Utility of Carbon Dioxide Venography and Intraprocedural CT for Adrenal Venous Sampling in Patients with an Allergy to Iodinated Contrast Media.

PURPOSE: To assess the diagnostic performance of carbon dioxide (CO2) and intraprocedural unenhanced computed tomography (CT) for adrenal venous sampling (AVS) (CO2-intraprocedural unenhanced CT-AVS) in patients with primary aldosteronism (PA) and a history of iodine contrast medium allergy. MATERIALS AND METHODS: CO2-intraprocedural unenhanced CT-AVS was performed in 18 patients with iodine contrast media allergies at the authors' hospital between December 2015 and January 2021. CT and noncontrast magnetic resonance angiography were used to evaluate the preoperative adrenal vein anatomy. CO2 venography was performed to confirm adrenal vein catheterization. Additionally, intraprocedural unenhanced CT was also performed to confirm catheter position in the right adrenal gland. RESULTS: In all cases in which CO2-intraprocedural unenhanced CT-AVS was performed, the right and left adrenal veins were catheterized appropriately, leading to a localized diagnosis. Catheterization of the left adrenal vein was confirmed using CO2 venography in all cases. In 7 of the 18 cases, CO2 venography demonstrated selection of the right adrenal vein. In 15 of 18 cases, intraprocedural unenhanced CT demonstrated selection of the right adrenal vein. CONCLUSIONS: CO2-intraprocedural unenhanced CT-AVS demonstrated the same diagnostic ability for PA localization as conventional AVS with iodine contrast media. The proposed method is clinically feasible for AVS, in which iodine contrast media use is restricted.

Shear-induced platelet aggregation and distribution of thrombogenesis at stenotic vessels.

OBJECTIVE: SIPA, which is mediated by vWF, is a key mechanism in arterial thrombosis under an abnormally high shear rate of blood flow. We investigated the influence of SIPA on thrombogenesis, focusing on alterations in blood flow at stenotic vessels. METHODS: We carried out a computer simulation of thrombogenesis in stenotic vessels at three different injury positions (ie, upstream, apex, and downstream of the stenosis) to evaluate the effect of SIPA. RESULTS: The results demonstrated that thrombus volume increased downstream of the stenosis. In particular, growth was enhanced significantly as blood flow velocity and severity of stenosis increased. The influence of SIPA was induced by continuous exposure to high shear rate; thus, SIPA had a greater effect from the apex to downstream of the stenosis along the vessel wall. The asymmetry of the impact of SIPA contributed to the distribution of the thrombus. Furthermore, we found that the degree of SIPA was prolonged in a stenotic vessel with a distal injury, whereas it was moderate with thrombus growth in a nonstenosed vessel. This occurred because platelets and vWF that underwent a high shear rate around the apex were transported to the region downstream of the stenosis. CONCLUSIONS: These results suggest that thrombus formation downstream of the stenosis is easily affected by SIPA and hemodynamics.

Prophylactic splenic artery embolization using n-butyl-2-cyanoacrylate and coils prior to endoscopic necrosectomy in a patient with necrotizing pancreatitis: A case report.

We present a case of prophylactic endovascular embolization in a 51-year-old man with necrotizing pancreatitis (NP) before undergoing endoscopic necrosectomy (EN). Contrast-enhanced CT imaging revealed the presence of a walled-off necrosis (WON) surrounding the pancreas, with the splenic artery coursing through the cavity. The splenic artery was embolized using n-butyl-2-cyanoacrylate (NBCA) and coils to mitigate the risk of massive bleeding in EN. A newly developed polytetrafluoroethylene (PTFE)-coated microcatheter was used to inject NBCA, enabling embolization of a long segment of the splenic artery without adhering to the vessel wall. Coils were placed distal and proximal to the embolized segment to optimize control. Over 5 sessions of EN, no massive bleeding was encountered. This report demonstrates the benefits of utilizing PTFE-coated microcatheters for enhanced safety and maneuverability during embolization with NBCA. Furthermore, it highlights the importance of prophylactic embolization during EN for managing NP.

