Effects of endothelial defects and venous interposition grafts on the acute incidence of thrombus formation within microvascular procedures.

Endothelial defects (ED) and the usage of interposition vein grafts (IVG) are known risk factors for free flap failure. This experimental study aimed to compare both situations of thrombus formation and fluorescence angiographic behavior. Indocyanine green videoangiography (ICGVA) with the FLOW 800 tool was systematically performed in groups I = ED, II = IVG, and III = ED and IVG (each n = 11). ICGVA was able to detect thrombosis in five animals and safely ruled it out in 26 with two false-positive cases (sensitivity, specificity, and positive and negative predictive values were 100%, 90%, 62%, and 100%, respectively). The difference between visually and ICGVA-assisted ED measurements was significant (p = 0.04). The areas of thrombosis showed no significant difference. Moreover, ICGVA detected a decrease of all parameters at the ED area and/or within the IVG section in all groups. The presence of an endothelial defect had a higher impact on thrombus formation than the IVG usage. ICGVA is qualitatively able to detect endothelial defects and clinically evident thrombosis. However, the quantitative values are not yet attributable to one of the clinical scenarios that may jeopardize free flap transfer.

Effects of acute angle, proximal bending, and distal bending in the deployment vessels on incomplete low-profile visualized intraluminal support (LVIS) expansion: an in vitro study.

BACKGROUND: A low-profile visualized intraluminal support (LVIS) device may incompletely expand during stent deployment in tortuous vessels. However, the cause of incomplete expansion remains uninvestigated. We aimed to examine in vitro the factors causing incomplete expansion in LVIS deployment by using various vessel models. METHODS: A linear model group was created by connecting linear silicone tubes (inner diameter 4 mm) at both sides of the LVIS deployment vessel (inner diameter 4 mm) with different curvature angles of 10-140° at 10° intervals. For comparison, proximal and distal bending model groups were created, both with 90° bending on the proximal/distal larger curvature side of the deployment vessel. A single operator macroscopically deployed an LVIS (4.5×32 mm) four times in each model and 56 times in each group. RESULTS: In each model group the LVIS deployment vessel with a narrow curvature angle incompletely expanded. Incomplete expansion occurred significantly more frequently in the distal bending model group (34%, 19/56) compared with that in the linear model group (14.3%, 8/56; p<0.001), as well as in the proximal bending model group (59%, 33/56) compared with that in the distal bending model group (p<0.05). Compared with the linear model group, the proximal bending model group had a significantly reduced angle between the LVIS and the direction of the LVIS pushing force, but no significant change was found in the distal bending model group compared with that in the linear model group. CONCLUSIONS: Factors such as acute angle, distal bending, and proximal bending of the deployment vessel can cause incomplete LVIS expansion.

NF-κB inhibition prevents acute shear stress-induced inflammation in the saphenous vein graft endothelium.

The long saphenous vein (LSV) is commonly used as a conduit in coronary artery bypass grafting. However, long term patency remains limited by the development of vascular inflammation, intimal hyperplasia and accelerated atherosclerosis. The impact of acute exposure of venous endothelial cells (ECs) to acute arterial wall shear stress (WSS) in the arterial circulation, and the subsequent activation of inflammatory pathways, remain poorly defined. Here, we tested the hypothesis that acute exposure of venous ECs to high shear stress is associated with inflammatory responses that are regulated by NF-κB both in-vitro and ex-vivo. Analysis of the LSV endothelium revealed that activation of NF-κB occurred within 30 min after exposure to arterial rates of shear stress. Activation of NF-κB was associated with increased levels of CCL2 production and enhanced binding of monocytes in LSVECs exposed to 6 h acute arterial WSS. Consistent with this, ex vivo exposure of LSVs to acute arterial WSS promoted monocyte interactions with the vessel lumen. Inhibition of the NF-κB pathway prevented acute arterial WSS-induced CCL2 production and reduced monocyte adhesion, both in vitro and in human LSV ex vivo, demonstrating that this pathway is necessary for the induction of the acute arterial WSS-induced pro-inflammatory response. We have identified NF-κB as a critical regulator of acute endothelial inflammation in saphenous vein in response to acute arterial WSS. Localised endothelial-specific inhibition of the NF-κB pathway may be beneficial to prevent vein graft inflammation and consequent failure.

