Objectives The goal of this study was to compare the limb tissue metabolomic profiles from differing clinical presentations of patients with peripheral artery disease (PAD). Background PAD presents clinically as intermittent claudication (IC) and chronic limb threatening-ischemia (CLTI; pain at rest with or without tissue necrosis or gangrene). Patients with CLTI suffer high morbidity and mortality rates, which is compounded by our lack of understanding of their unique tissue biology. Methods Gastrocnemius muscle was obtained from healthy-adult volunteers (HA; n=23), IC patients (n=15), and CLTI patients (n=24) and analyzed using Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS). Results We identified 1114 biochemicals via global metabolomic profiling. The IC muscle metabolome largely reflected the HA profile (biochemicals p<0.05; 117 increased and 67 decreased). The CLTI metabolome differentially presented 531 metabolites (p<0.05) v HA, defined by a majority increasing (343 v 188 decreased). IC and CLTI groups only shared 77 decreased and 127 increased metabolites, that were largely defined by alterations in lipids (including Fatty Acid, Dicarboxylate species). Altered (p<0.05) metabolites in IC/HA and CLTI/HA comparisons reflect substantial changes in the muscle amino acid and lipid profiles, but particularly in the CLTI presentation (220 Lipid species increased or decreased). Direct comparisons of CLTI and IC revealed 159 increased (p<0.1) and 90 decreased (p<0.1) biochemicals, including large changes in amino acids, lipids, and nucleotides. Conclusions The limb muscle metabolome of patients with CLTI is unique and reflects novel biochemical characteristics that underlie pathophysiology. CLINICAL RELEVANCE Metabolomic profiling of the lateral gastrocnemius muscle revealed unique alterations in the metabolic pathways of patients with chronic limb threatening ischemia (CLTI) compared to intermittent claudicants (IC) and healthy adults. This points to metabolic targets that may influence disease severity and patient outcomes. The most significantly changed metabolites were related to pain and inflammation, and energy and lipid metabolism, which mirror the primary symptoms (pain, inflammation, myopathy, myosteatosis) of the CLTI patient population. These data provide critical information that aids in identifying the CLTI disease etiology and may be leveraged for development of adjuvant therapies to supplement surgical intervention.
A patient-specific computational fluid dynamics (CFD) analysis was performed to explore hemodynamic contributors of recurrent limb thrombosis after endovascular aneurysm repair (EVAR) and its potential to guide revision strategies in a patient with repeated thromboembolic events associated with recurrent mural thrombus of an EVAR endograft. Key hemodynamic parameters, Time-averaged wall shear stress (TAWSS) and residence time (RT), were assessed showing a region with depressed TAWSS (below 0.1 Pa) at the site of mural thrombus and a quasi-infinite residence time of entrapped particles in that area. Next, CFD simulations tested a virtual limb relining configuration, with geometric modifications resulting in improved TAWSS and RT. After mimicking the CFD-based relining with the implantation of an endograft a post-procedural analysis was performed. The post-operative results were in line with the prediction model and showed a 544% reduction in low area of TAWSS (<0.1 Pa) and a normalization of RT to 5s. A contrast enhanced Computed Tomography one year after stent placement showed a patent endograft without any signs of recurrent mural thrombus. Therefore, Computational fluid dynamics may provide valuable insights into the hemodynamic mechanisms underlying endograft thrombosis and may support personalized planning of relining strategies to reduce recurrent thromboembolic risk.