Two-session embolization of portosystemic shunt presenting with hepatic encephalopathy via transvenous and trans-paraumbilical approaches: A case report.

We describe the endovascular embolization of a 65-year-old man with chronic hepatic encephalopathy. A contrast-enhanced computed tomography demonstrated a splenorenal shunt and a recanalized paraumbilical vein as a continuous portal shunt connecting the left branch of the portal vein and the right common femoral vein. A 2-session embolization was performed for the splenorenal shunt. First, the transvenous approach was used for coil embolization of the splenorenal shunt. It was difficult to advance the catheter system to the embolization site, and it was unstable during coil placement. Second, the paraumbilical venous approach was used to place additional coils. The catheter system had good maneuverability and easily reached the embolization site. Additionally, the stable system allowed for densely packed additional coil implantations. This report demonstrated the paraumbilical venous approach's effectiveness in catheter maneuverability and system stability during coil embolization.

Investigating the cut-off values of captopril challenge test for primary aldosteronism using the novel chemiluminescent enzyme immunoassay method: a retrospective cohort study.

The measurement evolution enabled more accurate evaluation of aldosterone production in hypertensive patients. However, the cut-off values for novel assays have been not sufficiently validated. The present study was undertaken to validate the novel chemiluminescent enzyme immunoassay for aldosterone in conjunction with other methods. Moreover, we also aimed to establish a new cut-off value for primary aldosteronism in the captopril challenge test using the novel assay. First, we collected 390 plasma samples, in which aldosterone levels measured using liquid chromatography-mass spectrometry ranged between 0.18 and 1346 ng/dL. The novel chemiluminescent enzyme immunoassay showed identical correlation of plasma aldosterone with liquid chromatography-mass spectrometry, in contrast to conventional radioimmunoassay. Further, we enrolled 299 and 39 patients with primary aldosteronism and essential hypertension, respectively. Plasma aldosterone concentrations measured using the novel assay were lower than those measured by radioimmunoassay, which resulted in decreased aldosterone-to-renin ratios. Subsequently, positive results of the captopril challenge test based on radioimmunoassay turned into "negative" based on the novel assay in 45% patients with primary aldosteronism, using the conventional cut-off value (aldosterone-to-renin activity ratio > 20 ng/dL per ng/mL/h). Receiver operating characteristic curve analysis demonstrated that aldosterone-to-renin activity ratios > 8.2 ng/dL per ng/mL/h in the novel assay was compatible with the conventional diagnosis (sensitivity, 0.874; specificity, 0.980). Our study indicates the great measurement accuracy of the novel chemiluminescent enzyme immunoassay for aldosterone, and the importance of measurement-adjusted cut-offs in the diagnosis of primary aldosteronism.

Computational study on thrombus formation regulated by platelet glycoprotein and blood flow shear.

Thrombogenesis results from the interaction between glycoprotein receptors and their ligands, although a thrombus is affected by multiple factors such as blood flow, platelet interactions, and changes in ligand characteristics. In this study, we propose a platelet adhesion and aggregation model, focusing on the interaction between the glycoprotein receptor and its ligand. First, we conducted thrombogenesis simulations to compare physiological and pathological conditions. The results suggested that simulations of thrombogenesis differed in distribution, volume, and stability of the thrombus based on disorders of platelet adhesion, aggregation, and the activation. For example, distribution and volume were affected by the activation of GPIIb/IIIa with a GPIb/IX/V deficiency. The thrombus was also unstable, but formed from the upstream side of the injured site, with a GPIIb/IIIa deficiency. Second, we investigated thrombogenesis enhanced by the shear-induced platelet aggregation (SIPA) mechanism. The results demonstrated that the degree of SIPA decreased gradually with thrombus growth in a straight vessel. This result suggests that SIPA is a key hemostasis mechanism in an injured healthy arteriole, although it can lead to the formation of an occlusive thrombus in stenosed vessels.