Papillary Endothelial Hyperplasia (Masson Tumor) of the Hand. Surgical and Pathological Consideration from Seven Cases Using New Vascular Markers.

Although papillary endothelial hyperplasia may occur at almost any site, one of the most common sites is the hand. It is generally regarded as a reactive vascular proliferation i.e. exuberant form of organizing thrombus. Diagnosis of Masson tumor can be challenging due to its close clinical, radiological and even histopathological resemblance to angiosarcoma. We present seven cases of Masson tumor of the hand; wanting to reveal its nature using new vascular markers and discuss the treatment options and expected outcomes, present clinical and radiological features that may aid diagnosis and also offer treatment plans. A multicenter retrospective study was performed between January 2014 and November 2019. Immunohistochemical stains of Glut1, WT1, ERG, CD31 and alpha smooth muscle actin (ASMA) were performed on each cases. We found seven cases during the examined period. 4 out of 7 cases were women. All lesions occurred in the hands. 3 out of 7 cases appeared in a previously present vascular malformation. All cases were treated with surgical excision and the diagnosis of papillary endothelial hyperplasia was made by histology. Pre-operative testing (radiograph/MRI/US/fine needle aspiration biopsy) did not suggest the diagnosis of Masson tumor; however, aspiration cytology could rule out malignancy. The proliferative endothelial cells proved to be Glut1 negative and WT1 positive and the accompanying pericytic cells were ASMA positive in all cases. Though Masson tumor is a rare vascular lesion in the hand among other vascular tumors, it should be considered in the differential diagnostics even in the case of previously existing vascular malformation. WT1 positivity of the endothelial cells and the accompanying pericytic cells raises the question whether the initially reactive endothelial proliferation may transform into a true benign vascular tumor.

Endothelin-1, endothelin receptor antagonists, and vein graft occlusion in coronary artery bypass surgery: 20 years on and still no journey from bench to bedside.

The saphenous vein is the most commonly used bypass graft in patients with coronary artery disease. During routine coronary artery bypass, grafting the vascular damage inflicted on the vein is likely to stimulate the release of endothelin-1, a potent endothelium-derived vasoconstrictor that also possesses cell proliferation and inflammatory properties, conditions associated with vein graft failure. In both in vitro and in vivo studies, endothelin receptor antagonists reduce neointimal thickening. The mechanisms underlying these observations are multifactorial and include an effect on cell proliferation and cell/tissue damage. Much of the data supporting the beneficial action of endothelin-1 receptor antagonism at reducing intimal thickening and occlusion in experimental vein grafts were published over 20 years ago. The theme of the recent ET-16 conference in Kobe was "Visiting Old and Learning New". This short review article provides an overview of studies showing the potential of endothelin receptor antagonists to offer an adjuvant therapeutic approach for reducing saphenous vein graft failure and poses the question why this important area of research has not been translated from bench to bedside given the potential benefit for coronary artery bypass patients.

Endothelial loss during the surgical procedure in saphenous veins harvested by open and endoscopic techniques in coronary artery bypass surgery.

The patency of the vein graft in coronary artery bypass grafting could be dependent on the conventional open (vsO) or endoscopic (vsE) harvesting and on the hypoxic damage of endothelial cells. We aimed to evaluate both surgical techniques according to endothelial loss that occurs in the time between harvesting and implantation. Twenty-six saphenous veins were divided into vsO (n = 16) and vsE (n = 10) group. Three samples were taken from each vein. The first sample was taken after removal, the second before implantation of the distal part, and the third before the implantation of the proximal part, and they were stained with HE, Movat, and immunohistochemically with CD31. A significant loss of endothelial cells within both groups was found at the time of implantation of the distal and the proximal part of the vein graft compared to the endothelial cells at the time of harvesting. There were no significant differences in the endothelial loss between vsE and vsO groups at the time of harvesting and at the time before the implantation of the distal part. A higher number of endothelial cells was found in vsE group compared to vsO group at the time just before the implantation of the proximal part. The comparison of the implanted portions of vsE and vsO grafts to mammary arteries revealed a significant loss of endothelial cells only in vsO graft. We conclude that, at the time of implantation, the endothelial layer of the vein graft harvested endoscopically is more preserved than of the vein graft harvested openly.

Intravascular Papillary Endothelial Hyperplasia of the Maxillary Sinus in Patient with Tricuspid Atresia.

