Native Artery Research Articles

Branched Endovascular Aortic Repair After a Migrated EVAR Bypassing a Severely Kinked Previous Endograft

Purpose: To describe a novel technique to repair a juxtarenal abdominal aortic aneurysm (JAAA) after failed endovascular aortic repair (EVAR) with severely kinked anatomy. Technique: We present a patient who underwent an EVAR with a Medtronic Talent device 15 years ago and a proximal cuff extension 3 years earlier for an abdominal aortic aneurysm. Computed tomography (CT) done for a known gastritis showed a 12 cm JAAA, with a migrated endograft and a type Ia endoleak (EL). Endovascular repair was performed, accessing and navigating the aneurysmal sac outside the previous graft. The type I EL was reached and the suprarenal aorta catheterized. A 4-vessel inner-branched EVAR device was deployed in the distal thoracic aorta and their target vessels bridged through femoral access. A distal bifurcated component was deployed and both iliac limbs were extended to the native distal iliac arteries. Completion angiogram as well as early and 12-month CT showed a fully patent straight course branched EVAR with no ELs. Conclusion: Complex aortic reinterventions in the presence of previous EVAR can be performed by choosing a straighter course along and parallel to the previous endograft. Several technical aspects must be considered to successfully perform this type of reinterventions. Clinical Impact We present a technique of a complex endovascular aortic repair in a failed EVAR with kinked anatomy, navigating through the thrombosed aneurysmal sac, outside the previously placed endograft and thus obtaining a straighter path for a new branched endograft. The novelty lies in a different approach to repair a failed EVAR with a branched graft through an uncommon access on the side of the previous endograft, avoiding repeated displacement or occlusion of the new endograft. We exemplify the feasibility of such a complex procedure and highlight important steps to perform it, whether in the abdominal or even thoracic Aorta.

Efficacy of Coronary Stenting Versus Ballon Angioplasty in Small Coronary Arteries

Background and aim: The most common approach of percutaneous myocardial revascularization is stent placement. In de novo focal lesions found in big native arteries, balloon angioplasty had lower efficacy than coronary stenting. However, the usefulness of stenting in small arteries remains debatable. The purpose study aimed to compare the efficacy of coronary stenting vs. balloon angioplasty in small coronary arteries. Patients and Method: This comparative study was carried out on 132 patients with lesion in small coronary arteries (reference diameter <3mm) in the department of Interventional Cardiology, MTI- Hayat Abad Medical Complex, Peshawar from 16th January 2021 to 15th July 2022. Patients were arbitrarily assigned to stent implantation and standard balloon angioplasty. Study protocol was approved by research and ethical committee. Each individual provided written informed consent. The rates of clinical event were evaluated within 1 year. Descriptive statistics was carried out in SPSS version 26. Results: Of the total patients, there were 80 (60.6%) male and 52 (39.4%) were females. Both groups were assigned 66 patients and had similar baseline characteristics and angiography data. Based on treatment analysis, the major adverse cardiac events (MACEs) and angiographic success rate were similar: 5.2% and 96.8% in coronary stenting versus 5.9% and 92.4% in balloon angioplasty group respectively. About 4.2% patients underwent abrupt closure changes within 30 days. Stenting convened the substantially larger lumen (1.52 mm vs. 1.32 mm, p<0.001) at 6 months and larger post-procedural lumen diameter (2.31 vs. 1.82 mm, p<0.001) as compared to balloon angioplasty. The incidence of restenosis was found 36% and 56% in coronary stenting and balloon angioplasty respectively. The survival rate (event-free) was achieved in 79% and 69% (p=0.021) in coronary stenting and angioplasty respectively. Conclusion: The present study found that optimum balloon angioplasty with preliminary stenting may be a viable therapeutic option for small coronary arteries lesions. Restenosis was found to be 36% and 56% in coronary stenting and balloon angioplasty, respectively. Keywords: Restenosis, Small coronary arteries, Balloon angioplasty, Coronary stenting

Long-term outcomes of transcatheter pulmonary valve implantation with melody and SAPIEN valves