Update on the roles of imaging in the management of chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH), classified as group 4 pulmonary hypertension (PH), is caused by stenosis and obstruction of the pulmonary arteries by organized thrombi that are incompletely resolved after acute pulmonary embolism. The prognosis of patients with CTEPH is poor if untreated; however, in expert centers with multidisciplinary teams, a treatment strategy for CTEPH has been established, dramatically improving its prognosis. CTEPH is currently not a fatal disease and is the only curable form of PH. Despite these advances and the establishment of treatment approaches, early diagnosis is still challenging, especially for non-experts, for several reasons. One of the reasons for this is insufficient knowledge of the various diagnostic imaging modalities, which are essential in the clinical practice of CTEPH. Imaging modalities should detect the following pathological findings: lung perfusion defects, thromboembolic lesions in pulmonary arteries, and right ventricular remodeling and dysfunction. Perfusion lung scintigraphy and catheter angiography have long been considered gold standards for the detection of perfusion defects and assessment of vascular lesions, respectively. However, advances in imaging technology of computed tomography and magnetic resonance imaging have enabled the non-invasive detection of these abnormal findings in a single examination. Cardiac magnetic resonance (CMR) is the gold standard for evaluating the morphology and function of the right heart; however, state-of-the-art techniques in CMR allow the assessment of cardiac tissue characterization and hemodynamics in the pulmonary arteries. Comprehensive knowledge of the role of imaging in CTEPH enables appropriate use of imaging modalities and accurate image interpretation, resulting in early diagnosis, determination of treatment strategies, and appropriate evaluation of treatment efficacy. This review summarizes the current roles of imaging in the clinical practice for CTEPH, demonstrating the characteristic findings observed in each modality.

Hypersensitivity of myelinated A-fibers via toll-like receptor 5 promotes mechanical allodynia in tenascin-X-deficient mice associated with Ehlers-Danlos syndrome.

Deficiency of an extracellular matrix glycoprotein tenascin-X (TNX) leads to a human heritable disorder Ehlers-Danlos syndrome, and TNX-deficient patients complain of chronic joint pain, myalgia, paresthesia, and axonal polyneuropathy. We previously reported that TNX-deficient (Tnxb-/-) mice exhibit mechanical allodynia and hypersensitivity to myelinated A-fibers. Here, we investigated the pain response of Tnxb-/- mice using pharmacological silencing of A-fibers with co-injection of N-(2,6-Dimethylphenylcarbamoylmethyl) triethylammonium bromide (QX-314), a membrane-impermeable lidocaine analog, plus flagellin, a toll-like receptor 5 (TLR5) ligand. Intraplantar co-injection of QX-314 and flagellin significantly increased the paw withdrawal threshold to transcutaneous sine wave stimuli at frequencies of 250 Hz (Aδ fiber responses) and 2000 Hz (Aß fiber responses), but not 5 Hz (C fiber responses) in wild-type mice. The QX-314 plus flagellin-induced silencing of Aδ- and Aß-fibers was also observed in Tnxb-/- mice. Co-injection of QX-314 and flagellin significantly inhibited the mechanical allodynia and neuronal activation of the spinal dorsal horn in Tnxb-/- mice. Interestingly, QX-314 alone inhibited the mechanical allodynia in Tnxb-/- mice, and it increased the paw withdrawal threshold to stimuli at frequencies of 250 Hz and 2000 Hz in Tnxb-/- mice, but not in wild-type mice. The inhibition of mechanical allodynia induced by QX-314 alone was blocked by intraplantar injection of a TLR5 antagonist TH1020 in Tnxb-/- mice. These results suggest that mechanical allodynia due to TNX deficiency is caused by the hypersensitivity of Aδ- and Aß-fibers, and it is induced by constitutive activation of TLR5.

Transvenous Radiofrequency Catheter Ablation for an Aldosterone-Producing Tumor of the Left Adrenal Gland: A First in Human Case Report.