Intravascular papillary endothelial hyperplasia (IPEH) is a benign, highly vascularized, endothelial growth that can be mischaracterized as a malignancy. While hundreds of IPEH cases are reported, only four occurred in the maxillary sinus. We present the case of a 28-year-old male who underwent surgical resection of IPEH of the right maxillary sinus. An additional consideration was the patient's condition of univentricular tricuspid atresia which contributed to chronic hypoxemia and polycythemia. After complete resection from the maxillary sinus, post-operational workup determined the lesion to be IPEH. Given the potential for misdiagnosis of IPEH, careful histopathologic evaluation is required in order to avoid improper treatment.

Sex differences in vascular reactivity of coronary artery bypass graft conduits.

Females have increase in-hospital mortality and poorer outcomes following coronary artery bypass grafting (CABG). Biological differences in the reactivity of the graft conduits to circulating catecholamine may contribute to this sex difference. This study examined sex differences in the vasoconstrictor responses of internal mammary artery (IMA) and saphenous vein (SV) conduits to phenylephrine (PE) and endothelin-1 (ET-1). Functional IMA and SV were obtained from 78 male and 50 female patients undergoing CABG (67.7 ± 11 and 69 ± 10 years, respectively) and subjected to the following experimental conditions. (1) Concentration response curves for PE and ET-1 were generated in an intact IMA and SV and endothelium denuded IMA segments, (2) in the presence of the nitric oxide synthase inhibitor (L-NAME) or the cyclooxygenase inhibitor (indomethacin) in an endothelium-intact IMA and (3) the activity state (abundance and phosphorylation) of the α1-adrenergic receptor was investigated using Phos-tag™ western blot analysis. (1) Compared to male, female IMA and SV were hypersensitive to PE but not ET-1 (p < 0.05). The female IMA hypersensitivity response to PE was abolished following endothelial denudation, (2) persisted in the presence of L-NAME but was abolished in the presence of indomethacin and (3) there was no sex differences in the abundance and phosphorylation of the α1-adrenergic receptor in IMA. Female IMA and SV graft conduits are hypersensitive to α1-adrenergic stimuli. This endothelial cyclooxygenase pathway-mediated hypersensitivity may produce excessive IMA and SV graft constriction in females administered catecholamines and could contribute to their poorer CABG outcomes.

Vessel Wall Imaging After Subarachnoid Hemorrhage in Patients with Multiple Intracranial Aneurysms: A Cautionary Case.

BACKGROUND: Almost 30% of patients with subarachnoid hemorrhage (SAH) are found to have multiple aneurysms. This can potentially present a serious management dilemma when planning treatment. Magnetic resonance imaging vessel wall imaging (VWI) has been proposed as a reliable technique in differentiating between ruptured and unruptured aneurysms in patients with multiple intracranial aneurysms who present with SAH. Expert consensus now supports this as a possible use for the technique. CASE DESCRIPTION: Here we present a patient presenting a particular clinical dilemma with SAH and a left third nerve palsy and transient speech disturbance who had circumferential enhancement in the left larger 3.5-mm irregular middle cerebral artery aneurysm and no detectable enhancement in what was angiographically either a 1.5-mm smooth noncompressive left posterior communicating artery aneurysm or infundibulum, but was proved at surgery to be the culprit aneurysm. CONCLUSION: Although a case of concurrent false positive and false negative in the same patient has not previously been reported, the positive predictive value of VWI for rupture status is known to be much lower than its negative predictive value, and a case like this might be expected to occur in 0.6% of patients. Therefore, whereas VWI is a valuable tool, it should be used in conjunction with, and not in lieu of, traditional indicators of aneurysm rupture.

Arteriovenous fistula and pre-surgery mapping: Potential role of physical exercise on endothelial function.

