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

Authors: White, Jennell | Moira, Lancelot | Gao, Xiufeng | Tarasev, Michael | Chakraborty, Sumita | Emanuele, Marty | Hines, Patrick C.

Article Type: Research Article

Abstract: BACKGROUND: Red blood cell (RBC)-modifying therapies have provided new opportunities for patients with sickle cell disease, although the absence of validated biomarkers of RBC function is a barrier to FDA approval and clinical adoption. Flow Adhesion (FA) and Mechanical Fragility (MF) biomarkers objectively stratify individuals with SCD into pro-adhesive vs pro-hemolytic phenotypes respectively, which may potentially help predict therapeutic responses. OBJECTIVE: A Phase 3 clinical trial to determine the effectiveness of vepoloxamer, an RBC-modifying therapy in sickle cell disease (SCD), failed to meet its primary clinical outcome. The aim of this study was to determine whether standardized flow …adhesion and mechanical fragility bioassays could differentiate cellular level “responders” from “non-responders” to vepoloxamer treatment. METHODS: Standardized biomarkers of RBC function (adhesion and mechanical fragility) were utilized in this study to assess the effect of veploxamer on blood samples collected from SCD subjects and to determine whether our assays could differentiate cellular-level “responders” from “non-responders” to vepoloxamer treatment. A Wilcoxon signed-rank test was used to test for differences in adhesion in response to varying vepoloxamer treatments and a Wilcoxon Mann-Whitney test was used to assess differences in mechanical fragility, pre- and post-vepoloxamer treatment. A p -value<0.05 was considered significant. RESULTS: In this study, we report that in vitro treatment with vepoloxamer reduced adhesion by >75%in 54%of patient samples and induced changes in the membranes of sickle erythrocytes (SSRBCs) making sickle cells behave more like normal erythrocytes (AARBCs) in terms of their resistance to hemolysis. CONCLUSION: This study demonstrates that the standardized flow adhesion and mechanical fragility biomarkers described here may be useful tools to predict clinical responders to RBC-modifying therapies. Show more

Keywords: Sickle cell disease, adhesion, vepoloxamer, mechanical fragility, blood function assays

DOI: 10.3233/CH-200944

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

Authors: Sohn, Sung-Hwa | Kim, Tae Sik | Kim, Ji-Won | Yoo, Sung Mook | Jo, Won-Min

Article Type: Research Article

Abstract: BACKGROUND: Although the number of vascular surgeries performed is increasing, the incidence of complications associated with this surgery has not improved and re-operations are frequently required. Thrombosis in a vessel is the most hazardous postoperative complication. OBJECTIVE: The aim of this study was to evaluate the anti-thrombotic and anti-inflammatory effects of sulodexide compared to aspirin in a rat model. METHODS: We divided the animals into three groups (sham (saline), aspirin, and sulodexide). The abdominal aorta was surgically opened and closed, primarily with 8/0 Prolene sutures. Postoperatively, saline, aspirin, or sulodexide was administered by oral gavage for …14 days to the rats. The degree of neovascularization, thrombus, calcification, inflammatory infiltrates, and fibrosis were analyzed histopathologically by hematoxylin and eosin staining. RESULTS: There was no significant difference in the incidence of postoperative thrombogenesis, but less calcification and inflammatory infiltrates were observed in the sulodexide group compared to the aspirin group. Histopathologic score revealed less infiltration of inflammatory cells and mild calcification for the sulodexide group (0.17±0.41 and 1.33±0.52, respectively) compared to the aspirin group (0.67±0.52 and 1.67±0.52, respectively) at days 14. CONCLUSIONS: This study offers the possibility that sulodexide could be used as an aspirin substitute for the postoperative management of vascular patients, with low gastrointestinal discomfort. In addition, it may also offer reduced postoperative calcification and inflammation. Show more