PURPOSE: To describe a novel technique of transvenous radiofrequency catheter ablation of an aldosterone-producing adenoma (APA) of the left adrenal gland using the GOS System (Japan Lifeline, Tokyo, Japan). Using the GOS system, a flexible radiofrequency tip catheter can be inserted into the adrenal central and tributary veins, the drainers for functional tumors. MATERIALS AND METHODS: An APA at the left adrenal gland, which was diagnosed by segmental adrenal venous sampling following administration of 0.25 mg cosyntropin, was ablated using the GOS catheter inserted into adrenal tributary veins via a right femoral vein 7-Fr sheath. The effect of radiofrequency ablation on APA was assessed using the international consensus on surgical outcomes for unilateral primary aldosteronism (PA). RESULTS: No device-related complications were observed. The patient was deeply sedated under blood pressure and heart rate control with continuous administration of ß-blockers. Then, the tumor and surrounding adrenal gland were cauterized at 7000 J two times each in sequence. The output time was 7-11 min for each ablation and 80 min in total. For blood pressure and pulse rate control, esmolol hydrochloride and phentolamine mesylate were used. The contrast enhancement of APA disappeared on dynamic CT immediately after the procedure. PA was biochemically cured until 12 months after the procedure. CONCLUSION: Using the radiofrequency device with the GOS catheter and system is a method for cauterizing adrenal tumors from blood vessels. This approach resulted in a marked reduction in aldosterone concentrations and a complete biochemical cure of PA over the observation period.

Clinical Application of 4D Flow MR Imaging to Pulmonary Hypertension.

Pulmonary hypertension (PH) is characterized by elevated pulmonary arterial pressure (PAP). Although right-heart catheterization is the gold standard method for the diagnosis of PH by definition, various less-invasive imaging tests have been used for screening, detection of underlying diseases-causing PH, and monitoring of diseases. Among them, 4D flow MRI is an emerging and unique imaging test that allows for comprehensive visualization of blood flow in the right heart and proximal pulmonary arteries. The characteristic blood flow pattern observed in patients with PH is vortical flow formation in the main pulmonary artery. Recent studies have proposed the use of these findings to determine not only the presence of PH but also estimate the mean PAP. Other applications of 4D flow MRI for PH include measurement of wall shear stress, helicity, and 3D flow balance in the pulmonary arteries. It is worth noting that 4D flow has also the potential for longitudinal follow-ups. In this review, the clinical definition of PH, summary of conventional imaging tests, characteristics of pulmonary arterial flow as shown by 4D flow MRI, and clinical application of 4D flow MRI in the management of patients with PH will be discussed.

Blood flow analysis with computational fluid dynamics and 4D-flow MRI for vascular diseases.

Both computational fluid dynamics (CFD) and time-resolved, three-dimensional, phase-contrast, magnetic resonance imaging (4D-flow MRI) enable visualization of time-varying blood flow structures and quantification of blood flow in vascular diseases. However, they are totally different. CFD is a method to calculate blood flow by solving the governing equations of fluid mechanics, so the obtained flow field is somewhat virtual. On the other hand, 4D-flow MRI measures blood flow in vivo, thus the flow is real. Recently, with the development and enhancement of computers, medical imaging techniques, and related software, blood flow analysis has become more accessible to clinicians and its usefulness in vascular diseases has been demonstrated. In this review, we have outlined the methods and characteristics of CFD and 4D-flow MRI, respectively. We have discussed the differences in the characteristics between both methods; reviewed the milestones achieved by blood flow analysis in various vascular diseases; and discussed the usefulness, challenges, and limitations of blood flow analysis. We have discussed the difficulties and limitations of current blood flow analysis. We have also discussed our views on future directions.

Quantification of vortex flow in pulmonary arteries of patients with chronic thromboembolic pulmonary hypertension.

