Distal Artery Research Articles

Manual compression hemostasis using a hemostatic pad for the distal radial artery approach

BackgroundThe method of hemostasis for the distal radial approach has not been standardized, although this approach has become increasingly popular due to its advantages. In this study, we investigated the feasibility of manual compression hemostasis using a calcium alginate pad after coronary angiography via the distal radial approach. MethodsWe retrospectively collected 150 consecutive patients (mean age, 74.9 ± 8.0 years; male, 75 %) who underwent coronary angiography via the distal radial artery with a predominantly 4 Fr sheath from April 2021 to December 2022 and were hemostatic according to the following methods. After sheath removal, hemostasis was achieved by manual compression for 10 min using a hemostatic pad containing calcium alginate. When hemostasis was confirmed, a small log-shaped gauze was placed over the pad and fixed using a self-adhesive elastic bandage for 2 h. All procedures were performed by four fellows just beginning the distal radial approach. ResultsThe mean compression time was 12.4 ± 4.8 min, and hemostasis was successfully achieved in all patients, allowing the release of the elastic bandage after 2 h, with only one patient oozing the next morning. There were no major complications, while one patient had a >10 cm hematoma. Compared to that of the first 15 patients, for each fellow, the compression time of the subsequent patients was significantly shorter (14.5 ± 6.7 vs 11.1 ± 2.1 min, p < 0.01). ConclusionsManual compression hemostasis using calcium alginate pads for the distal radial artery approach appears feasible with a simple learning.

Na+/H+ exchanger isoform 1 (NHE1) confers resistance to apoptosis in pulmonary arterial smooth muscle cells (PASMCs)

Pulmonary hypertension (PH) is a condition caused by remodeling of the lung vasculature due to abnormal cell turnover involving increased cell proliferation and resistance to apoptosis. The mechanisms controlling abnormal cell growth and survival are incompletely understood. We previously found that Na+/H+ exchanger (NHE) activity is increased in PASMCs from PH patients and the Sugen Hypoxia (SuHx) animal model of PH. NHE isoform 1 (NHE1) is a membrane protein that regulates intracellular pH (pHi) and cell volume via export of H+ and import of Na+. This protein also has a cytosolic tail region shown to be involved in non-canonical functions such as cytoskeletal interactions and cell signaling via protein-protein interactions. NHE1 has been associated with increased PASMC proliferation; however, it is unclear if increased NHE activity, dysregulation of pHi or cytoskeletal interactions are involved in resistance to apoptosis. In this study, we tested the hypothesis that increased expression of NHE1 leads to apoptosis resistance in PASMCs via dysregulation of pHi. We first used the rat SuHx model of PH in which male Wistar rats receive a single subcutaneous injection of the vascular endothelial growth factor receptor inhibitor, SU5416, followed by 3 wks of exposure to hypoxia (10% O2) and 2 wks of normoxia. PASMCs were isolated from distal pulmonary arteries of control and SuHx Wistar rats and treated with the NHE inhibitor, 5-(N-ethyl-N-isopropyl)-amiloride (EIPA; 1 uM), or vehicle for 24 h before analyzing cell apoptosis via Hoechst staining under baseline and stimulated conditions (250 uM H2O2). Endoplasmic reticulum stress was measured using the fluorescent stain, Thioflavin T (ThT). In some experiments, cells from control rats were infected with adenovirus containing green fluorescent protein (AdGFP; control for infection), wild-type NHE1 (AdNHE1-WT) or NHE1 mutants: AdNHE1-E262I lacking ion translocation activity and AdNHE1-EM lacking the ezrin binding site which prevents cytoskeletal interactions. NHE1 protein expression and localization were assessed via immunoblotting (total and surface proteins). Effcacy of Na+/H+ translocation was assessed from Na+-dependent recovery following an ammonium pulse. At baseline, despite increased ThT levels in SuHx cells, apoptosis was not different compared to control cells, indicating SuHx cells have suppressed apoptotic response to increased ER stress. Following treatment with EIPA, apoptosis was increased in SuHx cells, possibly indicating they became sensitized to the high levels of ER stress and were able to proceed into the apoptotic pathway. Similarly, following treatment with H2O2, SuHx PASMCs showed resistance to apoptosis compared to control cells, which was alleviated with pre-treatment with EIPA. In control cells, wild-type NHE1 and NHE1 mutants were expressed in similar amounts which led to an expected increase in NHE activity for WT and NHE1-EM, but not for NHE1-E262I when compared to GFP. We found that enhanced expression of NHE1-WT was suffcient to inhibit apoptosis following treatment with H2O2. Interestingly, both NHE1 mutants also significantly decreased PASMC apoptosis following H2O2 stimulation. Our results indicate NHE1 is necessary for apoptosis resistance in PASMCs from animals with PH and that increased expression is suffcient to confer resistance to apoptosis in control PASMCs. Additionally, these results suggest neither pHi regulation nor interaction between NHE1 and ezrin are essential for NHE1-induced apoptosis resistance, indicating another mechanism through which NHE1 confers resistance to apoptosis in PH. Based on these findings, we speculate that development of NHE1-related therapeutic targets could potentially restore cell apoptosis and reverse disease. AHA 23PRE1022720, HL159906, HL073859. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract 103: Acly Inhibition As A Novel Therapeutic Approach For Vascular Remodeling In Coronary Artery Disease

