Oral Resolvin D1 attenuates early inflammation but not intimal hyperplasia in a rat carotid angioplasty model.

Inflammation ensuing from vascular injury promotes intimal hyperplasia (IH) and restenosis. Resolvin D1 (RvD1) is a lipid mediator that attenuates IH in vivo when delivered locally to the vessel wall in animal models. We tested the hypothesis that peri-procedural oral administration of RvD1 could blunt the local inflammatory response to angioplasty, and attenuate downstream IH. Carotid angioplasty was performed on rats fed with either RvD1 or vehicle through oral gavage, starting one day prior to injury until post-operative day (POD) 3 or 14 when arteries were harvested. To study pharmacokinetics and bioactivity of oral RvD1, we measured plasma RvD1 by ELISA, whole blood phagocytosis activity using flow cytometry, and cAMP levels in the thoracic aorta by ELISA. Carotid arteries were harvested on POD3 for staining (anti-CD45, anti-Myeloperoxidase (MPO), anti-Ki67 or dihydroethidium (DHE) for reactive oxygen species), mRNA expression of target genes (quantitative RT-PCR), or on POD14 for morphometry (elastin stain). RvD1 plasma concentration peaked 3 h after gavage in rats, at which point we concurrently observed an increase in circulating monocyte phagocytosis activity and aortic cAMP levels in RvD1-treated rats vs. vehicle. Oral RvD1 attenuated local arterial inflammation after angioplasty by reducing CD45+, MPO+, Ki67+ cells, and DHE staining intensity. Oral RvD1 also reduced the expression of several pro-inflammatory genes within the injured vessels. However, oral RvD1 did not significantly reduce IH. Oral RvD1 attenuated acute inflammation within the arterial wall after angioplasty in rats, but did not significantly affect IH.

External Stents for Vein Grafts in Coronary Artery Bypass Grafting: Targeting Intimal Hyperplasia.

INTRODUCTION: Progressive saphenous vein graft (SVG) failure remains a key limitation to the long-term success of coronary artery bypass grafting (CABG). SVG disease after the first year is dominated by intimal hyperplasia, which predisposes the SVG to thrombosis and accelerated atherosclerosis. The objective of this study was to review and summarize the latest experimental and clinical data on the use of mechanical external stents for vein grafts. METHODS: In January 2020, the PubMed database was searched using the terms "external stent", "CABG", "saphenous vein graft" and "intimal hyperplasia". The results were reviewed and only randomized experimental and clinical studies that analyzed the effect of external stenting on venous intimal hyperplasia were included in the analysis, together with studies that investigated the clinical benefit of external stenting. RESULTS: Eight experimental and four clinical trials met the search criteria. Controlled trials in different large animal models concluded that external stenting significantly reduced intimal hyperplasia 3-6 months post implantation, and reduced both thrombosis rates and the development of lumen irregularities. Data from randomized controlled trials with a follow-up period of 1-4.5 years supported the pre-clinical findings and demonstrated that external stents significantly reduced vein graft disease. CONCLUSION: Strong evidence indicates that supporting the vein with external stents is safe and leads to clear advantages at both the anatomical and cellular levels. With the further accumulation of consistent positive results, external stenting of SVG may become the standard of care in future CABG.

Alterations in Surgically Created Intimal Lesions: An Observation Study in the Aortic Rat Model.

