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

Authors: Wei, Wenbo | Tang, Min | Wang, Qi | Li, Xiaoming

Article Type: Research Article

Abstract: BACKGROUND: Coronary artery disease (CAD) is a common coronary artery disease. The functional mechanism of circular RNA (circRNA) HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2 (circ_HECW2, hsa_circ_0057583) in ox-LDL-treated human cardiac microvascular endothelial cells (hCMECs) is still unclear. METHODS: Expression levels of circ_HECW2, microRNA (miR)-942-5p, and toll-like receptor 4 (TLR4) were analyzed by quantitative real-time PCR (qRT-PCR) and western blot assays. Cell proliferation and apoptosis were analyzed by 5-ethynyl-2’-deoxyuridine (EdU) assay, cell counting kit-8 (CCK8) assay, and flow cytometry, respectively. Tube formation assay was performed to analyze the angiogenesis of cells. Luciferase reporter and …RNA pull-down assays were performed to analyze the target relationship among circ_HECW2, miR-942-5p and TLR4. RESULTS: Circ_HECW2 and TLR4 expression levels were up-regulated and miR-942-5p expression was decreased in the serum of CAD patients and oxidized low-density lipoprotein (ox-LDL)-induced hCMECs. Knockdown of circ_HECW2 enhanced cell proliferation and inhibited cell apoptosis in ox-LDL-treated hCMECs. MiR-942-5p was the target of circ_HECW2 and directly targeted TLR4. Moreover, the effect of circ_HECW2 knockdown could be weakened by anti-miR-942-5p, and TLR4 could restore the function of miR-942-5p on cell damage of ox-LDL-induced hCMECs. CONCLUSION: Circ_HECW2 could regulate ox-LDL-induced cardiovascular endothelial cell dysfunction through targeting miR-942-5p/TLR4 axis. Show more

Keywords: Circ_HECW2, miR-942-5p, TLR4, coronary artery disease

DOI: 10.3233/CH-221550

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2022

Authors: Chen, Jianfei | Guan, Peishan | Sun, Pei | Yu, Qing | Yuan, Haixia

Article Type: Research Article

Abstract: As a rare biliary tract tumor, intraductal papillary neoplasm of the bile duct (IPNB) is most common in elderly men and can progress to cholangiocarcinoma- (CCa) if left untreated. It is reported that IPNB usually communicates with the bile duct. As a result, the downstream bile ducts are imaged asymmetrically dilated. However, a case of IPNB that we report here is different. Enhanced MRI revealed a lack of connectivity with the bile duct in this case. Based on this, the purpose of this case study is to suggest that the majority of imaging doctors should widely understand the various imaging …manifestations of the disease to avoid misdiagnosis. In addition, although this feature was not indicated by ultrasound in this case, given previous studies and considering the convenience and non-ionizing radiation damage of CEUS, we recommend its use as a screening method for IPNB to improve diagnostic accuracy. Show more

Keywords: Intraductal papillary neoplasm of the bile duct, cholangiocarcinoma, contrast-enhanced ultrasound

DOI: 10.3233/CH-242167

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-6, 2024

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

Article Type: Research Article

Abstract: BACKGROUND: Despite the well-recognized effectiveness of Ruscus aculetus extract combined or not with ascorbic acid (AA) and hesperidine methyl chalcone (HMC) on ischemia reperfusion (I/R) injury protection, little is known about the contribution of each constituent for this effect. OBJECTIVE: To investigate the effects of AA and HMC combined or not with Ruscus extract on increased macromolecular permeability and leukocyte-endothelium interaction induced by I/R injury. METHODS: Hamsters were treated daily during two weeks with filtered water (placebo), AA (33, 100 and 300 mg/kg/day) and HMC (50, 150 and 450 mg/kg/day) combined or not with Ruscus …extract (50, 150 and 450 mg/kg/day). On the day of experiment, the cheek pouch microcirculation underwent 30 min of ischemia, and the number of rolling and adherent leukocytes and leaky sites were evaluated before ischemia and during 45 min of reperfusion. RESULTS: Ruscus extract combined with AA and HMC (Ruscus extract mixture) significantly prevented post-ischemic increase in leukocyte rolling and adhesion and macromolecular permeability compared to placebo and these effects were more prominent than AA and HMC alone on leukocyte adhesion and macromolecular leakage. CONCLUSION: Ruscus extract mixture were more effective than its isolated constituents in protect the hamster cheek pouch microcirculation against I/R injury. Show more

Keywords: Ruscus extract, ischemia/reperfusion injury, hamster cheek pouch preparation, microcirculation

DOI: 10.3233/CH-242111

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-21, 2024

Authors: Jin, Dong-Dong | Lin, Jin-Hua | Li, Shi-Hui | Zhuang, Bo-Wen | Xie, Xiao-Yan | Xie, Xiao-Hua | Wang, Yan

Article Type: Research Article

Abstract: OBJECTIVE: This study aimed to evaluate the clinical characteristics and features of conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) in differentiating between renal urothelial carcinomas (RUC) and endophytic clear cell renal cell carcinomas (EccRCC). METHODS: A total of 72 RUCs and 120 EccRCCs confirmed by pathology were assessed retrospectively. Both CUS and CEUS were performed within 4 weeks before the surgery. Logistic regression analyses were used to select statistically significant variables of clinical, CUS, and CEUS features for the differentiation of RUC and EccRCC. Sensitivity (SEN), specificity (SPE), and the area under the receiver-operating characteristic curve (AUC) were …assessed for diagnostic performance. Inter- and intra-observer agreements of CUS and CEUS features were evaluated using the intra-class correlation coefficient(ICC). RESULTS: Multiple logistic regression analysis demonstrated that clinical (age >50 years old and hematuria), CUS (size <4.0 cm, hypo-echogenicity, irregular shape, hydronephrosis) and CEUS (absence of non-enhancement area, iso- /hypo-enhancement in cortical phase and absence of rim-like enhancement) features were independent factors for RUC diagnosis. When combining clinical characters with CUS and CEUS features into an integrated diagnostic criterion, the AUC reached 0.917 (95% CI 0.873–0.961), with a sensitivity of 95.8% and specificity of 87.5%. ICC ranged from 0.756 to 0.907 for inter-observer agreement and 0.791 to 0.934 for intra-observer agreement for CUS and CEUSfeatures. CONCLUSIONS: The combination of clinical features of age and hematuria with imaging features of CUS and CEUS can be useful for the differentiation between RUC and EccRCC. Show more

Keywords: Contrast-enhanced ultrasound, conventional ultrasound, urothelial carcinomas, endophytic clear cell renal cell carcinomas, differential diagnosis

DOI: 10.3233/CH-242119

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 2024

Authors: Tastekin, Fatih | Akay, Olga Meltem | Colak, Ertugrul | Gunduz, Eren

Article Type: Research Article

Abstract: BACKGROUND: Although plateletpheresis donation is commonly accepted as a safe procedure, its influence on platelet function, coagulation system and fibrinolysis is not completely elucidated. OBJECTIVES: In this study, we tried to assess the effects of plateletpheresis on donor’s hemostasis system by measuring platelet activation, development of platelet-leukocyte aggregates, and coagulation activation. STUDY DESIGN: Prospective observational study. METHODS: We used flow cytometry to determine the levels of platelet-monocyte complexes (PMC) and platelet-neutrophil complexes (PNC). sP-selectin and prothrombin fragment (PF) 1 + 2 values were determined by ELISA. RESULTS: The PMC levels increased significantly seven days …after apheresis in comparison with just after apheresis and 24 h after apheresis (p  < 0.05). The PNC levels increased significantly seven days after apheresis compared to immediately after apheresis (p  < 0.05). sP-selectin values decreased significantly immediately after apheresis (p  < 0.05). While sP-selectin values increased seven days after apheresis in comparison with immediately after apheresis and 24 h after apheresis, but there were not statistically significant differences for sP-selectin levels (p  > 0.05). PF1 + 2 levels decreased significantly immediately after apheresis compared to pre-apheresis (p  < 0.05) and increased 24 h after apheresis and seven days after apheresis, but these differences were not statistically significant. CONCLUSION: We concluded that plateletpheresis affects platelet activation but does not cause any change in coagulation activation. Show more

Keywords: Plateletpheresis, platelet-leucocyte aggregate, P-selectin, prothrombin fragment

DOI: 10.3233/CH-242325

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2024

Authors: Li, Wei-Wei | Guo, Ze-Ming | Wang, Bing-Cai | Liu, Qing-Quan | Zhao, Wen-An | Wei, Xiao-Lan

Article Type: Research Article

Abstract: OBJECTIVE: Atherosclerosis is a chronic inflammatory disease of the arteries, and its pathogenesis is related to endothelial dysfunction. It has been found that the protein convertase subtilin/kexin9 type (PCSK9) plays an important role in AS, but its specific mechanism is still unclear. METHODS: In this study, we first cultured human umbilical vein endothelial cells (HUVECs) with 50 or 100μg/ml oxidized low-density lipoprotein (ox-LDL) for 24 hours to establish a coronary atherosclerosis cell model. RESULTS: The results showed that ox-LDL induced HUVEC injury and autophagy and upregulated PCSK9 protein expression in HUVECs in a concentration-dependent …manner. Silencing PCSK9 expression with siRNA inhibited ox-LDL-induced HUVEC endothelial dysfunction, inhibited the release of inflammatory factors, promoted HUVEC proliferation and inhibited apoptosis. In addition, ox-LDL increased the expression of LC3B-I and LC3B-II and decreased the expression of p62. However, these processes are reversed by sh-PCSK9. In addition, sh-PCSK9 can inhibit PI3K, AKT and mTOR phosphorylation and promote autophagy. CONCLUSION: Taken together, our research shows that silencing PCSK9 inhibits the PI3K/ATK/mTOR pathway to activate ox-LDL-induced autophagy in vascular endothelial cells, alleviating endothelial cell injury and inflammation. Show more

Keywords: PCSK9, atherosclerotic coronary, autophagy, endothelial cell, PI3K

DOI: 10.3233/CH-242172

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2024

Authors: Xue, Xiaolei | Wu, Liping | Zhang, Jinqing | Sun, Wei | Jiang, Shiqin | Chu, Xiaoling | Sun, Yingzi

