Clinical Hemorheology and Microcirculation - Volume Pre-press, issue Pre-press

Authors: Kim, Kwan Wook | Kim, Sang Woo | Lim, Soyeon | Yoo, Kyung-Jong | Hwang, Ki-Chul | Lee, Seahyoung

Article Type: Research Article

Abstract: Hexokinase 2 (HK2) is a metabolic sensor that couples glycolysis and oxidative phosphorylation of mitochondria by binding to the outer mitochondrial membrane (OMM), and it also has been implicated in induction of apoptotic process by regulating the integrity of OMM. When HK2 detaches from the mitochondria, it triggers permeability increase of the OMM and subsequently facilitates the cytosolic release of cytochrome c, a major apoptosis-inducing factor. According to previous studies, a harsh microenvironment created by ischemic heart disease such as low tissue oxygen and nutrients, and increased reactive oxygen species (ROS) can cause cardiomyocyte apoptosis. Under these conditions, the expression …of HK2 in heart significantly decrease and such down-regulation of HK2 was correlated to the increased apoptosis of cardiomyocytes. Therefore, prevention of HK2 down-regulation may salvage cardiomyocytes from apoptosis. MicroRNAs are short, non-coding RNAs that either inhibit transcription of target mRNAs or degrade the targeted mRNAs via complementary binding to the 3’UTR (untranslated region) of the targeted mRNAs. Since miRNAs are known to be involved in virtually every biological processes, it is reasonable to assume that the expression of HK2 is also regulated by miRNAs. Currently, to my best knowledge, there is no previous study examined the miRNA-mediated regulation of HK2 in cardiomyocytes. Thus, in the present study, miRNA-mediated modulation of HK2 during ROS (H2 O2 )-induced cardiomyocyte apoptosis was investigated. First, the expression of HK2 in cardiomyocytes exposed to H2 O2 was evaluated. H2 O2 (500μM) induced cardiomyocyte apoptosis and it also decreased the mitochondrial expression of HK2. Based on miRNA-target prediction databases and empirical data, miR-181a was identified as a HK2-targeting miRNA. To further examine the effect of negative regulation of the selected HK2-targeting miRNA on cardiomyocyte apoptosis, anti-miR-181a, which neutralizes endogenous miR-181a, was utilized. Delivery of anti-miR-181a significantly abrogated the H2 O2 -induced suppression of HK2 expression and subsequent disruption of mitochondrial membrane potential, improving the survival of cardiomyocytes exposed to H2 O2 . These findings suggest that miR-181a-mediated down-regulation of HK2 contributes to the apoptosis of cardiomyocytes exposed to ROS. Neutralizing miR-181a can be a viable and effective means to prevent cardiomyocyte from apoptosis in ischemic heart disease. Show more

Keywords: Hexokinase 2, miR-181a, reactive oxygen species, ischemic heart disease, cardiomyocytes, apoptosis

DOI: 10.3233/CH-200924

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2021

Authors: Wilma, Schierling | Kathrin, Bachleitner | Piotr, Kasprzak | Thomas, Betz | Alexander, Stehr | Karin, Pfister

Article Type: Research Article

Abstract: BACKGROUND: Acute lower limb ischemia (ALI) is associated with a high risk of limb loss and death. OBJECTIVE: The present study evaluates the safety of intraoperative, local urokinase lysis in patients with ALI and crural artery occlusion. METHODS: A total of 107 patients (115 legs) were treated surgically for ALI with additional intraoperative urokinase lysis to improve the outflow tract. Minor and major bleeding as well as efficacy of treatment and amputation-free survival were investigated. RESULTS: Complete restoration of at least one run-off vessel was achieved in 64%. Collateralization was improved in 34%. Lysis …failed in 2%. Major amputation rate was 27%overall (12%within 30 days) and depended on Rutherford class of ALI (overall/30 day: IIa 11%/6%; IIb 20%/17%; III 37%/15%). Amputation-free survival turned out to be 82%after 30 days, 58%after one, and 41%after five years. Minor bleeding occurred in 21%(24/115) and major bleeding in 3.5%(4/115). One of these patients died of haemorrhage. No patient experienced intracranial bleeding. CONCLUSION: Intraoperative urokinase lysis improves limb perfusion and causes low major and intracranial bleeding. It can be safely applied to patients with severe ischaemia when surgical restoration of the outflow tract fails. Show more