BACKGROUND: Intimal injury in microvessels due to common risk factors such as atherosclerosis or inadequate manipulation are known to have a major impact on developing thrombosis and eventually vascular obstruction. Understanding of these injuries is therefore of great significance to prevent far-reaching consequences such as flap loss in free tissue transfer. It was the aim of this study to evaluate artificially induced intimal lesions with focus on alteration in size and configuration. METHODS: Intimal defects were created surgically in the abdominal aorta of 30 male Wistar rats. After planimetric measurement of the defect sizes, configuration of defects were classified as round, horizontal, or vertical. Seven days postoperatively, the rats underwent a second-look surgery. Finally, the abdominal aorta was harvested, and the endothelial defects were reevaluated concerning size and configuration using a defined pattern. RESULTS: The mean defect size created intraoperatively was 1.68 ± 0.6 mm2. The classification of the defects configurations resulted in 43.3% round, 20% horizontal, and 36.7% vertical defects. Reevaluation at 7 days after surgery showed defect shrinkage in 96.7% in total and 42.8% averaging due to reendothelialization. A shift in defect configuration was detected in 56.7%, the strongest being in vertical defect configurations (100%). Vascular occlusion did not occur in any of the specimen. CONCLUSION: Intimal injuries undergo a fast repair process in terms of size reduction and configuration modification due to reendothelialization. Especially vertical defects, representing a great risk for thrombus formation, convert into lower risk horizontal defect configurations. In high-flow vessels such as the rat aortas, small endothelial damage seems to have no significant impact to produce complete vascular occlusion. Still, all efforts should be made to avoid any kind of intimal injury.

Idiopathic myointimal hyperplasia is a distinct cause of chronic colon ischaemia.

AIM: Colon ischaemia (CI) is most commonly an acute and reversible manifestation of a transient, non-occlusive decrease of blood flow in the colonic microvasculature. Irreversible complications are uncommon and the progression to chronic CI remains controversial. Our objective was to identify cases of chronic CI and assess for distinct clinicopathological features. METHOD: A retrospective review was performed of CI patients having symptom chronicity of ≥ 1 month and ischaemic histology at our institution from 1994 to 2015. Demographic, clinical, endoscopic, radiological, pathological and outcome variables were abstracted. Histological evaluation was performed by two gastrointestinal pathologists. RESULTS: Fifteen patients (n = 9; 67% men) with a median age of 65 years (range 22-88) were identified. The most common presenting symptoms were diarrhoea and abdominal pain (n = 6, 86%; n = 5, 71%, respectively). The typical endoscopic appearance was segmental ulceration of the sigmoid colon (n = 6, 75%). Vascular imaging showed patent mesenteric vessels in all patients. Histopathological evaluation revealed venous intimal hyperplasia consistent with idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) in eight patients; the remainder showed non-specific ulceration and fibrosis. Surgical resection was performed in seven IMHMV patients, resulting in symptom resolution. On re-review of pre-resection biopsies, all IMHMV patients had characteristic changes of hyperplastic, thick-walled, hyalinized vessels in the lamina propria. CONCLUSIONS: IMHMV is a unique histopathological entity causing chronic CI. The small vessel histological changes in IMHMV are distinctive in colonic resections and undetectable by routine vascular imaging. Preoperative diagnosis of IMHMV is possible with endoscopic biopsy and segmental colon resection is curative.

A New Technique to Induce Experimental Myointimal Hyperplasia.

BACKGROUND: Arterial myointimal hyperplasia (MIH) has a significant impact on the long-term outcomes of vascular procedures such as bypass surgery and angioplasty. In this study, we describe a new and innovative technique to induce MIH using a dental flossing cachet in Wistar rats. METHODS: The intimal damage in the common carotid artery was induced by inserting the tip of the dental flossing cachet through the external carotid artery into the common carotid artery and turning it on for 3 rounds of 20 s each (n = 10). After 2 weeks, the rats were anesthetized and the common carotid arteries of the experimental side and the contralateral side (control) were harvested and preserved for histopathological studies. RESULTS: The experimental carotid arteries showed significant intimal proliferation and thickening compared to the controls. The intima/media ratio of the experimental and normal (control) common carotid arteries were 1.274 ± 0.162 and 0.089 ± 0.023 (mean ± SEM), respectively (p < 0.001). CONCLUSION: This technique is simple, inexpensive, and highly reproducible and it induces sufficient MIH to study this phenomenon in animal models.

Resident Arterial Cells and Circulating Bone Marrow-Derived Cells both Contribute to Intimal Hyperplasia in a Rat Allograft Carotid Transplantation Model.

