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

Authors: Magyar, Zsuzsanna | Molnar, Abel | Nachmias, David Belkin | Mann, Din | Sogor, Viktoria | Mester, Anita | Peto, Katalin | Nemeth, Norbert

Article Type: Research Article

Abstract: BACKGROUND: Flap hypoperfusion or ischemia-reperfusion (I/R) may occur during preparation-transposition procedures and by postoperative thrombotic complications. Behind the microcirculatory disturbances micro-rheological alterations are also supposed. OBJECTIVE: We aimed to investigate the groin flap I/R with following-up micro-rheological parameters. METHODS: Anesthetized rats were subjected to Control or I/R groups. Groin flaps were prepared bilaterally, pedicled on the superficial epigastric vessels. In Control group the flaps were re-sutured after one hour, while in I/R group microvascular clips were applied on the pedicles for 60 minutes, then the flaps were repositioned. Besides daily wound control, before the operation …and on the 1st, 3rd, 5th, 7th and 14th postoperative days blood samples were collected for testing red blood cell (RBC) deformability (rotational ektacytometry) and aggregation (light-transmission aggregometry). RESULTS: RBC deformability significantly worsened by the 3rd–7th postoperative day in I/R group. RBC aggregation enhanced significantly by the 1st day, in I/R group it remained elevated on the 3rd day as well. In a complicated case with unilateral flap necrosis, RBC deformability and aggregation worsening was outlined from its group (base, 1st, 3rd day). CONCLUSION: Wound healing affected micro-rheological parameters in the early postoperative period. Flap I/R exacerbated the alterations. The parameters markedly worsened in case of flap necrosis. Show more

Keywords: Ischemia, microcirculation, hemorheology

DOI: 10.3233/CH-170277

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2017

Authors: Taeger, Christian D. | Friedrich, Oliver | Horch, Raymund E. | Drechsler, Caroline | Weigand, Annika | Hopf, Fabio | Geppert, Carol I. | Münch, Frank | Birkholz, Torsten | Wenzel, Carina | Geis, Sebastian | Prantl, Lukas | Buchholz, Rainer | Präbst, Konstantin

Article Type: Research Article

Abstract: BACKGROUND: Extracorporeal perfusion (EP) is moving into focus of research in reconstructive and transplantation medicine for the preservation of amputates and free tissue transplants. The idea behind EP is the reduction of ischemia-related cell damage between separation from blood circulation and reanastomosis of the transplant. Most experimental approaches are based on a complex system that moves the perfusate in a circular course. OBJECTIVE AND METHODS: In this study, we aimed to evaluate if a simple perfusion by an infusion bag filled with an electrolyte solution can provide acceptable results in terms of flow stability, oxygen supply and …viability conservation for EP of a muscle transplant. The results are compared to muscles perfused with a pump system as well as muscles stored under ischemic conditions with a one-time intravasal flushing with Jonosteril. RESULTS: With this simple method a sufficient oxygen supply could be achieved and functionality could be maintained between 3.35 times and 4.60 times longer compared to the control group. Annexin V positive nuclei, indicating apoptosis, increased by 9.7% in the perfused group compared to 24.4% in the control group. CONCLUSIONS: Overall, by decreasing the complexity of the system, EP by one-way infusion can become more feasible in clinical situations. Show more

Keywords: Extracorporeal perfusion, external field stimulation, free flap perfusion, reperfusion, ischemia, free flap transplantation

DOI: 10.3233/CH-170298

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2017

Authors: Dragic, Sasa | Momcicevic, Danica | Zlojutro, Biljana | Jandric, Milka | Kovacevic, Tijana | Djajić, Vlado | Gajić, Aleksandar | Talić, Goran | Kovacevic, Pedja

Article Type: Research Article

Abstract: Roles of nitric oxide (NO) and endothelin-1 (ET-1) in the local regulation of blood flow under physiological conditions are important and well known, while data on their effects and interactions in conditions of hyperbaric hyperoxia is still insufficient. This was a prospective observational study which included patients who underwent hyperbaric oxygen therapy (HBOT) in accordance with existing therapeutic protocol for peripherial arterial disease (PAD) during time period of six months, between january and july of 2016. Clinical stage of PAD according to Fontain was taken into account, as well as risk factors, demographic, anthropometric and clinical characteristics of studied patients. …The study included 64 patients with a mean age (±Sd) 60.2±12.7 years, of whom 28 were female. Patients’ NO serum levels in all observed categories before and after HBOT were not signifficantly different, except for stage II PAD (NObefore HBOT 21.9±9.6 vs. NOafter HBOT 26.2±12.1 (p  = 0.04)). On the contrary, in all studied patients ET-1 level increased signifficantly after HBOT (ET-1before HBOT 4.2±11.6 vs. ET-1after 18.3±21.0 (p  < 0.001)). Treatment of PAD using HBOT leads to the predominance of vasoconstrictor effects probably caused by elevation of serum ET-1 concentrations, while other factors such as exposure time to hyperbaric conditions, activation of antioxidant molecules, and the influx of other interfering substances must be considered in interpreting the effects of NO molecules. Show more

Keywords: Peripherial arterial disease, hyperbaric oxygen therapy, endothelin-1, nitric oxide

DOI: 10.3233/CH-190796

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

Authors: Park, Seong Jun | Yoon, Jung | Seo, Hong Seog | Lim, Chae Seung

Article Type: Research Article

Abstract: BACKGROUND: Platelet function analysis is crucial in assessing the hemostatic status to evaluate congenital and acquired platelet function defects. The Anysis-200 analyzer is a new automated lab-on-a-chip-based platelet function analyzer. OBJECTIVE: We aimed to evaluate a new platelet function analyzing system, the Anysis-200 in comparison to the Platelet Function Analyzer (PFA)-200 in cardiac patients. METHODS: Citrated blood was collected from 174 patients who visited the Department of Cardiology. The Anysis-200 consists of two kits, the microchips with collagen and epinephrine-coated membrane (C/EPI) or adenosine diphosphate-coated membrane (C/ADP). Platelet clogging in the Anysis-200 is measured by the …blood migration distance obtained by a camera, which is compatible with the closure time in the PFA-200. We performed Anysis-200 and PFA-200 analyzers simultaneously and compared the results. RESULTS: The sensitivity and specificity of the Anysis-200 C/EPI kit in comparison to the PFA-200 C/EPI kit were 63.41% and 91.43%, respectively. Regarding the C/ADP kit, the sensitivity and specificity of the Anysis-200 were 58.97% and 74.29%, respectively. The agreement rate between the Anysis-200 and PFA-200 for C/EPI was 83.35% and 70.14% for C/ADP. CONCLUSIONS: The Anysis-200, which applies a novel method to detect platelet clogging, has shown moderate to fair agreement with the PFA-200. This test is potentially useful for screening cardiac patients with an abnormal platelet function. Show more

Keywords: Platelet function, Anysis-200 analyzer, PFA-200 analyzer

DOI: 10.3233/CH-190801

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

Authors: Liu, Xiaojun | Wang, Gang | Zhang, Tao

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the changes in the levels of plasm interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α ), C-reactive protein (CRP), matrix metalloproteinase-9 (MMP-9) and endotoxins in patients with acute aortic dissection (AAD). METHODS: 55 AAD patients who were admitted and scheduled to undergo emergency surgery in our hospital from January 2017 to July 2017 were selected and retrospectively analyzed. They were divided into the survival group (n  = 40) and the death group (n  = 15). The levels of plasma IL-6, TNF-α , CRP, MMP-9 and endotoxins at admission and at 6 h, 12 h and 24 h after admission (T0, T1, T2 …and T3) were measured, and the correlations of inflammatory cytokines with endotoxins were analyzed. RESULTS: At T1, T2 and T3, the levels of inflammatory cytokines and endotoxins were increased. The levels of plasma IL-6, TNF-α , CRP, MMP-9 and endotoxins in the death group were significantly higher than those in the survival group at each time point (p  < 0.05 in all comparisons). Neutrophil and platelet counts in the death group were higher than those in the survival group (p  < 0.05). Correlation analyses indicated that the levels of IL-6, TNF-α , CRP and MMP-9 were positively correlated with the level of endotoxin. CONCLUSION: Patients with AAD are often accompanied by systemic inflammatory responses, with inflammation-related cytokines (IL-6, TNF-α , CRP and MMP-9) and endotoxins levels significantly elevated. Combined monitoring of dynamic changes in inflammatory cytokines and endotoxins, as well as early interventions, has important clinical implications for evaluating the prognosis of AAD and reducing mortality. Show more