Keywords: Acute limb ischemia, bleeding, lysis, safety, thrombectomy, urokinase

DOI: 10.3233/CH-201049

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2021

Authors: Lei, Weijuan | Lin, Juliar | Liu, Fang | Chen, Nina

Article Type: Research Article

Abstract: PURPOSE: Acute myeloid leukemia (AML) is a type of hematologic malignancy. This study was attempt to explore the effect of long noncoding RNA GAS6 antisense RNA1 (GAS6-AS1) on pediatric AML and the regulation mechanisms. METHODS: GAS6-AS1, microRNA-370-3p (miR-370-3p), and Tetraspanin3 (TSPAN3) expression in bone marrow (BM) tissues and cells was determined by qRT-PCR. The correlation between GAS6-AS1 and clinicopathological features of pediatric patients with AML was assessed. In vitro , viability and migration and invasion of AML cells were evaluated via MTT and transwell assays, respectively. Interactions among GAS6-AS1, miR-370-3p, and TSPAN3 were revealed by dual-luciferase reporter assays. …Western blot was applied to confirm the protein expression of TSPAN3. RESULTS: GAS6-AS1 and TSPAN3 expression was elevated in BM tissues of pediatric patients with AML and AML cells, but miR-370-3p expression was reduced. GAS6-AS1 expression was positively related to French-American-British (FAB) classification in pediatric patients with AML. In vitro , GAS6-AS1 deficiency restrained the viability, migration, and invasion of AML cells. Additionally, GAS6-AS1 mediated miR-370-3p expression indeed and TSPAN3 was identified as a target of miR-370-3p. Furthermore, miR-370-3p overexpression repressed the protein expression of TSPAN3. The feedback experiments demonstrated that miR-370-3p inhibition or TSPAN3 overexpression mitigated the suppressive effect of sh-GAS6-AS1 on the tumorigenesis of AML cells. CONCLUSION: GAS6-AS1 silencing restrained AML cell viability, migration, and invasion by targeting miR-370-3p/TSPAN3 axis, affording a novel therapeutic target for pediatric AML. Show more

Keywords: GAS6-AS1, acute myeloid leukemia, viability, miR-370-3p, TSPAN3

DOI: 10.3233/CH-201039

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2021

Authors: Wiesinger, Isabel | Jung, Friedrich | Jung, Ernst Michael

Article Type: Research Article

Abstract: The external perfusion software (VueBox™ ) for contrast-enhanced ultrasound (CEUS), enables the quantitative analysis of micro-vascularization within non-cystic lesions in terms of characterization and detection. This review summarizes our work about parathyroid gland, thyroid gland, liver, prostate and other tissues as well as original studies in the use of parametric perfusion imaging. Useful perfusion parameters are introduced.

DOI: 10.3233/CH-201040

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2021

Authors: Lian, Kai-Mei | Lin, Teng

Article Type: Research Article

Abstract: BACKGROUND: Researchers have evaluated the VTI value in the diagnosis of breast lesions, mostly based on gray-scale. PURPOSE: This study aimed to evaluate the value of color-map virtual touch tissue imaging (CMV) in the diagnosis of breast lesions. METHODS: We retrospectively analyzed the virtual touch tissue imaging (VTI) images of 55 breast lesions in 49 female patients who underwent an examination of breast lesions in our hospital from January 2019 to December 2019. The pathological results were taken as the gold standard. The receiver operating characteristic (ROC) curve of CMV was analyzed, and its diagnostic performance …was evaluated. Weighted Kappa (k ) statistics were used to assess the inter-observer agreement for CMV. RESULTS: A total of 55 breast lesions were included, including 19 malignant lesions and 36 benign lesions. Multivariate analysis showed that patients with higher CMV scores (P  = 0.014, odds ratio [OR] = 13.667, 95% CI = 1.702–109.773) were independent predictors of breast cancer. The sensitivity, specificity, and the area under curve (AUC) of CMV were 94.47%, 72.22%, and 0.912. The CMV’s inter-observer agreement was almost perfect among radiologists with different work experience (k  = 0.854, standard error = 0.049, 95% confidence interval = 0.758–0.950). CONCLUSIOS: CMV has high accuracy and repeatability in the diagnosis of malignant breast lesions. Show more