BackgroundTranscatheter pulmonary valve implantation (TPVI) is effective for treating right ventricle outflow tract (RVOT) dysfunction. Factors associated with long-term valve durability remain to be investigated. MethodsConsecutive patients successfully treated by TPVI with Melody valves (n = 32) and SAPIEN valves (n = 182) between 2008 and 2020 at a single tertiary centre were included prospectively and monitored. ResultsThe 214 patients had a median age of 28 years (range, 10–81). The RVOT was a patched native pulmonary artery in 96 (44.8%) patients. Median follow-up was 2.8 years (range, 3 months–11.4 years). Secondary pulmonary valve replacement (sPVR) was performed in 23 cases (10.7%), due to stenosis (n = 22, 95.7%) or severe regurgitation (n = 1, 4.3%), yielding an incidence of 7.6/100 patient-years with melody valves and 1.3/100 patient-years with SAPIEN valves (P = 0.06). The 5- and 10-year sPVR-freedom rates were 78.1% and 50.4% with Melody vs. 94.3% and 82.2% with SAPIEN, respectively (P = 0.06). The incidence of infective endocarditis (IE) was 5.5/100 patient-years with Melody and 0.2/100 patient-years with SAPIEN (P < 0.0001). Factors associated with sPVR by univariate analysis were RV obstruction before TPVI (P = 0.04), transpulmonary maximal velocity > 2.7 m/s after TPVI (p = 0.0005), valve diameter ≤ 22 mm (P < 0.003), IE (P < 0.0001), and age < 25 years at TPVI (P = 0.04). By multivariate analysis adjusted for IE occurrence, transpulmonary maximal velocity remained associated with sPVR. ConclusionsTPVI is effective for treating RVOT dysfunction. Incidence of sPVR is higher in patients with residual RV obstruction or IE. IE add a substantial risk of TPVI graft failure and is mainly linked to the Melody valve. Social media abstractTranscatheter pulmonary valve implantation is effective for treating right ventricular outflow tract dysfunction in patients with congenital heart diseases. Incidence of secondary valve replacement is higher in patients with residual obstruction or infective endocarditis.

Unravelling the impact of aging on the human endothelial lncRNA transcriptome.

The incidence and prevalence of cardiovascular disease is highest among the elderly. There is a need to further understand the mechanisms behind endothelial cell aging in order to achieve vascular rejuvenation and minimize the onset of age-related vascular diseases. Long non-coding RNAs (lncRNAs) have been proposed to regulate numerous processes in the human genome, yet their function in vascular aging and their therapeutic potential remain largely unknown. This is primarily because the majority of studies investigating the impact of aging on lncRNA expression heavily rely on in vitro studies based on replicative senescence. Here, using a unique collection of young and aged endothelial cells isolated from native human arteries, we sought to characterize the age-related alterations in lncRNA expression profiles. We were able to detect a total of 4463 lncRNAs expressed in the human endothelium from which ∼17% (798) were altered in advanced age. One of the most affected lncRNAs in aging was the primate-specific, Prostate Cancer Associated Transcript (PCAT) 14. In our follow up analysis, using single molecule RNA FISH, we showed that PCAT14 is relatively abundant, localized almost exclusively in the nucleus of young endothelial cells, and silenced in the aged endothelium. Functionally, our studies proposed that downregulation of PCAT14 alters endothelial cell transcription profile and cell functions including endothelial cell migration, sprouting and inflammatory responses in vitro. Taken together, our data highlight that endothelial cell aging correlates with altered expression of lncRNAs, which could impair the endothelial regenerative capacity and enhance inflammatory phenotypes.

Rapid Regeneration of a Neoartery with Elastic Lamellae.

