Clinical Hemorheology and Microcirculation - Volume 70, issue 3

Authors: Kim, Jeongho | Nafiujjaman, Md | Nurunnabi, Md | Lim, Sinye | Lee, Yong-Kyu | Park, Hun-Kuk

Article Type: Research Article

Abstract: BACKGROUND: Boron nitride (BN) nanomaterials are promising in biomedical research owing to their large surface area, graphene-like structure, and chemical and thermal properties. However, the toxicological effects of BN on erythrocytes and blood coagulation remain uninvestigated. OBJECTIVE: The aims of our study were to synthesize glycol chitosan (GC)- and hyaluronic acid (HA)-coated BNs, and to investigate the effects of these BNs on human cancer cells, erythrocytes, and whole blood. METHODS: We prepared hemocompatible forms of BN coated with GC and HA, and evaluated them using cell uptake/viability tests, hemolysis analysis and FE-SEM, as well as through …hemorheological evaluation methods such as RBC deformability and aggregation, and blood coagulation. RESULTS: GC/BN and HA/BN were both ∼200 nm, were successfully taken into cells, and emitted blue fluorescence. Both BNs were less toxic than bare BN, even at higher concentrations. The aggregation index of human red blood cells (RBCs) after 2 h incubation with BN, GC/BN, and HA/BN was greatly influenced, whereas RBC deformability did not dramatically change. CONCLUSIONS: We found that GC/BN affected the intrinsic coagulation pathway, whereas both GC/BN and HA/BN affected the extrinsic pathway. Therefore, HA/BN is less detrimental to RBCs and blood coagulation dynamics than bare BN and GC/BN. Show more

Keywords: Boron nitride, cytotoxicity, erythrocyte, hemolysis, hemorheology, coagulation

DOI: 10.3233/CH-170307

Citation: Clinical Hemorheology and Microcirculation, vol. 70, no. 3, pp. 241-256, 2018

Authors: Kim, Jeeyong | Cho, Chi Hyun | Jung, Bo Kyeung | Nam, Jeonghun | Seo, Hong Seog | Shin, Sehyun | Lim, Chae Seung

Article Type: Research Article

Abstract: The objective of this study was to comparatively evaluate three commercial whole-blood platelet function analyzer systems: Platelet Function Analyzer-200 (PFA; Siemens Canada, Mississauga, Ontario, Canada), Multiplate analyzer (MP; Roche Diagnostics International Ltd., Rotkreuz, Switzerland), and Plateletworks Combo-25 kit (PLW; Helena Laboratories, Beaumont, TX, USA). Venipuncture was performed on 160 patients who visited a department of cardiology. Pairwise agreement among the three platelet function assays was assessed using Cohen’s kappa coefficient and percent agreement within the reference limit. Kappa values with the same agonists were poor between PFA-collagen (COL; agonist)/adenosine diphosphate (ADP) and MP-ADP (–0.147), PFA-COL/ADP and PLW-ADP (0.089), MP-ADP and …PLW-ADP (0.039), PFA-COL/ADP and MP-COL (–0.039), and between PFA-COL/ADP and PLW-COL (–0.067). Nonetheless, kappa values for the same assay principle with a different agonist were slightly higher between PFA-COL/ADP and PFA-COL/EPI (0.352), MP-ADP and MP-COL (0.235), and between PLW-ADP and PLW-COL (0.247). The range of percent agreement values was 38.7% to 73.8%. Therefore, various measurements of platelet function by more than one method were needed to obtain a reliable interpretation of platelet function considering low kappa coefficient and modest percent agreement rates among 3 different platelet function tests. Show more

Keywords: Multiplate analyzer, Platelet function analyzer-200, Plateletworks

DOI: 10.3233/CH-170331

Citation: Clinical Hemorheology and Microcirculation, vol. 70, no. 3, pp. 257-265, 2018

Authors: Dittfeld, C. | Bienger, K. | Andres, J. | Plötze, K. | Jannasch, A. | Waldow, T. | Tugtekin, S.M. | Matschke, K.