Article Type: Research Article

Abstract: OBJECTIVE: This study aimed to summarize the clinical manifestations and ultrasound characteristics of primary thyroid lymphoma (PTL) and explore the key aspects in the process of diagnosing PTL. METHODS: We conducted a retrospective analysis of the clinical and ultrasound features of 11 patients with PTL who were admitted to Shandong Provincial Third Hospital, China, between May 2009 and August 2023. The pathology was confirmed in all cases through an ultrasound-guided core needle biopsy or surgical resection. RESULTS: The mean age of the 11 patients was 64.45±9.85 years. In six patients, the main clinical manifestation was a …palpable mass in the neck, five of whom had a significant increase in the size of the mass within 3 months to 2 years. Eleven patients had coexisting Hashimoto’s thyroiditis (HT). Three patients were diagnosed as having diffuse-type PTL, wherein the ultrasound showed enlargement of the affected thyroid gland with diffusely uneven hypoechoic parenchyma. In 7 patients with nodular type PTL and 1 case of mixed type PTL, the ultrasonographic features of the nodular lesions were of irregular morphology and yet had distinct borders, and only 1 case had gross calcification. There were 7 cases of hypoechoic lesions (7/11 cases, 63.6%), 9 cases where the lesions had linear echo chains (9/11 cases, 81.8%), and 10 cases (90.9%) where there was echogenic enhancement posterior to the lesion. CONCLUSION: In elderly patients with HT, the thyroid volume increases significantly in a short period of time and symptoms associated with compression in the neck region appear. The ultrasound characteristics were extremely hypoechoic lesions in the thyroid parenchyma, with more linear echo chains visible inside, accompanied by posterior echo enhancement. When encountering such presentations, physicians must consider the possibility of PTL. Performing a core needle biopsy in cases that raise suspicion can reduce the incidence of misdiagnosis. Show more

Keywords: Clinical features, core needle biopsy, diagnosis, primary thyroid lymphoma, ultrasound

DOI: 10.3233/CH-242258

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2024

Authors: Li, Chen | Jia, Yong-Rui | Gou, Qiao | Ju, Zhong-Jian

Article Type: Research Article

Abstract: OBJECTIVE: Our prior research has established that X-ray exposure induces pyroptosis in human umbilical vein endothelial cells (HUVECs), with Cx43 playing a regulatory role in this process. However, the precise mechanism by which Cx43 regulates pyroptosis remains unclear. The objective of this study is to assess the involvement of the calcium signaling pathway in Cx43-mediated regulation of X-ray-induced pyroptosis in HUVECs. METHODS: HUVECs were exposed to 10 Gy X-ray radiation either alone or combined with Cx43 overexpression or knockdown. Calcium ions (Ca2+ ) were stained using Fluo-4/AM and analyzed via flow cytometry and confocal microscopy. Pyroptosis was assessed through …flow cytometry by staining with FLICA (fluorescent-labeled inhibitor of caspase) and propidium iodide (PI). Calcium signaling was inhibited using BAPTA/AM, 2-APB, or nifedipine. Protein expression levels were assessed by western blotting. RESULTS: X-ray irradiation induced an increase in intracellular calcium levels in HUVECs in a dose- and time-dependent manner. The results demonstrated that regulating calcium release with BAPTA/AM, 2-APB, or nifedipine significantly reduced pyroptosis. Also, the overexpression of Cx43 significantly attenuated the increase in intracellular calcium. Conversely, Cx43 knockdown via siRNA significantly increased the intracellular calcium levels. Also, interfering with calcium signaling using BAPTA/AM, 2-APB, or nifedipine reduced the raised pyroptosis levels induced by Cx43 knockdown. CONCLUSION: Individual HUVECs exposed to high-dose X-ray irradiation exhibited an increase in intracellular calcium, leading to pyroptosis. Also, upregulating Cx43 expression reduced the pyroptosis levels by inhibiting intracellular calcium concentration. This study introduces new concepts for identifying targets for the prophylaxis and therapy of radiation-induced damage. Show more

Keywords: Calcium, Connexin43, pyroptosis, x-ray

DOI: 10.3233/CH-242381

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2024

Authors: Zhang, Wei-Bing | Deng, Wen-Fang | He, Bei-Li | Wei, Ying-Ying | Liu, Yu | Chen, Zhe | Xu, Ren-Yan

Article Type: Research Article

Abstract: OBJECTIVES: To investigate the diagnostic value of CEUS combined with C-TIRADS for indeterminate FNA cytological thyroid nodules. METHODS: The clinical data, ultrasonic images, C-TIRADS categories and CEUS images of 192 patients with indeterminate FNA cytological thyroid nodules confirmed by the surgical pathology were analyzed retrospectively. The diagnostic efficacy of CEUS, C-TIRADS and CEUS-TIRADS were calculated. RESULTS: The AUCs of CEUS, C-TIRADS and CEUS-TIRADS were 0.905 (95% CI: 0.862∼0.949), 0.881 (95% CI: 0.825∼0.938) and 0.954 (95% CI: 0.922∼0.986), respectively. The sensitivity, specificity, PPV, NPV, accuracy, LR– and LR+ were 84.7% (116/137), 85.5% (47/55), 93.5% (116/124), …69.1% (47/68), 84.9% (163/192), 0.179, 5.82 and 84.7% (116/137), 83.6% (46/55), 92.8% (116/125), 68.7% (46/67), 84.4% (162/192), 0.183, 5.17, 92.7% (127/137), 89.1% (49/55), 95.5% (127/133), 83.1% (49/59), 91.7% (176/192), 0.082, and 8.50, respectively. Compared with CEUS and C-TIRADS, CEUS-TIRADS had improved the AUC, sensitivity and accuracy (all P  < 0.05). CONCLUSIONS: CEUS and C-TIRADS had high diagnostic values in indeterminate FNA cytological thyroid nodules. CEUS-TIRADS improved AUC, diagnostic sensitivity and accuracy, and helped to distinguish indeterminate FNA cytological nodules. Show more

Keywords: Thyroid nodule, contrast enhanced ultrasound, Chinese thyroid imaging reporting and system

DOI: 10.3233/CH-242363

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2024

Authors: Velcheva, Irena | Antonova, Nadia | Kmetski, Tsocho | Tsonevska, Galina | Stambolieva, Katerina | Alexandrova, Anika | Bechev, Blagovest

Article Type: Research Article

Abstract: OBJECTIVE: The carotid stiffness is an important factor in the pathogenesis of cerebrovascular small vessel disease. Our study aimed to evaluate the relation of the local arterial stiffness of the common carotid artery (CCA) to the hemodynamic forces and blood viscosity in patients with cerebral lacunar infarctions (LI). METHODS: Twenty-two patients with chronic LI and 15 age-matched controls were examined. An ultrasound examination of the CCA intima-media thickness (IMT), the parameters of local CCA stiffness: distensibility (DC) and compliance coefficients (CC), α and β stiffness indices and pulse wave velocity (PWV) was performed. The local hemodynamic forces …were calculated: circumferential wall tension (CWT) and wall shear stress (WSS). Whole blood viscosity (WBV) and shear stresses at shear rates of 0.277 s - 1 to 94.5 s - 1 were measured in patients and controls. RESULTS: Higher values of IMT, a significant decrease of DC and CC and an increase of α and β stiffness indices and PWV in the LI patients compared to the controls were obtained. A parallel significant increase in CWT and a decrease in WSS was found. An increase in WBV and a significant increase in shear stresses were detected. In the LI patients, the increased stiffness indices were associated with an increase in age, cholesterol and WBV at higher shear rates in the left CCA. In the controls, the IMT and stiffness indices correlated significantly with the hemodynamic factors and WBV in both CCAs, while the stiffness indices correlated with the hemodynamic forces in the left CCA. CONCLUSION: The results of the present study demonstrate different associations of the local carotid stiffness indices with the hemodynamic forces and WBV in patients with LI and controls. Show more

Keywords: Lacunar infarctions, common carotid artery, intima-media thickness, local carotid stiffness, hemodynamic forces, whole blood viscosity

DOI: 10.3233/CH-242333

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2024

Authors: Li, Yi-Xiang | Lv, Wei-Long | Qu, Meng-Meng | Wang, Li-Li | Liu, Xiao-Yu | Zhao, Ying | Lei, Jun-qiang

Article Type: Research Article

Abstract: Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer, accounting for approximately 90% of liver cancer cases. It currently ranks as the fifth most prevalent cancer worldwide and represents the third leading cause of cancer-related mortality. As a malignant disease with surgical resection and ablative therapy being the sole curative options available, it is disheartening that most HCC patients who undergo liver resection experience relapse within five years. Microvascular invasion (MVI), defined as the presence of micrometastatic HCC emboli within liver vessels, serves as an important histopathological feature and indicative factor for both disease-free survival and overall survival …in HCC patients. Therefore, achieving accurate preoperative noninvasive prediction of MVI holds vital significance in selecting appropriate clinical treatments and improving patient prognosis. Currently, there are no universally recognized criteria for preoperative diagnosis of MVI in clinical practice. Consequently, extensive research efforts have been directed towards preoperative imaging prediction of MVI to address this problem and the relative research progresses were reviewed in this article to summarize its current limitations and future research prospects. Show more

Keywords: Microvascular invasion, hepatocellular carcinoma, radiomics, texture analysis, diagnostic imaging, liver

DOI: 10.3233/CH-242286

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2024

Authors: Gouia, H.-F. | Duraes, M. | Delpont, M. | Herlin, C. | Biron-Andreani, C. | Jeziorski, E. | Captier, G. | Theron, A.