Coronary artery (CoA) disease (CAD) is characterized by neointimal hyperplasia (NH), which is driven by a cancer-like pro-proliferative phenotype of smooth muscle cells (SMCs). A metabolic shift towards glycolysis and changes in the epigenetic landscape contribute to this abnormal phenotype. ATP Citrate Lyase (ACLY) is an enzyme that plays a role in promoting the Warburg effect, lipid synthesis, and chromatin remodeling in cancer. However, its role in CAD remains unknown. We hypothesized that ACLY is upregulated in CAD and supports the abnormal phenotype of CAD-CoASMCs. To investigate this hypothesis, we measured ACLY expression in human distal coronary arteries and isolated CoASMCs from CAD patients. We found increased expression and activation of ACLY in CAD-CoASMCs, with preferential localization in the nucleus. Inhibition of ACLY using BMS-303141 or siACLY decreased CAD-CoASMCs proliferation and survival. ACLY inhibition also reduced glycolysis markers and increased mitochondrial respiration. Additionally, ACLY inhibition lowered cholesterol levels and lipid droplet accumulation in CAD-CoASMCs. Further analysis showed that ACLY promotes nuclear acetyl-CoA production, leading to acetylation of specific histone proteins and GCN5-mediated transcriptional activation of genes involved in cell cycle progression. The transcription factor FOXM1 appeared to mediate this genetic signature. In vivo , pharmacological inhibition of ACLY using BMS-303141 attenuated NH in a rat model of carotid injury (CI). SMC-specific Acly K.O mice were protected against CI-induced NH. Consistently, tamoxifen-induced SMC-specific Acly deletion mitigated NH in mice subjected to CI. The therapeutic effects were associated with reduced histone acetylation. To assess the translational potential of our findings, we tested the effects of ACLY inhibition on ex vivo human coronary artery and saphenous vein explants stimulated with growth factors cocktail. We found that ACLY inhibition prevent NH development, supporting the potential of ACLY as a therapeutic target. In conclusion, our study reveals that ACLY plays a critical role in vascular remodeling in CAD and its pharmacological inhibition may represent a novel avenue as therapeutic treatment.

Abstract 2029: Augmenting Mitochondrial Respiration In Immature Smooth Muscle Cells Is A Therapeutic Target For Moyamoya-like Cerebrovascular Disease

