Carotid Cannulation Research Articles

Left Transradial Access Using a Radial-Specific Neurointerventional Guiding Sheath for Coil Embolization of Anterior Circulation Aneurysm Associated With the Aberrant Right Subclavian Artery: Technical Note and Literature Review

Aberrant right subclavian artery (ARSA) is a rare condition, but the most common anomaly of the aortic arch. Although neurointerventions via transradial access (TRA) are becoming increasingly popular worldwide, transradial carotid cannulation has been extremely challenging in patients with an ARSA. Herein, we present a case of ARSA-associated anterior communicating artery (ACoA) aneurysm that was successfully treated with a radial-specific 6F Simmons guiding sheath via left TRA. We also review the relevant literature. A 68-year-old-woman who was diagnosed as having an ARSA-associated ACoA aneurysm underwent simple coiling via left TRA. After the 6F Simmons guiding sheath was engaged into the right common carotid artery using the pull-back-technique, transradial quadraxial system (6F Simmons guiding sheath/6F intermediate catheter/3.2F intermediate catheter/coil-delivery microcatheter) was implemented. Simple coiling of the aneurysm was successfully achieved without catheter kinking or system instability. The postprocedural course was uneventful. A follow-up magnetic resonance angiography showed no evidence of recanalization 1 years 9 months after the procedure. Transradial anterior circulation intervention has been rarely used for patients with an ARSA due to unfavorable catheter trajectory. Left TRA using the 6F Simmons guiding sheath is a useful treatment option to address anterior circulation interventions for patients with an ARSA. Preoperative diagnosis of ARSA is necessary for the application of our method.

Letter: Transradial Flow-Diverting Stent Placement Through an Arteria Lusoria: 2-Dimensional Operative Video.

To the Editor: We read with great interest the article “Transradial Flow-Diverting Stent Placement Through an Arteria Lusoria: 2-Dimensional Operative Video” by Hackett et al.1 The authors present a case of a patient with an arteria lusoria who received effective flow-diverting stent therapy for a large left internal carotid artery (ICA) aneurysm using a large bore guide catheter through right transradial access (TRA). Diagnostic angiography showed that the left ICA could be accessed through the right TRA. A 6F radial sheath was introduced into the right radial artery, and the sheath was then exchanged over a 0.035″ guidewire for an 8F 90-cm guide catheter (Infinity; Stryker Neurovascular). After navigating a 5F 130-cm Simmons catheter into the left common carotid artery through the arteria lusoria, the 8F guide catheter was delivered into the left ICA using the telescoping technique. The large left ICA-ophthalmic artery aneurysm was successfully treated with a pipeline embolization device (Medtronic). The importance of evaluating transradial diagnostic angiography to determine whether a catheter system can safely track into the target supra-aortic vessels is critical for successful transradial neurointervention in patients with arteria lusoria, and we wholeheartedly concur with the authors' conclusion on this point. Cannulation into the supra-aortic vessels through right TRA can be extremely challenging in patients with arteria lusoria because of unfavorable catheter trajectory.2 In addition, the right TRA can cause fatal arteria lusoria dissection.3 Therefore, transfemoral access is frequently employed as first-line access if neurointerventionalists encounter arteria lusoria.2 Previous study reported that left TRA is a technically feasible alternative in neurointerventions for patients with arteria lusoria.4 Nevertheless, a guide catheter may result in a failed TRA that necessitates a crossover to transfemoral access because of a failed cannulation, a kinked catheter, or an unstable system. We have used transradial access as the first-line access for neurointerventions.5-18 The first-line TRA using a 6F preshaped Simmons guiding sheath (outer diameter, 2.70 mm; inner diameter, 0.088″; usable length, 90 cm; 6F Axcelguide Stiff-J; Medikit) offers a large bore working channel and a high procedural success rate without catheter kinking or system instability even in patients with an unfavorable steep supra-aortic take-off.5-7,13 The 6F Simmons guiding sheath is fully engaged into the target common carotid artery with a pull-back maneuver (the pull-back technique) after reforming the Simmons curve within the ascending aorta. The Simmons curve can be reformed by anchoring the 6F Simmons guiding sheath to the descending aorta (the descending aorta anchoring technique) or contralateral subclavian artery (the subclavian artery anchoring technique) through the left TRA. Transradial carotid cannulation with the pull-back technique is technically simple and promising. As a result, left TRA with the 6F Simmons guiding sheath can be a beneficial treatment choice for performing anterior circulation procedures in patients with arteria lusoria. Finally, we would like to express our appreciation to the authors for their interesting article that advances the transradial neurointerventional method.