Keywords: Acute aortic dissection, IL-6, TNF-α, CRP, MMP-9

DOI: 10.3233/CH-190674

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

Authors: Carlisi, Melania | Mancuso, Salvatrice | Caimi, Gregorio | Siragusa, Sergio

Article Type: Research Article

Abstract: The complement system is an essential component of the innate immune defence that, if overly activated, may damage organs and tissues. For this reason, there is a fine complement regulatory system. The complement modulation system includes two proteins with important regulatory activity, CD55 or decay accelerating factor (DAF) and CD59 or membrane inhibitor of reactive lysis (MIRL). The paroxysmal nocturnal hemoglobinuria (PNH) is a clonal and non-neoplastic disease characterized by intravascular haemolysis, occurrence of thrombosis and bone marrow failure. In clinical practice, in opposition to PNH, a variety of pathological conditions have been observed with an acquired and …non-genetic deficiency of the regulatory proteins CD55 and CD59. This abnormal, non-clonal, reduced expression of complement regulatory proteins configures what we may define as PNH-like phenotype. Similarly to PNH, even in the PNH-like phenotype diseases there has been a greater exposure to the mediated complement cellular lysis and, a likely increased risk of thromboembolic events. Therefore, the knowledge of the potential roles of the complement system becomes necessary for a deeper understanding of several pathological conditions and for an improved clinical management of the patients. Show more

Keywords: Paroxysmal nocturnal hemoglobinuria, complement system, CD55, CD59, thromboembolic risk

DOI: 10.3233/CH-190735

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

Authors: Xu, Guang | Xiang, Lihua | Wu, Jian | Shao, Hongda | Liu, Hui | Ding, Shisi | Wu, Rong

Article Type: Research Article

Abstract: PURPOSE: Prostate cancer (PCa) is one of the most common cancers in elderly men worldwide. Systematic biopsy guided by transrectal ultrasound remains the standard for PCa diagnosis; however, the false negative rate is 10–20%. Multiparametric magnetic resonance imaging (mpMRI) allows PCa visualization with a more precise localization and a higher accuracy and specificity for the detection of PCa. The physician can mentally relocate the most appropriate area detected on the prebiopsy mpMRI, based on its zonal topography and anatomical landmarks, called cognitive fusion. Herein, we concentrated on the accuracy of PCa localization in cognitive fusion compared with MRI-TRUS fusion and …explored the applied scope of cognitive fusion. METHODS: Thirty-two eligible patients with 36 PCa lesions were recruited for our study. TRUS examinations and MRI-TRUS fusion procedures were performed by experienced operators. The cognitive fusion images were compared using the TRUS image in a MRI-TRUS fusion workstation. RESULTS: Using cognitive fusion imaging, 86.1% of the lesions were accurately located by the senior sonographer and 69.4% of the lesions were accurately located by the junior sonographer. The maximum diameter and PI-RADS score of the lesions were important factors that affected the accuracy of cognitive fusion (P  < 0.05). Furthermore, the lesions with high PI-RADS scores and the lesions with large diameters were more accurately located using cognitive fusion (P  < 0.05). CONCLUSIONS: Cognitive fusion is a reliable technique with dependency on working experience, and its accuracy of locating suspicious lesions is consistent with MRI-TRUS fusion in patients with high PI-RADS score and large lesions. Show more

DOI: 10.3233/CH-180423

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

Authors: Lerchbaumer, Markus Herbert | Putz, Franz Josef | Rübenthaler, Johannes | Rogasch, Julian | Jung, Ernst-Michael | Clevert, Dirk-Andre | Hamm, Bernd | Makowski, Marcus | Fischer, Thomas

Article Type: Research Article

Abstract: PURPOSE: Contrast-enhanced-ultrasound (CEUS) has been frequently used in assessment of cystic renal lesions. OBJECTIVE: The aim of this study was to investigate the Bosniak classification in CEUS compared to CT and MRI in a multi-center setting. METHODS: Bosniak classification in CEUS examinations of cystic renal lesions were compared to imaging findings in computed-tomography (ceCT) and magnetic-resonance-imaging (ceMRI). Imaging results were correlated to histopathological reports. All examinations were performed by experts (EFSUMB level 3) using up-to-date CEUS examination-protocols. RESULTS: Overall, 173 cystic renal lesions were compared to subgroups CT (n  = 87) and MRI (n  = 86). …Using Bosniak-classification 64/87 renal cysts (73.6%) were rated equal compared to CT with upgrade of four lesions (4.6%) and downgrade of 19 lesions (21.8%) by CT (Intra-class-correlation [ICC] coefficient of 0.824 [p  < 0.001]). CEUS compared to MRI, presenting different scoring especially in classes Bosniak IIF (n  = 16/31) and Bosniak III (n  = 16/28) with an ICC coefficient of 0.651 (p  < 0.001). CONCLUSION: CEUS can visualize even finest septal and small nodular wall enhancement, which may result in an upgrade of cystic lesions into a higher Bosniak class compared to CT or MRI. Thus, a modification of the Bosniak classification on CEUS may reduce unnecessary biopsies and surgery. Show more

Keywords: Contrast-enhanced ultrasound, CEUS, Bosniak, renal cyst

DOI: 10.3233/CH-190764

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2020

Authors: Huang, Yunqian | Liu, Qi | Xu, Junmei | Zhu, Wenqian | Jiang, Jianwei | Tang, Lei | Chen, Man

Article Type: Research Article

Abstract: BACKGROUND: Early identification of vulnerable plaques at risk of rupture could help prevent cerebral ischemic stroke in patients with carotid artery disease. OBJECTIVE: To investigate the correlation between contrast-enhanced ultrasound (CEUS) perfusion patterns and serum lipid signatures of carotid artery plaques with the degree of carotid stenosis. METHODS: A total of 80 patients with carotid artery plaques who underwent CEUS were included. All patients underwent CEUS, computed tomography angiography or digital subtraction angiography, and serum lipid testing. RESULTS: The contrast agent enhancement levels and the CEUS perfusion patterns in the plaques were associated with …the degree of carotid stenosis (P  < 0.05). Serum free fatty acid (FFA) was associated with the contrast agent enhancement levels (P  < 0.05), but did not correlate with the degree of stenosis (P  > 0.05). There was no significant difference in total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides with respect to contrast agent enhancement levels (P  > 0.05) or the degree of stenosis (P  > 0.05). CONCLUSION: A high level of CEUS perfusion and increased serum FFA levels are indicative of vulnerable carotid plaques, which may be useful for the prediction of stroke in patients with carotid artery disease. Show more

DOI: 10.3233/CH-190804

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2020

Authors: Ulker, Pinar | Ozkan, Ozlenen | Amoroso, Matteo | Ubur, Mehmet Can | Aslan, Mutay | Ozcan, Filiz | Bassorgun, Ibrahim | Ozkan, Omer

Article Type: Research Article

Abstract: BACKGROUND: Ischemic preconditioning (IPC) is defined as raising tolerance to subsequent ischemic stress by exposing tissues to sub-lethal ischemia. Although many candidates have been suggested, recent studies have clearly demonstrated that adenosine-mediated ADORA2B receptor (ADORA2BR) activation is the main mechanism involved in IPC. While the tissue-protective role of this mechanism has been demonstrated in different ischemia/reperfusion (I/R) models, its role in flap surgery-derived I/R damage has not to date been investigated. OBJECTIVE: To investigate the role of adenosine and ADORA2BR activation in IPC-mediated tissue protection in an epigastric flap model. METHODS: Animals were divided into five …main groups, all of which were then divided into two subgroups depending on whether or not they were exposed to IPC before the I/R procedure, which consisted of 6 hours of ischemia and 6 days of reperfusion. No drugs were administered in Group 1 (the control group). Animals in Group 2 were pretreated with CD73-inhibitor before IPC application or the ischemic period. Animals in Group 3 were pretreated with adenosine. Animals in Group 4 were pretreated with an ADORA2BR antagonist, and those in Group 5 with an ADORA2BR agonist. After 6 days of reperfusion, tissue survival was evaluated via histological and macroscopic analysis. RESULTS: IPC application significantly enhanced CD73 expressions and adenosine concentrations (p  < 0.01). Flap survivals were increased by IPC in Group 1 (p  < 0.05). However, CD73 inhibition blocked this increase (Group 2). In Group 3, adenosine improved flap survival even in the absence of IPC (p  < 0.01). While an ADORA2BR antagonist attenuated the tissue-protective effect of IPC (p  < 0.01), the ADORA2BR agonist improved flap survival by mimicking IPC in groups 4 and 5. CONCLUSION: These results provide pharmacological evidence for a contribution of CD73 enzyme-dependent adenosine generation and signaling through ADORA2BR to IPC-mediated tissue protection. They also suggest for the first time that ADORA2BR agonists may be used as a potential preventive therapy against I/R injury in flap surgeries. Show more