Native arteries contain a distinctive intima-media composed of organized elastin and an adventitia containing mature collagen fibrils. In contrast, implanted biodegradable small-diameter vascular grafts do not present spatially regenerated, organized elastin. The elastin-containing structures within the intima-media region encompass the elastic lamellae (EL) and internal elastic lamina (IEL) and are crucial for normal arterial function. Here, the development of a novel electrospun small-diameter vascular graft that facilitates de novo formation of a structurally appropriate elastin-containing intima-media region following implantation is described. The graft comprises a non-porous microstructure characterized by tropoelastin fibers that are embedded in a PGS matrix. After implantation in mouse abdominal aorta, the graft develops distinct cell and extracellular matrix profiles that approximate the native adventitia and intima-media by 8 weeks. Within the newly formed intima-media region there are circumferentially aligned smooth muscle cell layers that alternate with multiple EL similar to that found in the arterial wall. By 8 months, the developed adventitia region contains mature collagen fibrils and the neoartery presents a distinct IEL with thickness comparable to that in mouse abdominal aorta. It is proposed that this new class of material can generate the critically required, organized elastin needed for arterial regeneration.

From In Vitro to Perioperative Vascular Tissue Engineering: Shortening Production Time by Traceable Textile-Reinforcement

Background:The production of tissue-engineered vascular graft (TEVG) usually involves a prolonged bioreactor cultivation period of up to several weeks to achieve maturation of extracellular matrix and sufficient mechanical strength. Therefore, we aimed to substantially shorten this conditioning time by combining a TEVG textile scaffold with a recently developed copolymer reinforced fibrin gel as a cell carrier. We further implemented our grafts with magnetic resonance imaging (MRI) contrast agents to allow the in-vitro monitoring of the TEVG’s remodeling process.Methods:Biodegradable polylactic-co-glycolic acid (PLGA) was electrospun onto a non-degradable polyvinylidene fluoride scaffold and molded along with copolymer-reinforced fibrin hydrogel and human arterial cells. Mechanical tests on the TEVGs were performed both instantly after molding and 4 days of bioreactor conditioning. The non-invasive in vitro monitoring of the PLGA degradation and the novel imaging of fluorinated thermoplastic polyurethane (19F-TPU) were performed using 7T MRI.Results:After 4 days of close loop bioreactor conditioning, 617 ± 85 mmHg of burst pressure was achieved, and advanced maturation of extracellular matrix (ECM) was observed by immunohistology, especially in regards to collagen and smooth muscle actin. The suture retention strength (2.24 ± 0.3 N) and axial tensile strength (2.45 ± 0.58 MPa) of the TEVGs achieved higher values than the native arteries used as control. The contrast agents labeling of the TEVGs allowed the monitorability of the PLGA degradation and enabled the visibility of the non-degradable textile component.Conclusion:Here, we present a concept for a novel textile-reinforced TEVG, which is successfully produced in 4 days of bioreactor conditioning, characterized by increased ECM maturation and sufficient mechanical strength. Additionally, the combination of our approach with non-invasive imaging provides further insights into TEVG’s clinical application.

Systemic thrombolytic therapy in treatment of acute limb ischemia

Background and aim Owing to the increased risk of morbidity and mortality, the treatment of acute limb ischemia (ALI) is challenging. The authors aimed to investigate the outcomes of thrombolysis in the treatment of ALI and limb salvage. Patients and methods A retrospective observational study was conducted to revise the data of 49 patients who underwent catheter-direct thrombolysis for ALI. A total of 33 cases were at lower limb and 16 cases were at upper limb. The assessed outcomes were primary and secondary patency, survival, amputation-free survival, and conversion to surgery. Results The patients were classified according to the Rutherford classification into class I (52%), class IIa (38%), class IIb (8%), and class III (2%). The primary patency was present in 34% of the patients after the first year and 22% after the second year. On the contrary, 28% of the patients were subjected to conversion to open surgery, 8% were subjected to reintervention, and 6% were subjected to amputation within the first month. The mortality rate within 1 month was 6%. The worst primary and secondary patency rates were seen in the prosthetic grafts in addition to vein bypasses, whereas the native artery was the most successful one regarding the primary patency, secondary patency, and amputation-free survival (P&lt;0.05 for each). Conclusion The thrombolysis of vein bypass and prosthetic grafts did not show technical success as that seen with native artery. Additional treatment at the time of thrombolysis was shown to be associated with better outcomes.