Keywords: Sulodexide, aspirin, thrombogenesis, calcification, inflammation

DOI: 10.3233/CH-201043

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2020

Authors: Wang, Zheng-Dong | Li, Hao | Liu, Ming | Li, Ping | Chen, Jian | Liang, Xiang-Wen | Zhu, Xian-Zhang | Liao, Wang

Article Type: Research Article

Abstract: OBJECTIVE: The aim of the present study was to evaluate the effectiveness and safety of nicorandil in improving the area of myocardial infarction in patients with acute myocardial infarction (AMI). METHODS: One hundred and twenty patients with acute ST-segment elevation myocardial infarction (STEMI) admitted to our hospital between December 1, 2018 and December 31, 2019 were selected and randomly allocated to the experimental group (group A, n  = 60) and the control group (group B, n  = 60). In the experimental group, an infusion of nicorandil was given intravenously before the first balloon dilation or 1 minute before the stent …placement, and with the completion of the infusion, nicorandil maintenance infusion was given. In the control group, only balloon dilation and stent placement were undertaken. RESULTS: The postoperative peak levels of myoglobin, creatine kinase isoform and hypersensitive troponin T were significantly lower in group A than in group B (p  <  0.05). Moreover, the left ventricular ejection fraction (LVEF) on the 180th day post operation was substantially greater in group A than in group B (p  <  0.01), and the area of myocardial infarction was significantly smaller in patients in group A than those in group B on the 180th day post operation (p  <  0.01). In terms of the safety, there were no statistically significant differences in the incidence of slow flow/no reflow, malignant arrhythmias, and hypotension within 24 hours post operation between the two groups (p  >  0.05), and no major adverse cardiovascular event (MACE) occurred in either group during the postoperative follow-up period of 180 days (p  >  0.05). CONCLUSION: Intravenous administration of nicorandil in patients with STEMI during the perioperative percutaneous coronary intervention (PCI) period was effective in reducing the area of myocardial infarction and myocardial injury without increasing the incidence of malignant arrhythmias, hypotension, or composite cardiovascular events during the drug administration period. Show more

Keywords: Percutaneous coronary intervention, acute ST-segment elevation myocardial infarction, nicorandil, myocardial infarction area, myocardial injury

DOI: 10.3233/CH-200998

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2020

Authors: Li, Bao-Hua | Fang, Kuai-Fa | Lin, Pei-Huan | Zhang, Yi-Hui | Huang, Yong-Xiang | Jie, Hai

Article Type: Research Article

Abstract: OBJECTIVE: The aim of the present study was to observe the effect of sacubitril valsartan on cardiac function and vascular endothelial function in patients with chronic heart failure with reduced ejection fraction (HFrEF). METHODS: A total of 80 patients with HFrEF were randomly divided into an observation group and a control group, with 40 patients in each group. Sacubitril valsartan was added to the conventional treatment in the observation group, and perindopril was added to the conventional treatment in the control group. Both groups were treated continuously for 12 weeks. The left ventricular ejection fraction (LVEF), left ventricular …end-diastolic diameter (LVEDD), flow-mediated vasodilatory function (FMD) of the brachial artery, and levels of plasma Ang II, endothelin 1 (ET-1), and calcitonin gene-related peptide (CGRP), together with the serum nitric oxide (NO) and NO synthase (NOS) were compared before and after treatment in the groups. RESULTS: Before the treatment, the levels of LVEF, LVEDD, FMD, Ang II, ET-1, CGRP, NO, and NOS in the observation group were not significantly different from those in the control group (P  >  0.05). However, the levels of LVEF, FMD, CGRP, NO, and NOS in both groups were significantly higher after the treatment than those before the treatment (P  <  0.05) and significantly higher in the observation group than those in the control group. The difference was statistically significant (P  <  0.05). Meanwhile, the levels of LVEDD, Ang II, and ET-1 in both groups decreased significantly after the treatment (P  <  0.05) and were significantly lower in the observation group than those in the control group. The difference was statistically significant (P  <  0.05). CONCLUSION: Sacubitril valsartan might improve endothelial function while increasing cardiac function in HFrEF patients. Show more

Keywords: Sacubitril valsartan, left ventricular ejection fraction, chronic heart failure, cardiac function, endothelial function

DOI: 10.3233/CH-201032

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2020

Authors: Farber, Paulo L. | Dias, Ana | Freitas, Teresa | Pinho, Ana C. | Viggiano, Diego | Saldanha, Carlota | Silva-Herdade, Ana S.