Article Type: Research Article

Abstract: Idiopathic purpura fulminans (IPF) is a rare and severe form of purpura fulminans caused by acquired protein S deficiency. It can lead to severe thrombotic complications, such as large skin necrosis and amputation. The lesions almost exclusively affect the lower limbs, and their distribution is similar among patients with IPF, unlike classical purpura fulminans lesions. Our hypothesis is that vascular structures called perforasomes may be involved in IPF, possibly caused by protein S deficiency. We analyzed all case reports and case series published in the literature that provided sufficient data for an anatomical study of limb injuries. For precise …localization of areas of necrosis, we examined each case using descriptions and images to determine whether they overlapped with vascular territories that include perforasomes. We analyzed twelve cases from the literature and identified six vascular territories: the anterolateral, anteromedial, and posterior territories of the upper leg, as well as the anterolateral, anteromedial, and posterolateral territories of the lower leg. For each territory, we described the most probable vascular damage and the corresponding perforasome. IPF is a complex multifactorial disease in which a direct involvement of perforating arteries may be suspected and taken into account in the surgical of lesions. Show more

Keywords: Idiopathic purpura fulminans, protein S deficiency, perforasome, thrombosis, necrosis

DOI: 10.3233/CH-242162

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2024

Authors: Kordi, Negin | Saydi, Ali | Azimi, Maliheh | Mazdarani, Farivar | Gadruni, Keivan | Jung, Friedrich | Karami, Sajad

Article Type: Research Article

Abstract: Copper is an essential element in the human body, involved in many physiological and metabolic functions, including coagulation, oxidative metabolism, and hormone production. The maintenance of copper homeostasis within cells is a complex procedure that is intrinsically controlled by a multitude of intricate mechanisms. Disorders of copper homeostasis encompass a wide range of pathological conditions, including degenerative neurological diseases, metabolic disorders, cardio-cerebrovascular diseases, and tumors. Cuproptosis, a recently identified non-apoptotic mode of cell death mode, is characterized by copper dependence and the regulation of mitochondrial respiration. Cuproptosis represents a novel form of cell death distinct from the previously described modes, …including apoptosis, necrosis, pyroptosis, and ferroptosis. Excess copper has been shown to induce cuproptosis by stimulating protein toxic stress responses via copper-dependent abnormal oligomerization of lipoylation proteins within the tricarboxylic acid cycle and the subsequent reduction of iron-sulfur cluster protein levels. Ferredoxin1 facilitates the lipoacylation of dihydrolipoyl transacetylase, which in turn degrades iron-sulfur cluster proteins by reducing Cu2+ to Cu+ , thereby inducing cell death. Furthermore, copper homeostasis is regulated by the copper transporter, and disturbances in this homeostasis result in cuproptosis. Current evidence suggests that cuproptosis plays an important role in the onset and development of several cardiovascular diseases. Copper-chelating agents, including ammonium tetrathiomolybdate (VI) and DL-penicillamine, have been shown to facilitate the alleviation of cardiovascular disease by inhibiting cuproptosis. It is hypothesized that oxidative phosphorylation inhibitors such as physical training may inhibit cuproptosis by inhibiting the protein stress response. In conclusion, the implementation of physical training may be a viable strategy to reducte the incidence of cuproptosis. Show more

Keywords: Copper, exercise, cell death, physical activity, cuproptosis

DOI: 10.3233/CH-242329

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2024

Authors: Gogilashvili, Nino | Tsinamdzgvrishvili, Bezhan | Momtselidze, Nana | Jung, Friedrich | Plantl, Lukas | Urdulashvili, Tamar | Mantskava, Maia

Article Type: Research Article

Abstract: BACKGROUND: “Slow flow” is one very important concept in modern fundamental and clinical biomedicine. Slow coronary flow is indicative of delayed filling of the terminal coronary artery vessels, occurring in the absence of significant coronary stenosis. This group patient of patients exhibits a high incidence of disability and represents a significant financial and material burden for the state and the healthcare system in general. OBJECTIVE: The primary objective of our study was to examine patients with slow coronary flow. METHODS: We studied the standard parameters recommended by the international health care system (electrocardiography (by Medica QRS-12, …Germany), through the electrical activity of a patient’s heart by the electrical impulses (beating) of the heart; HC1(Germany); coagulogramma by Coatron M1 (Germany), troponin by AQT 90 (Germany); general blood test we used automatic human counting device HC1(Germany). Also, we investigate the original parameters (non-standard parameters, which we use in this pilot study) that we were first studied for this diagnosis and non-standard parameters. RESULTS: A general blood test showed that patients with slow flow had a higher blood leukocyte count than the control group, but the amount of hemoglobin was normal, the hematocrit was much higher than in the control group, and the platelet count was close to the lower limit of clinical standards. We obtained details of blood flow by coagulation situation, such as prothrombin time, prothrombin index, international normalized ratio, activated partial thromboplastin time, thrombin time, fibrinogen, and rheological properties such as index of erythrocyte aggregability, index of erythrocyte deformability, plasma viscosity, in silico blood rheological index. CONCLUSSION: Blood flow can be considered as a superposition of vortices with similar frequencies and wave vectors that change after bifurcations or other obstacles in the vascular network. These factors together determine the conditions for structuring the flow of moving blood. Disruption or alteration of these factors results in slow flow. It has been found that the speed of blood flow in the coronary arteries depends on changes in the number and function of red blood cells. Slow flow is directly influenced by the aggregation and deformation of red blood cells, their number, and plasma viscosity. Consequently, the rheological status plays a crucial role in determining blood flow and its velocity. Show more

Keywords: Slow flow, aggregation, deformation, coagulation/anticoagulation, in silico blood rheological index, plasma viscosity

DOI: 10.3233/CH-249104

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2024

Authors: Liang, Ming | Qiu, Haolin | Ou, Bing | Wu, Jiayi | Zhao, Xinbao | Luo, Baoming

Article Type: Research Article

Abstract: OBJECTIVE: The study aimed to evaluate the utility of qualitative and quantitative analysis employing contrast-enhanced ultrasound (CEUS) in predicting the WHO/ISUP grade of small (≤4 cm) clear cell renal cell carcinoma (ccRCCs). METHODS: Patients with small ccRCCs, confirmed by histological examination, underwent preoperative CEUS and were classified into low- (grade I/II) and high-grade (grade III/IV) groups. Qualitative and quantitative assessments of CEUS were conducted and compared between the two groups. Diagnostic performance was assessed using receiver operating characteristic curves. RESULTS: A total of 72 patients were diagnosed with small ccRCCs, comprising 23 individuals in the high-grade group …and 49 in the low-grade group. The low-grade group exhibited a significantly greater percentage of hyper-enhancement compared to the high-grade group (79.6% VS 39.1%, P  < 0.05). The low-grade group showed significantly higher relative index values for peak enhancement, wash-in area under the curve, wash-in rate, wash-in perfusion index, and wash-out rate compared to the high-grade group (all P  < 0.05). The AUC values for qualitative and quantitative parameters in predicting the WHO/ISUP grade of small ccRCCs ranged from 0.676 to 0.756. CONCLUSIONS: Both qualitative and quantitative CEUS analysis could help to distinguish the high- from low-grade small ccRCCs. Show more

Keywords: Contrast-enhanced ultrasound, WHO/ISUP grade, clear cell renal cell carcinoma, quantitative analysis, small renal mass

DOI: 10.3233/CH-231990

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2024

Authors: Saydi, Ali | Behpoor, Naser | Khamis Abadi, Fatemeh | Jung, Friedrich | Kordi, Negin

Article Type: Research Article

Abstract: OBJECTIVE: This study aimed to investigate the effects of six weeks of continuous training and Nutrition Bio-shield (NBS) Superfood Supplementation on the state of oxidative stress by the expression of Nrf2, NOX4, superoxide dismutase, and malondialdehyde genes in the lungs of rats after methamphetamine withdrawal. METHODS: Forty male Wistar rats were randomly divided into five groups (n  = 8, per group), undergoing methamphetamine administration (six weeks, 5 mg/kg ip, and once per day) followed by a 21-day withdrawal period. The rats were supplemented NBS superfood at a dosage of 25 g/kg per day for six weeks. The training protocol was 30 …minutes of daily continuous training (treadmill running), five days a week for six weeks. The regimen escalated from a pace of 3 m/min for the initial 5 minutes, to 5 m/min for the following 5 minutes, culminating at 8 m/min for the remainder of the session, all at a 0° incline. A one-way analysis of variance was performed to analyze the gene expression of Nrf2, NOX4, MDA, and SOD in the lungs tissue of rats. RESULTS: The results indicated that, in the experimental groups which underwent continuous training and NBS Superfood supplementation, the expression of the Nrf2 gene exhibited a significant elevation compared to the control group (P  < 0.05), while the NOX4, MDA, and SOD genes expression exhibited a significant decline in comparison to the control group (P  < 0.05). CONCLUSION: In general, both exercise interventions and NBS superfood supplementation, when employed separately or in combination after methamphetamine withdrawal, can enhance the state of oxidative stress in the lung. Show more

Keywords: Nrf2, NOX4, MDA, SOD, Lung, Nutrition Bio-shield

DOI: 10.3233/CH-242306

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2024

Authors: Ma, Yue | Du, Jin | Wang, Xin-Xin | Deng, Tong | Qi, Jia-Li | Cheng, Hong | Li, Lu

Article Type: Research Article

Abstract: OBJECTIVE: In this study, we developed an exercise training protocol for assessing both blood pressure dynamics and mRNA expression levels of purine receptors in various vascular tissues during physical activity. The objective is to assess the impact of exercise training on blood pressure regulation in spontaneously hypertensive rats (SHR) and purine receptors in vascular tissues. METHODS: Wistar Kyoto (WKY) and SHR rats were randomly allocated into sedentary (Sed) and exercise training (ExT) groups. Rats in the Sed groups were allowed unrestricted movement, whereas those in the ExT groups underwent a 16-week regimen of low- to moderate-intensity treadmill exercise. …Throughout the intervention period, blood pressure measurements and body weight recordings were conducted. Additionally, mRNA expressions of purine receptors P2X1, P2Y1, and P2Y2 in renal artery (RA), internal carotid artery (Int), thoracic aorta (Aor), and caudal artery (Cau) tissues were assessed. RESULTS: In the Sed group, body weight of SHR rats was observed to be lower compared to the three other groups. Over the course of the exercise regimen, blood pressure in the ExT group of SHR rats reduced gradually, converging towards levels similar to those observed in WKY rats by the conclusion of the exercise period. Regarding mRNA expression patterns of P2X1 receptors across the four blood vessels, WKY and SHR rats demonstrated similar sequences, consistently displaying the highest expression levels in the Cau. Conversely, mRNA expressions of P2Y1 and P2Y2 receptors exhibited distinct sequences across the four blood vessels in both WKY and SHR rats. Notably, compared to the Sed group of WKY rats, mRNA expression of P2X1 receptor in the Int of SHR rats revealed an increase, while expressions in the Aor of WKY rats and the Cau of SHR rats decreased following exercise. Expression of P2Y1 receptor mRNA decreased across all four types of blood vessels in SHR rats. Post-exercise, P2Y1 receptor mRNA expression increased in the Aor, decreased in the Cau of WKY rats, and increased in the Int and renal artery (RA) of SHR rats. Conversely, expressions of P2Y2 receptor mRNA decreased in the Int and Aor of SHR rats. Except for the Aor of WKY rats, expressions of P2Y2 receptor mRNA increased in the other arteries of both rat types following exercise. CONCLUSION: Differences in the distribution of purine receptor subtypes among distinct arterial segments in both WKY and SHR rats were observed. Exercise training was found to enhance mRNA expression levels of P2Y receptors in these rat models. This finding implies that exercise training might reduce hypertension in SHR rats by bolstering the purinergic relaxation response. Show more