Keywords: Adenosine, ADORA 2B, ischemia, reperfusion, flap survival

DOI: 10.3233/CH-190730

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Zhang, Qi | Wu, Lili | Yang, Daohui | Qiu, Yijie | Yu, Lingyun | Dong, Yi | Wang, Wen-Ping

Article Type: Research Article

Abstract: OBJECTIVES: To investigate the value of dynamic contrast enhanced ultrasound (D-CEUS) in monitoring the chemoradiotherapy (CRT) therapeutic response of local advanced pancreatic ductal adenocarcinoma (LAPC). PATIENTS AND METHODS: From October 2017 to December 2018, 11 patients diagnosed as LAPC were included (7 men, 4 women; mean age: 61.1±8.6 years). The algorithm of CRT was as following: the radiotherapy dose was 50.4 Gy/28Fx with S-1 40 mg bid orally taken in radiotherapy day. Conventional ultrasound scan and CEUS were performed before and 4 weeks after CRT. All ultrasound examinations were performed by an ACUSON Oxana 2 ultrasound equipment (Siemens Medical Solutions, …Germany) with a C 6-1 convex array transducer (1–6 MHz). Time intensity curves (TICs) were generated in the region of interests (ROIs) both in LAPC lesions and in its surrounding pancreas parenchyma by SonoLiver software (TOMTEC Imaging Systems). Quantitative perfusion parameters including maximum intensity (MI), rise time (RT), mean transit time (mTT) and time to peak (TTP) were analyzed and compared before and after CRT. RESULTS: No significant difference could be found by conventional B mode ultrasound scan after CRT. TICs of CEUS showed lower ascending and descending slopes rate after CRT. Among all perfusion quantitative parameters, MI decreased significantly after CRT (42.1±18.8% vs 27.8±17.2%, P  < 0.05). CONCLUSIONS: Depending on its unique advantages as non-radiation, effective and convenient, D-CEUS analysis and quantitative parameters, particularly MI, has potential application value in following up of the CRT treatment response in LAPC patients. Show more

Keywords: Dynamic contrast enhanced ultrasound (D-CEUS), locally advanced pancreatic ductal adenocarcinoma (LAPC), chemoradiotherapy (CRT), therapeutic response, blood perfusion

DOI: 10.3233/CH-190786

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2019

Authors: Schulz, Christian | Krüger-Genge, Anne | Jung, Friedrich | Lendlein, Andreas

Article Type: Research Article

Abstract: Implantation of synthetic small-diameter vascular bypass grafts is often associated with an increased risk of failure, due to thrombotic events or late intimal hyperplasia. As one of the causes an insufficient hemocompatibility of the artificial surface is discussed. Endothelialization of synthetic grafts is reported to be a promising strategy for creating a self-renewing and regulative anti-thrombotic graft surface. However, the establishment of a shear resistant cell monolayer is still challenging. In our study, cyto- and immuno-compatible poly(ether imide) (PEI) films were explored as potential biomaterial for cardiovascular applications. Recently, we reported that the initial adherence of primary human umbilical vein …endothelial cells (HUVEC) was delayed on PEI-films and about 9 days were needed to establish a confluent and almost shear resistant HUVEC monolayer. To accelerate the initial adherence of HUVEC, the PEI-film surface was functionalized with an aptamer-cRGD peptide based endothelialization supporting system. With this functionalization the initial adherence as well as the shear resistance of HUVEC on PEI-films was considerable improved compared to the unmodified polymer surface. The in vitro results confirm the general applicability of aptamers for an efficient functionalization of substrate surfaces. Show more

Keywords: Aptamer, endothelialization, physical functionalization, poly(ether imide) films, shear resistance

DOI: 10.3233/CH-190775

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-17, 2020

Authors: Prantl, Lukas | Gehmert, Sebastian | Brébant, Vanessa | Hoesl, Vanessa

Article Type: Research Article

Abstract: BACKGROUND: Lipolytic injectables for body contouring procedures have been reported for necrotic effects on adipose tissue causing side effects as swelling, pain and hematoma. Deoxycholic acid is widely used as a solvent in lipolytic injectables and is associated with necrosis when applied to cells. A new lipolytic preparation (NWL-10) containing only polyenylphosphatidylcholine in nano particle size, glycerrhizinate and maltose has been reported for its lipolytic action on adipose tissue. However, no data exist whether the NWL-10 mixture is responsible for apoptosis or necrosis in adipose tissue which can be associated with severer side effects as reported for deoxycholic acid preparation. …METHODS: 3T3-L1 mouse cells and human adipose tissue derived stem cells were exposed to the NWL-10 mixture and to each ingredient of the mix in order to investigate cytotoxic, lipolytic, necrotic or apoptotic effects. Furthermore, a Balb/C mouse animal model was used to investigate inflammatory responses to NWL-10 by bioluminescence monitoring and histological examination. RESULTS: A high extent of lipolysis was detected for the NWL-10 mixture when applied to both cell types with no cytotoxic effect. Interestingly, low concentration of NWL-10 resulted in necrosis whereas high concentration of NWL-10 showed a certain amount of apoptosis. Application of single ingredients of NWL-10 or various combinations of two component mixtures did not result in any apoptosis or necrosis. In addition, no inflammatory effects of NWL-10 were observed in the mouse model. CONCLUSIONS: The NWL-10 mixture provided promising results regarding lipolysis on adipose tissue with limited apoptosis and necrosis when compared to currently available injectables. These first promising results require further fundamental and more detailed research on essentials for drug approval. NWL-10 has the potential to become a second generation product for future lipolytic injectables. Show more

DOI: 10.3233/CH-190715

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

Authors: Jurischka, Christoph | Dinter, Franziska | Efimova, Anastasia | Weiss, Romano | Schiebel, Juliane | Schulz, Christian | Fayziev, Bekzodjon | Schierack, Peter | Fischer, Thomas | Rödiger, Stefan

Article Type: Research Article

Abstract: BACKGROUND: The 3D printing is relevant as a manufacturing technology of functional models for forensic, pharmaceutical and bioanalytical applications such as drug delivery systems, sample preparation and point-of-care tests. OBJECTIVE: Melting behavior and autofluorescence of materials are decisive for optimal printing and applicability of the product which are influenced by varying unknown additives. METHODS: We have produced devices for bioanalytical applications from commercially available thermoplastic polymers using a melt-layer process. We characterized them by differential scanning calorimetry, fluorescence spectroscopy and functional assays (DNA capture assay, model for cell adhesion, bacterial adhesion and biofilm formation test). …RESULTS: From 14 tested colored, transparent and black materials we found only deep black acrylonitrile-butadiene-styrene (ABS) and some black polylactic acid (PLA) useable for fluorescence-based assays, with low autofluorescence only in the short-wave range of 300–400 nm. PLA was suitable for standard bioanalytical purposes due to a glass transition temperature of approximately 60°C, resistance to common laboratory chemicals and easy print processing. For temperature-critical methods, such as hybridization reactions up to 90°C, ABS was better suited. CONCLUSIONS: Autofluorescence was not a disadvantage per se but can also be used as a reference signal in assays. The rapid development of individual protocols for sample processing and analysis required the availability of a material with consistent quality over time. For fluorescence-based assays, the use of commercial standard materials did not seem to meet this requirement. Show more

Keywords: 3D printing, cell adhesion, autofluorescence, polylactic acid, PLA, polyethylene terephthalate glycol, PETG, acrylonitrile-butadiene-styrene, ABS, thermoplastic polyurethane elastomers, TPU, medicine, pharmaceutical

DOI: 10.3233/CH-190713

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-28, 2019

Authors: van Leeuwen, Anoek L.I. | Naumann, David N. | Dekker, Nicole A.M. | Hordijk, Peter L. | Hutchings, Sam D. | Boer, Christa | van den Brom, Charissa E.