Keywords: Breast lesion, ultrasound, elastography

DOI: 10.3233/CH-201088

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2021

Authors: Farber, Paulo Luiz

Article Type: Research Article

Abstract: Low plasma estrogens, vitamin D deficiency, obesity, diabetes, cardiovascular diseases, thromboembolism, and impaired microcirculation are linked to the severity of covid-19. Studies have suggested that these comorbidities also are related to erythrocyte factors linked to increased blood viscosity in microcirculation such as erythrocyte aggregation and erythrocyte deformability. Increased blood viscosity in microcirculation can lead to a decrease in oxygenation and nutrition of tissues. Therefore erythrocyte aggregation and erythrocyte deformability may be involved in covid-19 severity, leading to tissue hypoxia and a decrease of drug concentration in affected organs. If this relationship is demonstrated, erythrocytes factors can be used to monitor …treatments for improve microcirculatory fluidity that may decrease covid-19 severity. Lifestyle improvement and treatments such as vitamin D and estrogens supplementation are some possible approaches to improve microcirculation and covid-19 prevention and treatment. Show more

Keywords: Covid-19, hemorheology, microcirculation, estrogen, diabetes, vitamin D, obesity, cardiovascular diseases

DOI: 10.3233/CH-201082

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2021

Authors: Ashraf, Fahmida | Ambreen, Tehmina | Park, Cheol Woo | Kim, Dong-ik

Article Type: Research Article

Abstract: PURPOSE: Cross limb stent graft (SG) configuration technique for endovascular aneurysm repair (EVAR) is employed for splayed aortic bifurcations to avoid device kinking and smoothen cannulation. The present study investigates three types of stent graft (SG) configurations for endovascular aneurysm repair (EVAR) in abdominal aortic aneurysm. A computational fluid dynamic analysis was performed on the pulsatile non-Newtonian flow characteristics in three ideally modeled geometries of abdominal aortic (AA) SG configurations. METHODS: The three planar and crosslimb SG configurations were ideally modeled, namely, top-down nonballet-type, top-down ballet-type, and bottom-up nonballet-type configurations. In top-down SG configuration, most of the device …is deployed in the main body in the vicinity of renal artery and the limbs are extended to the iliac artery. While in the bottom-up configuration, some of the SG device is deployed in the main body, the limbs are deployed in aortic bifurcation, and the extra stent graft of the main body is extended to the proximal aorta until the below of the renal artery. The effects of non-Newtonian pulsatile flow on the wall stresses and flow patterns of the three models were investigated and compared. Moreover, the average wall shear stress (AWSS), oscillatory shear stress index (OSI), absolute helicity, pressure distribution, graft displacement and flow visualization plots were analyzed. RESULTS: The top-down ballet-type showed less branch blockage effect than the top-down nonballet-type models. Furthermore, the top-down ballet-type configuration showed an increased tendency to sustain high WSS and higher helicity characteristics than that of the bottom-up and top-down non-ballet type configurations. However, displacement forces of the top-down ballet-type configuration were 40%and 9.6%higher than those of the bottom-up and top-down nonballet-type configurations, respectively. CONCLUSIONS: Some complications such as graft tearing, thrombus formation, limb disconnection during long term follow up periods might be relevant to hemodynamic characteristics according to the configurations of EVAR. Hence, the reported data required to be validated with the clinical results. Show more

Keywords: Abdominal aortic aneurysm, EVAR, hemodynamics, non-newtonian flow

DOI: 10.3233/CH-200996

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-27, 2021

Authors: Dong, Yi | Qiu, Yijie | Yang, Daohui | Yu, Lingyun | Zuo, Dan | Zhang, Qi | Tian, Xiaofan | Wang, Wen-Ping | Jung, Ernst Michael

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the clinical value of dynamic contrast enhanced ultrasound (D-CEUS) in predicting the microvascular invasion (MVI) of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: In this retrospective study, 16 patients with surgery and histopathologically proved HCC lesions were included. Patients were classified according to the presence of MVI: MVI positive group (n  = 6) and MVI negative group (n  = 10). Contrast enhanced ultrasound (CEUS) examinations were performed within a week before surgery. Dynamic analysis was performed by VueBox ® software (Bracco, Italy). Three regions of interests (ROIs) were set in the center of HCC lesions, at the margin …of HCC lesions and in the surrounding liver parenchyma accordingly. Time intensity curves (TICs) were generated and quantitative perfusion parameters including WiR (wash-in rate), WoR (wash-out rate), WiAUC (wash-in area under the curve), WoAUC (wash-out area under the curve) and WiPi (wash-in perfusion index) were obtained and analyzed. RESULTS: All of HCC lesions showed arterial hyperenhancement (100 %) and at the late phase as hypoenhancement (75 %) in CEUS. Among all CEUS quantitative parameters, the WiAUC and WoAUC were higher in MVI positive group than in MVI negative group in the center HCC lesions (P  <  0.05), WiAUC, WoAUC and WiPI were higher in MVI positive group than in MVI negative group at the margin of HCC lesions. WiR and WoR were significant higher in MVI positive group. CONCLUSIONS: D-CEUS with quantitative perfusion analysis has potential clinical value in predicting the existence of MVI in HCC lesions. Show more

