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Introduction: Resuscitative endovascular balloon occlusion of the aorta (REBOA) may be used in severely injured patients with uncontrollable bleeding. However, zone-dependent effects of REBOA are rarely described. We compared the short-term zone- and organ-specific microcirculatory changes in abdominal organs and the extremity during occlusion of the aorta in a standardized porcine model., Methods: Male pigs were placed under general anesthesia, for median laparotomy to expose intra-abdominal organs. REBOA placement occurred in Zone 1 (from origin left subclavian artery to celiac trunk), Zone 2 (between the coeliac trunk and most caudal renal artery) and Zone 3 (distal most caudal renal artery to aortic bifurcation). Local microcirculation of the intra-abdominal organs were measured at the stomach, colon, small intestine, liver, and kidneys. Furthermore, the right medial vastus muscle was included for assessment. Microcirculation was measured using oxygen-to-see device (arbitrary units, A.U). Invasive blood pressure measurements were recorded in the carotid and femoral artery (ipsilateral). Ischemia/Reperfusion (I/R)-time was 10 min with complete occlusion., Results: At baseline, microcirculation of intra-abdominal organs differed significantly (p < 0.001), the highest flow was in the kidneys (208.3 ± 32.9 A.U), followed by the colon (205.7 ± 36.2 A.U.). At occlusion in Zone 1, all truncal organs showed significant decreases (p < 0.001) in microcirculation, by 75% at the colon, and 44% at the stomach. Flow-rate changes at the extremities were non-significant (n.s). During occlusion in Zone 2, a significant decrease (p < 0.001) in microcirculation was observed at the colon (- 78%), small intestine (- 53%) and kidney (- 65%). The microcirculatory changes at the extremity were n.s. During occlusion in Zone 3, truncal and extremity microcirculatory changes were n.s., Conclusion: All abdominal organs showed significant changes in microcirculation during REBOA. The intra-abdominal organs react differently to the same occlusion, whereas local microcirculation in extremities appeared to be unaffected by short-time REBOA, regardless of the zone of occlusion.

Background: Resistance and elasticity of normal and aneurysmal aorta walls are directly associated with this vessel's growth and rupture. This study aims to experimentally analyze the biomechanical behavior of aneurysmal specimens found at autopsy, comparing them with normal diameter aortas removed from age-matched donors., Methods: Thirty-eight human aortas (30 normal aortas; 8 infrarenal abdominal aortic aneurysms) were harvested during autopsy. An apparatus was built with a digital gauge, plastic tray, connections, and hoses that conducted fluid (air) from a pump through the system. Specimens were dissected, and a flexible balloon was introduced in each of them to avoid leakage. The specimens were fastened on the test tray, and activation of the air pump enhanced system pressure up to their rupture., Results: All 8 aneurysms and all 30 normal aortas specimens evolved to rupture under inflation pressures above 590 mm Hg (mean ± standard deviation = 1,035 ± 375 mm Hg) and 840 mm Hg (mean ± SD = 1,405 ± 342 mm Hg), respectively. In the aneurysm group, 25% of specimens did not rupture in their most dilated region. Percentage of increment in diameter was higher in normal aortas (mean ± SD = 0.2106 ± 0.144) than in aneurysms (mean ± SD = 0.093 ± 0.070)., Conclusions: In the present experiment, unruptured infrarenal abdominal aortic aneurysms could support high pressures nearly as much as nonaneurysmal abdominal aortas. In some specimens, the most dilated part of the aneurysm was not the most vulnerable under pressure. Normal aortas presented higher elasticity than aneurysms., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Computational fluid dynamics were used to assess hemodynamic changes in an actively rupturing abdominal aortic aneurysm (AAA) over a 9-day period. Active migration of contrast from the lumen into the thickest region of intraluminal thrombus (ILT) was demonstrated until it ultimately breached the adventitial layer. Four days after symptom onset, there was a discrete disruption of adventitial calcium with bleb formation at the site of future rupture. Rupture occurred in a region of low wall shear stress and was associated with a marked increase in AAA diameter from 6.6 to 8.4 cm. The cross-sectional area of the flow lumen increased across all time points from 6.28 to 12.08 cm2. The increase in luminal area preceded the increase in AAA diameter and was characterized by an overall deceleration in recirculation flow velocity with a coinciding increase in flow velocity penetrating the ILT. We show that there are significant hemodynamic and structural changes in the AAA flow lumen in advance of any appreciable increase in aortic diameter or rupture. The significant increase in AAA diameter with rupture suggests that AAA may actually rupture at smaller sizes than those measured on day of rupture. These findings have implications for algorithms the predict AAA rupture risk., (© 2021 S. Karger AG, Basel.)

Background: Iliac limb stent grafting to the external iliac artery (EIA) is a commonly performed procedure in various situation during endovascular abdominal aneurysm repair (EVAR). However, this procedure is associated with a risk of graft occlusion. We evaluated risk factors affecting occlusion among patients who underwent iliac limb stent-graft extension to the EIA., Materials and Methods: We compared occluded limbs with patent limbs during the follow-up period using variables, including anatomical values, demographics, and other factors. Thereafter, we divided the occluded limbs into early and late occlusion subgroups. The main and subgroup analyses used the same variables. Survival analysis was performed to evaluate time-dependent risk factors for late limb occlusion., Results: From 2007 to 2016, 766 iliac limbs from 383 patients who underwent EVAR were initially included in our analysis. Among them, 134 iliac limbs underwent limb extension to the EIA. The limb extension was a significant risk factor for occlusion (hazard ratio = 6.34, P < 0.001). Occlusion occurred in 10 patients who underwent iliac limb extension. The size of common iliac artery (CIA) was associated with occlusion. The most significant factor was iliac bifurcation diameter (patent vs. occluded limbs, 21.6 ± 7.6 vs. 27.5 ± 9.5 mm, P = 0.005). Subgroup analysis revealed that the CIAs of the early occlusion subgroup were generally more tortuous (1.16 ± 0.33 vs. 1.47 ± 0.25, P = 0.091) and longer (53 ± 24 vs. 74 ± 9, P = 0.01) than those of the patent limb group. In addition, the EIA diameters of the late occlusion subgroup were narrower than those of the patent limb group (10.9 ± 1.6 mm vs. 9.1 ± 0.8 mm, P = 0.011). Using the log-rank test, those patients with an EIA diameter narrower than 10.1 mm had a higher risk for late limb occlusion (log-rank χ 2  = 5.73, P = 0.017) and the patients who did not take at least a single antiplatelet agent had a significantly higher chance of limb occlusion (log-rank χ 2  = 11.029, P = 0.001). In addition, the patients who did not take a statin had a higher risk for late limb occlusion (log-rank χ 2  = 7.41, P = 0.007)., Conclusions: Among patients who underwent EVAR with iliac limb extension, the CIA length affected early limb occlusion and predisposed patients to vessel injury or stent-graft kinking, and there was the possibility that CIA tortuosity was associated with a higher risk. The late occlusion subgroup had narrower EIAs than the patent limb group. Appropriate antiplatelet and statin therapy is expected to play a key role in the prevention of late limb occlusion after EVAR., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Vascular cells restructure extracellular matrix in response to aging or changes in mechanical loading. Here, we characterized collagen architecture during age-related aortic remodeling in atherosclerosis-prone mice. We hypothesized that changes in collagen fiber orientation reflect an altered balance between passive and active forces acting on the arterial wall. We examined two factors that can alter this balance, endothelial dysfunction and reduced smooth muscle cell (SMC) contractility. Collagen fiber organization was visualized by second-harmonic generation microscopy in aortic adventitia of apolipoprotein E (apoE) knockout (KO) mice at 6 wk and 6 mo of age on a chow diet and at 7.5 mo of age on a Western diet (WD), using image analysis to yield mean fiber orientation. Adventitial collagen fibers became significantly more longitudinally oriented with aging in apoE knockout mice on chow diet. Conversely, fibers became more circumferentially oriented with aging in mice on WD. Total collagen content increased significantly with age in mice fed WD. We compared expression of endothelial nitric oxide synthase and acetylcholine-mediated nitric oxide release but found no evidence of endothelial dysfunction in older mice. Time-averaged volumetric blood flow in all groups showed no significant changes. Wire myography of aortic rings revealed decreases in active stress generation with age that were significantly exacerbated in WD mice. We conclude that the aorta displays a distinct remodeling response to atherogenic stimuli, indicated by altered collagen organization. Collagen reorganization can occur in the absence of altered hemodynamics and may represent an adaptive response to reduced active stress generation by vascular SMCs. NEW & NOTEWORTHY The following major observations were made in this study: 1 ) aortic adventitial collagen fibers become more longitudinally oriented with aging in apolipoprotein E knockout mice fed a chow diet; 2 ) conversely, adventitial collagen fibers become more circumferentially oriented with aging in apoE knockout mice fed a high-fat diet; 3 ) adventitial collagen content increases significantly with age in mice on a high-fat diet; 4 ) these alterations in collagen organization occur largely in the absence of hemodynamic changes; and 5 ) circumferential reorientation of collagen is associated with decreased active force generation (contractility) in aged mice on a high-fat diet.