Article Type: Research Article

Abstract: BACKGROUND: Endothelial hyperpermeability is suggested to play a role in the development of microcirculatory perfusion disturbances and organ failure following hemorrhagic shock, but evidence is limited. OBJECTIVE: To study the effect of plasma from traumatic hemorrhagic shock patients on in vitro endothelial barrier function. METHODS: Plasma from traumatic hemorrhagic shock patients was obtained at the emergency department (ED), the intensive care unit (ICU), 24 h after ICU admission and from controls (n  = 8). Sublingual microcirculatory perfusion was measured using incident dark field videomicroscopy at matching time points. Using electric cell-substrate impedance sensing, the effects of plasma …exposure on in vitro endothelial barrier function of human endothelial cells were assessed. RESULTS: Plasma from traumatic hemorrhagic shock patients collected at ED admission induced a 19% loss of in vitro endothelial resistance compared to plasma from controls (p  < 0.001). This loss was due to reduced cell-cell contacts (p  < 0.01). Plasma withdrawn at later time points did not affect endothelial barrier function (p  > 0.99). Interestingly, in vitro endothelial resistance showed a positive association with in vivo microcirculatory perfusion (r  = 0.56, p  < 0.01). CONCLUSIONS: Plasma from traumatic hemorrhagic shock patients obtained following ED admission, but not at later stages, induced in vitro endothelial hyperpermeability. This coincided with in vivo microcirculatory perfusion disturbances. Show more

Keywords: Hemorrhagic shock, endothelial barrier function, microcirculation, plasma, endothelial permeability

DOI: 10.3233/CH-190642

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2019

Authors: Brettner, Florian | Heitzer, Markus | Thiele, Friederike | Hulde, Nikolai | Nussbaum, Claudia | Achatz, Stefan | Jacob, Matthias | Becker, Bernhard F. | Conzen, Peter | Kilger, Erich | Chappell, Daniel

Article Type: Research Article

Abstract: BACKGROUND: Hypotension and bradycardia are known side effects of general anesthesia, while little is known about further macro- and microhemodynamic changes during induction. Intriguing is furthermore, why some patients require no vasopressor medication to uphold mean arterial pressure, while others need vasopressor support. OBJECTIVE: Determination of macro- and microhemodynamic changes during induction of general anesthesia. METHODS: We enrolled 150 female adults scheduled for gynaecological surgery into this prospective observational, single-blinded trial. Besides routinely measuring heart rate (HR) and mean arterial blood pressure (MAP), the non-invasive technique of thoracic electrical bioimpedance was applied to measure cardiac output …(CO), cardiac index (CI), stroke volume (SV), stroke volume variability (SVV) and index of myocardial contractility (ICON) before induction of anesthesia, 7 times during induction, and, finally, after surgery in the recovery room. Changes in microcirculation were assessed using sidestream dark field imaging to establish the perfused boundary region (PBR), a validated gauge of glycocalyx health. Comparisons were made with Friedman’s or Wilcoxon test for paired data, and with Mann-Whitney-U test for unpaired data, with post-hoc corrections for multiple measurements by the Holm-Bonferroni method. RESULTS: 83 patients did not need vasopressor support, whereas 67 patients required therapy (norepinephrine, atropine or cafedrine/theodrenaline) to elevate MAP values to ≥70mmHg during induction, 54 of these receiving norepinephrine (NE) alone. Pre-interventional (basal) values of CO, CI, ICON, SV and SVV were all significantly lower in the group of patients later requiring NE (p  < 0.04), whereas HR and MAP were identical for both groups. HR, MAP and CO decreased from baseline to 12 min after induction of general anesthesia in both the patients without and those with NE support. Heart rate decreased significantly by about 25% in both groups (–19 to –21 bpm). The median individual decrease of MAP amounted to –26.7% (19.7/33.3, p  < 0.001) and –26.1% (11.6/33.2, p  < 0.001), respectively, whereas for CO it was –40.7% (34.1/50.1, p  < 0.001) and –43.5% (34.8/48.7). While these relative changes did not differ between the two groups, in absolute values there were significantly greater decreases in CO, CI, SV and ICON in the group requiring NE. Noteably, NE did not restore ICON or the other cardiac parameters to levels approaching those of the group without NE. PBR was measured in a total of 84 patients compiled from both groups, there being no intergroup differences.It increased 6.4% (p  < 0.001) from pre-induction to the end of the operation, indicative of damage to microvascular glycocalyx. CONCLUSION: Non-invasive determination of CO provides additional hemodynamic information during anesthesia, showing that induction results in a significant decrease not only of MAP but also of CO and other cardiac factors at all timepoints compared to baseline values. The decrease of CO was greater than that of MAP and, in contrast to MAP, did not respond to NE. There was also no sign of a positive inotropic effect of NE in this situation. Support of MAP by NE must consequently result from an increase in peripheral arterial resistance, posing a risk for oxygen supply to tissue. In addition, general anesthesia and the operative stimulus lead to an impairment of the microcirculation. Show more

Keywords: Blood pressure, cardiac output, general anesthesia, heart rate, microcirculation

DOI: 10.3233/CH-190691

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-16, 2019

Authors: Abraham, Pierre | Hersant, Jeanne | Ramondou, Pierre | Thouveny, Francine | Feuilloy, Mathieu | Picquet, Jean | Henni, Samir

Article Type: Research Article

Abstract: BACKGROUND: Non-invasive tests are still required to improve the holistic diagnostic approach of thoracic outlet syndrome (TOS). OBJECTIVES: We aimed to analyze the diagnostic accuracy of the decrease from rest oxygen pressure (DROP) index of transcutaneous oximetry (TcpO2) in TOS. METHODS: Seventy-six patients and 40 asymptomatic volunteers (Controls) were enrolled. In TOS-suspected patients, the arteriograms were investigated for the presence of≥75% stenosis. The area under receiver operating characteristics curve (AUC) analysis tested the ability of forearm TcpO2 during provocative maneuvers to discriminate Patients from controls and, to predict a positive arteriographic findings in the 44 TOS-suspected …patients that had an arteriography. RESULTS: The media [25/75° centile] DROP values of controls and patients were -14 [-8/-22] mmHg and -22 [-12/-42] mmHg, respectively (p for Mann-Whitney<0.02). AUC analysis showed a significant ability of TcpO2 to predict the presence of subclavian arterial compression on arteriography (AUC, 0.694). CONCLUSIONS: Although time consuming, tcpO2 is independent of the observer expertise and could be useful in TOS-suspected patients to select the patients that should undergo arteriography. Show more

Keywords: Ischemia, subclavian artery, thoracic outlet syndrome; transcutaneous oxygen pressure, diagnosis, diagnostic accuracy

DOI: 10.3233/CH-190751

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2019

Authors: Zhang, Guang | Zhang, Tao | Sun, Xiubin | Tang, Fang | Lin, Haiyan | Liu, Yanxun | Zhang, Chengqi | Xue, Fuzhong

Article Type: Research Article

Abstract: The association between whole blood viscosity (WBV) and metabolic syndrome (MetS) is still scarcely investigated in the population-based prospective cohort. We aim to explore the longitudinal effect of WBV on MetS, and to verify whether WBV measures can be used as early predictors for MetS. The longitudinal cohort consisted of 3,508 adults (2,350 males and 1,158 females) who visited the health check-up system twice. WBV were measured at four shear rate (200, 50, 10 and 1 s-1 ), and their values were classified into quartiles. Multivariate Cox models were used to estimate the adjusted hazard ratios (HRs) and 95% confidence …intervals (CIs) in men and women, respectively. A total of 444 (12.66%) incident MetS were observed at follow-up period. The incidences of MetS significantly increased with increasing quartiles of WBVs at all of the shear rate in men. After adjusting for baseline age, smoking, obesity, hypertension, hyperglycemia, and hyperlipidemia status, all of the WBV measures were significantly associated with incident MetS in men, and the HRs showed clear increasing trend across the quartiles of baseline WBVs. There were no significant association between WBVs and incident MetS in women. These findings suggest that MetS has a hemodynamic basis, and WBVs could be used as independent early predictor for MetS in men. Show more

Keywords: Whole blood viscosity, metabolic syndrome, prospective cohort

DOI: 10.3233/CH-15120

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2019

Authors: Zhang, Wei-Bing | Xu, Hui-Xiong | Zhang, Yi-Feng | Guo, Le-Hang | Xu, Shi-Hao | Zhao, Chong-Ke | Liu, Bo-Ji