Keywords: Blood vessels, exercise training, purine receptors, spontaneous hypertension rat

DOI: 10.3233/CH-242366

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2024

Authors: Li, Shuo | Wang, Yu

Article Type: Research Article

Abstract: BACKGROUND: Endothelial dysfunction is an early and pre-clinical manifestation of coronary heart disease (CHD). OBJECTIVE: This study investigates the role of DDX5 in oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell injury to confer novel targets for the treatment of CHD. METHODS: Endothelial cells were induced by ox-LDL. DDX5, pri-miR-640, pre-miR-640, miR-640, and SOX6 expressions were analyzed by RT-qPCR and Western blot. DDX5 expression was intervened by shRNA, followed by CCK-8 analysis of proliferation, flow cytometry detection of apoptosis, and tube formation assay analysis of angiogenic potential of cells. The binding between DDX5 and pri-miR-640 was determined by …RIP, and the pri-miR-640 RNA stability was measured after actinomycin D treatment. Dual-luciferase assay verified the targeting relationship between miR-640 and SOX6. RESULTS: DDX5 and miR-640 were highly expressed while SOX6 was poorly expressed in ox-LDL-induced endothelial cells. Silence of DDX5 augmented cell proliferation, abated apoptosis, and facilitated angiogenesis. Mechanistically, RNA binding protein DDX5 elevated miR-640 expression by weakening the degradation of pri-miR-640, thereby reducing SOX6 expression. Combined experimental results indicated that overexpression of miR-640 or low expression of SOX6 offset the protective effect of DDX5 silencing on cell injury. CONCLUSION: DDX5 elevates miR-640 expression by repressing the degradation of pri-miR-640 and then reduces SOX6 expression, thus exacerbating ox-LDL-induced endothelial cell injury. Show more

Keywords: Coronary heart disease, DDX5, miR-640, SOX6, ox-LDL, endothelial cell injury

DOI: 10.3233/CH-242254

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2024

Authors: Hong, Ji-Ge | Zheng, Hui-Lei | Wang, Peng | Huang, Ping | Gong, Dan-Ping | Zeng, Zhi-Yu

Article Type: Research Article

Abstract: Circular RNAs (circRNAs) have been reported to participate in the development of various diseases. In this study, we investigated the potential mechanism underlying the role of circRNAs in atherosclerosis. Human umbilical vein endothelial cells (HUVECs) were treated with 100 μg/mL oxidized low-density lipoprotein (ox-LDL) to simulate atherosclerosis. We observed that hsa_circ_0006867 (circ_0006867), a circRNA markedly increased in ox-LDL-treated endothelial cells, acted as a molecular sponge of miR-499a-3p and regulated its expression. This interaction led to changes in the downstream target gene ADAM10, thus affecting cell apoptosis and migration. Thus, our study suggests that circ_0006867 regulates ox-LDL-induced endothelial injury via the …circ_0006867/miR-499a-3p/ADAM10 axis, indicating its potential as an exploitable therapeutic target for atherosclerosis. Show more

Keywords: Atherosclerosis, ox-LDL, circ_0006867, miR-499a-3p, endothelial cells, ADAM10

DOI: 10.3233/CH-231895

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2024

Authors: Chen, Po-Yu | Huang, Hsing-Hao | Chan, Wing-Sum | Liu, Chih-Min | Wu, Tsung-Ta | Chen, Jyun-Han | Chao, Anne | Tien, Yu-Wen | Chiu, Ching-Tang | Yeh, Yu-Chang

Article Type: Research Article

Abstract: BACKGROUND: Recent studies have shown that dexmedetomidine may improve microcirculation and prevent organ failure. However, most evidence was obtained from experimental animals and patients receiving cardiac surgery with cardiopulmonary bypass. This study aimed to investigate the effect of dexmedetomidine on microcirculation and organ injuries in critically ill general surgical patients. METHODS: In this prospective randomized trial, patients admitted to the surgical intensive care unit after general surgery were enrolled and randomly allocated to the dexmedetomidine or propofol groups. Patients received continuous dexmedetomidine or propofol infusions to meet their requirement of sedation according to their grouping. At each time …point, sublingual microcirculation images were obtained using the incident dark field video microscope. RESULTS: Overall, 60 patients finished the trial and were analyzed. Microcirculation parameters did not differ significantly between two groups. Heart rate at 4 h after ICU admission and mean arterial pressures at 12 h and 24 h after ICU admission were lower in the dexmedetomidine group than in the propofol group. At 24 h, serum aspartate aminotransferase (41 (25–118) vs 86 (34–129) U/L, p  = 0.035) and alanine aminotransferase (50 (26–160) vs 68 (35–172) U/L, p  = 0.019) levels were significantly lower in the dexmedetomidine group than in the propofol group. CONCLUSION: Microcirculation parameters did not differ significantly between the dexmedetomidine and propofol groups. At 24 h after ICU admission, serum liver enzyme levels were lower in patients receiving dexmedetomidine as compared to propofol. Show more

Keywords: Microcirculation, dexmedetomidine, propofol, surgery, critical care

DOI: 10.3233/CH-232093

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2024

Authors: Oh, Ju Seok | Prabhakaran, Prem | Seo, Dong Kil | Kim, Do Yeon | Lee, Woonhyoung | Ahn, Kyung Hyun

Article Type: Research Article

Abstract:  The greater the viscosity of the blood, the more difficult its flow becomes, leading to an increased incidence of diseases caused by blood circulation disorders. These diseases are commonly associated with the cardiovascular and cerebrovascular systems. High blood viscosity is a primary cause of circulatory system diseases. Studies have shown that accurately measuring blood viscosity and applying this data in clinical trials can help prevent circulatory system diseases. Viscosity data can vary depending on the measurement methods used, even when these methods are based on hydrodynamic principles. Despite using approved blood viscometers, the results often differ depending on …the type of viscometer used, potentially causing confusion within the medical field. Informing the medical community about these differences and the level of error associated with each measurement method can help reduce this confusion. To our knowledge, the degree of difference in viscosity measurement results due to different measurement methods and the reasons for these differences have not yet been thoroughly explored. In this study, we selected three blood viscosity measurement methods registered with the Ministry of Food and Drug Safety of Korea to analyze the same canine blood. The viscosity measurements were carried out using each device and compared. The parallel plate and scanning capillary methods yielded similar viscosity values, while the cone plate method showed lower viscosity values. The viscosity of blood, as measured by the three viscometers, differed, indicating that more experimental data must be accumulated to evaluate the cause of these differences. In this paper, we identified several causes of inconsistency and suggested measures to avoid this confusion. However, confirming that the test results show systematic differences is expected to assist clinicians who diagnose and prescribe treatments based on blood viscosity results. The findings of this comparative study are anticipated to serve as a starting point for establishing guidelines or standards for blood viscosity measurement methods. Show more

Keywords: Whole blood, viscosity, viscosity measurement standard, parallel plate viscometer, capillary viscometer, cone-plate viscometer

DOI: 10.3233/CH-242256

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2024

Authors: Wang, Yali | Ye, Qing | Cui, Yongqi | Wu, Yunjiang | Cao, Sipei | Hu, Feng

Article Type: Research Article

Abstract: BACKGROUND: Pulmonary hypertension (PH) is a refractory disease characterized by elevated pulmonary artery pressure and resistance. Drag-reducing polymers (DRPs) are blood-soluble macromolecules that reduce vascular resistance by altering the blood dynamics and rheology. Our previous work indicated that polyethylene oxide (PEO) can significantly reduce the medial wall thickness and vascular resistance of the pulmonary arteries, but the specific mechanism is still unclear. METHODS: This study was designed to investigate the role and mechanism of PEO on intracellular calcium [Ca2 + ] i and cytoskeletal proteins of endothelial cells (ECs) induced by low shear stress (LSS) in PH. Primary …Pulmonary Artery Endothelial Cells (PAECs) were subjected to steady LSS (1 dyn/cm2 ) or physiological shear stress (SS) (10 dyn/cm2 ) for 20 h in a BioFlux 200 flow system. Calcium influx assays were conducted to evaluate the mechanisms of PEO on [Ca2 + ] i . Subsequently, taking the key protein that induces cytoskeletal remodeling, the regulatory light chain (RLC) phosphorylation, as the breakthrough point, this study focused on the two key pathways of PEO that regulate phosphorylation of RLC: Myosin light chain kinase (MLCK) and Rho-associated kinase (ROCK) pathways. RESULTS: Our current research revealed that PEO at LSS (1 dyn/cm2 ) significantly suppressed LSS-induced [Ca2 + ] i and the expression level of transient receptor potential channel 1(TRPC1). In addition, ECs convert LSS stimuli into the upregulation of cytoskeletal proteins, including filamentous actin (F-actin), MLCK, ROCK, p-RLC, and pp-RLC. Further experiments using pharmacological inhibitors demonstrated that PEO at the LSS downregulated cytoskeleton-related proteins mainly through the ROCK and MLCK pathways. CONCLUSIONS: This study considered intracellular calcium and cytoskeleton rearrangement as entry points to study the application of PEO in the biomedical field, which has important theoretical significance and practical application value for the treatment of PH. Show more

Keywords: Pulmonary hypertension, drag-reducing polymers, shear stress, myosin light chain kinase, Rho-associated kinase