BACKGROUND/AIMS: Neointimal formation following vascular injury remains a major mechanism of restenosis, whereas the precise sources of neointimal cells are still uncertain. We tested the hypothesis that both injured arterial cells and non-arterial cells contribute to intimal hyperplasia. METHODS: Following allograft transplantation of the balloon-injured carotid common artery (n = 3-6), the cellular composition of the transplant grafts and the origins of neointimal cells were measured by immunohistochemistry and immunofluorescence staining. RESULTS: Smooth muscle actin (SMA)-positive and CD68-positive cells were clearly observed 14 days later in the neointima after allograft transplantation of the balloon-injured carotid common artery, where re-endothelialization was not yet complete. Green fluorescent protein (GFP) and wild-type (WT) allograft transplantation revealed that the majority of the neointima cells were apparently from the recipient (≈85%) versus the donor (≈15%). Both monocyte chemotactic protein-1 (MCP-1)/CCR2 and stromal cell-derived factor-1 (SDF-1)/CXCR4 signaling were involved in intimal hyperplasia, with bone marrow-derived cells also playing a role. CONCLUSION: These data support the hypothesis that intimal hyperplasia could develop in our novel rat allograft transplantation model of arterial injury, where neointima is attributable not only to local arterial cells but also non-arterial cells including the bone marrow.

Dialysis Arteriovenous Fistula Failure and Angioplasty: Intimal Hyperplasia and Other Causes of Access Failure.

The arteriovenous fistula (AVF) is the preferred hemodialysis access type because it has better patency rates and fewer complications than other access types. However, primary failure remains a common problem impeding AVF maturation and adding to patients' morbidity and mortality. Juxta-anastomotic (or inflow) stenosis is the most common reason leading to primary failure, and percutaneous transluminal angioplasty continues to be the gold-standard treatment with excellent success rates. Intimal hyperplasia (IH) has been traditionally blamed as the main pathophysiologic culprit, but new evidence raises doubts regarding the contribution of IH alone to primary failure. We report a 64-year-old man with a 2-stage brachiobasilic AVF that was complicated by failure 4 months after creation. An angiogram showed multiple juxta-anastomotic and midfistula stenotic lesions. Percutaneous transluminal angioplasty was successful in assisting maturation and subsequently cannulating the AVF for hemodialysis treatment. We failed to identify the underlying cause of stenosis because biopsy specimens from fistula tissue obtained at the time of transposition revealed no occlusive IH. This case emphasizes the need for additional research on factors contributing to AVF failure besides IH and highlights the need for more therapeutic options to reduce AVF failure rate.

Associations of Osteocalcin, Osteoprotegerin, and Calcitonin with Inflammation Biomarkers in Atherosclerotic Plaques of Coronary Arteries.

We studied associations of osteocalcin, osteoprotegerin, and calcitonin with markers of inflammation in atherosclerotic plaques in coronary arteries and assessed the influence of these biomolecules on calcification of atherosclerotic plaques. The initial stage of calcification of atherosclerotic plaques is characterized by activation of inflammatory processes, which is seen from increased levels of proinflammatory biomarkers (IL-6, IL 8, TNF-α, and IL-1ß). Progressive calcification of atherosclerotic plaques is accompanied by insignificant accumulation of calcitonin and osteoprotegerin. The exception is osteocalcin, its concentration significantly increased during calcification. The results suggest that severe vascular calcification can be regarded as non-specific marker of atherosclerosis. Instability of atherosclerotic plaques is associated with higher level of calcification.

Subintimal angioplasty for lower limb arterial chronic total occlusions.