Article Type: Research Article

Abstract: OBJECTIVE: To compare the diagnostic performance and the unnecessary biopsy rates for recommending fine needle aspiration (FNA) of Thyroid Imaging Reporting and Data Systems proposed by American College of Radiology (ACR TI-RADS), American Thyroid Association (ATA) guidelines, TI-RADS proposed by Kwak (Kwak TI-RADS), and Korean Thyroid Association/Korean Society of Thyroid Radiology (KTA/KSThR) guidelines for malignancy risk stratification of thyroid nodules (TNs). METHODS: The study included 1271 TNs whose cytologic results or surgical pathologic findings were available. Ultrasound images of these TNs were retrospectively reviewed and categorized according to the four guidelines. The diagnostic performances and the unnecessary biopsy …rates for recommending FNA of the four guidelines were evaluated. RESULTS: After multivariate analysis, the most significant independent predictor for malignancy was hypoechogenicity/marked hypoechogenicity (OR: 9.37, 95% CI: 5.40-16.26) (P  <  0.001) among the suspicious ultrasound images features. For all nodules and two subgroups (i.e. nodules <10 mm group and nodules ≥10 mm group), ACR TI-RADS demonstrated higher specificities (all P  <  0.05) and lower sensitivities (all P  <  0.001) than the other guidelines. In the all nodules group and the nodules<10 mm group, ACR TI-RADS and Kwak TI-RADS had higher Azs than the other guidelines (all P  <  0.01). The unnecessary biopsy rates for recommending FNA of ACR TI-RADS in the all nodules (≥10 mm) group and the subgroup (10∼19 mm) were all lower than those of the others guidelines (P  <  0.001 for all). For the subgroup (≥20 mm), the unnecessary biopsy rate of ACR was lower than that of ATA guidelines and KTA/KSThR guidelines (P  <  0.001). CONCLUSIONS: The four guidelines have good diagnostic efficiency in differentiating TNs. ACR TI-RADS and Kwak TI-RADS have better diagnostic performance than the other guidelines in the all nodules group and the nodules<10 mm group. Considering the comprehensive diagnostic efficacy and unnecessary biopsy rate, ACR TI-RADS is a more desirable classification guideline in clinical practice. Show more

Keywords: Thyroid nodules, ultrasound, thyroid imaging reporting and data system, american thyroid association guidelines, Korean thyroid association/Korean society of thyroid radiology guidelines

DOI: 10.3233/CH-190778

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2019

Authors: Lee, Jayoung | Oh, Seung Hwan | Kim, Hye Ran

Article Type: Research Article

Abstract: BACKGROUND: Elevated whole blood viscosity (WBV) is associated with increasing blood flow resistance in the microcirculation and is used to predict the occurrence and outcome of cardiovascular diseases. OBJECTIVE: We evaluated the analytical performance of the ZL 6000i (Zonci Technology, Beijing, China), new fully automated cone-plate rotational type viscometer. METHODS: We collected blood samples from 287 adults to establish a reference range. We evaluated total precision for 20 days using quality control (QC) samples and within-run precision was evaluated by performing 50 consecutive measurements of blood samples. Aliquots of blood samples were stored at room temperature …and 5°C to assess the effect of storage time and temperature on viscosity measurement. RESULTS: The reference ranges and median values of WBV were significantly higher in males than in females due to difference in hematocrit level. The coefficients of variation (CVs) for precision using QC and human blood samples were <  7.5% at all shear rates. WBV of the samples stored at room temperature for up to 6 h, and at 5°C for samples stored up to 2 days was not different from the control. CONCLUSIONS: In this study, the ZL 6000i viscometer yields reproducible WBV data and is clinically useful for monitoring viscosity. Show more

Keywords: Blood viscosity, viscometer, validation, reference values, stability

DOI: 10.3233/CH-190701

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2019

Authors: Lerchbaumer, Markus Herbert | Kleemann, Tobias | Jung, Ernst-Michael | Nagel, Sebastian | Hamm, Bernd | Fischer, Thomas

Article Type: Research Article

Abstract: BACKGROUND: Contrast-enhanced ultrasound (CEUS) has been used as an additional imaging technique in order to clarify rare focal splenic lesions (FSL). CEUS is a safe and cost-effective modality for assessment of perfusion. OBJECTIVE: To validate contrast enhancement pattern and evaluate the diagnostic accuracy of CEUS in unclear FSL. METHODS: CEUS examinations of the spleen in 50 patients between 2012 and 2018 were included in the study. Examinations were performed using B-mode, colour-coded Doppler ultrasound (CCDS) and CEUS after injection of sulphur hexafluoride microbubbles and interpreted in consensus by two experienced radiologists. Reference standard was defined as …histopathological report and clinical course (treatment response, long term follow up). RESULTS: All patients were successfully examined by CEUS without an adverse reaction. CEUS presented the correct differentiation of benign and malignant alterations in 49/50 (98%). Lesion washout was found in all malignant but also 16.7% of all benign lesions. Matched to the histopathological report and clinical follow up, CEUS represented a sensitivity of 100% (95% -CI, 57–100), a specificity of 98% (95% -CI, 88–100), a positive predictive value (PPV) of 83% (95% -CI, 44–97) and a negative predictive value (NPV) of 100% (95% -CI, 92–100). CONCLUSION: CEUS may provide additional information by visualization of dynamic contrast enhancement pattern to differentiate benign and malignant lesions. Nevertheless, established criteria for malignancy (early enhancement or washout) in FSL should be considered with caution since they are also found in benign lesions. Show more

Keywords: Contrast-enhanced ultrasound, CEUS, focal splenic lesions

DOI: 10.3233/CH-190758

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Grambow, Eberhard | Klee, Gina | Klar, Ernst | Vollmar, Brigitte

Article Type: Research Article

Abstract: INTRODUCTION: Neointima formation is closely linked to vascular stenosis and occurs after endothelial damage. Hydrogen sulphide is an endogenous pleiotropic mediator with numerous positive effects on the cardio vascular system. OBJECTIVE: This study evaluates the effect of the slow releasing hydrogen sulfide donor GYY4137 (GYY) on neointimal formation in vivo . METHODS: The effect of GYY on neointimal formation in the carotid artery was studied in the FeCl3 injury model in GYY- or vehicle-treated mice. The carotid arteries were studied at days 7 and 21 after treatment by means of histology and immunohistochemistry for proliferating …cell nuclear antigen (PCNA) and alpha smooth muscle actin (α -SMA). RESULTS: GYY treatment significantly reduced the maximal diameter and the area of the newly formed neointima on both days 7 and 21 when compared to vehicle treatment. GYY additionally reduced the number of PCNA- and α -SMA-positive cells within the neointima on day 21 after FeCl3 injury of the carotid artery. CONCLUSIONS: Summarizing, single treatment with the slow releasing hydrogen sulfide donor GYY reduced the extent of the newly formed neointima by affecting the cellular proliferation at the site of vascular injury. Show more

Keywords: Pleiotropic mediator, gaseous transmitter, arterial stenosis, basic science, vascular disease

DOI: 10.3233/CH-190747

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2019

Authors: Haase, Tobias | Klopfleisch, Robert | Krost, Annalena | Sauter, Tilman | Kratz, Karl | Peter, Jan | Jung, Friedrich | Lendlein, Andreas | Zohlnhöfer, Dietlind | Rüder, Constantin

Article Type: Research Article

Abstract: Copolyetheresterurethane (PDC) is a biodegradable, shape-memory biomaterial, which has been shown to be of low toxicity and pro-angiogenic in vitro . In the present study we examined the in vivo compatibility of PDC as a compression molded film and as electrospun scaffolds and its well established constituent, the homopolymer poly(p -dioxanone) (PPDO), which were compared with the clinically used poly[(vinylidene fluoride)-co -hexafluoropropene] (PVDF) as reference material. The materials were implanted in the subcutaneous tissue of mice and the host responses were analyzed histologically 7 and 28 days after implantation. All materials induced a foreign body response (FRB) including …the induction of foreign body giant cells and a peripheral fibrous capsule. PDC, PPDO and PVDF films showed no signs of degradation after 28 days. PDC films showed a significantly reduced associated macrophage layer and fibrous capsule on their surface. Few fragments of PDC and PPDO scaffolds were present at the implantation site, while PVDF scaffolds were still present in large amounts at day 28. Especially aligned electrospun PDC scaffold induced a significantly thinner fibrous and a slightly reduced inflammatory response after 28 days of implantation. In addition, only PDC aligned fibrous scaffold structures induced a significant increase in angiogenesis. In summary, PDC films outperformed PPDO and PVDF films in terms of compatibility, especially in capsule and macrophage layer thickness. Through microstructuring of PDC and PPDO into scaffolds an almost complete degradation was observed after 28 days, while their respective films remained almost unchanged. However, the capsule thickness of all scaffolds was comparable to the films after 28 days. Finally, the parallel arrangement of PDC fibers enabled a strong enhancement of angiogenesis within the scaffold. Hence, material chemistries influence overall compatibility in vivo , while angiogenesis could be influenced more strongly by microstructural parameters than chemical ones. Show more