Article Type: Research Article

Abstract: Adipose tissue is not only a connective tissue but also an endocrine organ secreting adipokines like Leptin and Adiponectin, lipokines such as palmitoileic acid and extracellular vesicles. These factors and the expression of matrix remodeling enzymes impact surrounding tissues via paracrine effects. The expression of selected secretion factors and the effect of adipocyte conditioned media from four thoracal adipose tissue origins - subcutaneous, perivascular, pericardial and epicardial adipose tissues – in a fibroblast proliferation/wound healing scratch assay model were investigated. Results were compared directly and according to the type 2 diabetic mellitus (T2DM) status of the patients the tissues are …originated from. Adipocyte conditioned media from non-diabetic patients resulted in a significant higher scratch closure rate compared to the media with T2DM background. Linoleic acid incubation in scratch assay resulted in a reduced scratch closure rate. Leptin, Adiponectin and Visfatin/Nampt expression and MMP2, MMP9 and FSTL1 mRNA levels did not vary according to T2DM subgroups directly, leading to the assumption that these factors are not causal for scratch assay effects observed. In contrast significant mRNA expression differences were monitored between the thoracal tissue origins implying variations in the local effects of the different adipose tissue depots. Show more

Keywords: Thoracal adipose tissue depots, adipokines, MMP, scratch wound healing assay, fatty acids, type 2 diabetes mellitus

DOI: 10.3233/CH-170341

Citation: Clinical Hemorheology and Microcirculation, vol. 70, no. 3, pp. 267-280, 2018

Authors: Xie, Shao Wei | Dong, Bai Jun | Xia, Jian Guo | Li, Hong Li | Zhang, Shi Jun | Du, Jing | Yang, Wen Qi | Li, Feng Hua | Xue, Wei

Article Type: Research Article

Abstract: OBJECTIVE: To evaluate the ability of contrast-enhanced transrectal ultrasound (CETRUS) scanning for prostate cancer detection in different area, compared with conventional transrectal ultrasound (TRUS). METHODS: 228 patients underwent TRUS-guided prostate biopsy after examinations of TRUS and CETRUS scanning. Cancer detection between CETRUS and TRUS were compared by patient and by site in different areas (right, left; base, mid-gland, apex). The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic performance of CETRUS. RESULTS: 89 patients were malignant and 48 patients were significant cancer. Compared with TRUS, CETRUS could increase the detection rates of overall …and significant cancer (P  = 0.008; P  = 0.031). CETRUS had higher sensitivity, specificity (except right lobe), accuracy, positive predictive value (PPV) and negative predictive value (NPV) in total, right and left lobe (P  < 0.05). The sensitivity were greater for CETRUS in all areas except left base and right apex (P  < 0.05). The accuracy were greater for CETRUS in all areas except left mid-gland and right apex (P  < 0.05). ROC analysis showed CETRUS totally got the AUC of 0.816. The AUC was higher in left lobe than right lobe (0.837 vs. 0.793). It was most accurate at the base (0.833), then mid-gland (0.826), and lowest in apex (0.772). CONCLUSIONS: CETRUS had a significant advantage over conventional TRUS for prostate cancer detection in different areas. CETRUS much more easily missed the cancer in apex, we must focus more on apex and may add other imaging modalities to improve the visualization and detection of prostate cancer. Show more

Keywords: Prostate cancer, ultrasonography, contrast agent, scanning

DOI: 10.3233/CH-170346

Citation: Clinical Hemorheology and Microcirculation, vol. 70, no. 3, pp. 281-290, 2018