DOI: 10.3233/CH-242281

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 2024

Authors: Chen, Jian | Chen, Fei-yu | Lu, Chan-jun | Yi, Sheng-wu

Article Type: Research Article

Abstract: OBJECTIVE: Endothelial cells play a critical role in maintaining vascular function and kinetic homeostasis, but excessive accumulation of palmitic acid (PA) may lead to endoplasmic reticulum stress and trigger endothelial cell dysfunction. Baicalin (BCL), a natural plant extract, has received widespread attention for its biological activities in anti-inflammation and anti-oxidative stress. However, the mechanism of BCL on PA-induced endothelial cell dysfunction is unclear. Therefore, the aim of this study was to investigate whether BCL could inhibit PA-induced endoplasmic reticulum stress and thus attenuate endothelial cell dysfunction. METHODS: Human umbilical vein endothelial cells (HUVECs) were divided into Control, PA, …PA + BCL-10 μM, PA + BCL-20 μM, and PA + BCL-50 μM groups. The PA group was treated with PA (200 μM), while the PA + BCL groups were co-treated with different concentrations of BCL (10 μM, 20 μM, 50 μM) for 24 hours. Cell viability was detected by MTT. Cell migration ability was determined by Transwell assay, apoptosis level by flow cytometry, and tube formation ability by tube formation assay. Finally, the levels of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) and angiogenesis-related proteins (VEGFA and FGF2) were detected by western blot, MMP-9, as well as the protein levels of endoplasmic reticulum stress biomarkers (GRP78, CHOP, PERK, and ATF4). RESULTS: The results at the cellular level showed that cell viability, migration ability and tube formation ability of PA-induced HUVECs were significantly reduced, while apoptosis level was significantly increased. However, administration of different concentrations of BCL significantly enhanced PA-induced cell viability, migration ability and tube formation ability of HUVECs while inhibiting apoptosis. The results of protein levels showed that the protein levels of Bax and cleaved caspase-3 were observably up-regulated in the cells of the PA group, while the protein level of Bcl-2 was significantly down-regulated; compared with the PA group, the protein levels of Bax and cleaved caspase-3 were much lower and the Bcl-2 protein level was much higher in the PA + BCL group. Additionally, the protein levels of VEGFA, FGF2 and MMP-9 were raised and those of GRP78, CHOP, PERK and ATF4 were lowered in the PA + BCL group of cells in a concentration-dependent manner. CONCLUSION: BCL significantly attenuates PA-induced endothelial cell dysfunction by inhibiting endoplasmic reticulum stress. Show more

Keywords: Baicalein, endoplasmic reticulum stress, palmitic acid, endothelial cell, dysfunction

DOI: 10.3233/CH-242230

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2024

Authors: Caimi, G. | Urso, C. | Brucculeri, S. | Lo Presti, R. | Carlisi, M.

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: Asymptomatic atherosclerosis is an important early marker of vascular damage and, among its risk factors, hemorheological alterations play an important role. PATIENTS AND METHODS: In a cohort of 85 non-diabetic subjects with asymptomatic carotid atherosclerosis (ACA), we have measured whole blood viscosity (cWBV) according to the haematocrit and plasma fibrinogen level. The cWBV distinguish the subgroup of ACA subjects with 3-5 cardiovascular risk factors (CRFs) from that with 1-2 CRFs and the same behavior is present for haematocrit and plasma fibrinogen level. Therefore, we divided the whole group of ACA subjects according to the medians …of the four surrogate indexes with an insulin resistance degree of TG/HDL-C, TyG, VAI and LAP. RESULTS: The analysis of the correlation between cWBV and each index of insulin resistance has shown that no correlation is present in the whole group and in the group of ACA subjects with 1-2 CRFs, while in the subgroup with 3-5 CRFs there is a positive correlation between cWBV with TG/HDL-C and TyG at a low degree of statistical significance. CONCLUSIONS: The date underline that subjects with this clinical condition have an unaltered evaluation of the cWBV compared to the other indices. Show more

Keywords: Vascular damage, hemorheological determinants, calculated viscosity, asymptomatic carotid atherosclerosis

DOI: 10.3233/CH-221422

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2024

Authors: Wang, Fang | Guo, Zhangmei | Yang, Guiqi | Yang, Fan | Zhou, Qi | Lv, Hongbin

Article Type: Research Article

Abstract: PURPOSE: Diabetic retinopathy (DR) is a serious retinal vascular disease that affects many individuals in their prime working years. The present research aimed at whether and how LOC681216 (LNC-216) is involved in retinal vascular dysfunction under diabetic conditions. METHODS: Rat retinal microvascular endothelial cells (RRMECs) treated with high glucose (HG) were used for functional analysis. Gene expression analysis was conducted using the Clariom D Affymetrix platform. The wound healing, transwell, and vascular tube formation assays were used to identify the migration, invasion, and tube formation capability of RRMECs. The dual-luciferase reporter confirmed the binding interaction between miR-143-5p and …LNC-216 or matrix metallopeptidase 2 (MMP2). RESULTS: Lnc-216 was upregulated in RRMECs treated with HG. Lnc-216 knockdown markedly suppressed the tube formation, cell migration, and wound healing of cultured RRMECs under HG conditions. Mechanistically, Lnc-216 acted as a miR-143-5p sponge to affect the biological activity of miR-143-5p, which led to increased expression of matrix metallopeptidase 2 (MMP2). CONCLUSIONS: Lnc-216 attenuates diabetic retinal vascular dysfunction through the miR-143-5p/MMP2 axis, providing a potential therapeutic strategy for DR. Show more

Keywords: Lnc-216, miR-143-5p, microarray, diabetic retinopathy, MMP2

DOI: 10.3233/CH-242163

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2024

Authors: Stern, Manuel | Baasen, Sven | Wischmann, Patricia | Herbrand, Theresa | Schremmer, Johanna | Maier, Oliver | Stern, Marc | Jung, Christian | Heiss, Christian | Kelm, Malte | Sansone, Roberto | Busch, Lucas

Article Type: Research Article

Abstract: BACKGROUND: Data on the effect of transcatheter aortic valve implantation (TAVI) on peripheral microcirculation are limited. OBJECTIVE: The aim of this study is to evaluate peripheral microvascular tissue saturation (StO2 ) before and after TAVI in relation to central and peripheral hemodynamics, cardiac and renal function. METHODS: In this single-center prospective study, patients with severe aortic stenosis (sAS) scheduled for TAVI or cardiac catheterization (control) were assessed before and up to five days after the procedure. Cardiac function including cardiac output (CO) was assessed by echocardiography. Brachial (bBP) and central blood pressure (cBP), ankle brachial index …(ABI), and parameters of arterial stiffness, including augmentation pressure (AP) and augmentation index adjusted for heart rate (AIx@HR75) were measured to assess hemodynamic changes. StO2 was measured in all extremities using a near-infrared spectroscopy (NIRS) camera. Renal function was measured by creatinine levels. RESULTS: 26 patients underwent TAVI and 11 patients served as control. Cardiac output was significantly increased, whereas hemodynamic parameters and peripheral StO2 were significantly decreased after TAVI. At follow-up, StO2 returned to baseline values. Changes in StO2 were negatively related to creatinine levels. CONCLUSION: Transcatheter aortic valve implantation causes a temporary decrease in microvascular tissue saturation that is associated with renal function. Show more

Keywords: Microcirculation, microvascular tissue saturation, transcatheter aortic valve implantation, near-infrared spectroscopy

DOI: 10.3233/CH-232051

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2024

Authors: Zhu, Yi-Cheng | Zhou, Li | Zu, Dao-Ming | Deng, Shu-Hao | Zhang, Yuan | Shan, Jun | Shi, Xiu-Rong | Jiang, Quan

Article Type: Research Article

Abstract: BACKGROUND: Mesenteric lymphadenitis (ML) demonstrates a distinctive inclination for the pediatric and adolescent demographic and the diagnosis of ML in young children poses a substantial challenge. OBJECTIVE: This prospective study aimed to assess the diagnostic efficacy of Superb Microvascular Imaging (SMI) and Virtual Touch Tissue Imaging quantification (VTIQ) in distinguishing pediatric mesenteric lymphadentitis. METHODS: We examined 82 mesentric lymph node (MLN) in pediatric patients with mesenteric lymphadentitis and 50 MLN in a healthy group. SMI was utilized to evaluate vascularity within the MLN, while MLN stiffness, quantified as shear wave velocity (SWV) in meters per second …(m/s), was assessed using VTIQ. We compared the diagnostic performance of greyscale Ultrasound, US combined with SMI, US combined with VTIQ, and US combined with both SMI and VTIQ. RESULTS: SMI revealed a significant distinction between mesenteric lymphadentitis and normal MLN (p  <  0.001). MLN affected by mesenteric lymphadentis exhibited increased vascularity (marked vascularity: 13/82, 15.85%) compared to normal MLN (marked vascularity: 1/50, 2.00%). Statistically significant differences were observed in SWV values beween mesenteric lymphadentitis and normal MLN (all p -values <0.001). The mean and minimum SWV values for MLN with mesenteric lymphadentitis were 1.66±0.77 m/s and 1.51±0.53 m/s, respectively. Control group SWV values were approximately three times higher than those in the mesenteric lymphadenitis group. The highest area under the curve values were achieved with the combination of all three modalities (0.837, 95% confidence interval: 0.763– 0.896), followed by US + VTIQ (0.795, 0.716– 0.860), US + SMI (0.753, 0.670– 0.824) and US alone (0.642, 0.554– 0.724). CONCLUSION: SMI and VTIQ offer a promising noninvasive adjunct to grayscale ultrasound for identifying mesenteric lymphadentitis in pediatric patients. Show more

Keywords: Mesenteric lymphadenitis, pediatrics, Elastography, Doppler ultrasound

DOI: 10.3233/CH-242305

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2024

Authors: Zhang, Lei-Guang | Li, Hui-Juan | Liu, Shuai | Liu, Jie-Yun

Article Type: Research Article

Abstract: OBJECTIVE: The aim of this study is to investigate the correlation between the triglyceride-glucose-body mass index (TyG-BMI) and the characteristics of various carotid plaques in middle-aged and elderly patients with acute myocardial infarction (AMI). METHODS: A retrospective study was conducted on 380 patients with AMI hospitalized in the Cardiology Department of Kaifeng Central Hospital. Based on carotid ultrasound results, patients were divided into the following two groups: the stable plaque group and the unstable plaque group. Additionally, a control group comprising 380 healthy individuals visiting the hospital’s physical examination center during the same timeframe was established. Fasting venous …blood samples were collected from all participants to measure blood glucose and triglyceride. The baseline TyG-BMI index was calculated using the formula Ln [fasting triglyceride (mg/dL)×fasting blood glucose (mg/dL)/2]×BMI. The correlation between different plaque groups and the TyG-BMI index was analyzed. RESULTS: The TyG-BMI index was significantly higher in the unstable plaque group compared to the stable plaque group, with values of 252.81±29.99 and 201.92±28.72, respectively (P  = 0.034). Spearman’s correlation analysis showed a positive correlation between the instability of carotid plaques and the TyG-BMI index in patients with AMI (r  = 0.521, P  = 0.003). Logistic regression analysis indicated that the TyG-BMI index was an important risk factor for unstable carotid plaques in patients with AMI (OR = 2.691, 95% CI: 1.169–4.123). CONCLUSION: The findings of this study suggest that an elevated TyG-BMI index significantly increases the risk of unstable carotid plaques in patients with AMI, making it an important risk factor for carotid plaque instability. Show more