Keywords: Degradable polymer, electrospinning, scaffold, microstructure, in vivo compatibility, foreign body reaction, neovascularization, tissue integration, shape-memory polymer, homopolymer, copolymer

DOI: 10.3233/CH-190748

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2019

Authors: Pan, Pan | Su, Longxiang | Liu, Dawei | Wang, Xiaoting

Article Type: Research Article

Abstract: Microcirculatory shock is a condition defined by the presence of tissue hypoperfusion despite the normalization of systemic and regional blood flow. Currently, more evidence shows that intrinsic septic shock is microcirculatory shock, which results in septic shock that is difficult to resuscitate. At present, treatments are aimed at recovering macro-circulation functions and include fluid resuscitation, vasoactive drugs, positive inotropic drugs, de-obstruction, and even mechanical assistance to improve oxygen delivery. However, the application of these treatments to more accurately improve microcirculation or avoid further microcirculatory damage is more important in clinics. In this article, we discuss the need for microcirculation protection …and microcirculation-guided protection strategies in hemodynamic therapies. Show more

Keywords: Microcirculation protection, hemodynamic, shock, resuscitation, treatment

DOI: 10.3233/CH-190784

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

Authors: Wang, Jia-Wan | Wu, An-Shi | Yue, Yun | Wu, Yan

Article Type: Research Article

Abstract: BACKGROUND: Damage-associated molecular patterns (DAMPs) generated by major surgery can induce global inflammation response and may degrade the vascular endothelial glycocalyx layer (EGL); in turn, the resulting EGL fragments can act as DAMPs, in a destructive positive feedback loop, to promote exacerbation of inflammation. Ulinastatin (UTI) may attenuate EGL shedding by inhibiting serine proteases and hyaluronidase. OBJECTIVE: This trail evaluates whether EGL shedding elicited by Traditional Whipple Procedure (TWP) could be decreased by using UTI. METHODS: We divided 60 patients undergoing TWP into a control group and a UTI group (n  = 30 for both). Blood samples …were collected before (T0 ), near the end (T1 ), and 1 hour after (T2 ) surgery. Levels of syndecan-1, ICAM-1, VCAM-1, IL-6, C-reactive protein, thrombomodulin, Hbg and serum albumin were measured and plasma albumin leakage was estimated. RESULTS: IL-6 levels significantly elevated at T1 and T2 in the control group compared with T0 , but not the UTI group. Syndecan-1 levels significantly elevated at T1 and T2 in the control group but only T2 in the UTI group compared with T0 . CONCLUSIONS: We found global inflammation reaction and EGL degradation during TWP. Perioperative UTI treatment can attenuate this EGL shedding and might alleviate plasma albumin leakage. Show more

Keywords: Endothelial glycocalyx layer, Syndecan-1, Ulinastatin, traditional whipple procedure

DOI: 10.3233/CH-190688

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2019

Authors: Pan, Liangli | Liu, Zhenfeng | Chen, Yongjun | Yang, Bin | Cheng, Biao

Article Type: Short Communication

Abstract: BACKGROUND: The source of Ang1 is controversial. Although some people think that human endothelial cells can produce Ang1, more believe that endothelial cells produce Ang2 but not Ang1. However, in our recent study on endothelial cells and angiogenesis, we find that endothelial cells do produce Ang1. OBJECTIVE: This study aims to prove that endothelial cells can produce Ang1 and explore what manner does Ang1 act in. METHODS: Immunohistochemistry, western blotting and reverse transcription PCR were used to prove if human dermal microvascular endothelial cells, human brain microvascular endothelial cells and human umbilical vein endothelial cells produce …Ang1. In order to explore Ang1’s act manner, Ang1 expression of human dermal microvascular endothelial cells pre-treated by propranolol IC50 was detected by western blotting. RESULTS: Immunohistochemistry, western blotting and reverse transcription PCR showed that human dermal microvascular endothelial cells, human brain microvascular endothelial cells and human umbilical vein endothelial cells all expressed Ang1, and propranolol significantly inhibited Ang1 expression of human dermal microvascular endothelial cells. CONCLUSIONS: Endothelial cells can also produce Ang1. In addition, endogenous Ang1 may be an autocrine agonistic regulator, participating in endothelial cells angiogenesis process. Show more

Keywords: Angiopoietin-1, endothelial cells, angiogenesis, autocrine agonistic regulator

DOI: 10.3233/CH-190731

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-5, 2020

Authors: Ghanem, Souleiman | Lesznyak, Tamas | Fazekas, Laszlo | Tanczos, Bence | Barath, Barbara | Nasser, Maitham | Horvath, Laszlo | Bidiga, Laszlo | Szabo, Balazs | Deak, Adam | Peto, Katalin | Nemeth, Norbert

Article Type: Research Article

Abstract: Background: Chronic kidney disease (CKD) models are known to study pathophysiology and various treatment methods. Renal dysfunction could influence erythrocytes through several pathways. However, hemorheological and microcirculatory relation of CKD models are not completely studied yet. Objective: To evaluate erythrocyte micro-rheology, microcirculatory and structural compensatory mechanisms in a rat model of CKD. Methods: Female Sprague-Dawley rats were subjected to nephrectomy group (NG, n  = 6) or sham-operated group (SG, n  = 6). NG rats were subjected to 5/6 nephrectomy in two stages. In SG no intervention was made on kidneys. Hemorheological and hematological measurements were carried out after …each stage, and 5 weeks after the last operation. Histological and microcirculatory studies were done on the remaining kidney and compared with sham rats. Results: Serum creatinine increased in NG (p  = 0.008), accompanied with decrease of red blood cell count (p  = 0.028) and hemoglobin (p  = 0.015). Erythrocyte aggregation parameters slightly increased in NG, while the elongation index didn’t show significant changes. Microcirculation was intact in the remnant kidney of NG. However, in comparison with SG, the diameter of glomeruli increased significantly (p  < 0.01). Conclusions: Erythrocyte mass was influenced more than micro-rheological properties in this model. The main compensation mechanism was rather structural than at microcirculatory level. Show more

Keywords: Chronic renal failure, hemorheology, hematology, erythrocytes, rat model

DOI: 10.3233/CH-190763

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2019

Authors: Sengoz, Tarik | Kilic-Toprak, Emine | Yaylali, Olga | Kilic-Erkek, Ozgen | Ozdemir, Yasin | Oymak, Burak | Senol, Hande | Yuksel, Dogangun | Kucukatay, Vural | Bor-Kucukatay, Melek

Article Type: Research Article

Abstract: BACKGROUND: Although radioiodine theraphy (RAIT) is thought to affect blood cells and oxidative stress, hemorheological alterations following dose-dependent RAIT remains unknown. OBJECTIVE: The aim of this study was to determine the effects of RAIT on hemorheological and oxidative stress parameters in patients with differentiated thyroid cancers (DTC). METHODS: Totally 31 DTC patients (mean age 46.32±11.15 years) and 26 healthy controls (mean age 50.50±6.22 years) were included. Venous blood samples were collected from each patient before and after treatment (7th day, 1th month and 6th month). Erythrocyte aggregation-deformability and oxidative stress parameters were determined. …p  < 0.05 was considered as statistically significant. RESULTS: Erythrocyte deformability of the patients determined at 16.87 and 30 Pascal were significantly lower than healthy individuals. Erythrocyte aggregation index (AI) of the patients was higher, whereas erythrocyte aggregation half-time (t½) was lower compared to control. Erythrocyte deformability values and AI were not significantly different from the pre- and post-radioiodine treatment groups. There was no statistically significant difference between the oxidative stress parameters before and after the treatment. CONCLUSIONS: Patients were in a worse hemorheological condition compared to healthy individuals. After RAIT, RBC deformability and aggregation were not affected and no significant change in oxidative stress parameters was detected. Show more

Keywords: Differentiated thyroid cancer, I-131, erythrocyte deformability, erythrocyte aggregation, oxidative stress

DOI: 10.3233/CH-190717

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2019

Authors: Lee, Seahyoung | Ganesan, Ramakrishnan | Krüger-Genge, Anne | Kratz, Karl | Franke, Ralf-Peter | Lendlein, Andreas | Jung, Friedrich