Authors: Du, Yan-Ran | Wu, Yang | Chen, Man | Gu, Xin-Gang

Article Type: Research Article

Abstract: BACKGROUND: Breast cancer is the most common cancer in women worldwide. The purpose of the study was to observe the features of contrast-enhanced ultrasound (CEUS) and the combination with Breast Imaging-Reporting and Data System (BI-RADS) of conventional ultrasound for assessing small breast lesions. OBJECTIVES: The study was to explore the small breast lesions’ features of contrast-enhanced ultrasound (CEUS) and the combination with Breast Imaging-Reporting and Data System (BI-RADS) of conventional ultrasound, in order to improve the diagnostic accuracy of early breast cancer. METHODS: 105 lesions were subject to conventional US (ultrasound) and CEUS before operations or …biopsies. Among 105 breast lesions, six patient diagnoses were established by thick core-needle biopsy, while the rest were all confirmed by surgery and pathology. RESULTS: Significant differences were found between benign and malignant lesions in qualitative and quantitative indexes (peak) of CEUS (P  < 0.05). The qualitative features of malignant small breast lesions were as follows: (1) enhanced intensity within the lesion was not uniform (61/61,100%); (2) the speed of wash-in was earlier than the surrounding tissue (58/61, 95.1%); (3) lesion interior and the surrounding tissues had contrast vessel performance (61/61,100%). Peak of malignant lesions (35.77±11.45) was higher than that of benign lesions (31.96±10.76) (P  < 0.05). The diagnostic performance of BI-RADS-US plus qualitative indexes (method one) in terms of area under receiver operating characteristic curve (AUROC) were the highest (i.e., AUROC = 0.817), in comparison with other combined diagnostic methods. The associated sensitivity, specificity and accuracy were 78.69%, 84.09% and 80.95%, respectively. With method one, however, was similar with US-BI-RADS in specificity, 11 malignant breast lesions were regarded as a higher classification of BI-RADS and classified into malignant group, which were identified as benign on US-BI-RADS originally. CONCLUSIONS: CEUS was useful to differentiate benign from malignant small breast lesions, and the combination of CEUS and BI-RADS-US can improve the early diagnosis of breast cancers. Show more

Keywords: Small breast lesions, contrast-enhanced ultrasound, peak intensity, breast imaging-reporting and data system

DOI: 10.3233/CH-170368

Citation: Clinical Hemorheology and Microcirculation, vol. 70, no. 3, pp. 291-300, 2018

Authors: Wan, Jing | Wu, Rong | Yao, Minghua | Xu, Guang | Liu, Hui | Pu, Huan | Xiang, Lihua | Zhang, Shupin

Article Type: Research Article

Abstract: PURPOSE: To assess the elastographic features of triple-negative breast cancers and evaluate the diagnostic value of acoustic radiation force impulse imaging (ARFI) for the characterization of triple-negative breast cancers. MATERIALS AND METHODS: This study analyzed data from 234 women with breast cancer. Patients were categorized into three groups; 1) triple-negative breast cancers (n  = 48); 2) ER-positive tumors (n  = 128) and 3) HER2-positive tumors (n  = 58). Mean tumor stiffness was evaluated by virtual touch tissue imaging (VTI) and virtual touch tissue quantification (VTQ) and quantified as both qualitative scores (1–5) and shear wave velocity (SWV) (m/s). The relationship between …mean SWV and tumor parameters, including tumor size, tumor type, histologic grade and lymph node status, were investigated using multiple linear regression. RESULTS: Triple-negative tumor were more likely to have a large invasive size (p  = 0.002), high histological grade (p  < 0.001), lymph node involvement (p  = 0.022) and strong ki-67 expression (p  < 0.001). The highest mean SWV value were recorded in triple-negative tumors (7.36 m/s±1.83), followed by HER2+ tumors (6.65 m/s±2.26) and ER+ tumors (6.60 m/s±2.35) (p  = 0.122). Triple-negative tumors were also associated with increased stiffness than ER+ tumors and HER2+ tumors (p  = 0.016), as measured by qualitative VTI scores. Tumor size was independently associated with mean SWV value on adjusted regression (p  < 0.001). CONCLUSIONS: Triple-negative breast cancer is associated with high stiffness scores and SWV in ARFI. The latter may be considered a useful complementary tool in evaluation of triple-negative breast cancer. Show more

Keywords: Ultrasound, elastography, triple-negative breast cancer, virtual touch tissue imaging, virtual touch tissue quantification

DOI: 10.3233/CH-170363

Citation: Clinical Hemorheology and Microcirculation, vol. 70, no. 3, pp. 301-310, 2018

Authors: Schiffner, René | Lehmann, Thomas | Bischoff, Sabine J. | Zippelius, Timo | Nistor, Marius | Schmidt, Martin