Leriche syndrome was diagnosed in three patients aged 63, 71 and 73. They presented with a wide range of neurological symptoms such as impotence, pain or dysfunction of the lower extremities. Because a neurological diagnosis was initially suspected, there was a delay in two of the three patients before palpation for a distal pulse in the lower extremities was performed. A pulse was absent in all three patients. Duplex sonography, MR angiography and CT angiography revealed that a pulse was absent due to aortoiliac occlusive disease, also known as Leriche syndrome. They underwent treatment with covered endovascular reconstruction of the aortic bifurcation (CERAB), aortobifemoral bypass or intravenous thrombolysis. All patients significantly improved after treatment. Physicians should always consider aortoiliac occlusive disease in patients who present with neurological symptoms of the lower extremities and must check for a distal pulse in these patients.

Endovascular aneurysm repair (EVAR) is now the predominant method for treatment of infrarenal abdominal aortic aneurysms. Although EVAR has numerous advantages over standard open surgical repair, it also exposes patients to risks such as aneurysm sac enlargement, endoleaks, and graft migration, which make surveillance or follow-up mandatory. Fenestrated (FEVAR) and branched (BEVAR) endografts have extended the application of EVAR to juxtarenal, pararenal/paravisceral, and thoracoabdominal aneurysms, with some complex aneurysms requiring combined approaches (F-BEVAR). Duplex ultrasound has been recommended as an alternative to frequent computed tomography imaging for EVAR follow-up when it can provide the clinically necessary information. The major components of a post-EVAR duplex examination include measurement of aortic aneurysm sac size, assessment for endoleak, and evaluation of the endograft for patency and integrity. The duplex protocol for EVAR follow-up can be extended for follow-up after FEVAR, BEVAR, and F-BEVAR, with additional attention to the device components associated with fenestrations and branches. At the University of Washington, the physician-modified endovascular graft approach has been used for FEVAR. During these procedures, covered stents are placed in the renal arteries through fenestrations and the superior mesenteric artery is perfused through a fenestration, but typically remains unstented. Duplex scanning of the renal and mesenteric arteries has been performed preoperatively and at 30 days, 6 months, 1 year, and annually. In a review of patients having covered stents placed in non-stenotic renal arteries during FEVAR, both peak systolic velocity and the renal to aortic velocity ratio remained below the standard significant stenosis threshold in most patients. The duplex velocity criteria for stenosis in native renal arteries appeared to overestimate the severity of stenosis in renal artery covered stents. The unstented superior mesenteric artery remained widely patent in the presence of fenestrations or crossing struts and was not associated with endoleaks. Duplex ultrasound protocols for follow-up after FEVAR, BEVAR, and F-BEVAR can be based on those that have been established for standard EVAR, along with assessment of fenestrations and branches, as well as patency of the renal and mesenteric arteries., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) reduces blood loss and improves hemodynamics. Complete occlusion results in distal ischemia, limiting its use for prolonged care. This study evaluated two next-generation partial REBOA (pREBOA) catheters and their ability to achieve targeted distal aortic flow., Materials and Methods: Swine underwent hemorrhagic shock, complete aortic occlusion, controlled continuous balloon deflation, and targeted distal perfusion (TDP; 300-mL/min) phases. They were randomized into three groups (n = 6/group), one managed with the current ER-REBOA (ER), and two with the new pREBOA technologies: a bilobed (BL) device and a semicompliant pREBOA-PRO (PRP). Hemodynamics including flow rates and mean arterial pressures at the carotid artery and infrarenal aorta were recorded., Results: Hemodynamics were comparable between groups during hemorrhage and complete occlusion phases. During the controlled continuous balloon deflation phase, the distal aortic flow rate strongly correlated with percent balloon volume in BL and PRP groups, suggesting a precise control of distal perfusion. The slope of flow-balloon-volume curves was greater in the ER group than BL and PRP groups, indicating the change in distal aortic flow rate was more sensitive to the balloon volume (less titratable) when using ER. During the TDP phase, variation in distal aortic flow and mean arterial pressure with respect to the target flow was lower in ER and PRP groups, than the BL group., Conclusions: Pressure-regulated occlusion using the next-generation pREBOA catheters is more controlled than the first-generation ER-REBOA catheter and allow for targeted and precise distal perfusion., (Published by Elsevier Inc.)

The noninvasive vascular laboratory plays a critical role in screening patients at risk for development of abdominal aortic aneurysm (AAA). One-time duplex ultrasound screening reduces aneurysm-related mortality due to rupture and is cost-effective. Population screening based on AAA risk factors is recommended, as it allows for proactive, elective repair of aneurysms at risk for rupture, and surveillance of smaller aneurysms for enlargement. Utilization of societal screening guidelines, such as those published by the Society for Vascular Surgery, can be employed by vascular laboratories to justify individual patient screening, aid primary care physicians to refer patients for testing, and encourage integrated medical health care systems to build prompts in patient electronic health records to ensure compliance with a AAA screening program. Risk factors for developing AAA, that is, age older than 65 years, male sex, family history, and a smoking history of >100 cigarettes, should be used to recommend patient screening, including for women and other elderly (older than 75 years) patients who fall outside of professional societal guidelines., (Published by Elsevier Inc.)

Background: Renovascular hypertension (RVH) associated with renal artery and abdominal aortic narrowings is the third most common cause of pediatric hypertension. Untreated children may experience major cardiopulmonary complications, stroke, renal failure, and death. The impetus of this study was to describe the increasingly complex surgical practice for such patients with an emphasis on anatomic phenotype and contemporary outcomes after surgical management as a means of identifying those factors responsible for persistent or recurrent hypertension necessitating reoperation., Methods: A retrospective analysis was performed of consecutive pediatric patients with RVH undergoing open surgical procedures at the University of Michigan from 1991 to 2017. Anatomic phenotype and patient risk factors were analyzed to predict outcomes of blood pressure control and the need for secondary operations using ordered and binomial logistic multinomial regression models, respectively., Results: There were 169 children (76 girls, 93 boys) who underwent primary index operations at a median age of 8.3 years; 31 children (18%) had neurofibromatosis type 1, 76 (45%) had abdominal aortic coarctations, and 28 (17%) had a single functioning kidney. Before treatment at the University of Michigan, 51 children experienced failed previous open operations (15) or endovascular interventions (36) for RVH at other institutions. Primary surgical interventions (342) included main renal artery (136) and segmental renal artery (10) aortic reimplantation, renal artery bypass (55), segmental renal artery embolization (10), renal artery patch angioplasty (8), resection with reanastomosis (4), and partial or total nephrectomy (25). Non-renal artery procedures included patch aortoplasty (32), aortoaortic bypass (32), and splanchnic arterial revascularization (30). Nine patients required reoperation in the early postoperative period. During a mean follow-up of 49 months, secondary interventions were required in 35 children (21%), including both open surgical (37) and endovascular (14) interventions. Remedial intervention to preserve primary renal artery patency or a nephrectomy if such was impossible was required in 22 children (13%). The remaining secondary procedures were performed to treat previously untreated disease that became clinically evident during follow-up. Age at operation and abdominal aortic coarctation were independent predictors for reoperation. The overall experience revealed hypertension to be cured in 74 children (44%), improved in 78 (46%), and unchanged in 17 (10%). Children undergoing remedial operations were less likely (33%) to be cured of hypertension. There was no perioperative death or renal insufficiency requiring dialysis after either primary or secondary interventions., Conclusions: Contemporary surgical treatment of pediatric RVH provides a sustainable overall benefit to 90% of children. Interventions in the very young (<3 years) and concurrent abdominal aortic coarctation increase the likelihood of reoperation. Patients undergoing remedial surgery after earlier operative failures are less likely to be cured of hypertension. Judicious postoperative surveillance is imperative in children surgically treated for RVH., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background Long-term feeding with a high-fat diet (HFD) induces endothelial dysfunction in mice, but early HFD-induced effects on endothelium have not been well characterized. Methods and Results Using an magnetic resonance imaging-based methodology that allows characterization of endothelial function in vivo, we demonstrated that short-term (2 weeks) feeding with a HFD to C57BL/6 mice or to E3L.CETP mice resulted in the impairment of acetylcholine-induced response in the abdominal aorta (AA), whereas, in the thoracic aorta (TA), the acetylcholine-induced response was largely preserved. Similarly, HFD resulted in arterial stiffness in the AA, but not in the TA. The difference in HFD-induced response was ascribed to distinct characteristics of perivascular adipose tissue in the TA and AA, related to brown- and white-like adipose tissue, respectively, as assessed by histology, immunohistochemistry, and Raman spectroscopy. In contrast, short-term HFD-induced endothelial dysfunction could not be linked to systemic insulin resistance, changes in plasma concentration of nitrite, or concentration of biomarkers of glycocalyx disruption (syndecan-1 and endocan), endothelial inflammation (soluble form of vascular cell adhesion molecule 1, soluble form of intercellular adhesion molecule 1 and soluble form of E-selectin), endothelial permeability (soluble form of fms-like tyrosine kinase 1 and angiopoietin 2), and hemostasis (tissue plasminogen activator and plasminogen activator inhibitor 1). Conclusions Short-term feeding with a HFD induces endothelial dysfunction in the AA but not in the TA, which could be ascribed to a differential response of perivascular adipose tissue to a HFD in the AA versus TA. Importantly, early endothelial dysfunction in the AA is not linked to elevation of classical systemic biomarkers of endothelial dysfunction.