BACKGROUND: The success of the construction of an arteriovenous fistula for haemodialysis is related to the vascular function of the vessels involved in the anastomosis, with particular reference to radial artery distensibility after reactive hyperaemia test and to the fall of resistance index. Only few studies have evaluated the impact of exercise protocols on the endothelial and morphological characteristics of the vessels of the upper limb with inconclusive results. In this pilot longitudinal study, we aimed to evaluate the impact of a standardized exercise protocol on the haemodynamic and resistive index of the arteries of the upper limb of uraemic patients. METHODS: A total of 17 uraemic patients planned to construct arteriovenous fistula at the distal third of the forearm were enrolled and followed up for 30 days. All patients performed repeated handgrips for 30 min/day. The arterial parameters were detected before and after an ischaemic stress of 5 min and radial and brachial artery flow-mediated dilation was evaluated as well as radial artery resistance index. RESULTS: Pre-exercise measurements of radial artery diameter and resistance index and brachial artery diameter were not modified by 30 days hand physical exercise, whereas the post-exercise haemodynamic were improved. Consequently, flow-mediated dilation of the radial artery was improved (21% ± 14% vs 30% ± 19%; p = 0.03) and resistance index of the radial artery was reduced (p = 0.02). CONCLUSION: Exercise has beneficial effects on endothelial function of the radial artery by resistive index and, potentially, on the outcome of the arteriovenous fistula. Further studies with larger sample size are needed to confirm our preliminary data.

A novel histologic grading system based on lymphovascular invasion, perineural invasion, and tumor budding in colorectal cancer.

PURPOSE: This study aimed to evaluate the prognostic significance of lymphovascular (LVI), perineural invasion (PNI), and tumor budding positivity in patients with colorectal cancer. METHODS: From January 2008 to December 2011, 3707 consecutive patients who underwent curative surgery for stage I-III colorectal cancer were assessed. These patients were then categorized into four groups based on LVI, PNI, and tumor budding (risk grouping): all negative (n = 1495), 1 + only (n = 1063), 2 + only (n = 861), and all positive (n = 288). RESULTS: With a median follow-up period of 52 months, the 5-year disease-free survival rates of the risk groups were significantly different in terms of cancer staging (stage I, Stage II, and Stage III: P = 0.006, P < 0.001, and P < 0.001, respectively). In the multivariate analysis, risk grouping was an independent prognostic factor of disease-free survival. Preoperative carcinoembryonic antigen level, tumor size, T category, and N category were independent predictors of LVI, PNI, and tumor budding positivity. CONCLUSION: Risk grouping based on LVI, PNI, and tumor budding positivity is a strong predictor of disease-free survival in patients with colorectal cancer.

Intravascular papillary endothelial hyperplasia along the intrinsic muscle after hand contusion injury: Report of two cases.

Intravascular papillary endothelial hyperplasia (IPEH), also known as Masson's tumor or vegetant intravascular hemangioendothelioma, is a reactive condition representing an exuberant organization and recanalization of a thrombus. It can occur in normal blood vessels or in vascular malformations, perhaps in response to blood vessel injury or thrombosis. In this report, we present the diagnostic and therapeutic courses of a 55 year-old woman and an 18 year-old man, who had a progressive protruding hand mass following a hand contusion. The pathological examination confirmed the diagnosis of IPEH in both patients.

Down-regulation of vascular GLP-1 receptor expression in human subjects with obesity.

It has been thought that incretin signaling prevents arteriosclerosis, and very recently anti-arteriosclerotic effects through GLP-1 receptor were finally demonstrated in clinical human study. The purpose of this study was to investigate how vascular GLP-1 receptor expression is influenced in human subjects. First, we evaluated GLP-1 receptor expression in human arteries in immunostaining. Next, we separated the artery into the intima and media, and evaluated gene expression levels of various factors. We divided the subjects into obesity and non-obesity group and compared their expression levels between them. Finally, we evaluated which factors determine vascular GLP-1 receptor expression. GLP-1 receptor expression in intima and media was lower in obesity group compared to non-obesity group which was correlated with the alteration of TCF7L2 expression. Multiple regression analyses showed that BMI was an independent determining factor for GLP-1 receptor expression in the intima and media. Furthermore, using small interfering RNA method and TCF7L2-EGFP adenovirus, we showed that TCF7L2 was involved in GLP-1 receptor expression in human vascular cells. Taken together, vascular GLP-1 receptor and TCF7L2 expression was significantly down-regulated in human subjects with obesity. In addition, it is likely that TCF7L2 functions as a modulator of vascular GLP-1 receptor expression.