BACKGROUND: In recent years subintimal angioplasty (SIA) has become an established percutaneous procedure for the treatment of symptomatic lower limb arterial chronic total occlusions. However, the clinical benefits of this practice remain unclear. The aim of the review was to determine the effectiveness of SIA on clinical outcomes. This is an update of a review first published in 2013. OBJECTIVES: To assess the effectiveness of SIA versus other treatment for people with lower limb arterial chronic total occlusions, determined by the effects on clinical improvement, technical success rate, patency rate, limb salvage rate, and morbidity rates. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register (last searched January 2016) and Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 12). We also searched clinical trials registries. SELECTION CRITERIA: We included data from randomized controlled trials comparing the effectiveness of SIA and any other management method in the treatment of lower limb arterial chronic total occlusions. The primary intervention of interest was SIA, with or without a stent, for the restoration of vessel patency in people with occlusions of a lower limb artery. We compared SIA against alternative modalities used to restore vessel patency, including conventional percutaneous transluminal angioplasty, surgical bypass, or any other treatments. We compared different SIA devices and techniques against each other. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. The third review author resolved disagreements. MAIN RESULTS: Two studies, involving a total of 147 participants with TransAtlantic Inter-Society Consensus (TASC)-II D femoropopliteal lesions, met our inclusion criteria and were included in the review. Both studies were small but otherwise of high methodological quality. However, the treatment techniques and control groups of the two studies differed, precluding the combining of study results and resulting in the evidence being less applicable. We therefore considered the quality of the evidence to be low.In one study, participants with TASC-II D lesions were randomized to receive either SIA with stenting of the superficial femoral artery or remote endarterectomy (RE) with stenting of the superficial femoral artery. Three-year follow-up results showed a Rutherford classification improvement of 64% in the SIA group compared to 80% in the RE group (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.61 to 1.03; 95 participants; P = 0.079). Postexercise ankle brachial index improvements (defined as an increased value of 0.2) were reported in 70% of participants in the SIA group compared to 82% in the RE group (RR 0.86, 95% CI 0.68 to 1.08; 95 participants; P = 0.18). The study reported the technical success rate was 93% for the SIA group and 96% for the RE group (RR 0.97, 95% CI 0.88 to 1.07; 95 participants; P = 0.91). Primary patency at 12 months was 59.1% in the SIA group compared to 78.4% in the RE group (RR 0.75, 95% CI 0.57 to 1.00; 95 participants; P = 0.05). Primary patency at 24 months was 56.8% in the SIA group compared to 76.5% in the RE group (RR 0.74, 95% CI 0.55 to 1.00; 95 participants; P = 0.05) and 47.7% in the SIA group and 62.7% in the RE group at 36 months (RR 0.76, 95% CI 0.52 to 1.11; 95 participants; P = 0.15). Assisted primary patency was 52.3% in the SIA group compared to 70.6% in the RE group (P = 0.01) at 36 months. Secondary patency was better for the RE group (P = 0.03) at 36 months. Limb salvage at three years' follow-up was 95% in the SIA group and 98% in the RE group (RR 0.97, 95% CI 0.90 to 1.05; 95 participants; P = 0.4). There were no perioperative deaths, but complications occurred in two SIA participants (femoral pseudoaneurysm and pulmonary edema) and in three RE participants (seroma, femoral pseudoaneurysm, superficial femoral artery acute occlusion).In the second study, the effects of the SIA OUTBACK re-entry catheter device in people affected by TASC-II D superficial femoral artery chronic total occlusion were compared with the SIA manual re-entry technique. This study did not report clinical improvement and limb salvage. Technical success was achieved in all cases in both the OUTBACK device and manual groups. The primary 6-month patency rate was 100% in the OUTBACK group (26 of 26 participants) compared to 96.2% in the manual group (25 of 26 participants) (RR 1.04, 95% CI 0.94 to 1.15). The primary 12-month patency rate was 92.3% in the OUTBACK group (24 of 26 participants) compared to 84.6% in the manual group (22 of 26 participants) (RR 1.09, 95% CI 0.90 to 1.33). Patency rates at 24 and 36 months were not reported. The study reported that there were no complications. AUTHORS' CONCLUSIONS: Using the GRADE approach, we classified the quality of the evidence presented by both studies in this review as low due to small study size and the small number of studies. In addition, the two included trials differed from each other in the techniques and control used, and we were therefore unable to combine the data. Consequently there is currently insufficient evidence to support SIA over other techniques. Evidence from more randomized controlled trials is needed to assess the role of SIA in people with chronic lower limb arterial total occlusions.

