was covered after embolization of the branches of the celiac artery. Postoperatively, nausea and abdominal pain appeared, and the amylase level and white blood cell count were elevated. Contrast-enhanced computed tomography and abdominal ultrasonography revealed necrosis and cyst formation in the pancreatic tail, resulting in a diagnosis of acute pancreatitis caused by pancreatic ischemia. Conservative treatment was applied. After discharge, although walled-off necrosis remained, the patient was doing well, without any clinical symptoms.

Long-term Results After Open Mitral Commissurotomy for a One-Month-Old Infant With Mitral Stenosis.

The strategy for an infant with congenital mitral stenosis should be determined by three important factors: left ventricular volume, the degree of the systemic outflow tract obstruction, and the type of mitral valve dysfunction. A successful staged biventricular repair in early infancy for a patient who had congenital mitral stenosis with short chordae, hypoplastic left ventricle and coarctation of the aorta, and the long-term results are described. There were the following important hemodynamic factors that led to the successful biventricular repair in the patient. Total systemic output was barely supplied through the hypoplastic left ventricle after closure of the ductus arteriosus on admission. The neonate underwent repair of coarctation of the aorta alone as the initial stage at 9 days after birth. Also, spontaneous closure of the foramen ovale following repair of coarctation of the aorta accelerated the progressive left ventricular growth. Open mitral commissurotomy with an interatrial fenestration using the modified Brawley's approach was performed for a 40-day-old infant. Good left ventricular growth and good mitral valve function have been observed for 18 years after open mitral commissurotomy. Appropriate early augmentation of left ventricular inflow through the mitral valve might be effective for growth of a hypoplastic left ventricle. J. Med. Invest. 64: 187-191, February, 2017.

Effects of Transplanted Human Cord Blood-Mononuclear Cells on Pulmonary Hypertension in Immunodeficient Mice and Their Distribution.

OBJECTIVES: To investigate the effects of human umbilical cord blood-derived mononuclear cell (hUCB-MNC) transplantation on pulmonary hypertension (PH) induced by monocrotaline (MCT) in immunodeficient mice and their distribution. METHODS: MCT was administered to BALB/c Slc-nu/nu mice, and PH was induced in mice 4 weeks later. Fresh hUCB-MNCs harvested from a human donor after her delivery were injected intravenously into those PH mice. The medial thickness of pulmonary arterioles, ratio of right ventricular to septum plus left ventricular weight (RV/S+LV), and ratio of acceleration time to ejection time of pulmonary blood flow waveform (AT/ET) were determined 4 weeks after hUCB-MNC transplantation. To reveal the incorporation into the lung, CMTMR-labeled hUCB-MNCs were observed in the lung by fluorescent microscopy. DiR-labeled hUCB-MNCs were detected in the lung and other organs by bioluminescence images. RESULTS: Medial thickness, RV/S+LV and AT/ET were significantly improved 4 weeks after hUCB-MNC transplantation compared with those in mice without hUCB-MNC transplantation. CMTMR-positive hUCB-MNCs were observed in the lung 3 hours after transplantation. Bioluminescence signals were detected more strongly in the lung than in other organs for 24 hours after transplantation. CONCLUSIONS: The results indicate that hUCB-MNCs are incorporated into the lung early after hUCB-MNC transplantation and improve MCT-induced PH. J. Med. Invest. 64: 43-49, February, 2017.

Thoracic endovascular aortic repair of a severely angulated aorta using a double-wire technique.

When endovascular treatment is performed, angulation of the access route for a device can make the operative procedure difficult. We encountered a case in which we successfully completed thoracic endovascular aortic repair (TEVAR) in a patient with severely angulated aorta by applying 'double-wire technique'. The patient was an 80-year-old woman. An aneurysm with a 71-mm diameter was observed in the descending aorta. We performed TEVAR. Device delivery could not be achieved by a conventional procedure using one guide wire since the peripheral aorta was severely angulated. Therefore, in addition to a guide wire for main body, a stiff wire and a stiff sheath were introduced to straighten the angulation. The device was successfully introduced and TEVAR was completed. We used the Relay Plus(®) that facilitates tracking through the angulation. The device has a dual structure consisting of a hard sheath and a flexible sheath. We performed TEVAR successfully.

The pathophysiological role of oxidized cholesterols in epicardial fat accumulation and cardiac dysfunction: a study in swine fed a high caloric diet with an inhibitor of intestinal cholesterol absorption, ezetimibe.

Oxidized cholesterols (oxycholesterols) in food have been recognized as strong atherogenic components, but their tissue distributions and roles in cardiovascular diseases remain unclear. To investigate whether accumulation of oxycholesterols is linked to cardiac morphology and function, and whether reduction of oxycholesterols can improve cardiac performance, domestic male swine were randomized to a control diet (C), high caloric diet (HCD) or HCD+Ezetimibe, an inhibitor of intestinal cholesterol absorption, group (HCD+E) and evaluated for: (1) distribution of oxycholesterol components in serum and tissues, (2) levels of oxycholesterol-related enzymes, (3) paracardial and epicardial coronary fat thickness, and (4) cardiac performance. Ezetimibe treatment for 8weeks attenuated increases in oxycholesterols in the HCD group almost completely in liver, but reduced only levels of 4ß-hydroxycholesterol in left ventricular (LV) myocardium. Ezetimibe treatment altered the expression of genes for cholesterol and fatty acid metabolism and decreased the expression of CYP3A46, which catabolizes cholesterol to 4ß-hydroxycholesterol, strongly in liver. An increase in epicardial fat thickness and impaired cardiac performance in the HCD group were improved by ezetimibe treatment, and the improvement was closely related to the reduction in levels of 4ß-hydroxycholesterol in LV myocardium. In conclusion, an increase in oxycholesterols in the HCD group was closely related to cardiac hypertrophy and dysfunction, as well as an increase in epicardial fat thickness. Ezetimibe may directly reduce oxycholesterol in liver and LV myocardium, and improve cardiac morphology and function.