Multiaxis printing method for bent tubular structured gels in support bath for achieving high dimension and shape accuracy

Gels are soft materials that have high potential for use as alternative artificial blood vessels. 3D gel printing has attracted attention because it can be used to create gels with arbitrary and complicated shapes. The conventional 3D gel printing process (triaxial printing) is as follows: ⅰ) a sol material is patterned to form a layer on the XY plane, ⅱ) a crosslinker is added to it, ⅲ) the Z stage is lowered by the stacking pitch, and ⅳ) a new sol material is patterned on the previous layer. However, irregular protrusions and stepped structures appear at the overhang parts as the height and scale increase. In addition, there are non-adhesion sections between adjacent layers. To solve these problems, we propose a “multiaxis printing method,” in which layers are seamlessly stacked by changing the extruding direction by following the neutral line of a structure. We evaluate the dimension and shape accuracy of the proposed method by printing bent hollow tubular structured gels. The proposed method significantly suppresses irregular protrusions on outer walls. Moreover, each layer is seamlessly joined. The structures printed using the proposed method show good dimension and shape accuracy. The minimum lumen area ratio is 75%, which is comparable to native common carotid arteries. In addition, the maximum errors in the bending angle and curvature radius are 1.7% and 5.1%, respectively. However, the average outer and inner diameters are smaller than the patterning diameter, suggesting that the crosslinked gels attract each other in the circumferential direction. This indicates that a model should be designed considering gel shrinkage to further improve the accuracy of printing.

Modified biatrial heart transplantation after bilateral bidirectional cavo-pulmonary shunts.

We describe a patient who underwent modified biatrial anastomosis heart transplantation after the bilateral Glenn procedure. We introduced a new surgical technique to use the native central pulmonary artery as systemic venous return, which was anastomosed to right atrium, and then, biatrial anastomosis was performed.

A proteomics analysis of neointima formation on decellularized vascular grafts reveals regenerative alterations in protein signature running head: Proteomics analysis of neointima formation.

Background: Neointima formation contributes to vascular grafts stenosis and thrombosis. It is a complex reaction that plays a significant role in the performance of vascular grafts. Despite its critical implications, little is known about the mechanisms underlying neointima formation. This study compares neointima proteome in different stages and plasma samples. Methods: Heterogenous acellular native arteries were implanted as abdominal aortic interposition grafts in a rabbit model. Grafts were harvested at 0.5, 1, 4, 6, 7, 14, 21, and 28days post-surgery for histological and proteomic analysis of the neointima. Results: Histological examination showed a transformed morphological pattern and components, including serum proteins, inflammatory cells, and regenerative cells. Proteomics analysis of the neointima showed distinct characteristics after 14days of implantation compared to early implantation. Early changes in the neointima samples were proteins involved in acute inflammation and thrombosis, followed by the accumulation of extracellular matrix (ECM) proteins. A total of 110 proteins were found to be differentially expressed in later samples of neointima compared to early controls. The enriched pathways were mainly protein digestion and adsorption, focal adhesion, PI3K-Akt signaling pathway, and ECM-receptor interaction in the late stage. All distributions of proteins in the neointima are different compared to plasma. Conclusion: The biological processes of neointima formation at different stages identified with proteome found developmental characteristics of vascular structure on a decellularized small vascular graft, and significant differences were identified by proteomics in the neointima of early-stage and late-stage after implantation. In the acute unstable phase, the loose and uniform neointima was mainly composed of plasma proteins and inflammatory cells. However, in the relatively stable later stage, the most notable results were an up-regulation of ECM components. The present study demonstrates an interaction between biological matter and vascular graft, provides insights into biological process changes of neointima and facilitates the construction of a functional bioengineered small vascular graft for future clinical applications.

The effect of conservation in various cryoprotectants on the properties and morphological structure of the umbilical cord arteries