Transradial Mechanical Thrombectomy Using a Radial-specific Neurointerventional Guiding Sheath for Anterior Circulation Large-Vessel Occlusions: Preliminary Experience and Literature Review

Transradial mechanical thrombectomy (MT) is increasingly used because it is associated with a low incidence of vascular access site complications. However, transradial carotid cannulation can be technically challenging to perform in patients with an unfavorable supra-aortic takeoff. In this study, the feasibility and safety of a new transradial MT system with a radial-specific neurointerventional guiding sheath-6F Simmons guiding sheath was evaluated-in patients with anterior circulation large-vessel occlusions. Additionally, a literature review was performed. We retrospectively analyzed data from our institutional database about consecutive patients who underwent transradial MT for anterior circulation large-vessel occlusion. After the 6F Simmons guiding sheath was engaged into the target common carotid artery, a triaxial system (Simmons guiding sheath/aspiration catheter/microcatheter), was established. MT using the continuous aspiration prior to intracranial vascular embolectomy technique was performed. Then, procedural successrate, successful revascularization, and procedure-related complications were assessed. A total of 13 patients who had transradial MT were included in the analysis. All 13 patients underwent successful thrombectomy without catheter kinking or system instability, and 12 of them achieved successful revascularization (modified Thrombolysis in Cerebral Infarction score of ≥2b). No complications occurred. To the best of our knowledge, this is the first case series on transradial MT using a radial-specific neurointerventional system for anterior circulation large-vessel occlusions. This method may increase the success rate of transradial MT. Based on our initial experience, transradial MT, using this system, was feasible and safe for anterior circulation large-vessel occlusions.

Intraoperative ultrasound evidence of accidental simultaneous cannulation of the common carotid artery and internal jugular vein: illustrative case.

BACKGROUNDEstablishing central venous access is important to provide fluid resuscitation or medications intravenously to patients.OBSERVATIONSAlthough accidental cannulation of the internal carotid artery has been reported in the literature, to our knowledge this report is the first documented intraoperative ultrasound video demonstrating accidental and simultaneous common carotid artery and internal jugular cannulation during central line placement in the internal jugular vein.LESSONSUltrasound use minimizes accidental carotid cannulation during central line placement in the internal jugular vein. Carotid artery puncture can be managed by external application of pressure or surgical reexploration.

Inadvertent through-and-through internal jugular vein penetration and intracarotid placement of a central venous catheter: Microsurgical retrieval technique and operative video

Inadvertent carotid cannulation is a rare complication of internal jugular vein (IJV) catheterization, occurring in less than 1% of cases. Given the significant risk of embolic stroke, urgent catheter removal is indicated. In this technical report and operative video, we present our microsurgical technique for the retrieval and removal of an inadvertently placed, transjugular intracarotid central venous catheter (CVC). A 52-year old man presented with sepsis and hemodynamic lability. An attempt to catheterize the left IJV resulted in inadvertent intracarotid CVC placement, following a through-and-through transjugular path. An open microsurgical approach was used to retrieve the CVC and secure local hemostasis, resulting in excellent outcome. Though generally more invasive than percutaneous and endovascular approaches, open surgical retrieval of misplaced intracarotid CVC leads to consistently excellent outcomes, rendering it the preferred approach in the setting of complex catheter trajectories. The technical note and surgical video presented here can serve as a step-by-step guide for performing this procedure, both safely and effectively.

Study of secretome deregulation of a rat model of endotoxemic shock using a non-targeted mass spectrometry approach