Objective Limb Graft Occlusions (LGO) remain a significant complication following endovascular aneurysm repair (EVAR). Several clinical risk factors have been recognized, but these do not fully account for the consistently observed different LGO rates among major commercial stent graft systems. This paper investigates the thrombogenicity of stent graft materials as potential factor for thrombus formation and therefore LGO. Methods The thrombogenicity of the graft materials from three commercially available stent grafts (Zenith Alpha, Endurant, and Excluder) was evaluated in vitro using whole blood from four human donors, for one hour in a dynamic setup. Samples were examined qualitatively with Scanning Electron Microscopy (SEM), and the blood was further evaluated quantitatively via enzyme-linked immunosorbent assays (ELISAs) for key indicators of thrombogenesis: normalized platelet count in the blood as measure of platelets in the clot, thrombin-anti-thrombin complex (TAT), beta-thromboglobulin (βTG), and the soluble complement membrane attack complex (sC5b9). Results Qualitative analysis revealed voluminous blot clot formation on Zenith Alpha stent grafts, some blood components on Endurant fabric, and minimal thrombotic factors on Excluder fabric. Material from the Zenith Alpha exhibited the lowest normalized platelet count in the blood (p<.0001), and significantly higher TAT (p<.001), and βTG values compared to Excluder (p=0.002), indicating quantitatively the highest thrombogenicity among the evaluated stent graft materials. The Endurant fabric was significantly less thrombogenic compared to Zenith Alpha based on normalized platelet count (p<.001) and TAT values (p<.001). The Excluder graft material had the highest normalized platelet count (p<.0001) and lowest values of TAT (p<.0001) and βTG (p<.018), indicating it is significantly less thrombogenic compared to the other two fabrics. No clear trend was found for sC5b9 between the stent graft materials. Conclusion The materials used in three commercial stent graft systems have significantly different in vitro thrombogenic properties and thrombus formation on the fabrics.
Objective Vascular regenerative cell exhaustion (VRCE), a shift in the circulating progenitor cell profile has been linked with adverse cardiometabolic outcomes. Whether VRCE is also involved in the pathogenesis and vascular repair mechanisms of peripheral artery disease (PAD) is unknown. We sought to compare the circulating vascular regenerative cell content of adults living with PAD to those without PAD. Methods PAD-VRCE CardioLink-17 (NCT06626646) was an observational, cross-sectional study of 20 adults with symptomatic PAD and 20 without PAD. Circulating progenitor cell profiles were documented using a multiparametric flow cytometry assay based on differential expression of aldehyde dehydrogenase activity in pro-vascular progenitor cells combined with primitive and/or lineage-specific hematopoietic or endothelial cell markers. Results The group with PAD had a median (range) ankle brachial index of 0.82 (0.35-0.84)The two groups were well matched for age and gender, but individuals with PAD had higher rates of dyslipidemia, greater weight and blood pressure. Those with PAD had less circulating ALDHhiSSClowCD133+ (44.0±3.4% vs 49.7±3.0%, p<0.001) and ALDHhiSSClowCD34+CD133+ (42.5±4.9% vs 49.0±4.9%, p<0.001) cells representing rare multipotent myeloid progenitors with vessel reparative functions. The PAD group also had fewer ALDHhiSSCmidCD86+CD163- monocytes (2.5±2.4% vs 4.1±2.1%, p=0.001) indicating a reduced monocytic contribution to systemic inflammation. Contrastingly, PAD participants exhibited a higher frequency of ALDHhiSSChi granulocyte precursors (0.48±0.4% vs 0.22±0.1%, p=0.008) the primary drivers systemic inflammation. Conclusions Our findings suggest evidence of a novel association between PAD and a well-documented VRCE phenotype. Accordingly, reversal of VRCE may represent a potential therapeutic target in PAD patients.
Objective Current endovascular treatment of aortoiliac occlusive disease with kissing iliac stents has sub-optimal long-term patency and durability secondary to pathologic flow fields. The aortoiliac fenestrated (AIFEN) stent was previously introduced to provide an anatomically-preserving endovascular therapy that may improve flow dynamics compared to kissing iliac stents. The aim of this study was to compare flow dynamics between the AIFEN stent and conventional kissing iliac stents in vivo in an adult porcine model. Methods AIFEN stents were manufactured via benchtop modification of standard balloon-expandable covered stents. Three adult Yorkshire pigs underwent endovascular AIFEN implantation in the distal aorta with bilateral iliac stents (Group 1), while 3 pigs received conventional kissing iliac stents (Group 2). Over 4 weeks of survival, patency was assessed using weekly femoral ultrasonography. Pre-explant computed tomography angiography (CTA) with computational flow modeling was used to evaluate arterial flow dynamics, including vorticity and flow rate. Results All pigs in both groups survived the 4-week study period without complications. Fluoroscopy at implantation and terminal procedures confirmed patent stents in all animals. Serial ultrasonography demonstrated patent bilateral femoral artery outflow throughout the study. CTA-based flow dynamic analysis revealed that Group 1 had significantly reduced iliac artery vorticity (P = 0.02) and higher flow rates (P = 0.004) compared to Group 2. Conclusions The anatomically-designed AIFEN stent demonstrated superior flow dynamics compared to kissing iliac stents in a porcine model. These findings support further development of anatomically-preserving balloon-expandable stent designs to improve endovascular treatment of aortoiliac occlusive disease.