Introduction: Moyamoya disease (MMD), characterized by occlusive lesions in the distal internal carotid arteries, is a malignant cause of pediatric stroke. Surgical revascularization is the mainstay treatment, but peri- and postoperative ischemic complications are common. Multiple identified genes account for only a small percentage of cases. Identifying a common pathway of disease pathogenesis would enhance care for MMD patients. Goal and Approach: We used cellular and animal models for a rare cause of MMD-like cerebrovascular disease, heterozygous ACTA2 p.R179 pathogenic variants, to define molecular mechanisms and assess therapeutic strategies. Our prior work showed that smooth muscle cells (SMCs) with ACTA2 p.R179 variants are incompletely differentiated. We hypothesized that these immature phenotypes could be rescued by manipulation of cellular metabolism. We validated our results with cellular models of other pediatric MMD-associated variants: loss-of-function variants in Pcnt (explanted from a mouse model) and a pathogenic variant in RNF213 (generated via Crispr/Cas9 in human iPSCs). Results: Acta2 SMC-R179C/+ SMCs have increased glycolysis and reduced oxidative respiration on Seahorse analyses. Molecular characterization showed that Acta2 SMC-R179C/+ SMCs have reduced mitochondrial mass and decreased complex I activity, which is rescued by nicotinamide riboside (NR) treatment. NR surprisingly also increases SMC differentiation and decreases migration. Acta2 SMC-R179C/+ mice and littermate controls were subjected to carotid artery ligation, and 33% of Acta2 SMC-R179C/+ mice died due to strokes while all control mice survived (Kaplan-Meier p&lt;0.01). Surviving Acta2 SMC-R179C/+ mice have significant cerebrovascular remodeling and persistent occlusive carotid artery lesions. Treatment with NR reduces death (Kaplan-Meier p=0.08) and resolves persistent lesions (p&lt;0.05) in Acta2 SMC-R179C/+ mice after carotid ligation. Pcnt and RNF213 mutant SMCs have a similar phenotype of incomplete differentiation and decreased mitochondrial respiration as ACTA2 p.R179 and are responsive to NR treatment. Conclusions: These data provide evidence for a common and therapeutically targetable pathway in pediatric MMD patients.

One-Stage Combined Open and Endovascular Treatment Using a Hybrid Operating Room is Safe and Effective for Distal Middle Cerebral Artery Aneurysms

BackgroundAneurysms located in the distal middle cerebral artery (MCA) are relatively rare and lack an established treatment strategy. For distal MCA (DMCA) aneurysms, we performed a one-stage combined procedure of endovascular parent artery occlusion (PAO) with coils and superficial temporal artery to middle cerebral artery (STA-MCA) bypass in a hybrid operating room (HOR). The aim of this study was to evaluate the safety and efficacy of this procedure. MethodsCases of unruptured DMCA aneurysms treated with the one-stage combined PAO and STA-MCA bypass in HOR were retrospectively examined, and patients’ and aneurysmal backgrounds, surgical procedures, and treatment outcomes were analyzed. ResultsSix patients were included in the study. The average maximum diameter of the aneurysms was 14.4 mm. One aneurysm was located at M2 and five at M3. All aneurysms had a fusiform shape. No cases were associated with infection, trauma, or malignant tumors. In all six cases, the combined PAO and STA-MCA bypass was successfully completed. No postoperative hemorrhagic complications occurred. A symptomatic ischemic complication occurred in one case whose symptom disappeared in a week. Three months after surgery, complete obliteration of the aneurysm and patency of the bypass were confirmed in all cases. ConclusionsThe one-stage combined PAO and STA-MCA bypass in the HOR is safe and effective for DMCA aneurysms, potentially serving as a treatment option for this complex aneurysm.

Ankle Brachial Index (ABI) Versus Point-of-Care Arterial Duplex Ultrasound (DUS) in Early Detection and Diagnosis of Diabetic Foot Ischemia in Hemodialysis Unit

Background: Diabetes is a widespread noncommunicable disease affecting an estimated 463 million adults worldwide in 2019 and will affect 700 million by 2045. Diabetic foot lesions remain a major cause of morbidity in patients with renal failure, especially those on dialysis. Ankle Brachial Index (ABI) may inaccurately assess lower extremity perfusion in patients with highly calcified, no compressible tibial arteries. focused Arterial duplex ultrasound (DUS) of the distal anterior and posterior tibial arteries at the ankle can be readily learnt by novices (nurse/physician) and performed rapidly and accurately for early diagnosis and referral.

Identification of S100A8/A9 involved in thromboangiitis obliterans development using tandem mass tags-labeled quantitative proteomics analysis

Thromboangiitis obliterans (TAO) is characterized by inflammation and obstruction of small-and medium-sized distal arteries, with limited pharmacotherapies and surgical interventions. The precise pathogenesis of TAO remains elusive. By utilizing the technology of tandem mass tags (TMT) for quantitative proteomics and leveraging bioinformatics tools, a comparative analysis of protein profiles was conducted between normal and TAO rats to identify key proteins driving TAO development. The results unveiled 1385 differentially expressed proteins (DEPs) in the TAO compared with the normal group-comprising 365 proteins with upregulated expression and 1020 proteins with downregulated expression. Function annotation through gene ontology indicated these DEPs mainly involved in cell adhesion, positive regulation of cell migration, and cytosol. The principal signaling pathways involved regulation of the actin cytoskeleton, vascular smooth contraction, and focal adhesion. The roles of these DEPs and associated signaling pathways serve as a fundamental framework for comprehending the mechanisms underpinning the onset and progression of TAO. Furthermore, we conducted a comprehensive evaluation of the effects of S100A8/A9 and its inhibitor, paquinimod, on smooth muscle cells (SMCs) and in TAO rats. We observed that paquinimod reduces SMCs proliferation and migration, promotes phenotype switching and alleviates vascular stenosis in TAO rats. In conclusion, our study revealed that the early activation of S100A8/A9 in the femoral artery is implicated in TAO development, targeting S100A8/A9 signaling may provide a novel approach for TAO prevention and treatment.