The secretome is a set of proteins secreted by a cell at a given time and under certain conditions. The secretome, easily accessible from plasma and analyzable by a proteomic approach, represents a good opportunity to identify biomarkers in septic shock. This pathology corresponds to a systemic inflammatory response syndrome related to an infection and associated with cardiocirculatory failure leading to organ dysfunction with a mortality rate of 40%. The identification of diagnostic/prognostic biomarkers is crucial to improve patient outcome. Study the secretome of a rat model of endotoxemic shock to identify relevant deregulated proteins (DEP). Endotoxemic shock was induced by lipopolysaccharides injection (LPS, S. enterica typhi, 0.5 mg/kg, iv) and compared to controls (Ringer lactate, iv). Under isoflurane anesthesia, carotid cannulation allowed evaluation of mean arterial blood pressure (MAP), heart rate and blood sampling (T0, and T50 or T90 min on EDTA and protease inhibitor). Plasma was analyzed with tandem MS based on a label free quantification. Gene ontology (GO) analyses defined several groups of biological process (BP) in which the DEP were involved. Ninety minutes after shock induction, the LPS group present a reduction in MAP (−45%, P < 0.05) and increased lactate levels (+27%, P < 0.05). Proteomic analyses revealed 6 and 22 DEP, such as Ribonuclease 4, in the LPS group respectively at T50 and T90. At T50 and T90 Go-BP show common alterations in response to oxidative stress, tissue remodeling and coagulation. This study proposes an approach to identify DEP in septic shock. DEP need to be tested in cellular models in order to understand their role in the physiopathology of shock and to improve understanding of adaptations of the secretome during sepsis. The link between our results and patient prognosis will need to be studied for clinical use.

Fumarate exerted an antihypertensive effect and reduced kidney injury molecule (KIM)-1 expression in deoxycorticosterone acetate-salt hypertension

ABSTRACT Background: The tricarboxylic (TCA) acid cycle provides the energy needed for regulatory functions in the cardio-renal system. Recently, a genetic defect in the TCA cycle enzyme, fumarase hydratase, altered L-arginine metabolism and exacerbated hypertension in salt-sensitive rats. This study evaluated the effect of fumarate and its possible link to L-arginine metabolism in deoxycorticosterone (DOCA)-salt hypertension, a non-genetic model of hypertension.Method: Hypertension was induced with DOCA (25 mg/kg s.c, twice weekly) + 1% NaCL in uninephrectomised rats placed on fumarate (1 g/L, ad libitum). Blood pressure was measured in conscious rats via carotid cannulation. Biochemical and western blot analyses were carried out on kidney fractions.Results: Fumarate reduced mean blood pressure (198 ± 5 vs 167 ± 7 mmHg, p < .01), increased nitric oxide levels in the renal cortex (36.1 ± 2 vs 61.3 ± 4 nM/µg) and medulla (27.4 ± 1 vs 54.1 ± 2 nM/µg) of DOCA-salt rats (p < .01). Consistent with this, arginase activity was reduced (threefold) in the renal medulla but not cortex of DOCA-salt rats. Fumarate increased superoxide dismutase activity in the medulla (p < .001) of DOCA-hypertensive rats. However, catalase activity was exacerbated by fumarate in both renal cortex (4.5 ± 1 vs 11.2 ± 1) and medulla (3.7 ± 1 vs 16.3 ± 1 units/mg) of DOCA-salt rats (p < .001). Proteinuria (64.6%), kidney injury molecule-1 expression and kidney weight were reduced in DOCA-hypertensive rats treated with fumarate (p< .05). However, there was a paradoxical increase in TGF-β expression in fumarate-treated DOCA-salt rats. Conclusion: These data show that fumarate attenuated hypertension, renal injury and improved the redox state of the kidney in DOCA/salt hypertension by mechanisms involving selective reduction of L-arginine metabolism.

Use of carotid artery cannulation during redo sternotomy in congenital cardiac surgery: a single-centre experience.

Management of resternotomy is often a difficult challenge in patients with congenital diseases who have undergone multiple sternotomies. Our goal was to report our single-centre experience with carotid cannulation using a graft interposed during redo sternotomy in complex cardiac reintervention procedures. We performed a retrospective review of all patients who had undergone complex redo sternotomies between January 2019 and May 2020 utilizing a cervical cannulation technique with a Gore-Tex graft interposed on the carotid artery. We classified our population study on the basis of the primary diagnosis and the type of surgery. The primary outcomes of our analysis were the evaluation of the safety of the procedure in terms of survival and freedom from neurological events. We analysed 22 patients who had undergone previous complex operations. The median age and weight at the time of reintervention were 130.35 (range 0.46-435) months and 31.5 (range 2.2-85) kg, respectively. Composite graft carotid cannulation provided adequate arterial flow in all patients with a median arterial flow of 3.5 l/min/m2 (range 0.6-6). One major cardiac injury occurred during sternotomy when emergency cardiopulmonary bypass (CPB) was initiated. Moreover, during their hospital stays, all patients had an uneventful recovery without neurological or vascular complications and no cervical wound infections. Carotid cannulation using interposition of a side graft on the common carotid artery for arterial inflow is a reliable and safe method for initiation of CPB in complex redo surgeries in patients with congenital disease. Complications directly associated with this type of cannulation are uncommon and allow surgical re-entry with overall low risks.