Rol del receptor de adenosina A2A, óxido nítrico y factor de crecimiento de endotelio vascular en la sepsis: una revisión no sistemática / Role of adenosine A2A receptor, nitric oxide, and vascular endothelial growth factor in sepsis. A non-systematic review

La sepsis es una enfermedad de origen infeccioso con una prevalencia de 2.911 por 100.000 pacientes en Estados Unidos, y se caracteriza por el desbalance de la respuesta pro y antiinflamatoria por parte del sistema inmune. Sin embargo, la falta de comprensión de la respuesta del huésped frente a la infección justifica la importancia de su debate. En esta revisión no sistemática se plantea la relación funcional que existiría entre el receptor de adenosina A2A (A2A), óxido nítrico (NO) y factor de crecimiento vascular (VEGF), los cuales regulan la vasodilatación y la permeabilidad microvascular, y que en la sepsis se encuentran alterados. La evidencia revisada muestra que en el medio extracelular expuesto a infección se genera un estado de hipoxia celular, la que aumenta la producción de adenosina, nucleósido derivado del metabolismo del ATP. Esta molécula, al activar el receptor A2A presente en células del sistema inmune y endoteliales es capaz de reducir la respuesta inmunológica y aumentar la permeabilidad vascular, lo que a su vez ha sido asociado con una mayor progresión bacteriana y fallo multisistémico. Molecularmente, A2A activa la síntesis y producción de NO y VEGF. Por su parte, VEGF, al activar su receptor tipo 2 aumenta también la producción de NO, generando un circulo potenciador del efecto inmunológico y vascular. Pese a estas evidencias no hemos encontrado estudios que relacionen directamente estos 3 actores, A2A-NO y VEGF en la sepsis. Por ello, a la luz de la evidencia revisada, proponemos que la vía A2A-NO-VEGF sería un blanco de estudio en la fisiopatología y tratamiento de la sepsis (AU)

Sepsis is an infectious disease with a prevalence of 2.9 per 100 individuals in the United States. It is characterised by an unbalanced pro- and anti-inflammatory response driven by the immune system. However, further discussion is needed due to the lack of understanding on the details of the host response to the infection. This non-systemic review addresses the functional relationship between the Adenosine 2A receptor (A2A), Nitric Oxide (NO), and Vascular Epithelial Growth Factor (VEGF), which regulate vasodilation and micro-vascular permeability, which in turn are affected in sepsis. The evidence reviewed shows that an state of cellular hypoxia is generated due to infection, which increases the production of adenosine (ADO), a nucleoside derived from the metabolism of ATP. This molecule, by activating A2A receptor present in cells of the immune and endothelial systems reduces the immune response and increasing vascular permeability, which in turn has been associated with greater bacterial progression and multisystem failure. Molecularly, A2A activates the synthesis and production of NO and VEGF. In this regard, VEGF, by activating its type 2 receptor (VEGFR2) also increases NO production. This generates a cycle that enhances the immunological and vascular effect. Despite this, no studies were found that directly links these three actors, A2A-NO and VEGF, in sepsis. Therefore, taking into account the reviewed evidence, it is proposed that the A2A-NO-VEGF pathway could be a target of study in the pathophysiology and treatment of sepsis (AU)

Resveratrol combined with total flavones of hawthorn alleviate the endothelial cells injury after coronary bypass graft surgery.

OBJECTIVE: To explore the preventive and therapeutic effects of Resveratrol combined with total flavones of hawthorn, compatibility of traditional Chinese medicines, on the endothelial cells injury after artery bypass graft surgery. METHODS: The animal model of coronary artery bypass grafting (CABG) was prepared by transplanting a segment of autologous jugular vein onto the transected common carotid artery in rabbits. After CABG surgery, the rabbits were administrated with saline (model group), aspirin (Aspirin group), resveratrol (Res group), total flavones of hawthorn (Haw group) and resveratrol combined with total flavones of hawthorn (Res+Haw group) once a day for eight weeks, respectively. Eight weeks later, the grafting arteries from all group were obtained for the pathomorphism observation, peripheral blood was collected to detect circulating endothelial cells (CECs) by flow cytometry. And the concentration of albumen and mRNA of ICAM-1 in the serum were measured by western blot and quantitative real-time polymerase chain reaction, respectively. RESULTS: Compared with the model group, the level of CECs density and the expressions of albumen and mRNA of ICAM-1 were significantly decreased in the aspirin,resveratrol,total flavones of hawthorn and resveratrol combined with total flavones of hawthorn groups (P < .05). Of note, above all parameters were lower in Res group than aspirin group. CONCLUSION: The Resveratrol combined with total flavones of hawthorn could protect the endothelial cells after coronary artery bypass graft.

Staged Management of Intracranial Masson Tumor: An Unexpected Gauntlet: Case Report and Review of the Literature.