PURPOSE: This study proposes an objective method of quantifying the vortex flow in pulmonary arteries to compare the duration of its presence before and after balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Thoracic 4D-flow magnetic resonance imaging was performed in 28 CTEPH patients before and after BPA. Planes were set in pulmonary arteries to evaluate volume flow rate (VFR), the duration, and area of backward flow in the pulmonary trunk, which is a component of the vortex flow. The full width at half maximum (FWHM) of the peak of the time course of VFR of backward flow was assessed to quantify the duration of the vortical flow. RESULTS: Although overall flow patterns after BPA appeared to be the same as the one before BPA, significant decreases in the FWHM, area, and VFR of the backward flow after BPA were found (FWHM: before, 1.88 × 10-1 ± 1.51 × 10-2 [cardiac cycle] vs. after, 1.65 × 10-1 ± 1.86 × 10-2 [cardiac cycle]; area ratio: before, 2.67 × 10-1 ± 1.30 × 10-2 vs. after, 2.38 × 10-1 ± 1.31 × 10-2; VFR: before, 13.6 ± 2.21 [mL/s] vs. after, 11.3 ± 2.36 [mL/s]). CONCLUSION: BPA promoted significant decreases in the FWHM, area, and VFR of backward flow in the pulmonary trunk, thereby facilitating efficient blood transport. The tendencies for these changes were to be larger for cases where BPA more greatly decreased the pressure. The results suggest that the FWHM, area, and VFR are useful indicators for the noninvasive evaluation of the therapeutic effects of BPA.

Combined left thoracoscopic and median sternotomy approach to resect aortopulmonary mediastinal paraganglioma following feeding artery embolization: a case report.

BACKGROUND: Aortopulmonary mediastinal paragangliomas are rare. Complete resection of the tumor is desirable regardless of tumor size in view of the risk of sudden death induced by adjacent organ compression and poor prognosis after partial resection or untreated observation. Due to the hypervascularity of the tumor, the risk of intraoperative bleeding is significant, and cardiopulmonary bypass is often required for complete resection. CASE PRESENTATION: The patient was diagnosed as having bilateral carotid body tumors and supposedly an aortic body tumor at the age of 43 and eventually underwent resections of bilateral carotid body tumors at the age of 52. The pathology of the carotid body tumors was compatible with paraganglioma on both sides. A familial succinate dehydrogenase subunit D mutation was subsequently identified. Five years later, a contrast-enhanced computed tomography scan showed an enlarged tumor of 45 mm in size in the aortopulmonary mediastinum. Based on the previously known genetic mutation, the tumor was thought to be a paraganglioma. After confirming with an endocrinologist that the aortic body tumor was non-functional, radiologists performed preoperative embolization of the feeding vessels. Subsequently, a surgical team consisting of thoracic and cardiovascular surgeons resected the aortic body tumor using a video-assisted small left thoracotomy approach combined with a median sternotomy approach. The procedure was completed without cardiopulmonary bypass or blood transfusion. The patient was discharged home on postoperative day 9 uneventfully. CONCLUSIONS: After conduction of preceding interventional embolization of multiple feeding vessels, we employed a video-assisted thoracoscopic surgical approach to dissect the aspects of the tumor adjacent to the esophagus, descending thoracic aorta, and left pulmonary artery, followed by a median sternotomy approach to dissect the other aspects of the tumor adjacent to the ascending aorta, aortic arch, right pulmonary artery, and trachea. There have been no reports on scheduled preoperative embolization of feeding vessels to an aortopulmonary mediastinal paraganglioma. Multidisciplinary approach was effective for complete resection of this challenging rare mediastinal tumor.

Prevalence of rapid response systems in small hospitals: A questionnaire survey.