The Secretome Deregulations in a Rat Model of Endotoxemic Shock.

Introduction Septic shock is a systemic inflammatory response syndrome associated with organ failures. Earlier clinical diagnosis would be of benefit to a decrease in the mortality rate. However, there is currently a lack of predictive biomarkers. The secretome is the set of proteins secreted by a cell, tissue, or organism at a given time and under certain conditions. The plasma secretome is easily accessible from biological fluids and represents a good opportunity to discover new biomarkers that can be studied with nontargeted “omic” strategies. Aims To identify relevant deregulated proteins (DEP) in the secretome of a rat endotoxemic shock model. Methods Endotoxemic shock was induced in rats by intravenous injection of lipopolysaccharides (LPS, S. enterica typhi, 0.5 mg/kg) and compared to controls (Ringer Lactate, iv). Under isoflurane anesthesia, carotid cannulation allowed mean arterial blood pressure (MAP) and heart rate (HR) monitoring and blood sampling at different time points (T0 and T50 or T0 and T90, with EDTA and protease inhibitor). Samples were prepared for large-scale tandem mass spectrometry (MS-MS) based on a label-free quantification to allow identification of the proteins deregulated upon endotoxemic conditions. A Gene Ontology (GO) analysis defined several clusters of biological processes (BP) in which the DEP are involved. Results Ninety minutes after shock induction, the LPS group presents a reduction in MAP (-45%, p < 0.05) and increased lactate levels (+27.5%, p < 0.05) compared to the control group. Proteomic analyses revealed 10 and 33 DEP in the LPS group, respectively, at 50 and 90 minutes after LPS injection. At these time points, GO-BP showed alterations in pathways involved in oxidative stress response and coagulation. Conclusion This study proposes an approach to identify relevant DEP in septic shock and brings new insights into the understanding of the secretome adaptations upon sepsis.

A non-targeted quantitative mass spectrometry approach for the identification of new blood biomarkers of septic shock in the secretory of a rat model of endotoxemic shock

Septic shock is a systemic inflammatory response syndrome associated with circulation failure leading to organ failure with a mortality rate of 40%. Early diagnosis and prognosis of septic shock are necessary for timely and specific treatment but no predictive biomarkers are available. The plasma proteome is easily accessible and may contain biomarkers that can be studied with non-targeted “omic” strategies. We aim to decipher a relevant proteome signature through a non-targeted mass spectrometry (MS) analysis in a rat septic shock model. In 10-week-old Wistar rats ( n = 11/group), 30 min post-buprenorphine (0.05 mg/kg, s) endotoxemic shock was induced by lipopolysaccharides injection (LPS, S. enterica typhi, 0.5 mg/kg, iv) and compared to controls (NaCl 0.9%, iv). Under isoflurane anesthesia, carotid cannulation allowed mean arterial blood pressure (MAP), heart rate (HR) monitoring and blood sampling (T0, 50 and 150 min-EDTA with protease inhibitor). Each plasma was prepared for RPHPLC/MS by performing Proteominer, dialysis and trypsin digestion. RPHPLC-MS analysis was performed on a ESI-Q-Exactive mass spectrometer (ThermoFisher) according to a non-targeted label-free MS analysis. Data were analyzed with PEAKS and R software. LPS group present circulation failure (−40% MAP, +20% of HR vs Ctrl, P < 0.05) and an increase in lactate levels (LPS: 6.00 ± 0.86 mM, Ctrl: 1.70 ± 0.26 mM, P < 0.05). Proteomic analyses revealed 106 deregulated (21 down and 80 up-regulated) proteins with LPS. The interactome map highlighted pathways involved, as vascular homeostasis or stress responses. Some of these proteins have already been described in human septic proteome signature, demonstrating the relevance of this approach. This preliminary study revealed propose a new approach to identify relevant deregulated proteins in septic shock. The investigation of the link between our results and patients’ clinical features is in progress.