Objective: To provide a comprehensive review of small-diameter (<6 mm) tissue-engineered vascular grafts for peripheral vascular applications, examining mechanisms of graft failure, emerging biomaterial and fabrication strategies, and key considerations for clinical translation. Methods: A comprehensive literature review was performed using PubMed, Scopus, and Web of Science through January 2026. Studies were selected on the basis of relevance to peripheral vascular surgery, with emphasis on preclinical and clinical outcomes, biomaterial performance, fabrication approaches, and translational considerations, prioritizing recent studies while including seminal work. Results: Despite over four decades of research, small-diameter synthetic grafts continue to demonstrate poor patency in infrainguinal bypass, with expanded polytetrafluoroethylene and Dacron achieving 25% to 50% patency at 5 years compared with 60% to 80% for autologous saphenous vein in below-the-knee applications. Up to 20% of patients experience graft thrombosis within 6 months, with early failure associated with increased amputation rates. Graft failure is driven by acute thrombosis, intimal hyperplasia related to compliance mismatch and chronic inflammation, and incomplete endothelialization. Emerging strategies include multilayered scaffold architectures, hybrid biomaterials incorporating extracellular matrix components and bioactive molecules, advanced manufacturing techniques such as melt electrowriting, and immunomodulatory approaches promoting constructive remodeling. Recent preclinical studies report high patency rates approaching 100%, with complete endothelialization and minimal intimal hyperplasia in animal models. However, translation remains limited by inadequate study design, with median graft lengths of ∼5 cm and follow-up periods of ∼56 days, which do not reflect clinical scenarios where grafts often exceed 30 cm. Conclusions: Clinically viable small-diameter tissue-engineered vascular grafts for peripheral vascular reconstruction will require integrated optimization of hemocompatibility, endothelialization, biomechanical properties, and inflammatory response. Advances in biomaterials, manufacturing technologies, and mechanistic understanding suggest that grafts meeting clinical benchmarks may be achievable, but progress will depend on rigorous preclinical evaluation using clinically relevant models and end points.
Objective To evaluate the feasibility of sutureless repair for inferior vena cava injury using an elastomeric sealant (Hydrofit) and to characterize the histopathological pathway of vascular healing in a mouse model. Methods Nineteen male C57BL/6 mice underwent laparotomy under general anesthesia. A longitudinal incision exceeding 1 mm was made in the infrarenal inferior vena cava, and hemostasis was achieved using Hydrofit-applied sheets with 2 minutes of compression. The primary endpoint was immediate hemostatic success rate with exact 95% confidence intervals. Surviving mice were distributed across the three time points (n = 6, 6, and 6 at days 5, 10, and 30, respectively) by random allocation; one mouse at day 30 was excluded from histopathological scoring owing to inability to reliably identify the incision site. CD31 immunostaining was performed to assess endothelial coverage at the repair site. Findings were scored using a semi-quantitative system modified from the Histopathological Evaluation of Acute and Long-term healing Scores for Advancing wound healing science scale, with comparisons among time points using the Kruskal-Wallis test. Results Immediate hemostasis was achieved in all 19 mice (100%; 95% confidence interval, 82.4%–100%). One mouse died on postoperative day 2; anesthesia-related complications were the most likely cause, but because necropsy was not performed, procedure-related hemorrhage could not be definitively excluded, an unavoidable limitation of the primary and survival outcome estimates. The overall survival rate was 94.7% (18/19; 95% confidence interval, 74.0%–99.9%). No intra-abdominal adhesions were observed. Histopathological scoring demonstrated significant progression through wound healing phases (P = 0.001), with total scores increasing from 4.7 ± 1.2 at day 5 (inflammatory phase) to 7.7 ± 0.8 at day 10 (proliferative phase) and 11.4 ± 1.8 at day 30 (early maturation phase). CD31 (platelet endothelial cell adhesion molecule-1) immunostaining demonstrated CD31-positive cells at the luminal surface at all three time points; a morphologically confirmed endothelial monolayer on hematoxylin-eosin and Elastica van Gieson staining was identified at days 10 and 30, whereas elastic lamina regeneration was not observed. Conclusions Sutureless repair using an elastomeric sealant is feasible for inferior vena cava injury in this mouse model, achieving reliable hemostasis. While the initial wound healing response follows a physiological inflammatory–proliferative–maturation sequence culminating in endothelial coverage established by day 10, the late process is accompanied by material-driven fibrous encapsulation and intimal hyperplasia at the repair site. Clinical Relevance Venous injuries are challenging to repair due to the fragile vessel wall. This study provides histopathological evidence that sutureless repair using an elastomeric sealant facilitates initial vascular healing with endothelial coverage by day 10, although long-term material-driven responses such as fibrous encapsulation and intimal hyperplasia occur. These preclinical findings provide a mechanistic rationale for the further development of sutureless techniques for managing venous hemorrhage, particularly in situations where conventional suturing is technically difficult or time-consuming, such as during minimally invasive surgery or damage control procedures, but require confirmation in larger-animal and clinical studies before clinical application.
Background Autologous arteriovenous fistula (AVF) is the preferred vascular access for maintenance hemodialysis; however, long-term patency is frequently limited by stenosis and thrombosis. The molecular features distinguishing successful AVF maturation from failure remain incompletely defined. This study applied a multi-omics approach to characterize inflammatory, hypoxia-associated, and metabolic signatures in human AVF tissues. Methods Paired vascular specimens were collected from the same individuals at the time of AVF creation and at subsequent reoperation, enabling subject-level comparison between baseline (Pre-S or Pre-F) and postoperative (Po-S or Po-F) states. Bulk RNA sequencing was performed to identify differentially expressed genes and enriched signaling pathways using paired analytical models. Proteomic profiling was performed using a non-paired group-based design on Pre-AVF, Po-S, and Po-F specimens to characterize differential protein expression and associated metabolic alterations. Results Comparative transcriptomic analysis identified 463 differentially expressed genes (DEGs) in Po-S vs Pre-S, 833 DEGs in Po-F vs Pre-F, and 1,221 DEGs in Po-F vs Po-S. Relative to Po-S, Po-F specimens demonstrated enrichment of innate immune and inflammatory signaling pathways, including RIG-I–like receptor signaling, TNF/NF-κB cascades, IL-17 signaling, necroptosis, neutrophil extracellular trap formation, and oxidative stress–related processes. KEGG pathway analysis further revealed significant enrichment of hypoxia-associated pathways, including HIF-1 signaling, in Po-F tissues. In contrast, Po-S samples exhibited comparatively lower enrichment of inflammatory and hypoxia-related gene signatures. Proteomic profiling identified 111 differentially expressed proteins between Po-F and Po-S specimens. Functional annotation analysis indicated reduced representation of proteins involved in tricarboxylic acid (TCA) cycle and pyruvate metabolism, alongside increased representation of glycolysis-associated and metal-ion–binding proteins in Po-F tissues, consistent with altered metabolic pathway enrichment. Conclusion AVF failure is associated with heightened inflammatory pathway enrichment, including RIG-I–related innate immune signatures, increased representation of hypoxia-associated transcriptional programs, and metabolic alterations characterized by reduced oxidative metabolism and increased glycolytic signatures. In contrast, successful AVF maturation is accompanied by comparatively attenuated inflammatory and hypoxic pathway enrichment. These findings delineate a multi-layered molecular landscape linking innate immune signaling, hypoxia-associated remodeling, and metabolic pathway alterations in human AVF tissues and provide a framework for future mechanistic and therapeutic investigation.