Purpose of the study. The aim of this work was to study the effect of conservation in various cryoprotectants on the biomechanical and morphological properties of the umbilical cord (UCA) arteries.Materials and methods. The material for this work was 12 umbilical arteries, which were divided into 4 study groups: (1) native UCA – control without freezing; (2) APC frozen in 5 % dextran with the addition of dimethyl sulfoxide (DMSO) to 10 % and 7.5 % human serum albumin (HSA); (3) APC frozen in glycerin and (4) UCA frozen in propanediol. For all groups, morphological and biomechanical studies were carried out. The statistical data were processed using the GraphPad Prism 9.2.0 program. Analysis of variance was used to find significant differences.Results. Freezing with 5 % dextran, 10 % DMSO and 7.5 % human albumin did not lead to significant changes in the morphology of vascular tissue compared to control. The conserved vascular tissue retains a moderate level of type I collagen, regardless of the method of conservation. The presence of statistically significant differences between the control and frozen UCAs was shown for Young's modulus (p &lt; 0.05; 6.9 [6.8; 7.0] for the native artery; 2.3 [2.0; 2.6] for the artery preserved with the use of dextran, DMSO and human albumin; 2.3 [1.4; 3.2] for the artery preserved in glycerin and 0.8 [0.6; 1.0] – in propanediol, respectively).Conclusion. 1) Freezing and storage of UCA at 5 % dextran, 10 % DMSO and 7.5 % HSA does not lead to a significant change in the morphology of vascular membranes and cell nuclei; 2) The preservation of type I collagen according to the results of IHC is qualitatively reduced from a conditional indicator of +2 to +1 for frozen agroindustrial complexes compared with control ones; 3) Conservation leads to a significant decrease in the modulus of elasticity of the walls of the agroindustrial complex compared with control vessels (p &lt; 0.05).

Defining Duplex Ultrasound Criteria for In-Stent Restenosis of the Carotid Artery Using Computed Tomographic Angiography.

IntroductionDuplex ultrasound (DUS) velocity measurement is the preferred method for evaluating carotid artery stenosis. However, velocity criteria based upon native carotid arteries may not apply to internal carotid artery stents. Previously, catheter-based angiography was used to determine DUS velocity criteria for in-stent restenosis (ISR), but conventional angiography is invasive and can be limited. This study sought to define duplex ultrasound velocity criteria for predicting internal carotid artery in-stent restenosis by correlating in-stent velocities with computed tomographic angiography (CTA) measurements of percent stenosis.MethodsA retrospective chart review was conducted on all patients who underwent internal carotid artery (ICA) stenting within our health system between January 2013 and February 2020. Thirty-eight surveillance DUS studies from 32 patients were found to have CTA performed within 30 days. Centerline reconstructions of internal carotid artery stents were created using Aquarius iNtuition software (TeraRecon, Durham, NC, USA). Two independent observers measured percent stenosis by three built-in methods. Stenotic areas were matched to DUS-measured peak systolic velocities (PSV) and end-diastolic velocities (EDV). Internal carotid artery PSV (stent) to common carotid artery (CCA) PSV ratios (ICA/CCA) were calculated, and receiver operating characteristic (ROC) curves were generated. The optimal DUS velocity criteria in the stented ICA were determined by maximizing Youden’s index.ResultsMean vessel diameter measurement of percent stenosis resulted in the most accurate model for all DUS velocity parameters (PSV, EDV, and ICA/CCA ratio) and was used for threshold determinations (area under the receiver operating characteristics (AUROC): 0.99, 0.96, and 0.96, respectively). A PSV cutoff of 240 cm/s for ≥60% ISR resulted in the highest Youden’s index (97%) with 100% sensitivity and 97% specificity. Secondary DUS parameters included an EDV ≥50 cm/s (Youden’s index 84%) and an ICA/CCA ratio ≥ 2.2 (Youden’s index 91%).ConclusionsVelocity criteria to predict internal carotid artery ISR is needed to inform decisions for possible reintervention. Using CTA, we found that a PSV ≥240 cm/s on carotid DUS can predict ≥60% ISR with high sensitivity and specificity. This value can be used as an alternative to current velocity criteria based on native carotid arteries. However, the optimal thresholds for EDV and ICA/CCA ratio were similar to native carotid arteries.