Abstract P055: Smooth Muscle Cell-specific Conditional Knockout Of Lysine (K)-specific Demethylase 6a Causes Endothelial Dysfunction, Increased Blood Pressure And Arterial Stiffness

Arterial stiffening is the progressive loss of elasticity of the large vessels resulting from age. Increased arterial stiffening has been correlated with hypertension and other cardiovascular co-morbidities. KDM6A is a histone 3 lysine demethylase whose activity increases expression of target genes via removal of silencing methylation marks on lysine 27 of histone 3 (H3K27). The precise role of H3K27me3, or its absence in aortic vascular smooth muscle cells (VSMCs), remains to be investigated. The objectives of this study were to determine the effects of loss of KDM6A on arterial stiffness, blood pressure, and vascular cell function. We generated VSMC-specific Kdm6a knockout mice of C57BL/6 background and confirmed knockout by western blot. Knockout of Kdm6a resulted in increased resting systolic blood pressure and pulse wave velocity in male mice. Pulse wave velocity (PWV) is the gold-standard method for determination of arterial stiffness. PWVs of the knockout mice were significantly increased compared to controls four weeks after Kdm6a knockout (Controls 2.62 + 0.69 mm/ms; KO 3.13 + 0.30 mm/ms; P=0.0228). Systolic blood pressure was directly obtained for each mouse via carotid cannulation. The systolic blood pressures of knockout mice were significantly increased. Mesenteric arteries were isolated from three control and three Kdm6a knockout mice and mounted onto a wire myograph. Vessels were pre-constricted with norepinephrine and vasodilation was measured by treatment with increasing doses of acetylcholine and sodium nitroprusside to assess endothelial and VSMC function. Interestingly, despite Kdm6a knockout in VSMCs, vasodilation of VSMCs was not different between control and knockout arteries, but relaxation in response to acetylcholine, which stimulates the release of nitric oxide from endothelial cells, was decreased. This suggests endothelial dysfunction. These results indicate that loss of KDM6A in VSMCs leads to elevated systolic blood pressure and arterial stiffness.

Right watershed cerebral infarction following neck cannulation for veno-arterial extracorporeal membrane oxygenation in pediatric septic shock: a case series.

Children supported by extracorporeal membrane oxygenation present a high risk of neurological complications. Although carotid cannulation is known to be associated with neurologic injury, conflicting data exist with regard to the predominance of right- or left-sided lesions. We describe here two infants requiring veno-arterial extracorporeal membrane oxygenation for septic shock who encountered right watershed infarction ipsilateral to carotid artery cannulation. Hemodynamic failure seems to be the most probable underlying mechanism. The asymmetry of transcranial Doppler metrics in one case and the low right regional cerebral oxygen saturation value observed soon after right cannulation in both cases suggest an insufficient cerebral collateral flow compensation. The risk of ipsilateral watershed injury should be considered before cervical cannulation, notably in the context of sepsis and an evaluation of the cerebral collateral blood flow before and just after cannulation may be interesting in order to identify infants with higher risk of ipsilateral ischemic lesions.

Eukaryotic elongation factor 2 kinase inhibitor, A484954 lowered blood pressure in spontaneously hypertensive rats via inducing vasorelaxation

Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) suppresses protein translation. We previously reported eEF2K expression was upregulated in mesenteric arteries (MA) from spontaneously hypertensive rats (SHR). We have recently revealed A484954, an eEF2K inhibitor, acutely suppressed vasopressor agonists-induced increase of blood pressure (BP) in normal Wistar rats. In this study, we examined the acute effects of A484954 on BP in SHR and explored underlying mechanisms. BP was measured by a carotid cannulation method in SHR. Isometric contraction in MA from SHR was measured. Endothelial nitric oxide synthase (eNOS) dimerization was measured by low-temperature sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. A484954 lowered BP in 15-week-old SHR. A484954 induced relaxation in MA from both 4- and 7-9-week-old SHR. In MA from 4-week-old SHR, A484954-induced relaxation was inhibited almost completely by a NOS inhibitor, NG-nitro-l-arginine methyl ester (l-NAME) and significantly by a β blocker, propranolol. In MA from 7-9-week-old SHR, on the other hand, A484954-induced relaxation was inhibited partly either by l-NAME, indomethacin, a cyclooxygenase inhibitor, or l-NAME + indomethacin. A484954 promoted the dimerization of eNOS in human endothelial cells. In summary, we have revealed A484954 lowers BP in SHR perhaps through the vasorelaxation via the production of endothelium-derived relaxing factors.