A Secure Technique for Microvascular Anastomosis in Arteries with Intimal Dissection: Intimal Sleeve Fold-Over Technique.

BACKGROUND: Intimal dissection can cause an irregular internal surface with intimal flaps and subendothelial collagen exposure. This has been associated with a high risk of thrombosis. Trimming the artery to a healthy level is routinely recommended to avoid intimal dissection. However, this method is limited when there is inadequate vascular length to work with. METHODS: We dealt with an artery exhibiting severe intimal dissection by using a new suture technique: the intimal sleeve fold-over technique. Severe arterial intimal dissections were observed in 9 (6.9%) of 130 arterial microvascular anastomoses in free flap reconstruction for oral cancer patients from January 2013 to December 2013. We used this technique in 6 of the 9 patients. RESULTS: All 6 patients were discharged as scheduled without perioperative problems and complications during follow-ups. The mean diameters of the recipient and pedicle arteries with intimal dissection were 2.13 and 2.20 mm. The mean time for performing sleeve fold-over procedure of on each artery was 5.1 minutes. CONCLUSIONS: A secure intima-to-intima contact can be achieved using this technique. This technique can provide an alternative method to intimal dissection when the length of the artery is limited.

[Subintimal recanalization. Indications, technique and results]. / Subintimale Rekanalisation. Indikation, Technik und Ergebnisse.

CLINICAL/METHODICAL ISSUE: This article gives an overview of the current importance of so-called subintimal recanalization in the lower extremities. STANDARD RADIOLOGICAL METHODS: The primary technical goal of endovascular interventions in the lower extremities is the endoluminal restoration of blood circulation from the iliac arteries into the feet. METHODICAL INNOVATIONS: If endoluminal recanalization of e.g. high-grade flow-relevant stenoses or chronic total occlusion (CTO) is technically not possible, subintimal recanalization is a promising option and the only remaining minimally invasive alternative. During subintimal recanalization a channel is intentionally generated in the vessel wall (dissection) in order to bypass e. g. a chronic vascular occlusion over as short a distance as possible. PERFORMANCE: The technical success rate for subintimal recanalization of CTO of the lower extremities is 65-100 %. Technical failure occurs in approximately 25 % using the catheter and wire technique and is caused in most cases by difficulties in reaching the true lumen after the subintimal passage (the so-called re-entry). ACHIEVEMENTS: Compared to conventional subintimal recanalization, in recent years so-called re-entry devices have expanded the technical possibilities and depending on the medical experience and training level of the physician, provide an improvement in the technical success rate, a lower complication rate, a reduction of fluoroscopy time and the amount of necessary contrast medium but also result in higher costs. PRACTICAL RECOMMENDATIONS: Subintimal recanalization, whether carried out conventionally with a catheter and wire or using re-entry devices, of high-grade stenoses or CTO in the lower extremities provides a high technical success rate but requires an experienced and trained physician who is capable of operating the elaborate materials and mastering any possible complications.

Ovine femoral artery bypass grafting using saphenous vein: a new model.

BACKGROUND: Saphenous vein grafts (SVGs) are frequently used for multi-vessel coronary artery bypass grafting and peripheral arterial bypasses; however, the estimated 40% failure rate within the first 5 y due to intimal hyperplasia (IH) and the subsequent failure rate of 2%-4% per year pose a significant clinical problem. Here, we report a surgical model in sheep intended to study IH development in SVGs, which can also be used for the evaluation of potential alternative treatments. MATERIALS AND METHODS: Autologous bilateral SVGs were implanted as femoral artery interposition grafts using end-to-side anastomoses in adult sheep (n = 23), which were survived for 30 (n = 6), 90 (n = 7), 180 (n = 7), or 365 (n = 3) days. Post-implant, mid-term, and pretermination angiograms were quantified, and harvested SVGs were evaluated using quantitative histomorphometry. RESULTS: We describe a peripheral arterial surgical technique that models the progression of SVG pathology. Angiographic analysis showed a progressive dilation of SVGs leading to worsening diametrical matching to the target artery and reduced blood flow; and histomorphometry data showed an increase in IH over time. Multivariable regression analysis suggested that statistically significant (P < 0.05) time-dependent relationships exist between SVG dilation and both reduction in blood flow and IH development. CONCLUSIONS: Bilateral SVGs implanted onto the femoral arteries of sheep produced, controlled and consistent angiographic and histomorphometric results for which direct correlations could be made. This preclinical investigation model can be used as a robust tool to evaluate therapies intended for cardiovascular pathologies such as occlusive IH in SVGs.