Background: To examine intraheartbeat displacements (IHD) and geometrical changes of endografts for abdominal aortic aneurysm repair over the course of years, defined as follow-up displacements (FUD), and to correlate them with computational fluid dynamics (CFD). Despite the widespread use of endovascular aneurysm repair (EVAR), we still know little about endograft behavior after deployment., Methods: Two cases, treated with either expanded polytetrafluoroethylene on a nitinol stent frame (PI) or with woven polyester fabric sutured to a stainless-steel Z stent skeleton (PII), were submitted to dynamic computed tomography angiography at 1, 12, and 60 months after implantation. After segmentation, IHD were computed as displacements of the reconstructed surface with respect to the diastolic instant. Similarly, FUD were studied using imaging techniques that align temporal successive segmentations. In addition, numerical simulations for blood dynamics were performed to compute viscous forces, specifically wall shear stress and time-averaged wall shear stress (TAWSS)., Results: IHD analysis showed slight translations without deformation for the PI endograft with respect to the stiffer stainless-steel endograft behavior of PII. FUD showed in PI motion of the metallic struts mainly focused on the distal main body of the endograft and in the zone overlapping with iliac branches. In PII, we observed a huge FUD in the middle and inferior-anterior regions of the main body. CFD analysis revealed changes of velocity patterns associated with remodeling of the iliac zone for PI and of the main body region for PII, where flow impinges the lumen wall and progressively induces deformation of the endograft wires. Measurement of TAWSS demonstrated flow disturbances in the enlarged region correlated with displacement analysis., Conclusions: Image-based displacement analysis associated with CFD enabled very subtle evaluations of endograft behavior on different temporal scales. This kind of study could be helpful both for physicians, forecasting evolution during the life span of the endograft, and manufacturers, giving them useful information about endograft implant performance and design., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The rupture of abdominal aortic aneurysms (AAAs) is associated with high mortality despite surgical developments. The determination of aneurysm diameter allows for follow up of aneurysm growth but fails in precisely predicting aneurysm rupture. In this study, time resolved three dimensional ultrasound (4D ultrasound) based wall motion indices (WMIs) are investigated to see if they are capable of distinguishing between uneven affected regions of the aneurysm wall., Methods: In a prospective study, 56 patients with an AAA were examined using 4D ultrasound. Local longitudinal, circumferential, and shear strains were computed using custom methods. The deformation of the neck and sac of each aneurysm was characterised by statistical indices of the obtained distributions of local wall strains (WMIs): mean and peak strain, heterogeneity index, and local strain ratio. The locations of regions with highest local peak strain were determined., Results: Compared with the aneurysm neck, the sac is characterised by low mean strain, but highly heterogeneous deformation, described by high local strain ratio and heterogeneity index. Differences were highly significant (p < .001) for all strain components. The regions with the highest circumferential peak strain were found more often in the posterior part of the aneurysm neck (p < .050) and sac (p < .001) regions, compared with other wall regions. No statistically significant correlation was found between the WMIs and maximum AAA diameter, except for longitudinal mean strain, which decreased with the increasing diameter (rho = -.42, p < .010)., Conclusion: Characterisation of wall kinematics by 4D ultrasound based WMIs provides a new and independent criterion for the distinction of diseased tissue in the AAA sac and the less affected neck region. This is a promising step towards the establishment of new biomarkers to differentiate between the mechanical instability of the AAA and rupture risk., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: The Altura (Alt) endograft is a new design, lacking the classic main body with the flow divider. Instead, 2 proximal D-shaped endografts form a round circumference in the aortic neck for secure sealing and land in the iliac arteries in a cross-limb fashion. The aim of this computational study was to compare hemodynamically this model with the classic bifurcated (Bif) and cross-limb (Cx) endograft designs of equal total length., Methods: All 3D endograft models were created using the finite volume analysis application ANSYS CFX (Ansys Inc., Canonsburg, PA, USA). The Alt inlet was constructed as 2 opposing D-shaped sections. The flow was quantified by time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and helicity. The displacement forces were also compared for all models with computational fluid dynamics analysis., Results: The Alt design was associated with lower forces (range 4.0-5.9Ν) than Bif (4.17-6.15 N) and Cx (4.43-6.53 N). The 2-piece inlet site of the separated limbs of Alt has higher TAWSS than the uniform inlet segment of the Cx and the Bif model. Most importantly, the mid-segment and distal segment of the limbs in the Alt design present higher TAWSS in a greater area than the other 2 models. The inlet of the Alt design showed higher OSI than the other accommodations and similar or comparable OSI values along their mid-limb and distal limb segments. The range, location, and values or RRT were comparable between the 3 models. Helicity in the iliac limbs is more prominent in the crossed accommodations (Alt and Cx)., Conclusions: Only small differences in the hemodynamic indices and displacement forces were detected between the Alt and classic accommodations. From this point of view, the Alt design could be theoretically considered not inferior to other widely used endograft configurations., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Abdominal aortic aneurysm (AAA) rupture is an important cause of death in older adults. In clinical practice, the most established predictor of AAA rupture is maximum AAA diameter. Aortic diameter is commonly used to assess AAA severity in mouse models studies. AAA rupture occurs when the stress (force per unit area) on the aneurysm wall exceeds wall strength. Previous research suggests that aortic wall structure and strength, biomechanical forces on the aorta and cellular and proteolytic composition of the AAA wall influence the risk of AAA rupture. Mouse models offer an opportunity to study the association of these factors with AAA rupture in a way not currently possible in patients. Such studies could provide data to support the use of novel surrogate markers of AAA rupture in patients. In this review, the currently available mouse models of AAA and their relevance to the study of AAA rupture are discussed. The review highlights the limitations of mouse models and suggests novel approaches that could be incorporated in future experimental AAA studies to generate clinically relevant results.