Clinical Features and Multimodality Diagnostic Tools of Pulmonary Hypertension

Pulmonary hypertension (PH) is defined as an increase in mean pulmonary arterial pressure (mPAP) above normal (&gt; 20 mmHg) and an increase in pulmonary vascular resistance (pulmonary vascular resistance / PVR) above normal in resting settings. The pathophysiology of PH involves remodeling of the pulmonary vessels, from the main pulmonary arteries, lobar arteries, segmental arteries, distal arteries, pulmonary arterioles, capillaries to the postcapillary pulmonary veins. In general, the epidemiological figures for PH are not known with certainty. The United Kingdom reported a PH prevalence of 97 cases per one million people, with a female-to-male ratio of 1.8. The diagnostic strategy for PH focuses primarily on two issues. The primary objective is to improve the early detection of PH and expedite the transfer of patients at high risk for PAH, CTEPH, or other forms of severe PH to a PH center. The second objective is to identify the underlying disease, including left heart disease (Group 2 PH) and lung disease (Group 3 PH), as well as comorbidities, in order to assure proper classification, risk assessment, and therapy. The gold standard for detecting and categorizing pulmonary hypertension is right heart catheterization (RHC). Clinical scoring in the form of shortness of breath without any obvious cause accompanied by physical examination, ECG and Thorax X-ray images which depict an enlarged right heart have good specificity and sensitivity for the diagnosis of pulmonary hypertension in patients with congenital heart disease. A high right ventricular pressure, mean PAP, and BNP values during observation, as well as heart size on chest X-ray can be predictors of a poorer prognosis in this population. Keyword: Clinical Risk Scoring, Pulmonary Hypertension, Right Heart Catheterization.

Increased diameter and stiffness of elastic but not muscular arteries in men with abdominal aortic aneurysm.

It has been proposed that formation of abdominal aortic aneurysm (AAA) is part of a systemic arterial dilatative disease. However, arteries in the upper extremities are scarcely studied and it remains unclear whether both muscular and elastic arteries are affected by the proposed systemic arterial dilatation. The aim of this study was to investigate the diameter and stiffness of muscular and elastic arteries in arterial branches originating from the aortic arch. Twenty-six men with AAA (69 ± 4 yr) and 57 men without AAA (70 ± 5 yr) were included in the study. Ultrasound was used to examine the distal and proximal brachial artery, axillary artery, and common carotid artery (CCA), and measurement of diameter and diameter change was performed with wall-tracking software. Blood pressure measurements were used to calculate local arterial wall stiffness indices. The AAA cohort presented larger arterial diameters in the CCA and axillary artery after adjustment for body surface area (P = 0.002, respectively), whereas the brachial artery diameters were unchanged. Indices of increased stiffness in CCA (e.g., lower distensibility, P = 0.003) were seen in subjects with AAA after adjustments for body mass index and mean arterial blood pressure. This study supports the theory of a systemic arterial dilating diathesis in peripheral elastic, but not in muscular, arteries. Peripheral elastic arteries also exhibited increased stiffness, in analogy with findings in the aorta in AAA.NEW & NOTEWORTHY We present data partially supporting the notion of abdominal aortic aneurysm being a systemic vascular disease with focal manifestation in the abdominal aorta, from two well-defined groups recruited from a regional screening program. We show that elastic arteries distal from the aorta exhibit vascular alterations without aneurysmal formation in subjects with AAA compared with controls while muscular arteries seem unaffected.

Spatial Atlas for Mapping Vascular Microcalcification Using 18F-NaF PET/CT: Application in Hyperphosphatemic Familial Tumoral Calcinosis.