Article Type: Research Article

Abstract: BACKGROUND: Previous studies on the recombinant form of human relaxin-2 (serelaxin) have shown a decrease of pulmonary hemodynamics after serelaxin injection. Currently, the effect of serelaxin treatment during hypovolemia in a large animal model remains mostly unknown. METHODS: 12 sheep were randomly assigned to a sham or serelaxin (30μg/kg serelaxin) group and underwent right heart catheterization. 50% of the estimated total blood volume were removed to induce hypovolemia, and subsequently retransfused 20 min later (reinfusion). Blood gases, heart rate, peripheral and pulmonary arterial oxygen saturation, systolic, diastolic and mean values of both pulmonary artery pressure (PAP) and pulmonary capillary …wedge pressure (PCW) were measured. Cardiac output (CO), pulmonary vascular resistance (PVR), pulmonary arterial compliance (PAcompl) and systemic vascular resistance (SVR) were calculated. RESULTS: Hypovolemia and shock led to a similar decrease of PAP and PCW in both groups (p ≤0.001). CO, SV and PAcompl decreased only in the control group (p ≤0.05) and remained higher in the serelaxin-treated group. The results of this study suggest that serelaxin treatment did not negatively influence hemodynamic parameters during hypovolemic shock. CONCLUSION: The main conclusion of this study is that cardiopulmonary adaption mechanisms are not critically altered by serelaxin administration during severe hypovolemia and retransfusion. Show more

Keywords: Pulmonary hemodynamics, relaxin-2, hypovolemia, reperfusion, reinfusion, shock, relaxin receptors, serelaxin, sheep model, right heart catheterisation

DOI: 10.3233/CH-180382

Citation: Clinical Hemorheology and Microcirculation, vol. 70, no. 3, pp. 311-325, 2018

Authors: Di Dedda, Umberto | Ranucci, Marco | Porta, Alberto | Bari, Vlasta | Ascari, Alice | Fantinato, Angela | Baryshnikova, Ekaterina | Cotza, Mauro

Article Type: Research Article

Abstract: BACKGROUND: Cardiac surgery with cardiopulmonary bypass is associated with important changes in the microcirculation, usually attributed to endothelial dysfunction. Another common finding of cardiac surgery is postoperative thrombocytopenia and platelet loss of function. OBJECTIVE: To investigate the association between microvascular flow pattern and postoperative changes in platelet count and function in cardiac surgery patients. METHODS: Twelve adult cardiac surgery patients received microvascular circulation (sidestream darkfield sublingual mucosa analysis) and platelet count and function (multiple electrode aggregometry ADPtest and TRAPtest) assessment before and after cardiopulmonary bypass. RESULTS: After cardiopulmonary bypass, sublingual microcirculation showed a significantly …(P  = 0.001) decreased microvascular flow index and increased heterogeneity index (P  = 0.006). Platelet function significantly decrease after cardiopulmonary bypass both at ADPtest (P  = 0.011) and TRAPtest (P  = 0.002). Preoperative patterns of poor microvascular perfusion (low perfused vessels density and total vessels density) were significantly associated with lower values of post-cardiopulmonary bypass platelet function (ADPtest, P  = 0.009, TRAPtest, P  = 0.031) and count (P  = 0.048). CONCLUSIONS: A preoperative disturbance of the microcirculation is associated with a greater postoperative platelet dysfunction. Endothelial damage, chemical and mechanical stimuli are the possible link between the two patterns. Show more

Keywords: Cardiac surgery, sublingual microcirculation, platelet function, multiple electrode aggegometry

DOI: 10.3233/CH-180391

Citation: Clinical Hemorheology and Microcirculation, vol. 70, no. 3, pp. 327-337, 2018

Authors: Farber, Paulo L. | Freitas, Teresa | Saldanha, Carlota | Silva-Herdade, Ana Santos

Article Type: Research Article

Abstract: BACKGROUND: Natural and synthetic estrogens seems to have opposite effects on thrombosis and female cardiovascular system, since natural estrogen was supposed to be protective against cardiovascular diseases and synthetic estrogen has been related to thrombosis and cardiovascular diseases. In this work we have investigated if these differences could be related with the effects on those hormones on some hemorheological parameters. OBJECTIVE: The objective of this work was to investigate the hemorheological changes of different concentrations of beta-estradiol and ethinylestradiol, on RBC aggregation and RBC deformability. METHODS: Samples of blood of healthy donors were added with different …concentrations of natural beta-estradiol or synthetic ethinylestradiol and were analyzed for red blood cell (RBC) aggregation and RBC deformability. RESULTS: There were no significant changes in RBC aggregation. Both beta-estradiol and ethinylestradiol increase the RBC deformability in shear stresses above 3.0 Pa accordingly with the hormone’s concentration. CONCLUSIONS: Beta-estradiol and ethinylestradiol enhance RBC deformability dependent of their concentration. These findings may explain the different patterns of thrombotic and cardiovascular effects in different phases of the menstrual cycle or different dosages of oral contraceptive or hormonal replacement therapy. Show more