Inhibitory effect of adenosine on intimal hyperplasia and proliferation of smooth muscle cells in a carotid arterial anastomosis animal model.

PURPOSE: The effect of adenosine (9-ß-0-ribifuranosyladenine) on the endothelial cell proliferation and neointimal hyperplasia is investigated in the rabbit carotid artery anastomosis model. METHODS: Twenty-eight New Zealand white rabbits were arranged in four groups of seven animals each. The right carotid arteries of each animal were transsected and re-anastomosed. The left sides remained as control. In Group A, no medication was used. In Group B, subcutaneous Adenosine was applied for 3 days. In Group C, the same dose was applied for 7 days, and in Group D for 21 days. After 28 days, the luminal diameters, luminal areas, intima/media ratios were all measured by using histopathological evaluation. FINDINGS: The mean luminal diameters and areas of the four groups were smaller than the control ones. Massive thickening of smooth muscle cell proliferation and dense intensifying in the connecting tissues were observed most prominently in Group A, in decreasing degrees within other groups. Intima/media ratio was highest in Group A. Scoring the quantity of e-NOS positive staining also revealed a significant difference between the experimental groups and their control associates. CONCLUSION: The process of endothelial cell proliferation and neointimal hyperplasia can be significantly reduced by the use of adenosine.

Clinical results of cystic excision for popliteal artery cystic adventitial disease: long-term benefits of preserving the intact intima.

Surgical treatment for popliteal artery cystic adventitial disease (PACAD) is still controversial. PACAD often occurs in young or middle-aged adults. Therefore, the maintenance of graft patency for very long periods is a concern if a prosthesis is used. Because the intima is intact in PACAD patients with popliteal artery stenosis, a treatment that preserves the healthy intima is ideal. We describe the cases of 3 patients who underwent cystic excision for PACAD with severe stenosis. No recurrence was observed for up to 11 years, and these long-term results revealed that cystic excision could be reconsidered as one of the first-line therapeutic methods.

Empty vein ablation (EVA) technique: an in-vivo animal model to assess the effects of sclerosing agent concentration and wall contact time on intima and media tunicae structure.

BACKGROUND: Sclerotherapy is a cornerstone of the treatment of chronic venous disease, despite some technical aspects (e.g., sclerosant liquid agent concentration [SLAC] and contact time between sclerosant agent and vein wall [ctSA/VW]) to maximize outcomes remain an unsolved problem and a source of debate. An innovative three-balloon catheter has been developed to allow sclerotherapy in empty vein conditions (Empty Vein Ablation technique, EVA), revolutionizing the definition of SLAC and ctSA/VW. Aim of this experimental study is to analyze EVA effects on intima and media vessel tunicae using different SLAC and ctSA/VW in an in-vivo animal model. METHODS: Two adult sheep were treated by EVA using jugular and common iliac vein axes (eight vein segments). Different SLAC (polidocanol 0.5% or 1%) and different ctSA/VW (3 or 5 minutes) were combined for testing residual circumferential intima percentage and media thickness after EVA. RESULTS: Intact circumferential residual intima after the treatment was 21.3±4.9%, 18.2±7.4%, 15.7±2.4% and 8.9±2.0% using 0.5% (3 min), 0.5% (5 min), 1% (3 min) and 1% (5 min), respectively (R2=0.945; control sample: 97.6%). Media thickness after the treatment was 121.6±35.3 µm, 110.9±7.8 µm, 96.1±30.4 µm and 79.1±34.1 µm using 0.5% (3 min), 0.5% (5 min), 1% (3 min) and 1% (5 min), respectively (R2=0.990; control sample 125.7 µm). No significant modifications were detected analyzing the adventitia in all samples. CONCLUSIONS: EVA proved to be effective in venous wall destruction even with a very low SLAC and ctSA/VW (0.5% in 3 minutes), in quite large caliber veins. Direct comparisons with foam/liquid sclerotherapy should be done to confirm therapeutic effectiveness of these results, despite EVA has provided a maximized and controlled SA/VW contact time and ratio.