BACKGROUND: Intravascular papillary endothelial hyperplasia (IPEH), also known as Masson tumor, is a benign lesion consisting of a reactive proliferation of endothelial cells with papillary formations related to thrombi. It has been reported in many different anatomic areas. Gross total resection is the elected treatment. Intracranial IPEH is rare, and only a few cases have been reported. This article reports a complicated case of cavernous sinus Masson tumor. CASE DESCRIPTION: A 51-year-old woman presented because of hemicraneal headache, left facial paresthesia, and diplopia (due to a slight left ocular external rectum muscle paresis) that she had experienced the previous 60 days. She had previously received a diagnosis of neurofibromatosis type I. Contrast-enhanced magnetic resonance imaging showed a 3.5-cm contrast-enhanced tumor adjacent to the left cavernous sinus involving the Meckel cave that extended around the distal petrous portion of the left internal carotid artery. Two possibilities as a differential diagnosis were suggested: meningioma or neurogenic tumor. After a staged surgical procedure, the histopathologic findings were unexpected and showed IPEH (Masson tumor) as the cause of the mass. Despite having benign features, the IPEH showed recurrences over time, so adjuvant 3-dimensional conformal radiation therapy was initiated. CONCLUSIONS: IPEH is prone to recurrences after subtotal resection. In the present case, successful surgical treatment and adjuvant radiotherapy showed an excellent outcome. To date, no adjuvant therapy has been established as a go-to option.

Endothelial shear stress 5 years after implantation of a coronary bioresorbable scaffold.

Aims: As a sine qua non for arterial wall physiology, local hemodynamic forces such as endothelial shear stress (ESS) may influence long-term vessel changes as bioabsorbable scaffolds dissolve. The aim of this study was to perform serial computational fluid dynamic (CFD) simulations to examine immediate and long-term haemodynamic and vascular changes following bioresorbable scaffold placement. Methods and results: Coronary arterial models with long-term serial assessment (baseline and 5 years) were reconstructed through fusion of intravascular optical coherence tomography and angiography. Pulsatile non-Newtonian CFD simulations were performed to calculate the ESS and relative blood viscosity. Time-averaged, systolic, and diastolic results were compared between follow-ups. Seven patients (seven lesions) were included in this analysis. A marked heterogeneity in ESS and localised regions of high blood viscosity were observed post-implantation. Percent vessel area exposed to low averaged ESS (<1 Pa) significantly decreased over 5 years (15.92% vs. 4.99%, P < 0.0001) whereas moderate (1-7 Pa) and high ESS (>7 Pa) did not significantly change (moderate ESS: 76.93% vs. 80.7%, P = 0.546; high ESS: 7.15% vs. 14.31%, P = 0.281), leading to higher ESS at follow-up. A positive correlation was observed between baseline ESS and change in lumen area at 5 years (P < 0.0001). Maximum blood viscosity significantly decreased over 5 years (4.30 ± 1.54 vs. 3.21± 0.57, P = 0.028). Conclusion: Immediately after scaffold implantation, coronary arteries demonstrate an alternans of extremely low and high ESS values and localized areas of high blood viscosity. These initial local haemodynamic disturbances may trigger fibrin deposition and thrombosis. Also, low ESS can promote neointimal hyperplasia, but may also contribute to appropriate scaffold healing with normalisation of ESS and reduction in peak blood viscosity by 5 years.

The effect of bioresorbable vascular scaffold implantation on distal coronary endothelial function in dyslipidemic swine with and without diabetes.

BACKGROUND: We studied the effect of bioresorbable vascular scaffold (BVS) implantation on distal coronary endothelial function, in swine on a high fat diet without (HFD) or with diabetes (DM+HFD). METHODS: Five DM+HFD and five HFD swine underwent BVS implantation on top of coronary plaques, and were studied six months later. Conduit artery segments >5mm proximal and distal to the scaffold and corresponding segments of non-scaffolded coronary arteries, and segments of small arteries within the flow-territory of scaffolded and non-scaffolded arteries were harvested for in vitro vasoreactivity studies. RESULTS: Conduit segments proximal and distal of the BVS edges showed reduced endothelium-dependent vasodilation as compared to control vessels (p≤0.01), with distal segments being most prominently affected(p≤0.01). Endothelial dysfunction was only observed in DM±HFD swine and was principally due to a loss of NO. Endothelium-independent vasodilation and vasoconstriction were unaffected. Surprisingly, segments from the microcirculation distal to the BVS showed enhanced endothelium-dependent vasodilation (p<0.01), whereas endothelium-independent vasodilation and vasoconstriction were unaltered. This enhanced vasorelaxation was only observed in DM+HFD swine, and did not appear to be either NO- or EDHF-mediated. CONCLUSIONS: Six months of BVS implantation in DM+HFD swine causes NO-mediated endothelial dysfunction in nearby coronary segments, which is accompanied by a, possibly compensatory, increase in endothelial function of the distal microcirculation. Endothelial dysfunction extending into coronary conduit segments beyond the implantation-site, is in agreement with recent reports expressing concern for late scaffold thrombosis and of early BVS failure in diabetic patients.