Article Type: Research Article

Abstract: Background: Calcium, vitamin D and insulin resistance are linked to osteoporosis and cardiovascular disease in menopause. Objective: Determine if hemorheological parameters related to blood viscosity in microcirculation are linked to calcium metabolism and insulin resistance in menopause. Methods: 25-Hydroxyvitamin D (25(OH)D)), 1, 25-dihydroxyvitamin D3 (1, 25(OH)2 D), Parathyroid Hormone, ionized calcium, Glucose, Insulin and Hemoglobin A1c were measured in blood from 43 volunteers. Red blood cells (RBC) aggregation, RBC deformability and Whole Blood Viscosity were also performed. Results: 25(OH)D showed a positive correlation with RBC deformability 0.60 Pa. Subjects with 25(OH)D≤29.00 ng/mL had lower RBC …deformability 0.60 Pa. and higher RBC Aggregation and higher HOMA-IR. Ionized calcium showed a negative correlation with RBC Aggregation. Subjects with ionized calcium ≤1.24 mmol/L showed higher RBC Aggregation. There was a positive correlation between HOMA-IR and RBC Aggregation and HOMA-IR showed a negative correlation with RBC deformability 0.30 Pa. Subjects with HOMA-IR <1.80 showed lower RBC aggregation and higher RBC deformability at 0.30 Pa, 0.60 Pa, 1.20 Pa, 3.0 Pa and 6.0 Pa. Conclusion: Low 25(OH)D, low ionized calcium and high HOMA-IR are related to impaired hemorheology in menopause. RBC aggregation and deformability can be used as biomarkers of calcium metabolism and insulin resistance in menopause. Show more

Keywords: Hemorheology, calcium metabolism, osteoporosis, vitamin D, insulin resistance, cardiovascular diseases

DOI: 10.3233/CH-200956

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-16, 2020

Authors: Boisson, Camille | Rab, Minke A.E. | Nader, Elie | Renoux, Céline | van Oirschot, Brigitte A. | Joly, Philippe | Fort, Romain | Stauffer, Emeric | van Beers, Eduard J. | Sheehan, Vivien A. | van Wijk, Richard | Connes, Philippe

Article Type: Research Article

Abstract: Sickle cell disease (SCD) is a genetic disorder characterized by the production of an abnormal hemoglobin (Hb), which, under deoxygenation, may polymerize and cause a mechanical distortion of red blood cell (RBC) into a crescent-like shape. Recently a method, using ektacytometry principle, has been developed to assess RBC deformability as a function of oxygen tension (pO2 ) and is called oxygen gradient ektacytometry (oxygenscan). However, standardization of this test is needed to properly assess the tendency of sickling of RBCs under deoxygenation and to allow comparisons between different laboratories. The study compared the oxygenscan responses during blood storage between distinct …populations of SCD patients. Blood from 40 non-transfused homozygous SCD patients (HbSS), 16 chronically transfused HbSS patients, and 14 individuals with compound heterozygous hemoglobin SC disease (HbSC)at steady-state was collected in EDTA tubes. Measurements were performed within 4 hours after collection and after 24 hours of storage at 4°C. We showed that storage affected the minimum RBC deformability reached during deoxygenation (EImin) in both non-transfused HbSS and HbSC patients and the maximum RBC deformability (EImax) measured before deoxygenation (i.e., in normoxia) in the three groups. In contrast, the tendency of RBCs to sickle under deoxygenation (i.e., the point of sickling; PoS) remained rather stable between the two time of measurements. Collectively, since the time between blood sampling and analysis affects some key oxygen gradient ektacytometry-derived parameters we recommend that each laboratory performs oxygenscan measurements at a standardized time point. Show more