Vitamin D deficiency has been associated with human abdominal aortic aneurysm (AAA); however, its role in AAA pathogenesis is unclear. The aim of the present study was to investigate the effect of vitamin D deficiency on AAA development and examine if administering cholecalciferol (CCF) could limit growth of established AAA within the angiotensin-II (AngII) infused apolipoprotein E-deficient mouse model. Mice were rendered vitamin D deficiency through dietary restriction and during AngII infusion developed larger AAAs as assessed by ultrasound and ex vivo morphometry that ruptured more commonly (48% vs. 19%; P=0.028) than controls. Vitamin D deficiency was associated with increased aortic expression of osteopontin and matrix metalloproteinase-2 and -9 than controls. CCF administration to mice with established aortic aneurysms limited AAA growth as assessed by ultrasound (P<0.001) and ex vivo morphometry (P=0.036) and reduced rupture rate (8% vs. 46%; P=0.031). This effect was associated with up-regulation of circulating and aortic sclerostin. Incubation of human aortic smooth muscle cells with 1,25-dihyroxyvitamin D3 (the active metabolite of vitamin D) for 48 h induced up-regulation of sclerostin (P<0.001) and changed the expression of a range of other genes important in extracellular matrix remodeling. The present study suggests that vitamin D deficiency promotes development of large rupture-prone aortic aneurysms in an experimental model. CCF administration limited both growth and rupture of established aneurysms. These effects of vitamin D appeared to be mediated via changes in genes involved in extracellular matrix remodeling, particularly sclerostin., (© 2020 The Author(s).)

Mammalian target of rapamycin (mTOR) and a ribosomal protein S6 kinase (p70S6K) mediate tissue fibrosis and negatively regulate autophagy. This study aims to investigate whether glucagon-like peptide-1 (GLP-1) analog liraglutide protects the heart against aortic banding-induced cardiac fibrosis and dysfunction through inhibiting mTOR/p70S6K signaling and promoting autophagy activity. Male SD rats were randomly divided into four groups (n = 6/each group): sham operated control; abdominal aortic constriction (AAC); liraglutide treatment during AAC (0.3 mg/kg, injected subcutaneously twice daily); rapamycin treatment during AAC (0.2 mg/kg/day, administered by gastric gavage). Relative to the animals with AAC on week 16, liraglutide treatment significantly reduced heart/body weight ratio, inhibited cardiomyocyte hypertrophy, and augmented plasma GLP-1 level and tissue GLP-1 receptor expression. Phosphorylation of mTOR/p70S6K, populations of myofibroblasts and synthesis of collagen I/III in the myocardium were simultaneously inhibited. Furthermore, autophagy regulating proteins: LC3-II/LC3-I ratio and Beclin-1 were upregulated, and p62 was downregulated by liraglutide. Compared with liraglutide group, treatment with rapamycin, a specific inhibitor of mTOR, compatibly augmented GLP-1 receptor level, inhibited phosphorylation of mTOR/p70S6K and expression of p62 as well as increased level of LC3-II/LC3-I ratio and Beclin-1, suggesting that there is an interaction between GLP-1 and mTOR/p70S6K signaling in the regulation of autophagy. In line with these modifications, treatment with liraglutide and rapamycin significantly reduced perivascular/interstitial fibrosis, and preserved systolic/diastolic function. These results suggest that the inhibitory effects of liraglutide on cardiac fibrosis and dysfunction are potentially mediated by inhibiting mTOR/p70S6K signaling and enhancing autophagy activity., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To test whether aneurysm biomechanical ratio (ABR; a dimensionless ratio of wall stress and wall strength) can predict aneurysm related events., Methods: In a prospective multicentre clinical study of 295 patients with an abdominal aortic aneurysm (AAA; diameter ≥ 40 mm), three dimensional reconstruction and computational biomechanical analyses were used to compute ABR at baseline. Participants were followed for at least two years and the primary end point was the composite of aneurysm rupture or repair., Results: The majority were male (87%), current or former smokers (86%), most (72%) had hypertension (mean ± standard deviation [SD] systolic blood pressure 140 ± 22 mmHg), and mean ± SD baseline diameter was 49.0 ± 6.9 mm. Mean ± SD ABR was 0.49 ± 0.27. Participants were followed up for a mean ± SD of 848 ± 379 days and rupture (n = 13) or repair (n = 102) occurred in 115 (39%) cases. The number of repairs increased across tertiles of ABR: low (n = 24), medium (n = 34), and high ABR (n = 44) (p = .010). Rupture or repair occurred more frequently in those with higher ABR (log rank p = .009) and ABR was independently predictive of this outcome after adjusting for diameter and other clinical risk factors, including sex and smoking (hazard ratio 1.41; 95% confidence interval 1.09-1.83 [p = .010])., Conclusion: It has been shown that biomechanical ABR is a strong independent predictor of AAA rupture or repair in a model incorporating known risk factors, including diameter. Determining ABR at baseline could help guide the management of patients with AAA., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Cardiac remodeling is accompanied by cardiac hypertrophy, fibrosis, dysfunction, and eventually leading to heart failure. Intermedin (IMD), as a paracrine/autocrine peptide, has a protective effect in cardiovascular diseases. In this study, we elucidated the role and the underlying mechanism of IMD in pathological remodeling. Pathological remodeling mouse models were induced by abdominal aorta constriction for 4 weeks or angiotensin II (Ang II) infusion for 2 weeks in wildtype, IMD-overexpression, IMD-knockout and klotho-knockdown mice. Western blot, real-time PCR, histological staining, echocardiography and hemodynamics were used to detect the role of IMD in cardiac remodeling. Cardiac hypertrophy, fibrosis and dysfunction were significantly aggravated in IMD-knockout mice versus wildtype mice, and the expression of klotho was downregulated. Conversely, cardiac remodeling was alleviated in IMD-overexpression mice, and the expression of klotho was upregulated. Hypertension induced by Ang II infusion rather than abdominal aorta constriction was mitigated by IMD. However, the cardioprotective effect of IMD was blocked in klotho-knockdown mice. Similar results were found in cultured neonatal rat cardiomyocytes, which was pretreated with IMD before Ang II stimulation. Mechanistically, IMD inhibited the phosphorylation of Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) and the activity of calcineurin to protect against cardiac hypertrophy through upregulating klotho in vivo and in vitro. Furthermore, peroxisome proliferator-activated receptor γ (PPARγ) might mediate IMD upregulating klotho. In conclusion, pathological remodeling may be alleviated by endogenous IMD, which inhibits the expression of calcineurin and p-CaMKII by upregulating klotho via the PPARγ pathway. It suggested that IMD might be a therapeutic target for heart disease., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: To characterize the non-laminar flow dynamics and resultant decreased wall shear stress (WSS) and high oscillatory shear index (OSI) of the infrarenal abdominal aortic dilatation, cardiac phase-resolved 3D phase-contrast MRI (4D-flow MRI) was performed., Methods: The prospective single-arm study was approved by the Institutional Review Board and included 18 subjects (median 67.5 years) with the dilated infrarenal aorta (median diameter 35 mm). 4D-flow MRI was conducted on a 1.5T MRI system. On 3D streamline images, laminar and non-laminar (i.e., vortex or helical) flow patterns were visually assessed both for the dilated aorta and for the undilated upstream aorta. Cardiac phase-resolved flow velocities, WSS and OSI, were also measured for the dilated aorta and the upstream undilated aorta., Results: Non-laminar flow represented by vortex or helical flow was more frequent and overt in the dilated aorta than in the undilated upstream aorta (P < 0.0156) with a very good interobserver agreement (weighted kappa: 0.82-1.0). The WSS was lower, and the OSI was higher on the dilated aortic wall compared with the proximal undilated segments. In mid-systole, mean spatially-averaged WSS was 0.20 ± 0.016 Pa for the dilated aorta vs. 0.68 ± 0.071 Pa for undilated upstream aorta (P < 0.0001), and OSI on the dilated aortic wall was 0.093 ± 0.010 vs. 0.041 ± 0.0089 (P = 0.013). The maximum values and the amplitudes of the WSS at the dilated aorta were inversely proportional to the ratio of dilated/undilated aortic diameter (r = -0.694, P = 0.0014)., Conclusion: 4D-flow can characterize abnormal non-laminar flow dynamics within the dilated aorta in vivo. The wall of the infrarenal aortic dilatation is continuously and increasingly affected by atherogenic stimuli due to the flow disturbances represented by vortex or helical flow, which is reflected by lower WSS and higher OSI.

Nutcracker syndrome (NCS) refers to compression of the left renal vein (LRV) between the abdominal aorta and the superior mesenteric artery (SMA). The clinical presentation of NCS includes hematuria, abdominal and left flank pain, gonadal varices, and varicocele formation. Theoretically, thrombosis can occur in the LRV in patients with NCS. However, an isolated solitary left renal vein thrombus (LRVT) complicating NCS is rare. In addition, the clinical features of an LRVT complicating NCS remain unclear. We describe a 43-year-old woman presenting with an asymptomatic LRVT complicating NCS. She was referred to our hospital for investigation of dysfunctional uterine bleeding, and detailed examination revealed endometrial cancer. Computed tomography angiography (CTA) and Doppler ultrasonography revealed compression of the LRV between the aorta and the SMA, as well as an LRVT. CTA performed 4 months after the administration of an anticoagulant showed complete disappearance of the LRVT. We have also included a review of published reports describing LRVT complicating NCS and discussed the clinical features of such a presentation.