Keywords: Atherosclerosis, acute myocardial infarction, carotid artery, TyG-BMI index, unstable plaques

DOI: 10.3233/CH-242354

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2024

Authors: Chen, Rongping | Liu, Dawei | Zhao, Hua | Wang, Xiaoting

Article Type: Research Article

Abstract: BACKGROUND: Renal perfusion status remains poorly studied at the bedside during sepsis associated acute kidney injury (AKI). The aim of the study is to examine renal cortical and medullary perfusion using renal contrast enhanced ultrasound (CEUS) in septic patients. METHODS: In this single-center, prospective longitudinal study, septic patients were enrolled. Renal ultrasonography was performed within 24 hours of ICU admission (D1), then repeated at D3, D5 and D7. Each measurement consisted of three destruction replenishment sequences that were recorded for delayed analysis with dedicated software (Vuebox). Renal cortex and medulla perfusion were quantified by measuring time to peak …(TTP). Receiver operating characteristic (ROC) analysis was used to evaluate 28-day renal prognosis. RESULTS: The study included 149 septic patients, including 70 non-AKI patients and 79 AKI patients. Both renal cortical and medullary TTP was longer in the AKI group than in the non-AKI group. The difference of TTP between renal cortex and medulla in AKI group was higher than that in the non-AKI group (p  = 0.000). Medullary TTP on day 3 had the best performance in predicting the prognosis of 28-day renal function (AUC 0.673, 95% confidence interval 0.528–0.818, p  = 0.024), and its cut-off value was 45 s with a sensitivity 52.2% and a specificity of 82.1%. Cortical TTP on day 3 also had the performance in predicting the prognosis of 28-day renal function (AUC 0.657, 95% confidence interval 0.514–0.800, p  = 0.039), and its cut-off value was 33 s with a sensitivity 78.3% and a specificity of 55.0%. CONCLUSION: Renal medullary perfusion alterations differ from those in cortex, with the medulla is worse. Simultaneous and dynamic assessment of cortical and medullary microcirculatory flow alterations necessary. TTP on day 3, especially medullary TTP, seems to be a relatively stable and useful indicator, which correlates with 28-day renal function prognosis in septic patients. Early correction of renal cortical and medullary perfusion alterations reduces the incidence of adverse renal events. Show more

Keywords: Contrast-enhanced ultrasound, renal cortex, renal medulla, sepsis, acute kidney injury, prognosis.

DOI: 10.3233/CH-242296

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-18, 2024

Authors: Ma, Lin | Song, Jun-Jie | Cui, Zhong-Ning | Niu, Zhi-Yong | Tian, Shao-Bin | Liu, Ming | Wang, Min | Zhang, Rong-Ping

Article Type: Research Article

Abstract: OBJECTIVE: This study was performed to explore the treatment of the injury caused by traumatic limb amputation. METHODS: From October 2002 to October 2021, 30 cases were enrolled in the present study. The reasons for injury were as follows: 8 cases with single hydraulic column crush injury, 12 cases with gear and wire rope stranding, 6 cases with belt avulsion injury, and 4 cases with carbon block smash injury. The present study application of a free or small saphenous vein bypass to reconstruct the injured artery and vein according to the concept of the angiosome model. The defective …vessels were bridged with the axial vessels of a flow-through flap, such as a medial calf flap or anterolateral femoral flap, to construct an additional blood supply and drainage vein for the severed limb. The clinical data of 30 cases with traumatic limb amputation of the lower leg and ankle were retrospectively analyzed. RESULTS: In all 30 cases of traumatic limb amputation, the replantation via the adoption of a flow-through flap was successful, and 85.6% of the patients remained in good postoperative condition. There were no symptoms of ischemia in the marginal segment after blood supply reconstruction of the transected limb by axial vascular bridging within the flap. CONCLUSION: Via the adoption of microsurgical techniques, the blood supply to the transected limb can be reconstructed by bridging the defective vessels with the adoption of the axial vessels of the flow-through flap is a feasible and advanced treatment option. Show more

Keywords: Angiosome concept, destructive amputation of limbs, replantation, flow-through flap

DOI: 10.3233/CH-242179

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2024

Authors: Tang, Feng | Tian, Long-hai | Zhu, Xiao-han | Yang, Sen | Zeng, Huan | Yang, Yong-yao

Article Type: Research Article

Abstract: BACKGROUND: The precise association between lncRNA H19 and ferroptosis in the context of atherosclerosis remains uncertain. OBJECTIVE: This study is to clarify the underlying process and propose novel approaches for the advancement of therapeutic interventions targeting atherosclerosis. METHODS: Assessment of ferroptosis, which entails the evaluation of cell viability using CCK-8 and the quantification of intracellular MDA, GSH, and ferrous ions. Simultaneously, the protein expression levels of assessed by western blot analysis, while the expression level of lncRNA H19 was also determined. Furthermore, HAECs that were cultured with ox-LDL were subjected to Fer-1 interference. HAECs were exposed …to ox-LDL and then transfected with H19 shRNA and H19 overexpression vector pcDNA3.1. The level of ferroptosis in the cells was then measured. Then, HAECs were subjected to incubation with ox-LDL, followed by transfection with H19 shRNA and treated with Erastin to assess the levels of ferroptosis, cell viability, and inflammatory factor production. and the ability for blood vessel development. RESULTS: The survival rate of HAECs in the ox-LDL group was much lower. Ox-LDL resulted in an upregulation of ACSL4 expression in HAECs, while the expression of SLC7A11 and GPX4 decreased. CONCLUSIONS: lncRNA H19 enhances ferroptosis and exacerbates arterial endothelial cell damage induced by LDL. Show more

Keywords: lncRNA H19, ferroptosis, arterial endothelial cell damage

DOI: 10.3233/CH-242261

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2024

Authors: Liu, Jinming | Jiao, Wei | Li, Fang | Xie, Yanan | Meng, Mingjie | Hao, Jie

Article Type: Research Article

Abstract: OBJECTIVE: This study intends to explore the effects of Rosuvastatin on ox-LDL induced platelet activation and its molecular mechanism. METHODS: Platelet aggregation rate was detected by aggregometer. ELISA kit was used to detect the levels of cAMP. Immunofluorescence staining was used to detect the platelet adhesion. The expression levels of platelet surface markers CD62p and PAC-1 were detected by flow cytometry. The protein levels of p-p38, p-IKKa and p-IKKB in platelets were detected by western blot. RESULTS: We found that rosuvastatin significantly inhibited platelet aggregation and increased the level of cAMP in a dose-dependent manner. Immunofluorescence …staining results showed that rosuvastatin could inhibit platelet adhesion. Flow cytometry results showed that rosuvastatin could reduce the expression of platelet activation markers. Western blot results showed that rosuvastatin could down-regulate the expression levels of p-p38, p-IKKa and p-IKKb. CONCLUSION: Our study revealed the rosuvastatin could inhibit the aggregation, adhesion and activation of platelet induced by ox-LDL, its mechanism may be related to inhibition of p38/MAPK signal pathway. Show more

Keywords: Rosuvastatin, platelet, aggregation, adhesion, p38/MAPK

DOI: 10.3233/CH-242359

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2024

Authors: Kordi, Negin | Sanaei, Masoumeh | Akraminia, Peyman | Yavari, Sajad | Saydi, Ali | Abadi, Fatemeh Khamis | Heydari, Naser | Jung, Friedrich | Karami, Sajad

Article Type: Research Article

Abstract: Regulated cell death, including pyroptosis, apoptosis, and necroptosis, is vital for the body’s defense system. Recent research suggests that these three types of cell death are interconnected, giving rise to a new concept called PANoptosis. PANoptosis has been linked to various diseases, making it crucial to comprehend its mechanism for effective treatments. PANoptosis is controlled by upstream receptors and molecular signals, which form polymeric complexes known as PANoptosomes. Cell death combines necroptosis, apoptosis, and pyroptosis and cannot be fully explained by any of these processes alone. Understanding pyroptosis, apoptosis, and necroptosis is essential for understanding PANoptosis. Physical exercise has been …shown to suppress pyroptotic, apoptotic, and necroptotic signaling pathways by reducing inflammatory factors, proapoptotic factors, and necroptotic factors such as caspases and TNF-alpha. This ultimately leads to a decrease in cardiac structural remodeling. The beneficial effects of exercise on cardiovascular health may be attributed to its ability to inhibit these cell death pathways. Show more

Keywords: PANoptosis, pyroptosis, apoptosis, necroptosis, activity, training

DOI: 10.3233/CH-242396

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2024

Authors: Li, Lisha | Wang, Hongjun | Pan, Yalong | Liu, Kun

Article Type: Research Article

Abstract: BACKGROUND: This article reviews the latest research results of the use of ultrasound technology in the perioperative period of carotid endarterectomy and carotid stenting and discusses the role of ultrasound technology in accurately evaluating carotid stenosis and plaque stability, assisting in selecting the most suitable surgical method, and providing optimal perioperative imaging to guide carotid endarterectomy (CEA) and carotid artery stenting (CAS) to reduce the occurrence and progression of stroke. METHODS: The research published in recent years on the application of ultrasound in the perioperative period of CEA and CAS was reviewed through the databases of CNKI, Pubmed, …and Web of Science. RESULTS: Ultrasound has high clinical value in preoperative screening for indications, assessing the degree of carotid artery stenosis and the nature of plaque; monitoring hemodynamic changes intraoperatively to prevent cerebral ischemia or overperfusion; and evaluating surgical outcomes postoperatively and in late follow-up review. CONCLUSION: Ultrasound is currently widely used perioperatively in CEA and CAS and has even become the preferred choice of clinicians to evaluate the efficacy of surgery and follow-up. The presence of vulnerable plaque is an important risk factor for ischemic stroke. Contrast-enhanced ultrasound is an excellent tool to assess plaque stability. In most studies, ultrasound has been used only in a short follow-up period after CEA and CAS, and data from longer follow-ups are needed to provide more reliable evidence. Show more