Noninvasive plaque characterization remains limited in peripheral arterial obstructive disease (PAOD), whereas ex vivo micro-computed tomography (micro-CT) enables quasihistological assessment. This study evaluates whether plaque-related structural information—defined as compositional and morphological plaque features learned from micro-CT segmentation—can be transferred to clinical computed tomography (CT) using a super-resolution (SR) framework. Popliteal artery segments from six patients with peripheral arterial obstructive disease were analyzed using micro-CT and histology. Annotated micro-CT images were used to train convolutional neural networks for plaque segmentation. Low-resolution clinical CT images were upsampled using a Laplacian pyramid SR approach, and segmentation models were applied without retraining. Performance was assessed using Dice scores on held-out micro-CT test data, and segmentation outputs on SR-CT images were qualitatively evaluated. Segmentation of calcified plaque components on micro-CT test images yielded Dice scores ranging from 0.58 to 0.67, indicating low-to-intermediate agreement. When applied to SR-CT images, segmentation revealed nonrandom identification of calcified structures in selected image sequences, with marked heterogeneity across slices. SR enables exploratory assessment of plaque information transfer but does not overcome the fundamental resolution gap. These findings define the current limits of CT-based plaque characterization and provide a framework for evaluating future imaging technologies. Clinical Relevance: Accurate plaque characterization remains a major unmet need in peripheral arterial disease, where treatment planning is largely guided by lesion length and stenosis severity rather than plaque composition. This study proposes using micro-computed tomography (micro-CT) as a histology-informed reference to evaluate how much plaque-related information can be transferred to clinical CT. By explicitly defining current limitations, our findings caution against premature clinical application while informing future developments in advanced CT technologies, multimodal imaging, and artificial intelligence.
Actin cytoskeleton dysregulation contributes to vascular anomalies such as cerebral cavernous malformation (CCM). Talin rod domain containing-1 (TLNRD1) has been reported to interact with cerebral cavernous malformations 2 protein (CCM2), yet the downstream signaling remains debated, as previous studies have described opposite directions of Krueppel-like factor 2/4 (KLF2/4) changes after TLNRD1 depletion. Here, we combined biochemical analyses, structural modeling, transcriptomics, and single-cell network perturbation to examine the TLNRD1-CCM2 axis in endothelial cells. Coimmunoprecipitation and mass spectrometry confirmed the association between TLNRD1 and the CCM complex. Furthermore, protein docking predicted a stable TLNRD1-CCM2 interface (ΔG ≈ -50.36 kcal/mol) supported by prominent hydrogen bonds. Bulk RNA sequencing following TLNRD1 knockdown identified 677 differentially expressed genes, which were heavily enriched for actin cytoskeleton organization, with limited support for activation of the canonical MEKK3-KLF2/4 program. To assess KLF2/4 more directly, we analyzed human CCM single-cell RNA sequencing using scTenifoldKnk alongside complementary in vitro perturbations. Across these orthogonal analyses, KLF2 and KLF4 showed little to no consistent transcriptional alterations. Instead, TLNRD1 perturbation prominently altered endothelial F-actin stress fiber formation. Together, these data support a model in which TLNRD1 preferentially modulates endothelial cytoskeletal remodeling largely independent of overt KLF2/4 transcriptional shifts, helping to contextualize previous discrepancies and refining our understanding of its role in vascular biology. Clinical Relevance:Current management of cerebral cavernous malformations (CCMs) remains limited by an incomplete understanding of the molecular basis of endothelial instability. This study identifies TLNRD1 as a CCM2-associated regulator of endothelial actin organization and cytoskeletal remodeling, while showing limited support for consistent KLF2/4 transcriptional changes. For clinicians, these findings add mechanistic context to a disease with few medical options and may help explain earlier conflicting experimental observations. Although direct clinical application is not immediate, the TLNRD1-CCM2 axis warrants further study as a biologically relevant pathway that may inform future translational research on cerebrovascular lesion progression.