Background: The perfused elastase AAA model and subcutaneous Angiotensin II infusion AAA model are widely used murine AAA models. We modified these two current models and developed a new murine model to study aneurysm formation and rupture., Methods: The murine abdominal aorta was treated with elastase. Angiotensin II was infused at a dose of 1,000 ng/kg/min via an osmotic pump placed subcutaneously. A saline osmotic pump was used as the control. The aortas were harvested from the mice 4 weeks later, or earlier if mice died. The abdominal aorta was inspected using ultrasound and microscopy for aneurysm formation and/or signs of rupture. The aneurysm outcome was measured using aortic expansion and proinflammatory cytokine expression. It was also compared with the established conventional elastase perfusion and angiotensin II infusion abdominal aortic aneurysm models., Results: By day 28 after surgery, all abdominal aortas of mice treated in the modified group had dilated and progressed to abdominal aortic aneurysms with 60% ruptured aneurysms, whereas none of the control aortas treated with saline became aneurysmal. In mice treated with elastase solution alone, 100% developed aneurysms and only one had a ruptured aneurysm. In mice given angiotensin II infusion alone, 37.5% developed aneurysms and none had a ruptured aneurysm. Histological examination of the modified murine abdominal aortic aneurysm rupture model was identical to that observed in the conventional elastase model. Quantitative polymerase chain reaction analysis revealed similarly increased levels of proinflammatory cytokines., Conclusions: We modified two current murine abdominal aortic aneurysm models to develop a murine abdominal aortic aneurysm model with consistent aneurysm formation and high rupture incidence, which can be used for studying abdominal aortic aneurysm rupture and treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Abdominal aortic aneurysm (AAA) is a permanent and irreversible dilation of the lower region of the aorta. It is typically an asymptomatic condition that if left untreated can expand to the point of rupture. In simple mechanical terms, rupture of an artery occurs when the local wall stress exceeds the local wall strength. It is therefore understandable that numerous studies have attempted to estimate the AAA wall stress and investigate the relationship between the AAA wall stress and AAA symptoms., Materials and Methods: We conducted computational biomechanics analysis for 19 patients with AAA (a proportion of these patients were classified as symptomatic) to investigate whether the AAA wall stress fields (both the patterns and magnitude) correlate with the clinical definition of symptomatic and asymptomatic AAAs. For computation of AAA wall stress, we used a very efficient method recently presented by the Intelligent Systems for Medicine Laboratory. The Intelligent Systems for Medicine Laboratory's method uses geometry from computed tomography images and mean arterial pressure as the applied load. The method is embedded in the software platform BioPARR-Biomechanics based Prediction of Aneurysm Rupture Risk, freely available from http://bioparr.mech.uwa.edu.au/. The uniqueness of our stress computation approach is three-fold: i) the results are insensitive to unknown patient-specific mechanical properties of arterial wall tissue; ii) the residual stress is accounted for, according to Y.C. Fung's Uniform Stress Hypothesis; and iii) the analysis is automated and quick, making our approach compatible with clinical workflows., Results: Symptomatic patients could not be identified from the plots (pattern) of AAA wall stress and stress magnitude. Although the largest stress was predicted for a patient who suffered from AAA symptoms, the three patients with the smallest stress were also symptomatic., Conclusions: The results demonstrate, contrary to the common view, that neither the wall stress magnitude nor the stress distribution appears to be associated with the presence of clinical symptoms., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Midaortic syndrome (MAS) is a rare congenital or acquired condition marked by segmental or diffuse stenosis of the distal thoracic and/or abdominal aorta and its branches. The optimal approach to medical or interventional management of MAS and long-term outcomes in adults are not well defined. We reviewed MAS cases to characterize the natural history of aortic disease, identify prognostic factors, and evaluate the durability of invasive interventions., Methods: We conducted a retrospective review of patients with MAS who presented to Memorial Hermann Hospital and Baylor College of Medicine between 1997 and 2018. We categorized cases according to demographic and clinical manifestations, etiologies, the extent of aortic involvement, interventions, and vascular outcomes., Results: We identified a cohort of 13 patients with MAS. The etiology of MAS was identified in 6 cases, including genetic syndromes (neurofibromatosis type 1 (2/13), Williams syndrome (1/13), fibromuscular dysplasia (2/13), and Takayasu arteritis (1/13)). Mean age at first documented clinical event was 25.2 (2-67) years, but cases with genetic etiologies presented significantly younger (18.2 years). The most common primary anatomic site was the suprarenal and infrarenal aorta (zones 5-8). Extra-aortic locations involved the renal (4/13), celiac (3/13), and superior mesenteric (3/13) arteries. Clinical manifestations included hypertension (13/13), claudication (9/13), and postprandial abdominal pain (5/13). All patients with available follow-up data underwent at least one surgical or endovascular intervention (range: 1-8). Postoperative complications included renal failure requiring postdischarge hemodialysis and respiratory failure. There were no deaths in long-term follow-up., Conclusions: MAS is a complex vasculopathy with substantial variability in clinical presentation and anatomic distribution. Extensive disease frequently requires multiple invasive interventions and results in refractory hypertension, which may predict subsequent clinical events. A multidisciplinary approach with long-term monitoring is essential for preservation of end-organ function and quality of life in this debilitating disease., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: One of the main drawbacks of endovascular aortic aneurysm repair (EVAR) compared to open aortic surgery is the possibility of developing endoleaks and secondary aneurysm rupture, requiring frequent imaging follow-up. This study aims to identify prognostic factors that could be incorporated in follow-up protocols, which might lead to better personalized, lower cost and safe EVAR follow-up., Methods: A retrospective study was performed including all patients who underwent elective EVAR from January 2000 to December 2015. Follow-up data were gathered by reviewing medical files for radiographic imaging. Linear and logistic regressions were used to assess predictive factors for aneurysm shrinkage., Results: In 361 patients, aneurysm sac shrinkage of 10 mm or more was measured in 152 (42.1%) patients. Patients with ≥10-mm aneurysm shrinkage had fewer endoleaks (4.3% vs. 24.6%, P<0.0001) and fewer re-interventions for endoleak (3.0% vs. 10.1%, P=0.007). Aneurysm sac shrinkage was correlated with the absence of endoleak development (OR 0.36, 95% CI 0.19-0.66, P=0.001). In patients who had achieved ≥10-mm shrinkage of the aneurysm sac, no further significant growth was seen, compared to 38 (15.3%) patients who did not attain size reduction (P<0.001)., Conclusions: Once patients achieve ≥10-mm aneurysm sac shrinkage, they are less prone to developing subsequent aneurysm growth and have significantly lower risk of requiring surgery for endoleaks. However, a small number of patients remain at risk of requiring endoleak surgery after aneurysm shrinkage. Therefore, we would not recommend ceasing life-long imaging follow-up after significant aneurysm sac shrinkage, though it might be safe to increase the interval of follow-up.

Purpose: To assess in silicone juxtarenal aneurysm models the gutter characteristics and compression of different types of chimney graft (CG) configurations. Materials and Methods: Fifty-seven combinations of Excluder C3 or Conformable Excluder stent-grafts (23, 26, and 28.5 mm) were deployed in 2 silicone juxtarenal aneurysm models with 3 types of CGs: Viabahn self-expanding (VSE; 6 and 13 mm) or Viabahn balloon-expandable (VBX; 6, 10, and 12 mm) stent-grafts and Advanta V12 balloon-expandable stent-grafts (ABX; 6 and 12 mm). Setups were divided into 4 groups on the basis of increasing CG and main graft (MG) diameters. Two independent observers assessed gutter size and type as well as CG compression on computed tomography scans using postprocessing software. Results: In the smaller diameter combinations (6-mm CG and 23-, 26-, and 28.5-mm MGs), both VSE (p=0.006 to 0.050) and ABX (p=0.045 to 0.050) showed lower gutter areas and volumes compared with VBX. In turn, the VBX showed a nonsignificant tendency to decreased compression, especially compared to ABX. Use of the Excluder C3 showed a 6-fold increase in type A1 gutters (related to type Ia endoleak) as compared to the Conformable Excluder (p=0.018). Balloon-expandable stent-grafts (both ABX and VBX) showed a 3-fold increase in type A1 gutters in comparison with self-expanding stent-grafts (p=0.008). Conclusion: The current study suggests that use of the Conformable Excluder in combination with VSE chimney grafts is superior to the other tested CG/MG combinations in terms of gutter size, gutter type, and CG compression.