Keywords: Carotid artery stent implantation, carotid artery ultrasound, carotid endarterectomy, ischemic stroke, neovascularization

DOI: 10.3233/CH-242412

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2024

Authors: Carallo, Claudio | Destito, Michela | Zaffino, Paolo | Caglioti, Chiara | Silipo, Vittorio | De Masi, Paolo Maria | Gnasso, Agostino | Spadea, Maria Francesca

Article Type: Research Article

Abstract: BACKGROUND: Longitudinal Displacement (LD) is the relative motion of the intima-media upon adventitia of the arterial wall during the cardiac cycle, probably linked to atherosclerosis. It has a direction, physiologically first backward in its main components with respect to the arterial flow. Here, LD was investigated in various disease and in presence of a unilateral carotid stent. METHODS: Carotid acquisitions were performed by ultrasound imaging on both body sides of 75 participants (150 Arteries). LD was measured in its percent quantity and direction. RESULTS: Obesity (p  = 0.001) and carotid plaques (p  = 0.01) were independently associated to …quantity decrease of LD in the whole population. In a subgroup analysis, it was respectively 143% in healthy (n  = 48 carotids), 129% (n  = 34) in presence of cardiovascular risk factors, 121% (n  = 20) in MACE patients, 119% (n  = 24) in the carotid contralateral to a stent, 110% (n  = 24) in carotids with stents. Regarding the direction of LD, in a subgroup analysis an inverted movement was identified in aged (p  = 0.001) and diseased (p  = 0.001) participants who also showed less quantity of LD (p  = 0.001), but independently with age only (p  = 0.002) in the whole population. CONCLUSIONS: This observational study suggests that LD within carotid wall layers is lower additively with ageing, cardiovascular risk factors, cardiovascular diseases, and stent. Even if stent is surely beneficial, these data might shed some light on stent restenosis, emphasising the need for interventional studies. Show more

Keywords: Arterial displacement, longitudinal sliding, atherosclerosis, stent

DOI: 10.3233/CH-242357

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 2024

Authors: Blankfield, Robert P.

Article Type: Research Article

Abstract: Endothelial dysfunction, the earliest manifestation of atherosclerosis, can be initiated by both biochemicals and biomechanical forces. Atherosclerosis occurs predominantly at arterial branch points, arterial bifurcations and the curved segments of great arteries. These are the regions that blood flows turbulently. Turbulence promotes endothelial dysfunction by reducing shear stress upon endothelial cells. The endothelial glycocalyx mediates the effect of shear stress upon the endothelium. A mathematical analysis of cardiovascular hemodynamics demonstrates that fluid retention increases turbulence of blood flow. While there is no empirical data confirming this relationship, fluid retention is associated with adverse cardiovascular events. Every medical condition that …causes fluid retention is associated with increased risk of both atherosclerotic cardiovascular disease and venous thromboembolic disease. In addition, most medications that cause fluid retention are associated with increased adverse cardiovascular effects. Calcium channel blockers (CCBs) and pioglitazone are exceptions to this generalization. Even though data regarding CCBs and pioglitazone contradict the hypothesis that fluid retention is a cardiovascular risk factor, these medications have favorable cardiovascular properties which may outweigh the negative effect of fluid retention. Determining whether or not fluid retention is a cardiovascular risk factor would require empirical data demonstrating a relationship between fluid retention and turbulence of blood flow. While this issue should be relevant to cardiovascular researchers, clinicians and patients, it is especially pertinent to the pharmaceutical industry. Four-dimensional magnetic resonance imaging and vector flow Doppler ultrasound have the capability to quantify turbulence of blood flow. These technologies could be utilized to settle the matter. Show more

Keywords: Fluid retention, cardiovascular risk factor, endothelial dysfunction, turbulence, atherosclerotic cardiovascular disease, venous thromboembolic disease

DOI: 10.3233/CH-242128

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2024

Authors: Kaiser, Ulrich | Kaltenhauser, Simone | Kaiser, Florian | Vehling-Kaiser, Ursula | Herr, Wolfgang | Stroszczynski, Christian | Becker, Claus | Dropco, Ivor | Jung, Ernst Michael

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: Ultrasound-guided interventions (such as biopsies) of unclear lesions are indicated if microcirculatory changes indicate possible malignant lesions. These place high demands on the ultrasound device used. In order to potentially reduce the often associated high technical effort, the wireless ultrasound device Vscan AirTM was examined as a possible ultrasound device for the intervention biopsy. METHODS: As part of an advanced training course on Computertomographie- and ultrasound-guided biopsy and ablation procedures, participants were asked about the image quality of the handheld device used by means of questionnaires. Various lesions were evaluated at a depth of …1.0 to 5.0 cm in an in vitro liver model. The image quality was evaluated independently before, during and after the intervention. The rating scale contained values from 0 (no assessment possible) to 5 (maximum high image quality). A high-end device was used as a reference. RESULTS: A total of 11 participants took part in the study (n  = 4 male [36.4%], n  = 7 female [63.6%]). A total of five tumor like lesions at different depths (1 cm, 2 cm, 3 cm, 4 cm, >4 cm) were assessed separately. In all cases, an adequate biopsy of the target lesion (1 cm in length, core filling 5 mm) was successful. From a depth of 3 cm, the image quality of the mobile device increasingly decreased, but the image quality of the high-end system was still not impaired. Compared to the high-end device, there was a highly significant difference in image quality from a depth of 3 cm (p  < 0.01). Assessment by inexperienced examiners using a handheld device was adequately possible. CONCLUSIONS: Mobile interventional ultrasound represents a potential alternative for the biopsy of unclear tumorous lesions with microcirculatory disorders with limited depth localization. Show more

Keywords: Ultrasound, mobile ultrasound, high end ultrasound, in vitro model, tumor diagnostics, ultrasound interventions

DOI: 10.3233/CH-248104

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2024

Authors: Martin, Frank | Neubert, Annemarie | Lutter, Anne-Helen | Scholka, Jenny | Hentschel, Erik | Richter, Heiko | Anderer, Ursula

Article Type: Research Article

Abstract: BACKGROUND: Tissue engineering enables the production of three-dimensional microtissues which mimic naturally occurring conditions in special tissues. These 3D culture systems are particularly suitable for application in regenerative medicine or experimental pharmacology and toxicology. Therefore, it is important to analyse the cells in their 3D microenvironment with regard to viability and differentiation. Tetrazolium assays (WST-8 and MTS) are still the methods of choice for estimating the number of living, metabolically active cells, with WST-8 being cell-impermeable compared to MTS. In contrast to these methods, the ATP assay is an endpoint method based on the luciferase-induced reaction of ATP with luciferin …after cell lysis. OBJECTIVE: We compared three methodologically different proliferation/toxicity assays (MTS, WST-8, ATP) in monolayer (2D) and 3D culture systems to improve the technically challenging determination of the number of viable cells. METHODS: Chondrocytes were isolated from human articular cartilage. Three different test systems (MTS, WST-8, ATP) were applied to monolayer cells (2D, varying cell numbers) and spheroids (3D, different sizes) in 96-well plates. The intracellular ATP concentration was determined by luciferase-induced reaction of ATP with luciferin using a luminometer. Formazan formation was measured spectrophotometrically after different incubation periods. Evaluation was performed by phase contrast microscopy (toxicity), correlation of cell count and ATP concentration or absorption signal (Gompertz function) and propidium iodide (PI) staining to proof the cell lysis of all cells in spheroids. RESULTS: In 2D culture, all three assays showed a good correlation between the number of seeded cells and the ATP concentration or absorption data, whereas the MTS-assay showed the lowest specificity. In 3D culture, the spheroid sizes were directly related to the number of cells seeded. The absorption data of the WST-8 and MTS assay correlated only for certain spheroid size ranges, whereas the MTS-assay showed again the lowest specificity. Only the measured intracellular ATP content showed a linear correlation with all spheroid sizes ranging from 100–1000 μm. The WST-8 assay revealed the second-best sensitivity which allows the measurement of spheroids larger than 240 μm. Phase contrast observation of monolayer cells showed toxic effects of MTS after 6 h incubation and no signs of toxicity of WST-8. Staining with propidium iodide showed complete lysis of all cells in a spheroid in the ATP assay. CONCLUSION: Among tetrazolium-based assays, WST-8 is preferable to MTS because of its non-toxicity and better sensitivity. When determining the number of viable cells in the 2D system, caution is advised when using the ATP assay because of its two-phase slope of the correlation graph concerning cell number and intracellular ATP. In 3D systems of human chondrocytes, the ATP-assay is superior to the other two test systems, as the correlation graph between cell number and intracellular ATP is biphasic. Since differentiation processes or other metabolic events can influence the results of proliferation and toxicity assays (determination of viable cells), this should be taken into account when using these test systems. Show more

Keywords: ATP assay, MTS, WST-8, human chondrocytes, spheroid, 3D culture, 2D culture

DOI: 10.3233/CH-248101

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-17, 2024

Authors: Christer, T. | Hüner, A. | Robering, J.W. | Mrowietz, C. | Hiebl, B.