AIP1 prevents graft arteriosclerosis by inhibiting interferon-γ-dependent smooth muscle cell proliferation and intimal expansion.

RATIONALE: ASK1-interacting protein-1 (AIP1), a Ras GTPase-activating protein family member, is highly expressed in endothelial cells and vascular smooth musccells (VSMCs). The role of AIP1 in VSMCs and VSMC proliferative disease is not known. OBJECTIVE: We used mouse graft arteriosclerosis models characterized by VSMC accumulation and intimal expansion to determine the function of AIP1. METHODS AND RESULTS: In a single minor histocompatibility antigen (male to female)-dependent aorta transplantation model, AIP1 deletion in the graft augmented neointima formation, an effect reversed in AIP1/interferon-γ receptor (IFN-γR) doubly-deficient aorta donors. In a syngeneic aortic transplantation model in which wild-type or AIP1-knockout mouse aortas were transplanted into IFN-γR-deficient recipients and in which neointima formation was induced by intravenous administration of an adenovirus that encoded a mouse IFN-γ transgene, donor grafts from AIP1-knockout mice enhanced IFN-γ-induced VSMC proliferation and neointima formation. Mechanistically, knockout or knockdown of AIP1 in VSMCs significantly enhanced IFN-γ-induced JAK-STAT signaling and IFN-γ-dependent VSMC migration and proliferation, 2 critical steps in neointima formation. Furthermore, AIP1 specifically bound to JAK2 and inhibited its activity. CONCLUSIONS: AIP1 functions as a negative regulator in IFN-γ-induced intimal formation, in part by downregulating IFN-γ-JAK2-STAT1/3-dependent migratory and proliferative signaling in VSMCs.

Subintimal recanalization of peripheral chronic occlusive arterial disease with modified transseptal needle.

PURPOSE: To report an alternative technique of subintimal recanalization of chronically occluded lower-extremity arteries using a modified transseptal needle (MTSN) to reenter the true lumen. MATERIALS AND METHODS: From December 2008 to December 2010, 98 patients with chronic arterial occlusions were treated with endovascular techniques. True lumen reentry with conventional subintimal techniques failed in 23 of these patients (24%). Retrospective review of medical records and procedure data was performed, and clinical presentation, lesion location, Trans-Atlantic Inter-Society Consensus II classification, amount of calcification, procedure time, recanalization time with conventional subintimal technique, recanalization time with the MTSN, and complications were recorded. During the 24-month period, 11 common iliac arteries (CIAs), three external iliac arteries (EIAs), one combined CIA/EIA, six superficial femoral arteries (SFAs), and two combined SFA/popliteal arteries were treated with MTSNs. RESULTS: Successful recanalization with the MTSN was obtained in 21 patients (91%). There was one complication of pseudoaneurysm formation in the EIA. The average occlusion length of the CIA was 6.7 cm; that of the SFA was 15.9 cm. The average procedure time was 73 minutes, with 20 minutes used to attempt to reenter the true lumen and 6.3 minutes used to reenter the true lumen with the MTSN. CONCLUSIONS: The MTSN technique is safe and effective and offers another approach to reenter the true lumen of chronic total arterial occlusions during subintimal recanalization in difficult cases.

Subintimal recanalization of femoropopliteal occlusive lesions in patients with critical ischemia: 66 cases.