Background:We have recently demonstrated that muscle sympathetic nerve activity and normetanephrine levels are transiently increased for several days immediately after acute type B aortic dissection. We now report other markers of sympathetic activation, natriuresis and inflammation over the same time frame. Methods:In 13 patients with known acute type B aortic dissection (median age, 71 years; 95% confidence interval, 29-89 years), we undertook serial measurements of catecholamine metabolites including normetanephrine, metanephrine, and their second messenger cyclic adenosine monophosphate; renin and aldosterone; N terminal-pro-brain natriuretic peptide (NT-proBNP), and its second messenger cyclic, guanosine monophosphate; C-type natriuretic peptide; the inflammatory growth differentiation factor 15; the stress hormone copeptin; mid-regional-proadrenomedullin; and the marker of cardiac muscle damage Troponin T. Venous sampling times were on admission, then 12 hours, 24 hours, 1 week, and 6 weeks later. Serial measurements were also undertaken in 12 controls (median age, 61 years; 95% confidence interval, 25-86 years) who presented with chest pain. Results:During the first week after dissection, normetanephrine levels were increased: 617 to 792 vs 425 to 489 pmol/L in controls (analysis of variance [ANOVA] P = .01). There was also a simultaneous increase in NT-proBNP levels: 49 to 93 vs 14-21 pmol/L (ANOVA P = .07), and growth differentiation factor 15 levels: 1507 to 2873 vs 1146 to 1448 pg/mL (ANOVA P = .01) over the same period. Conclusions:The increase in normetanephrine levels during the week after type B dissection confirms sympathetic nerve activity as a likely mechanism for hypertension in these patients. This surge of sympathetic activity may be partially antagonized by a simultaneous increase in NT-proBNP, which is possibly triggered by acute inflammation and oxidative stress caused by the dissection. Clinical Relevance:This pilot study focused on assessing the timeline of neuroendocrine hormone release in acute type B aortic dissection. Our results demonstrated an increase in normetanephrine levels suggesting the involvement of the sympathetic nerve activity in driving hypertension in the acute setting of type B aortic dissection. There was also a concurrent increase in N-terminal pro-brain natriuretic peptide and growth differentiation factor 15 levels seen, suggesting an underlying inflammatory process and vascular stress. These can be the focus of future research in the development of pharmaceutical targets or the use of natriuretic drugs and anti-inflammatory agents in the mainstay treatment of type B aortic dissection.
Objective:Thoracic duct outflow obstruction is a recognized cause of refractory lymphatic leakage; however, the physiological consequences of such obstruction on thoracic duct pressure and its relationship to central venous pressure have not been fully characterized in vivo. This study aimed to evaluate changes in thoracic duct pressure and the pressure gradient between the thoracic duct and the central venous system in an experimental model of thoracic duct outflow obstruction. Methods:In a swine model, thoracic duct pressure and central venous pressure were directly measured using intravascular catheters positioned at matched vertebral levels. Thoracic duct embolization was performed at the upper thoracic level using coils and cyanoacrylate and was used as an experimental model of thoracic duct outflow obstruction. Pressure measurements were obtained before embolization and after confirmation of complete thoracic duct occlusion. Changes in thoracic duct pressure, central venous pressure, and the pressure relationship between the two systems were analyzed using paired statistical comparisons. Results:Thoracic duct outflow obstruction resulted in a significant increase in upstream thoracic duct pressure, with a median increase of approximately 6 to 8 mmHg compared with preobstruction values. Following obstruction, thoracic duct pressure consistently exceeded central venous pressure, creating a pressure gradient indicative of lymphatic hypertension. In contrast, central venous pressure did not change significantly after thoracic duct obstruction. No consistent cranio-caudal longitudinal pressure gradient along the thoracic duct was identified. Conclusions:Thoracic duct outflow obstruction induces lymphatic hypertension, as demonstrated by an increase in thoracic duct pressure relative to central venous pressure. This experimentally demonstrated pressure gradient provides physiological support for decompressive interventions by demonstrating a pressure gradient favorable for lymphatic drainage into the venous system. By directly quantifying intralymphatic and venous pressures in vivo, this study offers mechanistic insight into the pathophysiology of lymphatic leakage associated with thoracic duct obstruction and may help inform treatment selection between occlusive and decompressive strategies in lymphatic interventions. Clinical Relevance:Thoracic duct outflow obstruction is a cause of lymphatic leakage, yet the consequences of obstruction on thoracic duct pressure and its relationship to central venous pressure have remained unclear. In this experimental study, in vivo measurements demonstrated that thoracic duct outflow obstruction results in an increase in thoracic duct pressure, creating a pressure gradient relative to central venous pressure. This pressure relationship reflects lymphatic hypertension caused by outflow obstruction and supports decompressive interventions aimed at restoring lymphatic outflow.