ABSTRACT: The rapid response system (RRS) was introduced for early stage intervention in patients with deteriorating clinical conditions. Responses to unexpected in-hospital patient emergencies varied among hospitals. This study was conducted to understand the prevalence of RRS in smaller hospitals and to identify the need for improvements in the responses to in-hospital emergencies.A questionnaire survey of 971 acute-care hospitals in western Japan was conducted from May to June 2019 on types of in-hospital emergency response for patients in cardiac arrest (e.g., medical emergency teams [METs]), before obvious deterioration (e.g., rapid response teams [RRTs]), and areas for improvement.We received 149 responses, including those from 56 smaller hospitals (≤200 beds), which provided fewer responses than other hospitals. Response systems for cardiac arrest were used for at least a limited number of hours in 129 hospitals (87%). The absence of RRS was significantly more frequent in smaller hospitals than in larger hospitals (13/56, 23% vs 1/60, 2%; P < .01). METs and RRTs operated in 17 (11%) and 15 (10%) hospitals, respectively, and the operation rate for RRTs was significantly lower in smaller hospitals than in larger hospitals (1/56, 2% vs 12/60, 20%; P < .01). Respondents identified the need for education and more medical staff and supervisors; data collection or involvement of the medical safety management sector was ranked low.The prevalence of RRS or predetermined responses before obvious patient deterioration was ≤10% in small hospitals. Specific education and appointment of supervisors could support RRS in small hospitals.

Embolization of a paraumbilical shunt by the transparaumbilical venous approach and one-sheath inverse method: A case report.

We describe treatment of a 53-year-old man with chronic hepatic encephalopathy. Contrast-enhanced computed tomography demonstrated a recanalized paraumbilical vein as a portosystemic shunt connecting the left branch of the portal vein and bilateral iliac veins. Percutaneous embolization was performed. The paraumbilical vein was punctured under ultrasonographic guidance; a 7-Fr sheath was inserted in the cranial direction. The hepatic side of the shunt was embolized with a vascular plug. The sheath direction was inverted to the caudal side; the pelvic side of the shunt was then embolized with another vascular plug. This report demonstrates that the percutaneous transparaumbilical venous approach is useful and safe for portosystemic shunt intervention. Moreover, the one-sheath inverse method was useful for embolization of upstream and downstream sides of the puncture site.

18F-FDG PET/CT Imaging of Vasculitis Complicated With Relapsing Polychondritis.

We present a case of a 38-year-old woman who complained with cough, fever, and back pain with a weight loss. F-FDG PET/CT to search fever origin revealed uptake in the tracheobronchial and the left auricular cartilage and wall of the thoracic aorta. She underwent biopsy of the left auricle and was diagnosed with relapsing polychondritis (RP) complicating vasculitis. After steroid therapy, FDG PET/CT demonstrated regression of inflammation, showing decreases in the uptakes. Vasculitis should be considered in case of RP with systemic manifestations. Our case demonstrated the utility of FDG PET/CT in evaluation of RP lesions including aortitis.

Three cases of pulmonary tumor thrombotic microangiopathy (PTTM): Challenge in antemortem diagnosis using lung perfusion blood volume images by dual-energy computed tomography.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a specific type of tumor embolism in the small and medium pulmonary arteries, leading to rapid progressive pulmonary hypertension. Antemortem diagnosis of PTTM is extremely difficult. We encountered three patients who were histopathologically or clinically diagnosed with PTTM. In all cases, lung perfused blood volume (PBV) images on dual-energy computed tomography (CT) demonstrated multiple subpleural wedge-shaped defects with no evidence of pulmonary embolism on CT pulmonary angiography. The lung PBV images demonstrated small pulmonary arterial obstruction reflecting the pathology of PTTM. Therefore, lung PBV imaging would be useful for antemortem diagnosis of PTTM.

4D-flow MRI assessment of blood flow before and after endovascular intervention in a patient with pulmonary hypertension due to isolated pulmonary artery involvement in large vessel vasculitis.