Vascular calcification causes significant morbidity and occurs frequently in diseases of calcium/phosphate imbalance. Radiolabeled sodium fluoride positron emission tomography/computed tomography has emerged as a sensitive and specific method for detecting and quantifying active microcalcifications. We developed a novel technique to quantify and map total vasculature microcalcification to a common space, allowing simultaneous assessment of global disease burden and precise tracking of site-specific microcalcifications across time and individuals. To develop this technique, 4 patients with hyperphosphatemic familial tumoral calcinosis, a monogenic disorder of FGF23 (fibroblast growth factor-23) deficiency with a high prevalence of vascular calcification, underwent radiolabeled sodium fluoride positron emission tomography/computed tomography imaging. One patient received serial imaging 1 year after treatment with an IL-1 (interleukin-1) antagonist. A radiolabeled sodium fluoride-based microcalcification score, as well as calcification volume, was computed at all perpendicular slices, which were then mapped onto a standardized vascular atlas. Segment-wise mCSmean and mCSmax were computed to compare microcalcification score levels at predefined vascular segments within subjects. Patients with hyperphosphatemic familial tumoral calcinosis had notable peaks in microcalcification score near the aortic bifurcation and distal femoral arteries, compared with a control subject who had uniform distribution of vascular radiolabeled sodium fluoride uptake. This technique also identified microcalcification in a 17-year-old patient, who had no computed tomography-defined calcification. This technique could not only detect a decrease in microcalcification score throughout the patient treated with an IL-1 antagonist but it also identified anatomic areas that had increased responsiveness while there was no change in computed tomography-defined macrocalcification after treatment. This technique affords the ability to visualize spatial patterns of the active microcalcification process in the peripheral vasculature. Further, this technique affords the ability to track microcalcifications at precise locations not only across time but also across subjects. This technique is readily adaptable to other diseases of vascular calcification and may represent a significant advance in the field of vascular biology.

Attempted retrieval of guidewire fragment using the twisting wire technique causes coronary perfusion: Case report.

Guidewire fracture is one of the biggest risks of percutaneous coronary intervention, twisting wire technique is very useful for retrieving the fractured wire, but the potential risks have been inadequately reported. Herein, we present a case of retrieval of guidewire fragments using the twisting wire technique that causes coronary perfusion. A 37-year-old male patient was admitted to our hospital for elective percutaneous coronary intervention of the left circumflex coronary artery. For chronic total occlusion of the distal left circumflex coronary artery, antegrade recanalization by wire escalation, and parallel wire techniques were attempted. However, we shockingly found that the BMW guidewire, anchored in the right coronary artery, spontaneously fractured from the proximal right coronary artery, and a lengthy fragment of the guidewire remained in the coronary. Many attempts were made to retrieve the remnant guidewire including the twisting wire technique, which leads to the perforation of the coronary. Finally, percutaneous retrieving procedures were stopped in favor of surgical extraction via a small coronary arteriotomy. This procedure was successful. To the best of our knowledge, the present case is the first reported spontaneous fracture of the guidewire. Leaving such a lengthy remnant guidewire in the artery, or leaving stenting over the wire, would impose a high risk of coronary thrombosis, perforation, and embolization. Yet, the perforation of the artery that occurred in this case, which could have had life-threatening consequences, resulted from our attempts to retrieve the guidewire using the twisting wire technique.

Sealing of Iatrogenic Distal Coronary Artery Perforation by Liquid Embolization Agent—A Case Report

Percutaneous coronary intervention (PCI) is one of the most commonly performed cardiovascular interventions to treat significant coronary artery stenosis. Although a safe procedure, it carries the risk of complications like coronary artery perforation (CAP), bleeding, stroke, and acute kidney injury rarely resulting in death. The incidence of CAP is 0.84% of all PCI procedures and the incidence is increasing as cardiologists are accepting more and more challenging cases. CAP is caused by a guidewire (GW) or a vessel tear from balloon angioplasty, stenting, or rotational atherectomy. Though the majority of CAPs do not result in cardiac tamponade, some do lead to tamponade and death. The majority of distal wire perforations respond to prolonged balloon inflation, coils, glue, or fat embolization. Herein, we report a case of distal CAP in a 63-year-old woman occurring following left circumflex artery PCI caused by the exiting of coronary GW. The CAP was successfully sealed by the liquid embolization technique using ONYX. First described in 1990, Onyx is an elastic polymer composed of ethylene vinyl alcohol copolymer dissolved in dimethyl sulfoxide and mixed with micronized tantalum powder (Onyx). The Onyx is predominantly used by interventional radiologists while performing neurovascular and peripheral vascular interventions. There were only a few case reports of plugging of CAPs using Onyx. Our case highlights the safety and feasibility of closing distal CAPs using Onyx.