Although perioperative stroke is a recognized risk in thoracic endovascular aortic arch repair, the long-term impact of altered cervical flow resulting from different device configurations is underappreciated. We compared angiographic data from two aortic stents, with anatomical (in-line) and nonanatomical (retrograde inner branch) configurations, and demonstrated a persistent filling delay in the retrograde inner branch device. Using computational fluid dynamic modeling, we demonstrated that parameters such as turbulence, vorticity, and Q-criterion are elevated in an idealized retrograde inner branch geometry. By way of a fluid mechanic scaling analysis, we show that the retrograde inner branch configuration results in a larger Dean number, thereby explaining our observed angiographic and computational modeling results. Our work should prompt further investigation regarding the long-term impact of branch configuration and altered cervical blood flow. Clinical Relevance:Thoracic endovascular aortic arch repair is growing in prevalence. Perioperative stroke risk remains a major risk factor. A less studied phenomenon is the impact of differing branch configurations on long-term hemodynamics. This work compared angiographic data from two devices with differing branch flow configurations: antegrade vs retrograde. A persistent cervical branch filling was noted in the retrograde branch device. We applied fluid mechanic scaling analysis and validated with computational modeling to show that the retrograde branch configuration is promoting of disturbed flow. This work should promote further clinical investigation regarding long-term impact of branch configuration.
Objective: Electrified wire in situ fenestration (EW-ISF) has been recently described both in vivo and in vitro as a feasible alternative to laser ISF to address complex aortic pathologies in emergency situations. However, no data are currently available regarding the preferred dilatation method after puncture. The aim of this paper was to compare two established schemes of fenestration dilation after an EW-ISF setting. Methods: A total of 72 EW-ISFs were performed in 4 commercially available endografts: Zenith Alpha (n = 20), RelayPro (n = 20), Endurant IIs (n = 20), and Valiant Captivia (n =12). In group A, fenestrations were sequentially dilatated with a 2mm and a 6-mm plain balloon dilatation (PBD). In group B, fenestrations were dilatated with a 2-mm PBD, a 4-mm cutting balloon, and a 6-mm PBD. Postdilatation fenestration morphological features were analyzed, and diameters and surface were measured after dilatation and after 24 hours to assess the relative fabric elastic recoil. For each graft, in both group one bridging stent (BS) was implanted and its caliber measured with intravascular ultrasound. Results: In both the Zenith and the Endurant, group B showed more tearing (P = .302 and P < .001 respectively), less bulging (P = .039 and P < .001), and more frequent slit-like fenestration morphology (P = .015 and P = .001). The Valiant graft displayed major (>0.5 cm long) tearing in group B. Fenestration dimensions and recoil momentum were comparable between the two groups in all grafts, but the Endurant, where group B fenestrations had significantly higher fenestration area (6.5 mm(2) vs 2.3 mm(2); P < .001). BS caliber was comparable in both groups in the RelayPro and Zenith Alpha, but a significant stenosis was assessed in group A in the Endurant IIs. Conclusions: Both cutting balloon dilatation and PBD are feasible and comparable after EW-ISF in the in the RelayPro and the Zenith grafts. Cutting balloon provides more ideal fenestration dimensions in the Endurant IIs and might be preferred. It determines excessive damages in the monofilament graft and should, therefore, be avoided. Clinical Relevance: Electrified wire in situ fenestration is an emerging, low-cost alternative for urgent aortic branch revascularization, but optimal postfenestration dilation remains undefined. This study provides practical guidance on balloon selection according to graft fabric. Cutting balloons may improve fenestration enlargement and reduce the risk of bridging stent stenosis in multifilament grafts such as Endurant IIs, while causing excessive damage in monofilament devices. Tailoring dilation strategy to graft type may enhance safety, durability, and procedural success in emergency endovascular aortic repair.