Comparison of the endothelial coverage in everolimus and zotarolimus-eluting stents in normal, atherosclerotic, and bifurcation rabbit iliac arteries.

The aim of this study is to evaluate differences in stent endothelial coverage among the second generation of drug-eluting stents. Incomplete stent coverage is one of the major causes of late stent thrombosis. Rabbits fed a normal diet received an everolimus (Xience Prime; EES) and a zotarolimus-eluting stent (Resolute Integrity; R-ZES) in each iliac artery, followed by sacrifice at 14 and 28 days after stent implantation. In addition, a group of atherosclerotic rabbits similarly received EES and R-ZES, and were sacrificed at 28 days. The extent of stent endothelial coverage was assessed by scanning electron microscopy. To evaluate endothelial coverage after bifurcation stenting, rabbits received EES and R-ZES placed with culotte stenting at the iliac bifurcation, followed by sacrifice at 14 and 28 days. In rabbits fed a normal diet, the percent uncovered strut area 14 days after stent implantation was significantly higher in R-ZES than in EES (10.1% (IQR 9.8-15.5) vs. 3.0% (IQR 1.5-9.7), p = 0.03), whereas it was not significantly different at 28-days (3.9% (IQR 0.8-10.3) vs. 1.0% (IQR 0.0-2.8), p = 0.2). In rabbits with induced atheroma, R-ZES also showed less endothelial coverage 28 days after stent implantation (5.3% (IQR 2.2-9.9) vs. 1.1% (IQR 0-6.2), p = 0.03). In the culotte stenting model, the percent uncovered strut area of the proximal overlapped segment was significantly higher in R-ZES at 14 days (15.8% (IQR 14.3-17.7) vs. 8.8% (IQR 8.3-9.8), p = 0.03) and 28 days (9.9% (IQR 4.1-13.9) vs. 2.5% (IQR 1.6-6.7), p = 0.04) after stent implantation. The carina area also showed a better coverage in EES compared with R-ZES. EES showed a better stent endothelial coverage compared with R-ZES after stent implantation in the early phase in normals, in arteries with lipid rich plaque, and in bifurcation stented sites.

New Regenerative Vascular Grafts for Hemodialysis Access: Evaluation of a Preclinical Animal Model.

The purpose of this study was to evaluate a suitable animal model for the in vivo evaluation of patency and vascular tissue regeneration in small intestinal submucosa (SIS) vascular grafts for hemodialysis access. First, a 4-mm U-shaped SIS vascular graft was implanted between the internal carotid artery (CA) and the external jugular vein (JV) in five sheep and six swine. The U-shape grafts remained functional for 53 ± 4 days in sheep and 32 ± 2 days in swine. The sheep model presented exaggerated inflammation, so the swine model was selected for the in vivo study. Based on these initial results, a 4-mm C-shape SIS vascular graft with SIS circumferential reinforcement was developed to mechanically improve the vascular graft and manage complications identified during surgery in both sheep and swine. The C-shape vascular graft was implanted in a swine model (n = 3) between the CA and JV. GORE-TEX® vascular grafts were used as controls in the contralateral side of the neck. C-shape grafts remained patent for 47 ± 4 days, whereas the GORE-TEX® grafts were patent for 30 ± 15 days. The C-shape vascular graft was easier to handle during surgery, and its circumferential reinforcement improved in vivo patency, avoiding kinks in the graft after implantation. Histological results showed neovascularization and some regeneration with the alignment of endothelial cells in the vascular wall of the grafts. The model developed may be helpful in other research involving in vivo studies of vascular grafts for hemodialysis access.