Feasibility of Weight-based Tube Voltage and Iodine Delivery Rate for Coronary Artery CT Angiography.

The objective of this study was to evaluate the feasibility of weight-based tube voltage and iodine delivery rate (IDR) for coronary artery CT angiography (CCTA). A total of 193 patients (mean age: 58 ± 12 years) with suspected coronary heart disease indicated for CCTA between May and October 2022 were prospectively enrolled. The subjects were divided into five groups according to body weight: < 60 kg, 60 - 69 kg, 70 - 79 kg, 80 - 89 kg, and ≥ 90 kg. The tube voltage and IDR settings of each group were as follows: 70 kVp/0.8 gI/s, 80 kVp/1.0 gI/s, 80 kVp/1.1 gI/s, 100 kVp/1.5 gI/s, and 100 kVp/1.5 gI/s, respectively. Objective image quality data included the CT value and standard deviation (noise) of the aortic root (AR), the proximal left anterior descending branch (LAD), and the distal right coronary artery (RCA), as well as the signal-to-noise ratio and contrast-to-noise ratio of the LAD and RCA. Subjective image quality assessment was performed based on the 18-segment model. Contrast and radiation doses, as well as effective dose (ED), were recorded. All continuous variables were compared using either the one-way ANOVA or the Kruskal-Wallis rank sum test. No significant differences were observed in all objective and subjective parameters of image quality between the groups (P > 0.05). However, significant differences in contrast and radiation doses were observed (P < 0.05). The contrast doses across the weight groups were 27 mL, 35 mL, 38 mL, 53 mL, and 53 mL, respectively, while the ED were 1.567 (1.30, 2.197) mSv, 1.53 (1.373, 1.78) mSv, 2.113 (1.963, 2.256) mSv, 4.22 (3.771, 4.483) mSv, and 4.786 (4.339, 5.536) mSv, respectively. Weight-based tube voltage and IDR yielded consistently high image quality, and allowed for further reduction in contrast and radiation exposure during CCTA for coronary artery diseases.

Increased sensitivity in detection of deficits following two commonly used animal models of stroke

Stroke is a leading cause of death and disability in the United States. Most strokes are ischemic, resulting in both cognitive and motor impairments. Animal models of ischemic stroke such as the distal middle cerebral artery occlusion (dMCAO) and photothrombotic stroke (PTS) procedures have become invaluable tools, with their own advantages and disadvantages. The dMCAO model is clinically relevant as it occludes the artery most affected in humans, but yields variability in the infarct location as well as the behavioral and cognitive phenotypes disrupted. The PTS model has the advantage of allowing for targeted location of infarct, but is less clinically relevant. The present study evaluates phenotype disruption over time in mice subjected to either dMCAO, PTS, or a sham surgery. Post-surgery, animals were tested over 28 days on standard motor tasks (grid walk, cylinder, tapered beam, and rotating beam), as well as a novel odor-based operant task; the 5:1 Odor Discrimination Task (ODT). Results demonstrate a significantly greater disturbance of motor control with PTS as compared with Sham and dMCAO. Disruption of the PTS group was detected up to 28 days post-stroke on the grid walk, and up to 7 days on the rotating and tapered beam tasks. PTS also led to significant short-term disruption of ODT performance (1-day post-surgery), exclusively in males, which appeared to be driven by motoric disruption of the lick response. Together, this data provides critical insights into the selection and optimization of animal models for ischemic stroke research. Notably, the PTS procedure was best suited for producing disruptions of motor behavior that can be detected with common behavioral assays and are relatively enduring, as is observed in human stroke.