Purpose: To investigate the physiological uptake of hybrid fluorine-18-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) before and after an uncomplicated endovascular aneurysm sealing (EVAS) procedure as a possible tool to diagnose EVAS graft infection and differentiate from postimplantation syndrome. Materials and Methods: Eight consecutive male patients (median age 78 years) scheduled for elective EVAS were included in the prospective study ( ClinicalTrials.gov identifier NCT02349100). FDG-PET/CT scans were performed in all patients before the procedure and 6 weeks after EVAS. The abdominal aorta was analyzed in 4 regions: suprarenal, infrarenal neck, aneurysm sac, and iliac. The following parameters were obtained for each region: standard uptake value (SUV), tissue to background ratio (TBR), and visual examination of FDG uptake to ascertain its distribution. Demographic data were obtained from medical files and scored based on reporting standards. Results: Visual examination showed no difference between pre- and postprocedure FDG uptake, which was homogenous. In the suprarenal region no significant pre- and postprocedure differences were observed for the SUV and TBR parameters. The infrarenal neck region showed a significant decrease in the SUV and no significant decrease in the TBR. The aneurysm sac and iliac regions both showed a significant decrease in SUV and TBR between the pre- and postprocedure scans. Conclusion: Physiological FDG uptake after EVAS was stable or decreased with regard to the preprocedure measurements. Future research is needed to assess the applicability and cutoff values of FDG-PET/CT scanning to detect endograft infection after EVAS.

In this paper, we study the correlation between the wall shear stress, a hemodynamical index derived from numerical simulations, and an new index MFA-ILT for the characterization of intraluminal thrombus (ILT) in the presence of abdominal aortic aneurysms. Based on the processing of medical images, we define our index MFA-ILT by projecting onto lumen surface a measure of the ILT thickness. From the physical point of view, hemodynamical indexes describe the mechanical stimuli at which the luminal surface of the vessel wall is subject to, due to blood flow. Specifically, we consider the time-averaged wall shear stress and the oscillatory shear index. The first index provides a measurement of the averaged magnitude of the shear stress; the second index measures the rate of change of shear stress. To reconstruct the hemodynamical indexes, we build in silico three-dimensional models. We use the same physical parameters and boundary conditions for all the aneurysms in the sample. The computer simulations do not require any additional invasive patient examination. We consider eleven cases of abdominal aortic aneurysms spanning a wide range of different morphological features. All the cases are characterized by a thin intraluminal thrombus. We can, therefore, assume that the lumen we currently observe does not significantly differ from the one before the thrombus deposition. Our results suggest that the value of wall shear stresses and intraluminal thrombus deposition are correlated. Moreover, we conclude that in six cases time-averaged wall shear stress provides a preliminary indication of the area at risk of thrombus deposition.

Research describing fetal arterial structure and function is lacking within the literature. This study's purpose was to measure intima-media thickness (IMT), compliance and distensibility of 24- to 25-week fetuses' abdominal aortas using conventional ultrasonography from 16 diabetic (DM) and 25 non-diabetic mothers (NDM). We found no significant differences in fetal abdominal aorta IMT (P = .68), diameter distensibility (P = .22), or cross-sectional distensibility (P = .23). However, both fetal abdominal aortic diameter compliance (P = .03) and cross-sectional compliance (P = .005) were greater in DM than in NDM (P = .005). This study demonstrates that it is possible and potentially useful to measure fetal abdominal aorta biometrics and biomechanical characteristics., (© 2020 Wiley Periodicals, Inc.)

Objectives: The aim was to evaluate the impact of a modified frozen elephant trunk procedure (mFET) on remodeling of the downstream aorta following acute aortic dissections., Methods: Over a period of 8 years, 205 patients (mean age 62.6 ± 12.6 years) underwent a mFET (n = 69, 33.7%) or isolated ascending aorta replacement (n = 136, 66.3%) (iAoA). Aortic diameter was assessed at the aortic arch (AoA), at the mid of the thoracic aorta (mThA), at the thoracoabdominal transition (ThAbd) and at the celiac trunk level (AbdA)., Results: Mean follow-up was 3.3 ± 2.6 years. In-hospital mortality was 14% (n = 28), 7% in mFET and 17% in the iAoA group (p = 0.08). At the end of the follow-up, overall survival was 84% (95% CI 70-92%) and 75% (65-82%) and freedom from aorta-related reoperation was 100% and 95% (88-98%) for mFET and iAoA, respectively. At iAoA, the average difference in diameter change per year between mFET and iAoA was for total lumen 0 mm (- 0.95 to 0.94 mm, p = 0.99), and for true lumen, it was 1.23 mm (- 0.09 to 2.55 mm) per year, p = 0.067. False lumen demonstrated a decrease in diameter in mFET as compared to iAoA by - 1.43 mm (- 2.75 to - 0.11 mm), p = 0.034. In mFET, at the aortic arch level the total lumen diameter decreased from 30.7 ± 4.8 mm to 30.1 ± 2.5 mm (Δr  + 2.90 ± 3.64 mm) and in iAoA it increased from 31.8 ± 4.9 to 34.6 ± 5.9 mm (Δr + 2.88 ± 4.18 mm)., Conclusion: The mFET procedure provides satisfactory clinical outcome at short term and mid-term and has a positive impact on aorta remodeling, especially at the level of the aortic arch.

Abdominal aortic aneurysm (AAA) is an irreversible bulge in the artery with higher prevalence among the elderlies. Increase of the aneurysm diameter by time is a fatal phenomenon which will lead to its sidewall rupture. Invasive surgical treatments are vital in preventing from AAA development. These approaches however have considerable side effects. Targeted drug delivery using microbubbles (MBs) has been recently employed to suppress the AAA growth. The present study is aimed to investigate the surface adhesion of different types of drug-containing MBs to the inner wall of AAA through ligand-receptor binding, using fluid-structure interaction (FSI) simulation by using a patient CT-scan images of the vascular system. The effect of blood flow through AAA on MBs delivery to the intended surface was also addressed. For this purpose, the adherence of four types of MBs with three different diameters to the inner surface wall of AAA was studied in a patient with 40-mm diameter aneurysm. The effects of the blood mechanical properties on the hematocrit (Hct) percentage of patients suffering from anemia and diabetes were studied. Moreover, the impact of variations in the artery inlet velocity on blood flow was addressed. Simulation results demonstrated the dependency of the surface density of MBs (SDM) adhered on the AAA lumen to the size and the type of MBs. It was observed that the amount of SDM due to adhesion on the AAA lumen for one of the commercially-approved MBs (Optison) with a diameter of 4.5 μm was higher than the other MBs. Furthermore, we have shown that the targeted drug delivery to the AAA lumen is more favorable in healthy individuals (45% Hct) compared to the patients with diabetes and anemia. Also, it was found that the targeted drug delivery method using MBs on the patients having AAA with complicated aneurysm shape and negative inlet blood flow velocity can be severely affected.

Fluid responsiveness, defined as the response of stroke volume to fluid loading, is a tool to individualize fluid administration in order to avoid the deleterious effects of hypovolemia or hypervolemia in hospitalized patients. To evaluate the accuracy of two ultrasound indices, the caudal vena cava to abdominal aorta ratio (CVC/Ao) and the respiratory collapsibility of the caudal vena cava (cCVC), as independent predictors of fluid responsiveness in a heterogeneous population of spontaneously breathing, conscious, hospitalized dogs. A prospective, multicenter, observational, cross-sectional study was designed in twenty-five dogs. The accuracy of CVC/Ao and cCVC in predicting fluid responsiveness was evaluated by the area under the receiver operating characteristic curve (AUROC) in a group of hospitalized dogs after receiving a mini-fluid bolus of 4 ml/kg of Hartmann's solution. Dogs with an increased aortic velocity time integral >15% were classified as fluid responders. Twenty-two dogs were finally included. Ten were classified as responders and 12 as non-responders. The AUROC curves were 0.88 for the CVC/Ao ratio (95% confidence interval, CI, 0.67-0.98; P=0.0001) and 0.54 for cCVC (95% CI 0.32-0.75; P=0.75). The CVC/Ao threshold optimized for best sensitivity (SE) and specificity (SP) values was 0.83 (SE 100%; SP 75%). In spontaneously breathing hospitalized dogs, the CVC/Ao measurement predicted stroke volume increase after a fluid bolus, while the respiratory variations in the cCVC did not discriminate between fluid responders and non-responders.