High-frame-rate contrast-enhanced ultrasound particle image velocimetry in patients with a stented superficial femoral artery: a feasibility study

BackgroundLocal blood flow affects vascular disease and outcomes of endovascular treatment, but quantifying it is challenging, especially inside stents. We assessed the feasibility of blood flow quantification in native and stented femoral arteries, using high-frame-rate (HFR) contrast-enhanced ultrasound (CEUS) particle image velocimetry (PIV), also known as echoPIV.MethodsTwenty-one patients with peripheral arterial disease, recently treated with a stent in the femoral artery, were included. HFR CEUS measurements were performed in the native femoral artery and at the inflow and outflow of the stent. Two-dimensional blood flow was quantified through PIV analysis. EchoPIV recordings were visually assessed by five observers and categorised as optimal, partial, or unfeasible. To evaluate image quality and tracking performance, contrast-to-tissue ratio (CTR) and vector correlation were calculated, respectively.ResultsFifty-eight locations were measured and blood flow quantification was established in 49 of them (84%). Results were optimal for 17/58 recordings (29%) and partial for 32 recordings (55%) due to loss of correlation (5/32; 16%), short vessel segment (8/32; 25%), loss of contrast (14/32; 44%), and/or shadows (18/32; 56%). In the remaining 9/58 measurements (16%) no meaningful flow information was visualised. Overall, CTR and vector correlation were lower during diastole. CTR and vector correlation were not different between stented and native vessel segments, except for a higher native CTR at the inflow during systole (p = 0.037).ConclusionsBlood flow quantification is feasible in untreated and stented femoral arteries using echoPIV. Limitations remain, however, none of them related to the presence of the stent.Trial registrationClinicalTrials.gov, NCT04934501 (retrospectively registered).

Comparative Assessment of Various Concentration and Exposure Time of Sodium Dodecyl Sulfate as Decellularization Agents for Small-Vessels Vascular Tissue Engineering

BACKGROUND: Finding the optimum vascular grafts (VG) to replace damaged blood arteries in cardiac surgery is still a work in progress. To be employed, a tissue-engineered VG (TEVG) must have the appropriate biological and mechanical qualities. Decellularized arteries may be a better TEVG than synthetic grafts because of their natural three-dimensional architecture. AIM: The goal of this study was to compare different concentrations and times of sodium dodecyl sulfate (SDS) to decellularize tissue to find the best decellularized VG. METHODS: In all decellularized scaffolds, which are 1% SDS-2 weeks group, hematoxylin and eosin and Masson’s trichrome staining exhibited looser collagen networks and fewer nuclei. RESULTS: The orientation of collagen fibers was identical to native vascular scaffolds. Collagen I deposition was seen in the immunohistochemistry assay. A tensile strength test revealed that the decellularized scaffold (0.5% SDS for 4 weeks and 0.5% SDS for 2 weeks) had exceeded the native arteries’ maximal strength. In comparison to 1% SDS in 4 weeks treated groups, scanning electron microscopy following decellularization revealed no endothelial cells on the inner side of 1% SDS in 2 weeks group with minimum extracellular matrix damage. The endothelial cells remained marginally visible on the inner side of all 0.5% SDS treated groups. The 3-(4,5-dimethylthiazol-2yl)2,5-diphenyltetrazolium bromide test was used to determine the cytotoxicity of the decellularized scaffolds. CONCLUSION: This study reveals that exposing a bovine mesenteric artery to 1% SDS for 2 weeks is an excellent procedure for extracting the most acellular VG, potentially serving as a biological scaffold for TEVGs.

Percutaneous Coronary Intervention of Native Artery Versus Bypass Graft in Patients with Prior Coronary Artery Bypass Graft Surgery.

Percutaneous coronary intervention (PCI) is common in patients with prior coronary artery bypass graft surgery (CABG), however, there is limited data on the association between the PCI target-vessel and clinical outcomes. In this article, we provide a state-of-the-art overview of the contemporary management of patients with prior CABG and a clear indication for revascularization. We performed a structured literature search of PubMed and Cochrane Library databases from inception to March 2021. Relevant studies were extracted and synthesized for narrative review. Twenty-six observational studies focusing on PCI of bypass graft versus native coronary artery lesions in 366,060 patients with prior CABG were included. The data from observational studies suggest that bypass graft PCI is associated with higher short- and long-term major adverse cardiac events compared to native coronary artery PCI. Whenever feasible, native coronary artery PCI should be the prioritized treatment for saphenous vein graft failure. Prospective randomized trials are needed to elucidate the optimal revascularization strategy for patients with prior CABG.