Safety and efficacy of the novel Alpha stent for the treatment of intracranial wide-necked aneurysm

The Alpha stent is an intracranial closed-cell stent with a unique mesh design to enhance wall apposition. It recently underwent structural modifications to facilitate easier stent deployment. This study aimed to evaluate the safety and efficacy of stent-assisted coil embolization for unruptured intracranial aneurysms using the Alpha stent. Between January 2021 and November 2021, 35 adult patients with 35 unruptured intracranial aneurysms in the distal internal carotid artery were prospectively enrolled. For efficacy outcomes, magnetic resonance angiography at the 6-month follow-up was evaluated using the Raymond-Roy occlusion classification (RROC). The safety outcome evaluated the occurrence of symptomatic procedure-related neurological complications up to 6 months postoperatively. Technical success was achieved in 34/35 (97.1%). Six months postoperatively, aneurysm occlusion showed RROC I in 32/35 (91.4%) and RROC II in 3/35 (8.6%) patients. Procedure-related neurologic complications occurred in one patient (2.9%) who experienced hemiparesis due to acute lacunar infarction, which resulted in a 6-month mRS score of 1. The Alpha stent demonstrated excellent efficacy and safety outcomes in stent-assisted coil embolization of unruptured distal ICA aneurysms. The recent structural modifications allowed for easier stent delivery and deployment.Clinical trial registration number: KCT0005841; registration date: 28/01/2021.

Dl-3-n-butylphthalide improves stroke outcomes after focal ischemic stroke in mouse model by inhibiting the pyroptosis-regulated cell death and ameliorating neuroinflammation

Recent studies have highlighted the involvement of pyroptosis-mediated cell death and neuroinflammation in ischemic stroke (IS) pathogenesis. DL-3-n-butylphthalide (NBP), a synthesized compound based on an extract from seeds of Apium graveolens, possesses a broad range of biological effects. However, the efficacy and the underlying mechanisms of NBP in IS remain contentious. Herein, we investigated the therapeutic effects of NBP and elucidated its potential mechanisms in neuronal cell pyroptosis and microglia inflammatory responses. Adult male mice underwent permanent distal middle cerebral artery occlusion (dMCAO), followed by daily oral gavage of NBP (80 mg/kg) for 1, 7, or 21 consecutive days. Gene Expression Omnibus (GEO) dataset of IS patients peripheral blood RNA sequencing was analyzed to identify differentially expressed pyroptosis-related genes (PRGs) during the ischemic process. Our results suggested that NBP treatment effectively alleviated brain ischemic damage, resulting in decreased neurological deficit scores, reduced infarct volume, and improved neurological and behavioral functions. RNA sequence data from human unveiled upregulated PRGs in IS. Subsequently, we observed that NBP downregulated pyroptosis-associated markers at days 7 and 21 post-modeling, at both the protein and mRNA levels. Additionally, NBP suppressed the co-localization of pyroptosis markers with neuronal cells to variable degrees and simultaneously mitigated the accumulation of activated microglia. Overall, our data provide novel evidence that NBP treatment significantly attenuates ischemic brain damage and promotes recovery of neurological function in the early and recovery phases after IS, probably by negatively regulating the pyroptosis cell death of neuronal cells and inhibiting toxic neuroinflammation in the central nervous system.

Management of multiple cerebral embolisms due to polycythemia vera with acquired von Willebrand syndrome

AbstractPolycythemia vera (PV) is a rare blood disorder associated with thrombosis or acquired von Willebrand syndrome (AvWS); however, their coexistence is unusual. Here, we report about a 59‐year‐old man with PV who developed both ischemic stroke (IS) and AvWS. Although the patient had no history of thrombosis, he had refractory epistaxis 2 years prior. Brain magnetic resonance imaging and angiography (MRI and MRA) revealed new IS and mural thrombi at the left distal carotid artery. Laboratory investigations showed elevated hemoglobin and hematocrit levels with mild leukocytosis and thrombocytosis, corresponding to PV. Additionally, suppressed platelet aggregation and activity despite normal antigen of von Willebrand factor indicated AvWS. Appropriate repeated phlebotomies successfully resolved the MRA abnormalities and prevented IS recurrence, although the patient refused the recommended treatment with hydroxyurea. This case highlights the need for careful management to prevent recurrent IS and major bleeding in patients with PV who develop IS accompanying AvWS.

Effect of EDTA with porous balloon on calcified lesion: An atherosclerotic cadaver study.