Article Type: Research Article

Abstract: Establishing an endothelial cell (EC) monolayer on top of the blood contacting surface of grafts is considered to be a promising approach for creating a hemocompatible surface. Here we utilized the high affinity interactions between the EC plasma membrane expressed enzyme called endothelin converting enzyme-1 (ECE-1) and its corresponding substrate big Endothelin-1 (bigET-1) to engineer an EC-specific binding surface. Since enzymatic cleavage of substrates require physical interaction between the enzyme and its corresponding substrate, it was hypothesized that a surface with chemically immobilized synthetic bigET-1 will preferentially attract ECs over other types of cells found in vascular system such as …vascular smooth muscle cells (VSMCs). First, the expression of ECE-1 was significantly higher in ECs, and ECs processed synthetic bigET-1 to produce ET-1 in a cell number-dependent manner. Such interaction between ECs and synthetic bigET-1 was also detectible in blood. Next, vinyl-terminated self-assembled monolayers (SAMs) were established, oxidized and activated on a glass substrate as a model to immobilize synthetic bigET-1 via amide bonds. The ECs cultured on the synthetic bigET-1-immobilized surface processed larger amount of synthetic bigET-1 to produce ET-1 compared to VSMCs (102.9±5.13 vs. 9.75±0.74 pg/ml). The number of ECs bound to the synthetic bigET-1-immobilized surface during 1 h of shearing (5dyne/cm2 ) was approximately 3-fold higher than that of VSMCs (46.25±12.61 vs. 15.25±3.69 cells/100×HPF). EC-specific binding of synthetic bigET-1-immobilized surface over a surface modified with collagen, a common substance for cell adhesion, was also observed. The present study demonstrated that using the substrate-enzyme affinity (SEA) of cell type-specific enzyme and its corresponding substrate can be an effective method to engineer a surface preferentially binds specific type of cells. This novel strategy might open a new route toward rapid endothelialization under dynamic conditions supporting the long-term patency of cardiovascular implants. Show more

Keywords: Endothelin converting enzyme-1, big endothelin-1, endothelialization, shear resistance

DOI: 10.3233/CH-190736

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2019

Authors: Li, XiuMei | Li, Jun | Li, Yong | Wang, HongQiao | Yang, JingRu | Mou, Shuang | Zhou, MaoPing | Jiang, CaiYun | Ning, ChunPing

Article Type: Research Article

Abstract: OBJECTIVE: The aim of our study was to evaluate the role of preoperative US, CEUS, and 99m Tc-MIBI scanning with SPECT/CT in localizing diseased parathyroid glands in cases of refractory secondary hyperparathyroidism (SHPT). MATERIAL AND METHODS: Using pathological results as the gold standard, we compared the operative findings with the preoperative localization of each modality in 73 nodules and evaluated the accuracy, and sensitivity of each modality and combinations of the four modalities. RESULTS: The sensitivity of US, CEUS, 99m Tc-MIBI and SPECT/CT was 98.59%, 94.37%, 50.70% and 78.87%, respectively. US had the highest sensitivity of …the four imaging methods and the diagnostic sensitivity of US and CEUS was superior to that of 99m Tc-MIBI (p  < 0.001 and p  < 0.001) and SPECT/CT (p  = 0.001 and p  = 0.012). In addition, we found that the sensitivity of the combination of US with CEUS, US with 99m Tc-MIBI and/or SPECT/CT, CEUS with 99m Tc-MIBI and/or SPECT/CT, US with CEUS and two other imaging modalities (99m Tc-MIBI and/or SPECT/CT) was 98.59%, 100%, 95.77%, and 100%, respectively. CONCLUSIONS: The combination of US with SPECT/CT is the best choice for the comprehensive preoperative localization of glands in refractory SHPT. CEUS can elevate the accuracy of US in differential diagnosis via the interpretation of dynamic microvascular features. Show more

Keywords: Ultrasonography, CEUS, 99mTc-MIBI, SPECT/CT, refractory secondary hyperparathyroidism

DOI: 10.3233/CH-190723

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Wu, Hai-Bo | Shao, Kai | Wang, Yun-Can | Wang, Xue-Chao | Liu, Hui-Liang | Xie, Yue-Tao | Du, Rong-Pin

Article Type: Research Article

Abstract: BACKGROUND: At present, the treatment for acute myocardial infarction has achieved great progress. Reperfusion therapy in the short term can effectively reduce recurrence rates and mortality in patients with acute myocardial infarction. According to a report of a large national registry, the mortality of patients with acute coronary syndrome combined with acute heart failure is 10 times of that of patients without heart failure, and the mortality in nearly 10 years has no significant change. Therefore, people are constantly exploring indicators for acute heart failure prognosis to improve a patient’s prognosis. With the constant understanding and exploration of acute myocardial …infarction, more and more researches have focused in determining how to predict the occurrence of acute heart failure. The present study focuses on presenting the latest progress of Carbohydrate Antigen-125 (CA125) and Brain Derived Neurotrophic Factor (BDNF) in serum of patients with acute myocardial infarction in predicting acute heart failure. Show more

Keywords: Acute myocardial infarction, Acute heart failure, CA125, BDNF

DOI: 10.3233/CH-190738

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2019

Authors: Shao, Si-Hui | Li, Chun-Xiao | Yao, Ming-Hua | Li, Gang | Li, Xing | Wu, Rong

Article Type: Research Article

Abstract: OBJECTIVE: To identify the efficacy of contrast-enhanced ultrasound (CEUS) in re-evaluating masses with inconsistent Breast Imaging Reporting and Data System (BI-RADS) on mammography (MG) and conventional ultrasound (US). MATERIALS AND METHODS: A total of 637 breast lesions were evaluated with MG, US, and CEUS within 6 months and assessed as BI-RADS MG and US. CEUS was used as an additional screening to rerate BI-RADS US according to a five-point system. Lesions were divided into consistent or inconsistent group on the basis of BI-RADS MG and US assessment. The performance of MG, US, and CEUS in the overall and …inconsistent group as well as the clinicopathological differences between consistent and inconsistent group were compared using Z test, Mann–Whitney U test, and t -test. RESULTS: The respective AUCs of MG and US were 0.742, 0.843 for overall group and 0.412, 0.789 for inconsistent group. The corresponding values of rerated CEUS BI-RADS were 0.958 and 0.950, which were significantly prior to those of MG and US (p  < 0.001). Younger age, negative lymph node status, and dense breast were significantly associated with inconsistent group. CONCLUSION: Incorporation of CEUS to re-evaluate lesions can improve the diagnostic efficacy comparing to MG or US alone especially when disagreement occurred. Show more

Keywords: Contrast enhanced ultrasound, conventional ultrasound, inconsistent BI-RADS MG and BI-RADS US assessment

DOI: 10.3233/CH-190729

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

Authors: Mulder Pettersen, Erik | Avdal, Jørgen | Hisdal, Jonny | Torp, Hans | Seternes, Arne

Article Type: Research Article

Abstract: OBJECTIVE: In this proof-of-concept study we aim to validate a novel ultrasound Doppler monitoring device for evaluating microcirculation (earlybird) against LDF and pulsed Doppler. METHODS: In ten healthy subjects, we measured microcirculatory function at rest and during different autonomic tests (forced respiration, isometric exercise, Valsalva maneuver and cold pressor). Earlybird, LDF and pulsed Doppler were recorded simultaneously. We performed a ZNCC to determine correlation. RESULTS: The curves for earlybird and LDF or pulsed Doppler correlates visually well. Overall median ZNCC 0.87 (interquartile range 0.77 –0.91) between the LDF and earlybird measurements, and 0.90 (0.82 – 0.95) …for pulsed Doppler and earlybird. Median ZNCC for baseline and each provocation test for earlybird against LDF and pulsed Doppler were calculated; baseline: LDF 0.87 (0.73 – 0.97) pulsed Doppler 0.91 (0.81 – 0.94), forced respiration: LDF 0.87 (0.28 – 0.90) pulsed Doppler 0.90 (0.85 – 0.96), isometric exercise: LDF 0.82 (0.59 – 0.90) pulsed Doppler 0.87 (0.68 – 0.94), Valsalva maneuver: LDF 0.88 (0.82 – 0.91) pulsed Doppler 0.94 (0.92 – 0.97) and cold pressor: LDF 0.90 (0.85 – 0.95) pulsed Doppler 0.89 (0.65 – 0.94). CONCLUSION: Earlybird records vasoconstrictions in healthy subjects as well as LDF and pulsed Doppler. Show more

Keywords: Ultrasonography, Doppler, Laser-Doppler Flowmetry, peripheral arterial disease, inventions, microcirculation

DOI: 10.3233/CH-190707

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Negrão de Figueiredo, G. | Mueller-Peltzer, K. | Schwarze, V. | Marschner, C. | Zhang, L. | Rübenthaler, J. | Siepmann, T. | Illigens, B.W. | Clevert, D.A.