3D Printed Bioreactor Enabling the Pulsatile Culture of Native and Angioplastied Large Arteries.

Routine interventions such as balloon angioplasty, result in vascular activation and remodeling, often requiring re-intervention. 2D in vitro models and small animal experiments have enabled the discovery of important mechanisms involved in this process, however the clinical translation is often underwhelming. There is a critical need for an ex vivo model representative of the human vascular physiology and encompassing the complexity of the vascular wall and the physical forces regulating its function. Vascular bioreactors for ex vivo culture of large vessels are viable alternatives, but their custom-made design and insufficient characterization often hinders the reproducibility of the experiments. The objective of the study was to design and validate a novel 3D printed cost-efficient and versatile perfusion system, capable of sustaining the viability and functionality of large porcine arteries for 7 days and enabling early post-injury evaluations. MultiJet Fusion 3D printing was used to engineer the EasyFlow insert, converting a conventional 50 ml centrifuge tube into a mini bioreactor. Porcine carotid arteries either left untreated or injured with an angioplasty balloon, were cultured under pulsatile flow for up to 7 days. Pressure, heart rate, medium viscosity and shear conditions were adjusted to resemble arterial in vivo hemodynamics. Tissue viability, cell activation and matrix remodeling were analyzed by immunohistochemistry, and vascular function was monitored by duplex ultrasound. Culture conditions in the EasyFlow bioreactor preserved endothelial coverage and smooth muscle organization and extracellular matrix structure in the vessel wall, as compared to static culture. Injured arteries presented hallmarks of early remodeling, such as intimal denudation, smooth muscle cell disarray and media/adventitia activation in flow culture. Duplex ultrasound confirmed continuous pulsatile blood flow conditions, dose-dependent vasodilator response to nitroglycerin in untreated vessels and impaired dilator response in angioplastied vessels. The scope of this work is to validate a low-cost, robust and reproducible system to explore the culture of native and injured large arteries under pulsatile flow. While the study of vascular pathology is beyond the scope of the present paper, our system enables future investigations and provides a platform to test novel therapies and devices ex vivo, in a patient relevant system.

Review of Polymeric Biomimetic Small-Diameter Vascular Grafts to Tackle Intimal Hyperplasia.

Small-diameter artificial vascular grafts (SDAVG) are used to bypass blood flow in arterial occlusive diseases such as coronary heart or peripheral arterial disease. However, SDAVGs are plagued by restenosis after a short while due to thrombosis and the thickening of the neointimal wall known as intimal hyperplasia (IH). The specific causes of IH have not yet been deduced; however, thrombosis formation due to bioincompatibility as well as a mismatch between the biomechanical properties of the SDAVG and the native artery has been attributed to its initiation. The main challenges that have been faced in fabricating SDAVGs are facilitating rapid re-endothelialization of the luminal surface of the SDAVG and replicating the complex viscoelastic behavior of the arteries. Recent strategies to combat IH formation have been mostly based on imitating the natural structure and function of the native artery (biomimicry). Thus, most recently, developed grafts contain a multilayered structure with a designated function for each layer. This paper reviews the current polymeric, biomimetic SDAVGs in preventing the formation of IH. The materials used in fabrication, challenges, and strategies employed to tackle IH are summarized and discussed, and we focus on the multilayered structure of current SDAVGs. Additionally, the future aspects in this area are pointed out for researchers to consider in their endeavor.

Design and Verification of a Novel Perfusion Bioreactor to Evaluate the Performance of a Self-Expanding Stent for Peripheral Artery Applications.