A 43-year-old woman presented with dyspnea during exertion and lower leg edema. Contrast-enhanced computed tomography images demonstrated extensive proximal narrowing in the right main pulmonary artery with thickening and enhancement. Right heart catheterization revealed the presence of precapillary pulmonary hypertension with a mean pulmonary arterial pressure of 45 mm Hg. The patient was diagnosed with large-vessel vasculitis with isolated pulmonary artery involvement. Takayasu's arteritis was suspected, but histological examination was not performed. Several sessions of pulmonary arterial intervention were stratified for the right main pulmonary artery. After treatment, mean pulmonary arterial pressure had decreased to 22 mm Hg with improvement in symptoms. Thoracic 4D-flow magnetic resonance imaging was performed before and after intervention to evaluate the volume flow rates of pulmonary arteries. The rates increased at the inlet of the right pulmonary artery (before: 23 mL/s vs after: 47.5 mL/s) and the main pulmonary artery (before: 71.2 mL/s vs after: 82.5 mL/s), and decreased at the inlet of the left pulmonary artery (before: 46.2 mL/s vs after: 31.7 mL/s). The split ratio of volume flow rate between the right and left pulmonary arteries improved after treatment (before. right:left = 33.1:66.9; after, right:left = 60.0:40.0), approaching normal values. This report quantitatively describes perioperative hemodynamic changes in a patient with pulmonary hypertension using 4D-flow magnetic resonance imaging. Stent placement for stenosis in the right pulmonary artery resulted in an increase in overall pulmonary blood flow and also improved blood flow balance between the right and the left pulmonary arteries.

Perioperative Hemodynamic Changes in the Thoracic Aorta in Patients With Aortic Valve Stenosis: A Prospective Serial 4D-Flow MRI Study.

This study investigated hemodynamic changes in the thoracic aorta and aortic arch branches before and after aortic valve replacement (AVR) by 4D-flow MRI in patients with aortic valve stenosis (AS). Thoracic 4D-flow MRI was performed in 10 AS patients before and after AVR (mean 27 ± 1.9 days). Fifteen aortic planes and 3 aortic arch branches planes were set to evaluate the mean volume flow rate in each plane during a cardiac cycle and the angle between the main flow direction in a specified plane and the axial direction of the aorta. We also focused on the distribution and magnitude of helicity density to evaluate the flow complexity. A significant increase in the volume flow rate after AVR was found in the ascending aorta (before 59.2 ± 8.7 mL/s vs after 77.3 ± 6.2 mL/s, P < 0.05) and the aortic arch branches (before 26.5 ± 2.8 mL/s vs after 35.8 ± 3.3 mL/s, P < 0.001). The flow angle significantly decreased in the ascending aorta (before 39.2 ± 2.7 degree vs after 25.2 ± 1.7°, P < 0.0001) and the arch aorta (before 19.3 ± 2.0 degree vs after 13.4 ± 0.9°, P < 0.001). The volume flow rate in the ascending aorta and the arch branches increased within 1 month after AVR, showing an increased blood supply to the upper body, including to the brain. The postoperative change was accompanied with an increased blood flow in the ascending aorta and a decreased flow complexity proximal to the arch branches.

Mechanical allodynia in mice with tenascin-X deficiency associated with Ehlers-Danlos syndrome.

Tenascin-X (TNX) is a member of the extracellular matrix glycoprotein tenascin family, and TNX deficiency leads to Ehlers-Danlos syndrome, a heritable human disorder characterized mostly by skin hyperextensibility, joint hypermobility, and easy bruising. TNX-deficient patients complain of chronic joint pain, myalgia, paresthesia, and axonal polyneuropathy. However, the molecular mechanisms by which TNX deficiency complicates pain are unknown. Here, we examined the nociceptive behavioral responses of TNX-deficient mice. Compared with wild-type mice, TNX-deficient mice exhibited mechanical allodynia but not thermal hyperalgesia. TNX deficiency also increased pain sensitivity to chemical stimuli and aggravated early inflammatory pain elicited by formalin. TNX-deficient mice were significantly hypersensitive to transcutaneous sine wave stimuli at frequencies of 250 Hz (Aδ fiber responses) and 2000 Hz (Aß fiber responses), but not to stimuli at frequency of 5 Hz (C fiber responses). In addition, the phosphorylation levels of extracellular signal-related kinase, an active neuronal marker, and the activity of NADPH-diaphorase, a neuronal nitric oxide activation marker, were enhanced in the spinal dorsal horns of TNX-deficient mice. These results suggest that TNX deficiency contributes to the development of mechanical allodynia and hypersensitivity to chemical stimuli, and it induces hypersensitization of myelinated A fibers and activation of the spinal dorsal horn.