Keywords: Hemorheology, erythrocyte deformability, erythrocyte aggregation, ethinyl estradiol, estradiol, contraceptives, oral, estrogens, menstrual cycle, thrombosis, cardiovascular diseases

DOI: 10.3233/CH-180392

Citation: Clinical Hemorheology and Microcirculation, vol. 70, no. 3, pp. 339-345, 2018

Authors: Liu, Shui-Qing | Liu, Yan-Ping | Zhou, Bang-Guo | Deng, Xiao-Hong | Li, Xiao-Long | Xiang, Li-Hua | Ren, Wei-Wei | Xu, Hui-Xiong

Article Type: Research Article

Abstract: OBJECTIVE: To determine the diagnostic performance of conventional ultrasound (US) and two-dimensional shear wave elastography (2D SWE) in the differential diagnosis between mastitis and breast malignancy. METHODS: Between January 2016 and March 2017, 105 patients with 105 pathologically proven breast lesions were enrolled. All the lesions were subject to conventional US and 2D SWE examinations. In 2D SWE, the qualitative parameter of stiff rim sign and quantitative parameter of maximal shear wave velocity (SWV) were obtained. The diagnosis performances of US and combination of US and 2D SWE were evaluated, including sensitivity, specificity and the area under the …receiver operating characteristic curve (AUROC). The AUROC of US and the combined method were also evaluated in subgroups with different diameters. RESULTS: Pathologically, 26 breast lesions were confirmed to be mastitis and 79 were malignant. The cut-off value for maximal SWV was 6.75 m/sec. The AUROC of stiff rim sign and maximal SWV were 0.701 (95% CI: 0.587–0.815) and 0.753 (95% CI: 0.659–0.832) respectively. Compared with US, the specificity and AUROC of the combined method increased significantly (specificity: 11.5% vs. 96.1%, AUROC: 0.520 vs. 0.752; both P  < 0.05). CONCLUSIONS: The combination of US and 2D SWE improved the diagnostic performance in the differential diagnosis between mastitis and breast malignancy in comparison with the conventional US alone. Show more

Keywords: Shear wave elastography, conventional ultrasound, mastitis, breast malignancy

DOI: 10.3233/CH-180400

Citation: Clinical Hemorheology and Microcirculation, vol. 70, no. 3, pp. 347-354, 2018

Authors: Ko, Eunji | Youn, Jung Min | Park, Hyung Sun | Song, Myeongjin | Koh, Kyung Hee | Lim, Choon hak

Article Type: Research Article

Abstract: BACKGROUND: Sepsis is a medical emergency during which early detection is closely associated with mortality. In sepsis, red blood cell (RBC) abnormalities have been reported. However, it is not known how early RBC abnormalities are expressed compared with various clinical manifestations used in sepsis-related organ failure assessment (SOFA). OBJECTIVE: Therefore, using a lipopolysaccharide (LPS)-induced sepsis model we investigated the clinical significance of RBC abnormalities as an early indicator in the detection of septic injury compared with clinical variables. METHODS: Sprague-Dawley rats received LPS (20 mg/kg) intraperitoneally. Aggregation indices (AIs) and aggregation half-time (T1/2), and …elongation indices (EI max ) were measured. Clinical data-related SOFA and lactate were measured at 2 h, 4 h, 8 h and 12 h after LPS injection. RESULTS: AIs increased at 4 h, and T1/2 decreased at 2 h after LPS injection. Platelet counts decreased at 4 h, and lactate increased at 2 h after LPS injection. AIs showed strong correlations with T1/2 and platelets, EI max increased at 2 h after LPS injection, while EI max had a positive correlation with lactate. CONCLUSIONS: RBC aggregation appears to be an early indicator of clinical deterioration in sepsis and may represent a diagnostic indicator in sepsis. Show more

Keywords: Red blood cell aggregation, red blood cell deformability, sepsis, sepsis-related organ failure assessment

DOI: 10.3233/CH-180430

Citation: Clinical Hemorheology and Microcirculation, vol. 70, no. 3, pp. 355-363, 2018