BACKGROUND: Subintimal recanalization allows for the treatment of percutaneously extended occlusive lesions. The aim of this study was to evaluate the feasibility and short- and mid-term results of subintimal recanalization in the treatment of femoropopliteal occlusive lesions in patients with critical ischemia. METHODS: Between January 2009 and December 2010, consecutive patients with critical ischemia presenting with femoropopliteal arterial occlusion were included in this study. These patients underwent subintimal recanalization, and all patients had clinical and ultrasound follow-up. RESULTS: Sixty-six procedures were performed on 66 patients (mean age, 79±10 yrs). All patients were American Society of Anesthesiologists classification 3 or 4. Thirty-two patients had diabetes and 27 had chronic renal insufficiency. More than two-thirds (76%) of the lesions had a Trans-Atlantic Inter-Society Classification of C or D. The mean occlusion length was 13.5±7 cm. The rate of technical success was 85%. The peroperative complication rate was 4.5%. There were no cases of operative mortality. Occlusion length was the only predictive factor of restenosis (P=0.049). At 1 year, primary and secondary patency rates were 56% and 70%, respectively, for a 92% rate of limb salvage. CONCLUSION: The subintimal recanalization technique is feasible and minimally invasive. At 1 year postprocedure, the primary patency is poor, but this technique is associated with a high rate of limb salvage. It is suitable for the treatment of critical ischemia, taking into account the often precarious clinical backgrounds of these patients.

Remodeling leads to distinctly more intimal hyperplasia in coronary than in infrainguinal vein grafts.

BACKGROUND: Flow patterns and shear forces in native coronary arteries are more protective against neointimal hyperplasia than those in femoral arteries. Yet, the caliber mismatch with their target arteries makes coronary artery bypass grafts more likely to encounter intimal hyperplasia than their infrainguinal counterparts due to the resultant slow flow velocity and decreased wall stress. To allow a site-specific, flow-related comparison of remodeling behavior, saphenous vein bypass grafts were simultaneously implanted in femoral and coronary positions. METHODS: Saphenous vein grafts were concomitantly implanted as coronary and femoral bypass grafts using a senescent nonhuman primate model. Duplex ultrasound-based blood flow velocity profiles and vein graft and target artery dimensions were correlated with dimensional and histomorphologic graft remodeling in large, senescent Chacma baboons (n = 8; 28.1 ± 4.9 kg) during a 24-week period. RESULTS: At implantation, the cross-sectional quotient (Q(c)) between target arteries and vein grafts was 0.62 ± 0.10 for femoral grafts vs 0.17 ± 0.06 for coronary grafts, resulting in a dimensional graft-to-artery mismatch 3.6 times higher (P < .0001) in coronary grafts. Together with different velocity profiles, these site-specific dimensional discrepancies resulted in a 57.9% ± 19.4% lower maximum flow velocity (P = .0048), 48.1% ± 23.6% lower maximal cycling wall shear stress (P = .012), and 62.2% ± 21.2% lower mean velocity (P = .007) in coronary grafts. After 24 weeks, the luminal diameter of all coronary grafts had contracted by 63%, from an inner diameter of 4.49 ± 0.60 to 1.68 ± 0.63 mm (P < .0001; subintimal diameter: -41.5%; P = .002), whereas 57% of the femoral interposition grafts had dilated by 31%, from 4.21 ± 0.25 to 5.53 ± 1.30 mm (P = .020). Neointimal tissue was 2.3 times thicker in coronary than in femoral grafts (561 ± 73 vs 240 ± 149 µm; P = .001). Overall, the luminal area of coronary grafts was an average of 4.1 times smaller than that of femoral grafts. CONCLUSIONS: Although coronary and infrainguinal bypass surgery uses saphenous veins as conduits, they undergo significantly different remodeling processes in these two anatomic positions.

Intimal angiosarcoma presenting with common femoral artery aneurysm.

Intimal angiosarcoma is a rare malignant vascular tumor with an aggressive natural history. Presenting symptoms vary according to the location of the lesion, but symptoms are typically due to intravascular obstruction or embolization. We present a case of an intimal angiosarcoma presenting with a common femoral artery aneurysm.