Keywords: Oxygen gradient ektacytometry, sickle cell disease, red blood deformability, storage

DOI: 10.3233/CH-201037

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-4, 2020

Authors: Xiao, Huang | Pengfei, Chen | Fakuan, Tang | Ning, Hua

Article Type: Research Article

Abstract: BACKGROUD: Patients with chest pain and suspected of coronary artery disease(CAD) need further test to confirm the diagnosis. Magnetocardiography (MCG) is a non-invasive and emission-free technology which can detect and measure the weak magnetic fields created by the electrical activity of the heart. OBJECTIVE: This study aimed to investigate the usefulness of the 10 MCG parameters to detect CAD in patients with chest pain by means of a machine learning method of multilayer perceptron(MLP) neural network. METHODS: 209 patients who were suffering from chest pain and suspected of CAD were enrolled in this cross-sectional study. In …all patients, 12-lead electrocardiography(ECG) and MCG test were performed before percutaneous coronary angiography(PCA). 10 MCG parameters were analyzed by MLP neural networks. RESULTS: 11 diagnostic models(M1 to M11) were established after MLP analysis. The accuracies ranged from 71.2% to 90.5%. Two models(M10 and M11) were further analyzed. The accuracy, sensitivity, specificity, PPV, NPV, PLR and NLR were 89.5%, 89.8%, 88.9%, 92.7%, 84.7%, 11.10 and 0.11, of M10, and were 90.0%, 91.4%, 87.7%, 92.1%, 86.6%, 7.43 and 0.10, of M11. CONCLUSIONS: By a method of MLP neural network, MCG is applicable in identifying CAD in patients with chest pain, which seems beneficial for detection of CAD. Show more

Keywords: Magnetocardiography, percutaneous coronary intervention, coronary artery disease, diagnosis, machine learning

DOI: 10.3233/CH-200905

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2020

Authors: Braune, S. | Bäckemo, J. | Lau, S. | Heuchel, M. | Kratz, K. | Jung, F. | Reinthaler, M. | Lendlein, A.

Article Type: Research Article

Abstract: Nanoporous microparticles prepared from poly(ether imide) (PEI) are discussed as candidate adsorber materials for the removal of uremic toxins during apheresis. Polymers exhibiting such porosity can induce the formation of micro-gas/air pockets when exposed to fluids. Such air presenting material surfaces are reported to induce platelet activation and thrombus formation. Physical or chemical treatments prior to implantation are discussed to reduce the formation of such gas nuclei. Here, we report about the influence of different rewetting procedures – as chemical treatments with solvents – on the thrombogenicity of hydrophobic PEI microparticles and PEI microparticles hydrophilized by covalent attachment of poly(vinyl …pyrrolidone) (PVP) of two different chain lengths. Autoclaved dry PEI particles of all types with a diameter range of 200 – 250 μm and a porosity of about 84% ±2% were either rewetted directly with phosphate buffered saline (24 h) or after immersion in an ethanol-series. Thrombogenicity of the particles was studied in vitro using human sodium citrated whole blood (60 min, 5 rpm vertical rotation). Numbers of non-adherent platelets were quantified, and adhesion of blood cells was qualitatively analyzed by bright field microscopy. Platelet activation (percentage of CD62P positive platelets and amounts of soluble P-Selectin) and platelet function (PFA100 closure times) were analysed. Retention of blood platelets on the particles was similar for all particle types and both rewetting procedures. Non-adherent platelets were less activated after contact with ethanol-treated particles of all types compared to those rewetted with phosphate buffered saline as assessed by a reduced number of CD62P-positive platelets and reduced amounts of secreted P-Selectin (P  < 0.05 each). Interestingly, the hydrophilic surfaces significantly increased the number of activated platelets compared to hydrophobic PEI regardless of the rewetting agent. This suggests that, apart from wettability, other material properties might be more important to regulate platelet activation. PFA100 closure times were reduced and within the reference ranges in the ethanol group, however, significantly increased in the saline group. No substantial difference was detected between the tested surface modifications. In summary, rewetting with ethanol resulted in a reduced thrombogenicity of all studied microparticles regardless of their wettability, most likely resulting from the evacuation of air from the nanoporous particles. Show more