Keywords: Dynamic contrast enhanced ultrasound (D-CEUS), hepatocellular carcinoma (HCC), microvascular invasion (MVI), time intensity curves (TICs), prediction

DOI: 10.3233/CH-201085

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2021

Authors: Curta, Adrian | Jaber, Ahmad | Rieber, Johannes | Hetterich, Holger

Article Type: Research Article

Abstract: INTRODUCTION: Endothelial shear stress (ESS) is a local hemodynamic factor that is dependent on vessel geometry and influences the process of atherogenesis. As in vivo measurements of ESS are not possible, it must be calculated using computational fluid dynamics (CFD). In this feasibility study we explore CFD-models generated from coronary CT-angiography (CCTA) using an individualised blood viscosity and a pulsatile flow profile derived from in vivo measurements. MATERIALS AND METHODS: We retrospectively recruited 25 consecutive patients who received a CCTA followed by a coronary angiography including intravascular ultrasound (IVUS) and generated 3D models of the …coronary arteries from the CT-datasets. We then performed CFD-simulations on these models. Hemodynamically non-relevant stenosis were identified in IVUS. They were isolated in the CFD-model and separated longitudinally into a half with atherosclerotic lesion (AL) and one without (NAL). ESS was measured and compared for both halves. RESULTS: After excluding vessels with no IVUS data or relevant stenosis we isolated 31 hemodynamically non-relevant excentric AL from a total of 14 vessels. AL segments showed consistently significantly lower ESS when compared to their corresponding NAL segments when regarding minimum (0.9 Pa, CI [0.6, 1.2] vs. 1.3 Pa, CI [0.9, 1.8]; p  = 0.004), mean (5.0 Pa, CI [3.4, 6.0] vs. 6.7 Pa, CI [5.5, 8.4]; p  = 0.008) and maximum ESS values (12.4 Pa, CI [8.6, 14.6] vs. 19.6 Pa, CI [12.4, 21.0]; p  = 0.005). Qualitatively ESS was lower on the inside of bifurcations and curvatures. CONCLUSION: CFD simulations of coronary arteries from CCTA with an individualised flow profile and blood viscosity are feasible and could provide further prognostic information and a better risk stratification in coronary artery disease. Further prospective studies are needed to investigate this claim. Show more

Keywords: Coronary artery disease, endothelial shear stress, computational flow dynamics, pulsatile flow, coronary computed tomography, hemodynamics

DOI: 10.3233/CH-201025

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2021

Authors: de Souza, Maria das Graças C. | Cyrino, Fatima Z. G. A. | Sicuro, Fernando L. | Bouskela, Eliete

Article Type: Research Article

Abstract: BACKGROUND: Protective effects of Ruscus extract on macromolecular permeability depend on its capacity to stimulate muscarinic receptors on endothelial cells and induce the release of endothelium derived relaxing factors (EDRFs). OBJECTIVE: To investigate if these effects depend only on activation of muscarinic receptors or EDRFs release are also necessary. We have also investigated the participation of Ruscus extract on muscarinic-induced release of EDRFs on microvascular diameters. METHODS: Hamsters were treated daily during two weeks with Ruscus extract (50, 150 and 450 mg/kg/day) and then macromolecular permeability induced by histamine and arteriolar …and venular diameters after cyclooxygenase (COX) and nitric oxide synthase (NOS) inhibitors: indomethacin and Nω-Nitro-L-arginine (LNA), respectively applied topically at 10–8 M, 10–6 M and 10–4 M were observed on the cheek pouch preparation. RESULTS: Ruscus extract decreased macromolecular permeability in a dose-dependent fashion and did not affect microvascular diameters. NOS and COX inhibitors enhanced this effect. NOS inhibition reduced arteriolar diameter and COX blocking decreased arteriolar and venular diameters at the lowest dose and increased them at higher doses of Ruscus extract. CONCLUSION: The protective effect of Ruscus extract on macromolecular permeability seems to be mediated only via muscarinic receptors. Muscarinic activation attenuated vasoconstrictive tone through cyclooxygenase-independent endothelium derived relaxing factors. Show more

Keywords: Ruscus extract, muscarinic receptors, endothelium derived relaxing factors, macromolecular permeability, microvascular diameter, cyclooxygenase, nitric oxide synthase, hamster cheek pouch preparation

DOI: 10.3233/CH-201019

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-17, 2021