Correlations of perioperative coagulopathy, fluid infusion and blood transfusions with survival prognosis in endovascular aortic repair for ruptured abdominal aortic aneurysm.

BACKGROUND: Factors associated with survival prognosis among patients who undergo endovascular aortic repair (EVAR) for ruptured abdominal aortic aneurysms (rAAA) have not been sufficiently investigated. In the present study, we examined correlations between perioperative coagulopathy and 24-h and 30-day postoperative survival. Relationships between coagulopathy and the content of blood transfusions, volumes of crystalloid infusion and survival. METHODS: This was a retrospective study of the medical records of all patients who underwent EVAR for rAAA at Chiba-Nishi General Hospital during the period from October 2013 to December 2015. Major coagulopathy was defined using the international normalized ratio or activated partial thromboplastin time (APTT) ratio of at least 1.5, or platelet count less than 50 × 10/l. We quantified the amounts of blood transfusions and crystalloid infusions administered from arrival to the hospital to admission to ICU following operations. RESULTS: Coagulopathy among patients with rAAA was found to progress even after they had presented at the hospital. No statistically significant correlation between preoperative coagulopathy and mortality was found, although a significantly greater degree of postoperative coagulopathy was seen among patients who died both within 24-h and 30 days postoperatively. Among patients with postoperative coagulopathy, lesser quantities of fresh frozen plasma (FFP) compared with red cell concentrate (RCC) were used during the period from hospital arrival to postoperative ICU entry. In both groups of patients who did not survive after 24-h and 30 days, FFP was used less than RCC. Large transfusions of crystalloids administered during the periods from hospital arrival to surgery and from hospital arrival to the end of surgery were associated with postoperative incidence of major coagulopathy, death within 24-h, and death within 30 days. CONCLUSION: Coagulopathy progressed during care in the emergency outpatient clinic and operations. Postoperative coagulopathy was associated with poorer outcomes. Smaller FFP/RCC ratios and larger volumes of crystalloid infusion were associated with development of coagulopathy and poorer prognosis of survival. TRIAL REGISTRATION: This study is retrospectively registered in UMIN Clinical Trials Registry (Registration 19 April 2016, registered number is R000025334 UMIN000021978).

Novel Bioresorbable Vascular Graft With Sponge-Type Scaffold as a Small-Diameter Arterial Graft.

BACKGROUND: Current commercialized small-diameter arterial grafts have not shown clinical effectiveness due to their poor patency rates. The present study evaluated the feasibility of an arterial bioresorbable vascular graft, which has a porous sponge-type scaffold, as a small-diameter arterial conduit. METHODS: The grafts were constructed by a 50:50 poly (1-lactic-co-ε-caprolactone) copolymer (PLCL) scaffold reinforced by a poly (1-lactic acid) (PLA) nanofiber. The pore size of the PLCL scaffold was adjusted to a small size (12.8 ± 1.85 µm) or a large size (28.5 ± 5.25 µm). We compared the difference in cellular infiltration, followed by tissue remodeling, between the groups. The grafts were implanted in 8- to 10-week-old female mice (n = 15 in each group) as infrarenal aortic interposition conduits. Animals were monitored for 8 weeks and euthanized to evaluate neotissue formation. RESULTS: No aneurysmal change or graft rupture was observed in either group. Histologic assessment demonstrated favorable cell infiltration into scaffolds, neointimal formation with endothelialization, smooth muscle cell proliferation, and elastin deposition in both groups. No significant difference was observed between the groups. Immunohistochemical characterization with anti-F4/80 antibody demonstrated that macrophage infiltration into the grafts occurred in both groups. Staining for M1 and M2, which are the two major macrophage phenotypes, showed no significant difference between groups. CONCLUSIONS: Our novel bioresorbable vascular grafts showed well-organized neointimal formation in the high-pressure arterial circulation environment. The large-pore scaffold did not improve cellular infiltration and neotissue formation compared with the small-pore scaffold.

Contrast Medium Induced Nephropathy after Endovascular Stent Graft Placement: An Examination of Its Prevalence and Risk Factors.

Endovascular stent graft placement has become a major treatment for thoracic and abdominal aneurysms. While endovascular therapy is less invasive than open surgery, it involves the use of a contrast medium. Contrast media can cause renal impairment, a condition termed as contrast-induced nephropathy (CIN). This study sought to evaluate the incidence and risk factors of CIN following endovascular stent graft placement for aortic aneurysm repair. The study included 167 consecutive patients who underwent endovascular stent graft placement in our hospital from October 2013 to June 2014. CIN was diagnosed using the European Society of Urogenital Radiology criteria. Patients with and without CIN were compared. Chi-squared tests, t-tests, and multivariate logistic regression analyses were performed. Thirteen patients (7.8%) developed CIN. Left ventricular dysfunction and intraoperative blood transfusion were significantly more frequent in the CIN group (P = 0.017 and P = 0.032, resp.). Multivariate analysis showed that left ventricular dysfunction had the strongest influence on CIN development (odds ratio 9.34, P = 0.018, and 95% CI = 1.46-59.7). Patients with CIN also experienced longer ICU and hospital stays. Measures to improve renal perfusion flow should be considered for patients with left ventricular dysfunction who are undergoing endovascular stent graft placement.