Endovascular stenting presents a promising approach to treat peripheral artery stenosis. However, a significant proportion of patients require secondary interventions due to complications such as in-stent restenosis and late stent thrombosis. Clinical failure of stents is not only attributed to patient factors but also on endothelial cell (EC) injury response, stent deployment techniques, and stent design. Three-dimensional in vitro bioreactor systems provide a valuable testbed for endovascular device assessment in a controlled environment replicating hemodynamic flow conditions found in vivo. To date, very few studies have verified the design of bioreactors based on applied flow conditions and their impact on wall shear stress, which plays a key role in the development of vascular pathologies. In this study, we develop a computationally informed bioreactor capable of capturing responses of human umbilical vein endothelial cells seeded on silicone tubes subjected to hemodynamic flow conditions and deployment of a self-expanding nitinol stents. Verification of bioreactor design through computational fluid dynamics analysis confirmed the application of pulsatile flow with minimum oscillations. EC responses based on morphology, nitric oxide (NO) release, metabolic activity, and cell count on day 1 and day 4 verified the presence of hemodynamic flow conditions. For the first time, it is also demonstrated that the designed bioreactor is capable of capturing EC responses to stent deployment beyond a 24-hour period with this testbed. A temporal investigation of EC responses to stent implantation from day 1 to day 4 showed significantly lower metabolic activity, EC proliferation, no significant changes to NO levels and EC's aligning locally to edges of stent struts, and random orientation in between the struts. These EC responses were indicative of stent-induced disturbances to local hemodynamics and sustained EC injury response contributing to neointimal growth and development of in-stent restenosis. This study presents a novel computationally informed 3D in vitro testbed to evaluate stent performance in presence of hemodynamic flow conditions found in native peripheral arteries and could help to bridge the gap between the current capabilities of 2D in vitro cell culture models and expensive pre-clinical in vivo models.

Abstract No. 121 Differences in outcomes of catheter-directed thrombolysis in native and non-native vessels for lower extremity acute limb ischemia

Lower extremity acute limb ischemia (ALI) may be more difficult to treat with catheter-directed thrombolysis (CDT) in patients with non-native vasculature. The purpose of this study is to compare the characteristics and outcomes of CDT performed on native arteries, stented arteries, and bypass grafts for ALI.

Morphological and Physiological Characteristics of Ruptured Plaques in Native Arteries and Neoatherosclerotic Segments: An OCT-Based and Computational Fluid Dynamics Study.

BackgroundIntravascular imaging has been used to assess the morphology of lesions causing an acute coronary syndrome (ACS) in native vessels (NV) and identify differences between plaques that ruptured (PR) and caused an event and those that ruptured without clinical manifestations. However, there is no data about the morphological and physiological characteristics of neoatherosclerotic plaques that ruptured (PR-NA) which constitute a common cause of stent failure.MethodsWe retrospectively analyzed data from patients admitted with an acute myocardial infarction that had optical coherence tomography (OCT) imaging of the culprit vessel before balloon pre-dilation. OCT pullbacks showing PR were segmented at every 0.4 mm. The extent of the formed cavity, lipid and calcific tissue, thrombus, and macrophages were measured, and the fibrous cap thickness (FCT) and the incidence of micro-channels and cholesterol crystals were reported. These data were used to reconstruct a representative model of the native and neoatherosclerotic lesion geometry that was processed with computational fluid dynamics (CFD) techniques to estimate the distribution of the endothelial shear stress and plaque structural stress.ResultEighty patients were included in the present analysis: 56 had PR in NV (PR-NV group) and 24 in NA segments (PR-NA group). The PR-NV group had a larger minimum lumen area (2.93 ± 2.03 vs. 2.00 ± 1.26 mm2, p = 0.015) but similar lesion length and area stenosis compared to PR-NA group. The mean FCT (186 ± 65 vs. 232 ± 80 μm, p = 0.009) and the lipid index was smaller (16.7 ± 13.8 vs. 25.9 ± 14.1, p = 0.008) while the of calcific index (8.3 ± 9.5 vs. 2.2 ± 1.6%, p = 0.002) and the incidence of micro-channels (41.4 vs. 12.5%, p = 0.013) was higher in the PR-NV group. Conversely, there was no difference in the incidence of cholesterol crystals, thrombus burden or the location of the rupture site between groups. CFD analysis revealed higher maximum endothelial shear stress (19.1 vs. 11.0 Pa) and lower maximum plaque structural stress (38.8 vs. 95.1 kPa) in the PR-NA compared to the PR-NV model.ConclusionWe reported significant morphological and physiological differences between culprit ruptured plaques in native and stented segments. Further research is needed to better understand the causes of these differences and the mechanisms regulating neoatherosclerotic lesion destabilization.