EEG features of brain injury during extracorporeal membrane oxygenation in children.

To examine EEG features of major pathophysiology in children undergoing extracorporeal membrane oxygenation (ECMO). This was a single-center, retrospective study of 201 pediatric patients on ECMO, using the first 24 hours of continuous EEG (cEEG) monitoring, collating background activity and electrographic seizures (ES) with imaging, ECMO type, and outcome. Severely abnormal cEEG background occurred in 12% (25/201), and was associated with death (sensitivity 0.23, specificity 0.97). ES occurred in 16% (33/201) within 3.2 (0.6-20.3) hours (median [interquartile range]) of cEEG commencement, and higher ES burden was associated with death. ES was always associated with ipsilateral injury (p = 0.006), but occurred in only one-third of cases with abnormal imaging. In 28 patients with isolated hemisphere lesion, type of arterial ECMO cannulation was associated with side of injury: right carotid cannulation was associated with right hemisphere lesions, and ascending aorta cannulation with left hemisphere lesions (odds ratio, 0.29 [95% confidence interval, 0.08-0.98], p = 0.03). After starting ECMO, cEEG background activity has the potential to inform prognosis. Type of arterial (carotid vs aortic) ECMO correlates with side of focal cerebral injury, which in ≈33% is associated with presence of ES. We hypothesize that the differential distribution reflects abnormal flow dynamics or embolic injury.

Feasibility and Safety of Radial-First Approach with a Radial-Specific Neurointerventional Guiding Sheath for Intracranial Aneurysm Coiling in the Anterior Circulation

In cardiac intervention, the transradial approach (TRA) is increasingly used as the first-line approach owing to numerous advantages over the transfemoral approach. Neurointerventional TRA, especially in intracranial interventions, is predominantly restricted to an alternative approach, as transradial carotid cannulation using a conventional transfemoral system can be technically challenging for patients with unfavorable acute takeoff of the target common carotid artery. This study evaluated the feasibility and safety of first-line TRA with a radial-specific neurointerventional guiding sheath for a large series of consecutive intracranial anterior circulation aneurysm embolizations. We retrospectively analyzed our institutional database of first-line TRA for consecutive coil embolizations of anterior circulation aneurysms conducted between June 2018 and March 2020. A radial-specific 6-F Simmons guiding sheath (0.088-inch inner diameter) was engaged into the target common carotid artery, and subsequently a triaxial or quadraxial system was created for the embolization procedure. We assessed procedural success and procedure-related or vascular access site complications. A total of 119 patients with intracranial anterior circulation aneurysms underwent 121 coil embolization procedures. Of these, 101 patients who underwent 103 (85.1%) embolization procedures treated with first-line TRA were included. After the triaxial or quadraxial system was constructed, the embolization procedure was successful for all 103 cases without catheter kinking, system instability, or complications. A transradial 0.088-inch triaxial or quadraxial system provided sufficient stability and kink resistance for intracranial aneurysm embolization. This method is feasible, highly successful, and safe for intracranial anterior circulation aneurysm embolization.

Acute intracerebroventricular injection of chemerin-9 increases systemic blood pressure through activating sympathetic nerves via CMKLR1 in brain.

Chemerin is an adipocytokine involved in inflammation and lipid metabolism via G protein-coupled receptor, chemokine-like receptor (CMKLR)1. Since the important nuclei regulating pressure (BP) exist in the brain, we examined the effects of acute intracerebroventricular (i.c.v.) injection of chemerin-9 on systemic BP and explored underlying mechanisms. We examined the effects of acute i.c.v. injection of chemerin-9 (10nmol/head) on systemic BP by a carotid cannulation method in the control or CMKLR1 small interfering (si) RNA-treated Wistar rats (0.04nmol, 3days, i.c.v.). We examined protein expression of CMKLR1 around brain ventricles by Western blotting. We examined the effects of acute i.c.v. injection of chemerin-9 on serum adrenaline by a high performance liquid chromatography. In the control siRNA-treated rats, chemerin-9 significantly increased mean BP, which reached a peak at 2 to 4min after injection. On the other hand, in the CMKLR1 siRNA-treated rats, chemerin-9 did not affect the mean BP. Protein expression of CMKLR1 specifically in subfornical organ (SFO) and paraventricular nucleus (PVN) from the CMKLR1 siRNA-treated rats decreased compared with the control siRNA-treated rats. In the control siRNA-treated rats, chemerin-9 increased serum adrenaline level. On the other hand, in the CMKLR1 siRNA-treated rats, chemerin-9 did not affect the serum adrenaline level. Further, pretreatment with prazosin, an α-adrenaline receptor blocker, significantly prevented the pressor responses induced by chemerin-9. In summary, we for the first time demonstrated that chemerin-9 stimulates the sympathetic nerves via CMKLR1 perhaps expressed in SFO and PVN, which leads to an increase in systemic BP.