Keywords: Biomaterial, polymer, microparticle, thrombogenicity, hemocompatibility, dynamic in-vitro test, rewetting

DOI: 10.3233/CH-201029

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2020

Authors: Liu, Qin | Wang, Zhengrong

Article Type: Research Article

Abstract: OBJECTIVE: To evaluate the diagnostic value of real-time shear wave elastography (SWE) in children with chronic kidney disease (CKD). METHODS: Children with CKD diagnosed by the ultrasound-guided biopsy between January 2018 and May 2019 were enrolled as the case group. Age- and sex- matched healthy children were selected as the control group. The Young’s Modulus (YM) of the renal cortex was measured by SWE after the traditional ultrasound examination. Variance analysis was performed to compare the values of YM between the two groups. Receiver operating characteristic curve (ROC) analysis was used to compare the values of YM, and …explore the cut-offs of the YM. RESULTS: In the case group (n  = 60, 45% male, mean age of 9.2 years), the kidney YM modulus on the left side (16.8±4.8 kPa vs. 8.3±2.1 kPa) and the right side (16.0±4.7 kPa vs. 8.3±2.4 kPa) were both higher than the control group (all P values <  0.001). With the progress of CKD, the YM value of the left and right kidneys gradually increased. ROC analysis showed that when the left and right kidney YM value was 11.7 kPa and 11.0 kPa, the diagnostic sensitivity and specificity were the highest (left: respectively 93.3% and 95.0%; right: respectively 93.3 % and 91.7%). CONCLUSION: The increase of YM in CKD is related to the progression of renal dysfunction which may provide a new method for early diagnosis of CKD, dynamic monitoring of disease progression, and evaluation of curative effect and prognosis. Show more

Keywords: Shear wave elastography, chronic kidney disease, children

DOI: 10.3233/CH-200982

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2020

Authors: Krüger-Genge, A. | Tondera, C. | Hauser, S. | Braune, S. | Görs, J. | Roch, T. | Klopfleisch, R. | Neffe, A.T. | Lendlein, A. | Pietzsch, J. | Jung, F.

Article Type: Research Article

Abstract: Immunocompatibility and non-thrombogenicity are important requirements for biomedical applications such as vascular grafts. Here, gelatin-based hydrogels formed by reaction of porcine gelatin with increasing amounts of lysine diisocyanate ethyl ester were investigated in vitro in this regard. In addition, potential adverse effects of the hydrogels were determined using the “Hen’s egg test on chorioallantoic membrane” (HET-CAM) test and a mouse model. The study revealed that the hydrogels were immunocompatible, since complement activation was absent and a substantial induction of reactive oxygen species generating monocytes and neutrophils could not be observed in whole human blood. The density as well …as the activation state of adherent thrombocytes was comparable to medical grade polydimethylsiloxane, which was used as reference material. The HET-CAM test confirmed the compatibility of the hydrogels with vessel functionality since no bleedings, thrombotic events, or vessel destructions were observed. Only for the samples synthesized with the highest LDI amount the number of growing blood vessels in the CAM was comparable to controls and significantly higher than for the softer materials. Implantation into mice showed the absence of adverse or toxic effects in spleen, liver, or kidney, and only a mild lymphocytic activation in the form of a follicular hyperplasia in draining lymph nodes (slightly increased after the implantation of the material prepared with the lowest LDI content). These results imply that candidate materials prepared with mid to high amounts of LDI are suitable for the coating of the blood contacting surface of cardiovascular implants. Show more

Keywords: Gelatin-based hydrogels, immune cells, platelets, in vitro testing, mouse model

DOI: 10.3233/CH-201028

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-16, 2020