Abdominal aortic aneurysms (AAA) is a multifactorial vascular disease with a high rate of mortality and brings heavy burden to both human and society. The pathological process behind AAA is complex. Elastin degradation, chronic inflammation, and vascular smooth muscle cell phenotypic modulation are involved in AAA formation. Apigenin (API) has gained much attention due to its specific properties, such as anti-inflammation, antioxidant, and anti-cancer effects. Previous studies have demonstrated that API exert beneficial effects on prevention of cardiovascular diseases. However, the effects of API on AAA are still unknown. Here, we for the first time evaluated API-related effects on AAA formation using a Cacl2-induced AAA model. Compared with the AAA group, treatment with API reduced the incidence of AAA, attenuated pathological expansion of the aorta, and preserved elastic fiber in a dose-dependent manner. In addition, API attenuated vascular inflammation by inhibiting activation of matrix metalloproteinase and modulated vascular smooth muscle cell contractile phenotypic transition. The preventative effect of API on AAA might be associated with the downregulation of nuclear factor-kappa B (NF-κB) activity via the IKK-dependent signaling pathway. Our findings firstly revealed that API could suppress AAA formation in a dose-dependent manner by inhibiting the NF-κB signaling pathway, and API should be considered as a promising therapeutic drug in prevention of AAA.

Background: Subclinical cardiovascular risks of secondhand smoke (SHS) exposure among children and adolescents remains insufficiently described., Methods: This was a cross-sectional study of 298 children and adolescents (48.0% male, body mass index: 27.0 ± 8.9 kg/m 2 ), including 49 self-reported cases with SHS. Arterial elasticity and stiffness (distensibility, compliance, incremental elastic modulus [IEM]) were obtained via ultrasound imaging in the abdominal aorta, brachial, and carotid arteries. A one-way analysis of variance compared differences between groups, and multiple linear regression adjusted for covariates., Results: SHS was associated with lower abdominal aorta diameter distensibility (aDD) (13.4 ± 3.6% vs. 16.0 ± 5.2%, p = 0.009) and abdominal aorta cross-sectional distensibility (aCSD) (28.8 ± 8.3% vs. 35.1 ± 12.2%, p = 0.009), as well as higher abdominal aorta IEM (aIEM) (1241 ± 794 vs. 935 ± 388 mmHg, p = 0.001). After adjustment for covariates, aDD (p = 0.047), aCSD (p = 0.040), and aIEM (p = 0.017) remained significant; this significance persisted with the additional adjustment of percent body fat. Measures of brachial and carotid compliance and distensibility were not associated with SHS., Conclusions: SHS was associated with abdominal aorta stiffness; the majority of vascular measures within the brachial and carotid artery remained unaffected following adjustment for covariates, including hypertension and adiposity. SHS may predispose individuals to increased abdominal aorta stiffness, an artery previously reported to exhibit increased susceptibility to atherosclerosis.

Globally growing problems related to cardiovascular diseases lead to a considerable need for synthetic vascular grafts. For small-caliber vascular prosthesis, it remains essential to fulfill rapid endothelialization, inhibit intimal hyperplasia, and prevent calcification for keeping patency. To modulate vascular regeneration, herein, we developed a bioactive trilayered tissue-engineered vascular graft encapsulating both microRNA-126 and microRNA-145 in the fibrous inner and middle layers, respectively. In vitro cell activities demonstrated that the trilayered electrospun membranes had significant biological advantages in enhanced growth and intracellular nitric oxide production of vascular endothelial cells, modulation of phenotypes of vascular smooth muscle cells (SMCs), and restraint of calcium deposition through fast-releasing microRNA-126 and slow-releasing microRNA-145. Histological and immunofluorescent analyses of in vivo implantation in a rat abdominal aorta interposition model suggested that the dual-microRNA-loading trilayered electrospun graft exerted a positive effect on accelerating endothelialization, improving contractile SMC regeneration, and promoting normal extracellular matrix formation. Meanwhile, the local bioactivity of microRNA-126 and microRNA-145 in the trilayered vascular graft could regulate inflammation and depress calcification possibly by facilitating transformation of macrophages into the anti-inflammatory M2 phenotype. These findings indicated that the trilayered electrospun graft by local delivery of dual microRNAs could be possibly used as a bioactive substitute for replacement of artificial small-caliber blood vessels.