Ethylene diamine tetra-acetic acid (EDTA) is a chelating agent used to dissolve calcium deposits but evidence in decalcifying atherosclerotic lesions is limited. We assessed the feasibility and efficacy of EDTA delivered via porous balloon to target calcified lesions in cadaveric below-the-knee (BTK) arteries. Using porcine carotid arteries, EDTA concentration was measured in the arterial wall and outside the artery at the 0-, 0.5-, 4-, and 24-h circulation after the injection through a porous balloon. In cadaver BTK samples, the proximal and distal anterior tibial artery (ATA) and distal posterior tibial artery (PTA) were studied. EDTA-2Na/H2O or EDTA-3Na/H2O were administrated using a porous balloon, then circulated for 6 h for EDTA-3Na/H2O and 24 h for EDTA-2Na/H2O and EDTA-3Na/H2O. Micro-CT imaging of the artery segments before and after the circulation and cross-sectional analyses were performed to evaluate calcium burden. In the porcine carotid study, EDTA was delivered through a porous balloon present in the arterial wall and was retained there for 24 h. In BTK arteries, cross-sectional analyses of micro-CT revealed a significant decrease in the calcium area in the distal ATA segment under 24-h circulation with EDTA-2Na/H2O and in the distal ATA segment under 24-h circulation with EDTA-3Na/H2O. The proximal ATA segment under 6-h circulation with EDTA-3Na/H2O showed no significant change in any parameters of calcium CONCLUSION: EDTA-3Na/H2O or EDTA-2Na/H2O with longer circulation times resulted in greater calcium reduction in atherosclerotic lesion. EDTA may have a potential therapeutic option for the treatment of atherosclerotic calcified lesions.

Pulmonary artery stiffness in fetuses with tetralogy of Fallot.

This study evaluated the elastic characteristics of the pulmonary trunk and distal branches in fetuses diagnosed with tetralogy of Fallot (TOF) using Doppler echocardiography. Data on 42 fetuses diagnosed with TOF and 84 gestational age-matched normal fetuses were prospectively collected from the Second Xiangya Hospital of Central South University between August 2022 and January 2023. The severity of TOF was classified into three categories based on the z-score of the pulmonary annulus diameter: mild (z-score ≥-2), moderate (-4<z-score<-2), and severe (z-score ≤-4). Pulmonary artery stiffness (PAS) in the main pulmonary artery (MPA), distal left pulmonary artery (DLPA), and distal right pulmonary artery (DRPA) was measured using pulsed-wave Doppler imaging. Differences in clinical data and echocardiographic parameters were compared between the TOF group and the normal group, as well as among TOF subgroups. Compared with the normal group, the MPA-PAS in fetuses with TOF was significantly higher, while the DLPA-PAS and DRPA-PAS were notably lower (all P<0.05). The MPA-PAS of fetuses with severe TOF was higher than that of those with mild and moderate TOF (all P<0.05). However, there were no significant differences in the DLPA-PAS or DRPA-PAS among fetuses with mild, moderate, and severe TOF (all P>0.05). Fetuses diagnosed with TOF exhibited increased vascular stiffness in the MPA and reduced stiffness in the distal pulmonary artery (PA). Larger-scale follow-up studies are required to elucidate the relationships between these changes in vascular stiffness and PA development in patients with TOF.

Surgeon-modified fenestrated endovascular grafts and thoracoscope-assisted fixation for treatment of thoraco-abdominal aortic aneurysms.

Total endovascular technique with fenestrated endovascular graft might be hampered for the late dilatation of proximal landing zone, which may cause endografts migration. We describe a successful urgent hybrid procedure for extent III thoracoabdominal aortic aneurysm with aortic intramural hematoma. A 55-year-old female with thoracoabdominal aortic aneurysm was considered at high surgical risk and unfit for open repair due to multiple comorbidities. Therefore, a hybrid procedure of surgeon-modified fenestrated endovascular graft combined with thoracoscope-assisted Transaortic epicardial fixation of endograft was finally chosen and performed in the endovascular operating room. A 3-port technique was performed through a left video-assisted thoracoscopic approach. After the first tampering stent-graft was deployed, a double-needle suture was penetrated both the aortic wall and stent-graft to fixate it in the proximal descending aorta. Then the second endograft, which had been fenestrated on table, was introduced and oriented extracorporeally by rotating superior mesenteric artery and left renal artery fenestration radiopaque markers and deployed with perfect apposition between the fenestrations and target visceral artery. Each vessel was sequentially stented using Viabahn self-expandable stent to finish target vessel stenting. An Ankura cuff stent was deployed in the distal abdominal aortic artery. Surgeon-modified fenestrated endovascular graft combined with thoracoscope-assisted fixation may be an innovative and viable alternative for selected high-risk patients with extent III thoracoabdominal aortic aneurysm. A longer follow-up is needed to ascertain the success of this approach.