Article Type: Research Article

Abstract:  The pig (Sus scrofa ) is the most widely used large animal model in Europe, with cardiovascular research being one of the main areas of application. Adequate refinement of interventional studies in this field, meeting the requirements of Russell and Burch’s 3 R concept, can only be performed if blood-contacting medical devices are hemocompatible. Because most medical devices for cardiovascular interventional procedures are developed for humans, they are tested only for compatibility with human blood. The aim of this study was therefore to determine whether there are differences in behavior of human and porcine platelets from commercial hybrid …pigs when they come into contact with borosilicate glass, which was used as an exemplary thrombogenic material. For this purpose, changes in platelet count, platelet volume and platelet expression of the activation markers CD61, CD62P and CD63 were measured using a modified chandler loop-system simulating the fluidic effects of the bloodflow. Commercial hybrid pig and human platelets showed significant adhesions to borosilicate glass but the commercial hybrid pigs platelets showed a significantly higher tendency to adhere to borosilicate glass. In contrast to human platelets the platelets of commercial hybrid pigs showed significant activation after 4 to 8 minutes exposure to borosilicate glass and there were differences among the ratios of surface and activation markers in between the platelets of both species. Show more

Keywords: Pig, commercial hybrid pig, platelet activation, platelet count, platelet volume, FACS, CD42a, CD61, CD62P, CD63

DOI: 10.3233/CH-248103

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2024

Authors: Kaiser, Ulrich | Kück, Fabian | Stroszczynski, Christian | Jung, Ernst Michael | Greiner, Barbara

Article Type: Research Article

Abstract: OBJECTIVE: To assess diagnostic capabilities of a modern handheld ultrasound device (HUD) for portal vein (PV) evaluation in pediatric patients and to verify if age, body mass index (BMI) and object depth correlate to imagequality. METHODS: 45 patients (3.9 months– 17.9 years; 10.3 years±5.4) were examined using a HUD and cart-based high-end ultrasound system (HEUS). The intra-and extrahepatic PV was scanned using B-Mode and Color-coded Doppler sonography (CCDS). A five-point Likert scale was applied to evaluate image quality. Results were interpreted by two readers in consensus. Scores were compared between the scanners and correlated to age, BMI and …skin-to-portal-vein-distance (SPVD). The influence on image quality and the difference between the two devices were analyzed using ordinal and Bayesian logistic regression models. RESULTS: ≥4 points (mild or no limitations) were achieved by the HUD in 60% for B-Mode and 56% for CCDS. There was a statistically significant negative correlation between the image quality achieved by the HUD and the SPVD for B-Mode and CCDS. The effect of BMI and SPVD on having≥4 points differed significantly between the HUD and HEUS for B-Mode (OR = 0.191, p  = 0.005, and OR = 0.040, p  = 0.008) and for CCDS (OR = 0.209, p  = 0.009, and OR = 0.084,p  = 0.011). CONCLUSIONS: Sufficient to excellent image quality for portal vein assessment in pediatric patients was achieved by the HUD except for the most deep-lying structures. Compared to HEUS, diagnostic performance of the HUD is lower, based on a negative correlation with object depth. Show more

Keywords: Handheld ultrasound, Vscan Air, vascular, portal vein, pediatric

DOI: 10.3233/CH-248105

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2024

Authors: Hinestrosa, Camila A. | Fuchs, Jochen | Denecke, Timm | Storch, Christiane | Dreyer, Antje | Kuthning, Anja | Reinhardt, Martin | Rio Bartulos, Carolina | Wiggermann, Philipp | Busse, Harald | Moche, Michael

Article Type: Research Article

Abstract: OBJECTIVE: In uterine artery embolization (UAE) for the treatment of fibroids, nondegradable particles permanently occlude the uterine artery (UA). These particles remain in the vessels and can cause secondary undesirable effects, such as severe pain after embolization and fertility issues. In this prospective experimental study, we aimed to evaluate the angiographic recanalization, local and systemic reactions, and uterine damage occurring after performing UAE with newly developed degradable starch microspheres (DSMs) in sheep. MATERIALS AND METHODS: Under general anesthesia, eight nonpregnant sheep underwent bilateral UAE using DSMs to achieve stasis. Angiographic evaluation was performed on days 1, 3 and …7 after embolization to assess in vivo recanalization. In addition, the angiographic series were scored via a modified embolization score. A postmortem tissue examination was performed to determine whether DSMs and foreign body inflammatory reactions were present and to assess uterine necrosis. RESULTS: Complete bilateral embolization of the UA and cervicovaginal branches was achieved in all treated animals. Recanalization of the occluded arteries was evident in 25 of 27 arteries during the angiographic evaluation. In all sheep, there were multifocal areas of uterine necrosis, and some uterine vessels contained intraluminal material consistent with DSMs. The average weight of both uterine horns was significantly correlated with both the number of microspheres needed for complete embolization (r  = 0.69, ρ <0.01) and the average percentage of necrosis in both uterine horns (r  = 0.64, ρ <0.05). CONCLUSIONS: Our findings demonstrated the efficacy of vascular embolization with DSM by inducing ischemic changes in the uterus and subsequent recanalization of previously occluded arteries. Show more

Keywords: Uterine artery embolization, degradable starch microspheres, animal models, angiography, leiomyoma

DOI: 10.3233/CH-248106

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-16, 2024

Authors: Zeitler, Christina | Braune, Steffen | Waldeck, Peter | Jung, Conrad G.H. | Küpper, Jan-Heiner | Petrick, Ingolf | Jung, Friedrich

Article Type: Research Article

Abstract: The microalgae Arthrospira platensis (AP), commonly known as Spirulina, has gained widespread popularity as a food supplement in recent years. AP is particularly abundant in protein, B vitamins, iron, magnesium, potassium, and various antioxidants. In this study we aimed to evaluate the effect of nitrate limitation in the AP culture medium on AP growth and composition. In addition, the cytotoxicity of the respective aqueous AP extracts on three different mammalian cell-lines (HepG2, Caco2, L929) was tested. AP was cultivated over a 10-day period under nitrogen-rich (Nrich : 1.8 g/L) and nitrogen-deficient (Nlimited : 0.2–0.4 g/L) conditions in two separate experiments, …each with three biological replicates (three bioreactors). Throughout the cultivation, the kinetic progress of dry biomass, pH, pigment content, the levels of essential elements (sulphur, phosphate, and nitrate) and the composition of elements in the harvested biomass was determined. While the biomass slightly but significantly differed, the phycocyanin concentration differed considerably (around 10-fold higher in the Nrich medium, p  < 0.05). Aqueous extracts of the Nrich medium had significantly stronger effects on the cell membrane integrity and the metabolic activity of the cells than extracts of the Nlimited medium. Particularly was the finding that AP had a significantly stronger toxic effect on the two tumour cell types (HepG2, Caco2) than on the non-tumour cells (L929). This study underscores the significance of nitrate content in the cultivation media of AP. Show more

Keywords: Nitrogen deprivation, culture medium, Arthrospira platensis , biomass productivity, in-vitro cytotoxicity

DOI: 10.3233/CH-248108

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-17, 2024

Authors: Spiesecke, P. | Thiemann, J. | Conen, P. | Clevert, D.-A.

Article Type: Research Article

Abstract: Ultrasound is the most used interdisciplinary imaging technique in clinical routine for assessment of renal pathologies. This includes the monitoring of cystic renal lesions, which can be classified as non-complicated or complicated and by means of occurrence as solitary or multifocal lesions. The Bosniak-classification (I–IV) classifies renal cysts in 5 different categories and is used for decisions of further clinical treatment. This classification was developed for computed tomography and has been adopted for magnetic resonance imaging as well as contrast-enhanced ultrasound. In the following review article, cystic kidney lesions and their differentiation using contrast-enhanced ultrasound are presented and an overview …of the therapy options is given. In interventional procedures, CEUS can make a valuable contribution in histological sampling, reduce radiation exposure and, under certain circumstances, the number of interventions for the patient. Show more

Keywords: Contrast-enhanced ultrasound, kidney lesion, tissue vascularization, real-time imaging, intervention

DOI: 10.3233/CH-248102

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2024

Authors: Wu, Zehong | Li, Huajuan | Chen, Zihao | Zhou, Honglian | Liang, Xin | Huang, Xing | Wang, Jiexin | Chen, Ting | Xu, Xiaohong | Yang, Yuping

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the conventional ultrasound (US), contrast-enhanced ultrasound (CEUS) manifestations and the corresponding histopathological characteristics of patients diagnosed with breast encapsulated papillary carcinoma (EPC) and to explore the value of CEUS in diagnosis of EPC. METHODS: The clinical, pathological, US, and CEUS features of 16 patients (17 lesions) with EPC confirmed by postoperative histopathology were retrospectively analyzed. RESULTS: EPC was prevalent in the postmenopausal women. The majority of conventional US images of EPC showed complex cystic and solid masses with circumscribed margins (70.6%), enhanced posterior echo (94.1%), no sonographic calcification (88.2%), rich blood flow in …the solid components within lesions (70.6%) on Color Doppler flow imaging, and high resistance index of blood flow (94.1%). Moreover, CEUS showed mainly centripetal hyperenhancement of the solid components within the lesions with irregular outline, and the enhancement area of the whole masses was essentially the same as the B-mode US area. CONCLUSIONS: EPC typically presents as a complex cystic and solid mass. CEUS is helpful to clarify the extent of the solid component and facilitate preoperative core-needle biopsy. A comprehensive evaluation by CEUS is valuable for diagnosing EPC and combining it with clinical features are helpful to further improve the diagnosis of this rare kind of breast cancer. Show more

Keywords: Breast tumor, encapsulated papillary carcinoma of the breast, ultrasound features, contrast-enhanced ultrasound, pathology

DOI: 10.3233/CH-242263

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2024

Authors: Lusha, E. | Zhao, Ping

Article Type: Research Article

Abstract: Myocardial ischemia-reperfusion injury is accompanied by ferroptosis mediated by reactive oxygen species and iron ions, which aggravates myocardial tissue damage. The present study aims to explore the molecular mechanism underlying the mitigating effects f PCSK9 on myocardial ischemia-reperfusion injury. MI/R rat model and OGD/R induced H9c2 model were established. The interaction between PCSK9 inhibitor and LRP8 was predicted by STRING database and verified by Immunoprecipitation assay experiment. CCK-8 kit results confirmed that PCSK9 inhibitor effectively protected against cardiomyocyte damage induced by OGD/R. TTC and histological examination via H&E staining revealed a significant alleviation of myocardial infarction and pathological alterations upon …treatment with the PCSK9 inhibitor. Besides, DCFH-DA staining and biochemical kit results showed that PCSK9 inhibitor could regulate the changes of ferroptosis related indicators [ROS, iron level, MDA, SOD] and inhibit ferroptosis. Rescue experiments showed that PCSK9 inhibitors targeted LRP8 expression and inhibited GPX4/ROS-mediated ferroptosis in I/R-induced rats. Our study suggested that PCSK9 inhibitors could attenuate myocardial I/R injury, with the underlying mechanism intimately tied to the targeted modulation of LRP8/GPX4-mediated ferroptosis. Show more

Keywords: PCSK9 inhibitor, myocardial ischemia-reperfusion, LRP8, ferroptosis

DOI: 10.3233/CH-242444

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2024