Leukocyte Infiltration of Cremaster Muscle in Mice Assessed by Intravital Microscopy.

Intravital microscopy (IVM) is widely used to monitor physiological and pathophysiological processes within the leukocyte recruitment cascade in vivo. The current protocol represents a practical and reproducible method to visualize the leukocyte endothelium interaction leading to leukocyte recruitment in skeletal muscle derived tissue within the intact organism of the mouse. The model is applicable to all fields of research that focus on granulocyte activation and their role in disease. We provide a step by step protocol to guide through the method and to highlight potential pitfalls and technical difficulties. The protocol covers the following aspects: experimental settings and required material, anesthesia of the mouse, dissection of the cremaster muscle as well as tracheal and carotid cannulation, IVM recordings and offline analysis. Data formats like adherent leukocytes, rolling flux (RF) and rolling flux fraction (RFF) are explained in detail and appropriate applications are discussed. Representative results from dystrophin deficient mdx mice are provided in the results section. IVM is a powerful tool to assess leukocyte recruitment in an in vivo setting; however, delineating for example endothelial and leukocyte function may require a combination with ex vivo setups like flow chamber experiments. Furthermore, the genetic background of animals of interest may greatly influence baseline recruitment, requiring individual fine tuning of the protocol provided. Despite its limitations, IVM may serve as a platform to readily translate in vitro findings into a living vertebrate organism.

Fumarate Reduced Mean Arterial Blood Pressure and Improved Renal Outcomes in DOCA/salt Hypertension

The mitochondria, through the tricarboxylic (TCA) acid cycle, converts organic molecules into energy that drives intricate renal blood‐pressure regulatory functions. The TCA cycle intermediaries regulate the metabolic state of the mitochondria and by extension, the redox status of the cell. Recently, fumarase, a major TCA cycle enzyme that converts fumarate to malate, has been linked to L‐arginine metabolism and implicated in the pathophysiology of Dahl‐salt sensitive hypertension. This study aimed to investigate the role of fumarase and L‐arginine in deoxycorticosterone (DOCA)/salt hypertension, a non‐genetic model of hypertension. Hypertension was induced in uninephrectomised rats with DOCA (25 mg/kg) + 1 % NaCL. Mean arterial blood pressure was measured in conscious rats via carotid cannulation. Biochemical and western blot analyses were carried out on homogenized kidney fractions. Fumarate reduced arterial blood pressure (198±5 vs 167±7 mmHg, P&lt;0.01). There were no changes in urinary output and sodium excretion in fumarate‐treated DOCA rats (P&gt;0.05). Superoxide dismutase and catalase activities were higher in the cortex, but not the medulla of DOCA‐hypertensive rats and were exacerbated by fumarate (P&lt;0.01). There was a selective increase in catalase activity in the medulla of fumarate‐treated DOCA‐hypertensive rats (P&lt;0.01). Fumarate also reduced urinary protein excretion in DOCA‐hypertensive rats (23.6 %, P&lt;0.05). Fumarate evoked a selective increase in nitric oxide in the medulla (34.1±2.9 vs 47.3±2.8 nM/μg, P&lt;0.05) of DOCA‐hypertensive rats. Consistent with this, Fumarate also tended to increase arginase activity in the cortex but not the medulla of DOCA‐hypertensive rats. However, there was an increase in expression TGF‐β, an index of fibrosis, in DOCA‐hypertensive rats, which was paradoxically increased in fumarate‐treated rats (P&gt;0.05). In conclusion, fumarate attenuated the hypertension and renal injury but not the fibrosis in DOCA/salt hypertension by mechanisms involving selective reduction of L‐arginine metabolism in the medulla and amelioration of renal oxidative stress.Support or Funding InformationNational Institute of Health grant HL03674 and G12 MD0076056Mean arterial blood changes after 21‐day administration of fumarate to DOCA/salt induced hypertensive rats. Control (n=8), DOCA (n=8), fumarate (n=8). a=P&lt;0.001 when compared to control; b=P&lt;0.01 when compared to DOCA group.Figure 1Nitric oxide produced in homogenized kidneys (cortex and medulla) of DOCA salt induced hypertensive rats after 21‐day fumarate (1 mg/kg) administrationa=P&lt;0.05 when compared to control.Figure 2