Intestinal ischemia-reperfusion (I/R) injury is a major complication of aortic occlusion during resuscitative thoracotomy or resuscitative endovascular balloon occlusion of the aorta. We investigated whether targeted intra-arterial delivery of hemoglobin vesicles (HbVs) attenuates intestinal I/R injury in a rat thoracic aortic cross-clamping model. Male Wistar rats underwent 60 minutes of thoracic aortic occlusion followed by 60 minutes of reperfusion. Animals received intra-arterial HbV (1.25 mL/kg every 10 minutes; n = 5) or saline (n = 5) via the femoral artery; sham animals (n = 3) underwent instrumentation only. Compared with saline controls, HbV-treated rats demonstrated higher postreperfusion systolic blood pressure (56 ± 4 mm Hg vs 34 ± 8 mm Hg; P = .002) and lower plasma lactate levels (2.7 ± 0.4 mmol/L vs 7.5 ± 0.4 mmol/L; P < .001). Intestinal injury was significantly attenuated in the HbV group, with lower Chiu scores (median 2.0 vs 4.0; P = .018), reduced terminal deoxynucleotidyl transferase dUTP nick end labeling-positive area fraction (P = .003), and decreased inducible nitric oxide synthase-positive area fraction (P = .006). Targeted intra-arterial HbV administration significantly reduced early intestinal I/R injury in this exploratory proof-of-concept model and may represent a promising adjunctive oxygen-carrying strategy to protect distal organs during prolonged aortic occlusion.
Objective Femoral artery plaques are characterized by a long-standing inflammatory response and advanced calcification and bone formation not seen in other vascular beds as extensively. Our study aimed to characterize and analyze the immune cell profile of bone marrow in femoral artery plaques in order to direct future innovation of therapies targeted at atherosclerosis in peripheral arteries. Methods Atherosclerotic plaques were collected during femoral endarterectomy from 91 patients. Bone marrow was detected in 47.3% of samples and 25 of those with visually largest bone marrow area in hematoxylin and eosin stained samples were re-sectioned and subjected to multiplex immunofluorescence staining for CD34, CD117, CD3, CD56, CD11c, CD20, CD11b, CD68, CD45 and SMA. Machine learning techniques were employed to quantify the cells expressing each surface marker. Patient data were collected from electronic patient records and laboratory measurements were obtained prior to surgery. Magnetic resonance angiography (MRA) imaging of the lower limb arteries obtained prior to surgery were analyzed. Baseline data was collected at time of surgery and for overall mortality patients were followed until 31.10.2024. Results All patients analyzed had extensive atherosclerotic disease in the MRA imaging and 45% of patients had died by the end of follow-up. Bone marrow-like tissue in the plaques was lined by osteoblast-like cells (CD56+), was densely vascularized, and in three plaques megakaryocytes were observed. An arterial tertiary lymphoid organ rich in B and T cells was observed. The immune cell composition of the bone marrow-like areas varied with correlations to clinical characteristics. The proportion of CD56+ cells correlated with age, glomerular filtration rate and smoking (rho = -0.597, p=0.005, BH adjusted p=0.0125, rho= 0.541, p=0.014, BH adjusted p=0.023 and p=0.005, BH adjusted p=0.0125, respectively) and proportion of B cells (CD20+) with alkaline phosphatase (rho= -0.719, p<0.001, BH adjusted p=0.003). Conclusions Bone marrow-like tissue in conjunction with metaplastic bone in femoral artery plaques of patients with extensive atherosclerosis is not rare and is characterized by dense neovascularization, dense clusters of inflammatory cells, and on occasion megakaryocytes. The distribution of immune cells in the bone marrow-like tissue varies in relation to clinical characteristics of the patient and has potential implications for the development of novel treatment targets of atherosclerosis. Clinical Relevance Bone marrow is not uncommon in the femoral artery atherosclerotic plaques of patients undergoing femoral endarterectomy portraying the advanced and irreversible stage of atherosclerotic disease in these patients, some of which were operated on the basis of claudication. The femoral artery plaques contain large areas of calcified and fibrotic, mostly acellular tissue, but there are also hotspot areas of high cellular density and immunological activity as well as active bone remodeling with patient-to-patient variation. Our study highlights the need for a personalized approach to developing treatment strategies for atherosclerotic disease providing a roadmap for novel targets in further studies.