Existing animal models do not replicate all aspects of abdominal aortic aneurysms (AAAs), including the rupture mechanisms. From histopathological analyses conducted in humans, it has been found that the vasa vasorum of the AAA wall is the starting point of circulatory failure and that bulging and dilatation of the abdominal aorta occurs through inflammation and tissue degeneration. We created a new animal model (the hypoperfusion-induced model) of AAAs. In this study, we describe the current animal models of AAAs and present the utility of our new model of AAAs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: This study aimed to synthesize data from recently published literature to evaluate the safety and efficacy of endovascular treatment (EVT) for infrarenal aortic occlusion (IAO)., Methods: The PubMed and Embase were searched to identify all studies reporting EVT for IAO from January 1st, 2000 to December 31st, 2017. Information about patients' characteristics, comorbidities, technical success, mortality, complications, and patency was collected and analyzed., Results: 9 articles consisting of 220 patients were included in this meta-analysis. Patients often had severe symptoms and many comorbidities. The overall technical success and periprocedural mortality was 95.64% (95% confidence interval [CI], 88.60%-99.42%) and 0.35% (95% CI, 0.00% to 2.33%). In successful cases, ankle-brachial index was raised from 0.42 to 0.91. The complication described in one article is of the whole samples and that of the technical success cases was not represented separately. We made the meta-analysis on the other 8 articles. Periprocedural complications included vascular complications (11.35% [95% CI: 3.50%-19.20%]) mainly pseudoaneurysm, thromboses, hematoma, and dissections; limb complications 8.28% (95% CI: 4.86%-13.77%); and renal complications 1.25% (95% CI: 0.00%-3.65%). In an article, vascular complications of whole samples were 12.24%, limb complication 6.12%, and renal complication 10.20%. Overall primary patency was 93.53% (95% CI: 89.37%-97.68%) at 1 year, 78.96% (95% CI: 72.26%-84.96%) at 3 years, and 75.31% (95% CI: 66.42%-84.20%) at 5 years. Overall secondary patency was 98.25% (95% CI: 95.50%-99.73%) at 1 year, 95.92% (95% CI: 89.25%-99.47%) at 3 years, and 94.02% (95% CI: 88.10%-98.00%) at 5 years., Conclusions: EVT for IAO is acceptable with relatively high technical success rate, low mortality, and satisfying short-term patency. Although primary patency was lower than after surgery, secondary patency was roughly similar to that of surgical repair. However, this conclusion is based on retrospective observational studies, and the results could be imprecise due to the limited sample sizes, especially in midterm and long-term patency. More studies with longer follow-up and bigger sample size are needed to further elucidate this., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aging is associated with impaired vascular function characterized in part by attenuated vasorelaxation to acetylcholine (ACh) and sodium nitroprusside (SNP). Due to structural and functional differences between conduit and resistance arteries, the effect of aging on vasorelaxation responses may vary along the arterial tree. Our purpose was to determine age-related differences in vasorelaxation responses in large and small arteries. Responses to the endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium-independent vasodilator sodium nitroprusside (SNP) were assessed in abdominal aorta (AA), iliac arteries (IA), femoral arteries (FA), and gastrocnemius feed arteries (GFA) from young and old male rats. ACh-mediated vasorelaxation was significantly impaired in old AA and IA. SNP-mediated vasorelaxation was impaired in old AA. To investigate a potential mechanism for impaired relaxation responses in AA and IA, we assessed eNOS protein content and interactions with caveolin-1 (Cav-1), and calmodulin (CaM) via immunoprecipitation and immunoblot analysis. We found no age differences in eNOS content or interactions with Cav1 and CaM. Combined data from all rats revealed that eNOS content was higher in IA compared to AA and FA (p < .001), and was higher in GFA than AA (p < .05). Cav1:eNOS interaction was greater in FA than in AA and IA (p < .01), and in GFA compared to IA (p < .05). No differences in CaM:eNOS were detected. In conclusion, age-related impairment of vasorelaxation responses occurred in the large conduit, but not small conduit or resistance arteries. These detrimental effects of age were not associated with changes in eNOS or its interactions with Cav-1 or CaM., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Background: Open surgery of abdominal aortic aneurysm (AAA) or aortoiliac occlusive disease (AIOD) sometimes requires left renal vein division (LRVD) to gain adequate exposure of the abdominal aorta. The aim of this study is to evaluate the effect of LRVD on the postoperative renal function using propensity score matching (PSM)., Methods: From July 1996 to January 2018, we retrospectively reviewed 698 patients who underwent open aortic surgery, including 543 AAAs and 155 AIODs, at a single institution. 66 patients (9.6%, 47 AAAs, 19 AIODs) needed LRVD during the operation. A 1:3 ratio PSM was used to control the selective bias between the LRVD and non-LRVD groups. We investigated preoperative and postoperative renal function including serum creatinine (sCr) level and estimated glomerular filtration rate (eGFR, mL/min/1.73 m 2 ). Major complications, long-term renal function, and 30-day mortality were also compared., Results: The LRVD group had a significantly higher rate of renal artery reconstruction (15.2% vs. 3.3%, P < 0.001) and suprarenal clamping (54.6% vs. 9.5%, P < 0.001) and higher incidence of juxtarenal AIOD (24.2% vs. 5.4%, P < 0.001). With PSM, 63 patients in the LRVD group and 144 patients in the non-LRVD group were enrolled in this study. The baseline characteristics were well balanced in the groups after PSM. There were no significant differences in preoperative eGFR (72.4 ± 21.3 vs. 76.1 ± 25.0, P = 0.306) and postoperative eGFR on day 3 (69.5 ± 26.6 vs. 77.5 ± 28.5, P = 0.065), day 7 (73.3 ± 24.8 vs. 78.5 ± 27.4, P = 0.264), and in the long-term follow-up period (69.0 ± 22.2 vs. 68.9 ± 27.1, P = 0.986, 50.2 month ± 45.50) in the 2 groups. Only the sCr level (1.40 ± 0.59 vs. 1.21 ± 0.62, P = 0.045) and eGFR (59.5 ± 23.9 vs. 71.4 ± 26.0, P = 0.002) were significantly worse on postoperative day 1 in the LRVD than in the non-LRVD group. There were no significant differences in 30-day mortality (1.6% vs. 1.6%, P = 1.00)., Conclusions: The patients in the LVRD group underwent initial drop in renal function; however, eGFR improved during the follow-up period. There was no difference in renal function and postoperative mortality between LRVD and non-LRVD groups. Therefore, LRVD is a safe and durable procedure during complex abdominal aortic surgery., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Saccular aneurysms are thought to have a worse prognosis than fusiform aneurysms in humans, due to hemodynamic reasons. However, data comparing hemodynamic and biology in saccular and fusiform aneurysms are lacking. The main objective was to evaluate the impact of aneurysm morphology on intra-luminal thrombus (ILT) formation and activity., Methods: Forty Lewis rats were ran-domly divided into 2 groups of 20: "saccular" (Group A) and "fusiform" (Group B) aneurysms. Decellularized thoracic aortas from guinea pigs were xenografted to create saccular or fusiform aneurysms. Final imaging evaluation of the aneurysms was carried out during the third week, by quantitative Doppler ultrasound and magnetic resonance imaging. Assays of myeloperoxidase (MPO), platelet factor 4 (PF4), advanced oxidation protein products (AOPPs) iron and matrix metallopeptidase-9 (MMP-9) were performed as biological criteria., Results: Quantitatively, saccular aneurysms are characterized by a more thicker ILT, lower inflow velocities and more important relative backflow velocities as compared to fusiform aneurysms. Compared to fusiform, saccular aneurysms released significantly more MPO (p = 0.004), PF4 (p = 0.02), AOPPs (p < 0.002), iron (p < 0.0001) and MMP-9 (p < 0.04)., Conclusion: Experimental saccular and fusiform aneurysms show differential specific hemodynamics, which seem to impact the histology and the biology of the ILT in each type of aneurysm., (© 2020 S. Karger AG, Basel.)

Purpose: To validate new computed tomography (CT)-applied software used to determine endograft limb position and apposition after endovascular aneurysm repair (EVAR). Materials and Methods: Twelve EVAR patients (mean age 81±6 years; 10 men) with distal stent-graft extensions for 15 (3 bilateral) type Ib endoleaks during follow-up were selected based on the availability of the following CT studies: pre-EVAR, 1 month, and the penultimate scan prior to the scan disclosing the type Ib endoleak. Twelve patients (mean age 82±7 years; 11 men) without endoleak and a similar interval between the primary EVAR procedure and the penultimate CT scan of the endoleak group were selected as controls using measurements from both endograft limbs (n=21, 3 excluded). Prototype Vascular Imaging Analysis software was adapted to calculate 6 parameters for the distal apposition zone: fabric distance, shortest apposition length, endograft diameter, iliac seal surface (ISS), iliac endograft apposition surface (IEAS), and percentage of iliac surface coverage (IEAS/ISS × 100). Measurements were performed on the preoperative, first postoperative, and penultimate/matched follow-up CT scans. Interobserver variability was assessed with the intraclass correlation coefficient (ICC). Continuous data are presented as the median [interquartile range (IQR) Q1, Q3]. Results: CTA follow-up was not significantly different between the endoleak and control groups [30 months (IQR 18, 58) vs 36 months (IQR 21, 59), p=0.843]. Interobserver agreement was good to excellent for all parameters (ICC 0.879-0.985). Preoperative anatomy and endograft dimensions on the first follow-up CTA scan did not differ significantly between the groups. When the penultimate CTA scan was compared with the first postoperative CT scan, endograft dimensions had significantly changed in the endoleak group; importantly, apposition was significantly decreased, and fabric distance was significantly increased, indicating limb retraction. Differences in changes in endograft dimensions were significant between the groups. Conclusion: New CT-applied software was introduced to visualize apposition and position changes of endograft limbs during follow-up. The software demonstrated good-to-excellent interobserver agreement and enabled accurate analysis of post-EVAR endograft dimensions. Significant changes in apposition and position were observed with the software on the penultimate CT scan prior to diagnosis of type Ib endoleak.

Purpose: To evaluate if the radial force of the double sealing ring of the Anaconda stent-graft induces dilatation in the perirenal aortic neck adjacent to the rings. Materials and Methods: This study evaluated the serial electrocardiogram-gated computed tomography scans of 15 abdominal aortic aneurysm patients (mean age 72.8±3.7 years; 14 men) who were treated electively using an Anaconda stent-graft. Follow-up scans were conducted before discharge and at 1, 6, 12, and 24 months after endovascular repair. Diameter and area were assessed perpendicular to the aortic centerline along the perirenal aortic neck, which was subdivided into 3 zones: the suprastent, the stent, and the infrastent zones. Measurements were performed independently by 2 experienced observers using dedicated 3-dimensional image processing software. Results: Between discharge and the 2-year follow-up the diameter and area remained stable in the suprastent zone [average diameter change: -0.1±0.4 mm (-0.4%±1.7%), p=0.893; average area change: -2.9±17.2 mm 2 (-0.7%±3.4%), p=0.946], increased in the stent zone [average diameter change: +1.9±1.0 mm (+7.3%±4.0%), p<0.001; average area change: +84.3±48.3 mm 2 (+15.5%±8.7%), p<0.001], and diverged in the infrastent zone [average diameter change: -0.8±2.2 mm (-2.3%±7.4%), p>0.99; average area change: -34.6±102.3 mm 2 (-4.1%±14.8%), p>0.99; increased in 4 patients, decreased in 9 patients]. Conclusion: After Anaconda implantation the infrarenal aortic neck accommodated to the expansion of the sealing rings at the stent zone. Below the stent zone the neck diameter decreased in the majority of patients, while an increase was related to downstream displacement of the main body. A decrease in size in the infrastent zone may contribute to durable sealing and fixation. A personalized follow-up scheme based on geometric neck remodeling should be feasible if our observations are confirmed in larger, long-term studies.