Transradial Approach as the Primary Vascular Access with a 6-Fr Simmons Guiding Sheath for Anterior Circulation Interventions: A Single-Center Case Series of 130 Consecutive Patients

In coronary intervention, the transradial approach (TRA) is increasingly used as the primary vascular access because of its numerous advantages over the transfemoral approach. However, in neurointerventions, conventional TRA with a straight-shaped guiding system is used as an alternative vascular access because transradial carotid cannulation can be technically challenging for right common carotid artery (CCA) lesions with steep angulation to the right subclavian artery or left CCA lesions with a nonbovine origin. The purpose of the present study was to evaluate the feasibility and safety of TRA as the primary vascular access with a pre-shaped Simmons guiding sheath for anterior circulation interventions. Between June 2018 and September 2019, 130 consecutive patients (75 carotid artery stenting and 55 cerebral aneurysm coiling cases) who underwent TRA as the primary vascular access were included in this study. A 6-Fr Simmons guiding sheath was introduced into the target CCA by selecting a cannulation technique based on preprocedural image assessment. We retrospectively analyzed the carotid cannulation success, procedural success, and periprocedural or vascular access site complications. Carotid cannulation (69 right CCA, 6 left CCA with a bovine origin, and 55 left CCA with a nonbovine origin) and the subsequent procedure were successfully performed for all 130 patients without periprocedural or vascular access site complications. TRA with a 6-Fr Simmons guiding sheath for anterior circulation interventions is highly successful and safe for all target CCAs and aortic arch types. This method can be utilized as the primary vascular access for anterior circulation interventions.

Total arch replacement and frozen elephant trunk for aortic dissection in aberrant right subclavian artery.

Aortic dissection (AoD) in the presence of an aberrant right subclavian artery (ARSA) is very rare. Clinical experience is limited, and there is no consensus regarding the optimal management strategy. We seek to evaluate the safety and efficacy of the total arch replacement (TAR) and frozen elephant trunk (FET) technique as an approach to AoD in patients with ARSA by retrospectively analysing our single-centre experience. From 2009 to 2017, we performed TAR + FET for 22 patients with ARSA sustaining AoD (13 acute, 59.1%). The mean age was 46.0 years [standard deviation (SD) 8.3], and 19 patients were male (86.4%). ARSA orifice was dilated in 15 (68.2%) patients, and a Kommerall diverticulum was diagnosed in 13 (59.1%) patients with a mean diameter of 21.8 mm (SD 7.7; range 15-40). Surgery was performed via femoral and right/left carotid cannulation under hypothermic circulatory arrest at 25°C. The ARSA was reconstructed using a separate branched graft. ARSA was closed proximally by ligation in 16 (72.7%) patients, direct suture in 4 (18.2%) patients and both in 2 (9.1%) patients. Operative mortality was 13.6% (3/22). Type Ib endoleak occurred in 1 (4.5%) patient at 8 days. Follow-up was complete in 100% at mean 4.2 years (SD 2.0), during which 3 late deaths and 1 reintervention for type II endoleak occurred. Survival was 81.8% and 76.4% at 3 and 5 years, respectively. Freedom from reoperation was 89.2% up to 8 years. In competing risks analysis, the incidence was 22.1% for death, 10.8% for reoperation and 67.1% for event-free survival at 5 years. The false lumen, ARSA orifice and Kommerall diverticulum were obliterated in 100%. Grafts were patent in 100%. No patients experienced cerebral ischaemia and upper extremity claudication. Hypothermic circulatory arrest time (min) was sole predictor for death and aortic reintervention (hazard ratio 1.168, 95% confidence interval 1.011-1.348; P = 0.034). The TAR and FET technique is a safe and efficacious approach to AoD in patients with ARSA. Modifications of routine TAR + FET techniques are essential to successful repair, including femoral and right/left carotid artery cannulation, ligation of ARSA on the right side of the trachea and ARSA reconstruction with a separate graft.