Article Type: Research Article

Abstract: BACKGROUND: Focal nodular hyperplasia (FNH) is a hyperplastic mass of vascular abnormality and the second most common benign liver lesion. It can be discovered incidentally or during a surveillance examination in patients at risk for hepatic malignancy, mostly by conventional ultrasound. CEUS has been used as an additional alternative method for the rapid diagnosis of FNH. However, none of the previous studies compared the diagnostic performance of CEUS to MRI retrospectively in a 10-year observation. OBJECTIVE: The aim of this long-term retrospective study is to assess the diagnostic performance of CEUS in the imaging of FNH and compare …the results to MRI. MATERIAL AND METHODS: A single experienced physician performed CEUS examinations in 244 patients between 2009 and 2019 with suspected focal nodular hyperplasia after conventional ultrasound. A second-generation blood pool agent (SonoVue® , Bracco, Milan, Italy) was administered. Additional dynamic MRI with contrast agent was performed in a subgroup of 95 patients. RESULTS: Out of 244 patients, FNH could be displayed in 221 patients on CEUS. A subgroup of 95 patients had CEUS examinations and CEMRI for diagnosis comparison. In comparison with CEMRI, CEUS presented a sensitivity of 97%, a specificity of 76%, a positive predictive value of 93% and a negative predictive value of 89%. CONCLUSION: CEUS is a safe and feasible approach that assess the diagnosis of focal nodular hyperplasia equally to MRI. The focal lesion enhancement can be depicted in real-time in the arterial, venous and late phase facilitating the prompt diagnosis. Show more

Keywords: CEUS, focal nodular hyperplasia, MRI, long-term study

DOI: 10.3233/CH-190710

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Caimi, Gregorio | Hopps, Eugenia | Montana, Maria | Carollo, Caterina | Calandrino, Vincenzo | Gallà, Eleonora | Canino, Baldassare | Lo Presti, Rosalia

Article Type: Research Article

Abstract: Protein carbonylation is a marker of oxidative protein damage, that is likely involved in the pathogenesis of several diseases. The aim of this study was to evaluate the protein carbonyl (PC) groups in different clinical conditions. It included different groups of subjects: 81 trained subjects; 23 subjects with mild essential hypertension; 31 middle-aged subjects with metabolic syndrome (MS); 106 subjects with MS not selected for age (subdivided into two subgroups, with and without diabetes mellitus); 91 obese adults subdivided in two subgroups (BMI 30–35 Kg/m2 and BMI > 35 kg/m2 ); 48 subjects with obstructive sleep apnea syndrome (OSAS) subdivided in …accordance with the apnea/hypopnea index (AHI); 27 subjects with chronic kidney disease (CKD) on conservative therapy; 31 subjects with CKD on haemodialysis treatment; and 50 subjects with juvenile myocardial infarction. PC groups were reduced in trained subjects in comparison with sedentary controls, while no variation was observed in mild essential hypertension. PC groups were increased in MS subjects and in adult obese subjects. In MS subjects the PC groups were not influenced by the presence of diabetes mellitus and in adult obese subjects were not influenced by the obesity degree. In OSAS subjects only those with AHI > 30 showed an increase of PC groups. PC groups increased in CKD subjects undergoing conservative treatment and haemodialysis therapy. In dialyzed subjects, after a standard dialysis session, there was a marked increase in PC groups. In juvenile myocardial infarction PC groups were higher than in controls; there was no difference between STEMI and NSTEMI and their concentration was unaffected by the number of cardiovascular risk factors or stenosed coronary vessels. Show more

Keywords: Oxidative stress, arterial hypertension, metabolic syndrome, juvenile myocardial infarction, chronic kidney failure

DOI: 10.3233/CH-190689

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 2019

Authors: Liang, Ming | Ou, Bing | Wu, Jiayi | Xiao, Xiaoyun | Ruan, Jingliang | Tian, Jing | Xu, Xiaolin | Wang, Bin | Yang, Haiyun | Luo, Baoming

Article Type: Research Article

Abstract: OBJECTIVE: To evaluate the combined use of strain elastography (SE) and superb microvascular imaging (SMI) with grayscale ultrasound (US) according to the Breast Imaging Reporting and Data System (BI-RADS) classification for differentiating benign from malignant breast masses. METHODS: In total, 166 patients with 177 breast masses categorized as BI-RADS 3–5 were included in the study between April 2016 to September 2017. US, SMI and SE were performed to evaluate each mass. The following outcome measures were compared between US and the combinations of US, SMI, and SE: area under the receiver operating characteristic curve (AUC), sensitivity, specificity. …RESULTS: The addition of SMI and SE to US increased the AUC from 0.816 to 0.948 (P  < .001); and the specificity from 43.7% to 80.8% (P  < .001), without a significant decrease in the sensitivity. Meanwhile, 66.1% (37 of 56) of the benign masses that were indicated for unnecessary biopsy were correctly changed to follow-up. CONCLUSIONS: The addition SMI and SE to US could improve the diagnostic performance in differentiating benign from malignant breast masses compared to US alone. When US was combined with SMI and SE, the specificity were increased, thus significantly reducing unnecessary biopsies. Show more

Keywords: Breast cancer, superb microvascular imaging, strain elastography, ultrasonography

DOI: 10.3233/CH-190693

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2019

Authors: Gao, Yan | Zhu, Xiaolong | Huang, Lining | Teng, Jinliang | Li, Fulong

Article Type: Research Article

Abstract: OBJECTIVE: This study aimed to investigate the effects of dexmedetomidine on cerebral oxygen saturation [Sct(O2 )] and postoperative cognitive function in elderly patients undergoing minimally invasive coronary artery bypass graft surgery. METHODS: Sixty elderly patients who received minimally invasive coronary artery bypass graft surgery were randomly equally divided into dexmedetomidine group (group D) and control group (group N). The patients in group D were pumped with 1 μg/kg dexmedetomidine for 15 min before incision, followed by continuous pumping at 0.3–0.5 μg/(kg·h) till the end of the operation. The patients in group N received same dose of normal saline during …the operation. Sct(O2 ) was monitored at pre-induction (T0), post-induction (T1), 30 min (T2) after single-lung ventilation, and after surgery (T3). Mini-mental state examination (MMSE) was used to assess the cognitive function at 1 day before, 72 hour and 7 days after surgery. RESULTS: Sct(O2 ) level in group D was significantly higher than that in group N at T2 (P  < 0.05). Sct(O2 ) level was statistically lower at T2 than that at T0, T1 and T3 in the same group N (P  < 0.05). At 72 h and 7d after operation, the incidence of cognitive dysfunction in group D was markedly lower than that in group N (P  < 0.05), the MMSE score in group D was markedly higher than those in group N, but was significantly lower than that before surgery (P  < 0.05). CONCLUSION: Dexmedetomidine can alleviate the decrease of Sct(O2 ) during single-lung ventilation, improve postoperative cognitive function, and reduce the incidence of POCD in elderly patients with minimally invasive coronary artery bypass surgery. Show more

Keywords: Dexmedetomidine, minimally invasive coronary artery bypass surgery, elderly, cognitive dysfunction

DOI: 10.3233/CH-190590

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2019

Authors: Zhu, Jing | kang, Jing | Li, Xiaochen | Wang, Mengmei | Shang, Min | Luo, Yuchuan | Xiong, Mengqing | Hu, Ke

Article Type: Research Article

Abstract: BACKGROUND AND AIM: Both chronic intermittent hypoxia (CIH) and chronic continuous hypoxia (CCH) are risk factors for cardiovascular disease, which are associated with cardiac systolic function and associated with dysfunction of endothelia and coagulation-fibrinolysis system in the vasculature. However, the different effects of these two hypoxic models are not fully understood. In our study, we systemically compared the effects of CIH and CCH on cardiac function and related factor levels in serum using rat model. METHODS: Forty-five male Sprague-Dawley rats were randomly divided into the normoxia control (NC), CIH and CCH groups. The rat CIH and CCH models …were established, then the blood and tissue samples were collected to analyze the function of endothelium and the coagulation-fibrinolysis system. Also, the ultrasound cardiogram was performed to directly assess myocardial contractility. RESULTS: Both CIH and CCH significantly decreased the NO, eNOS, P-eNOS and AT-III levels in the rat serum but significantly increased the levels of ET-1, vWF, COX-2, NF-κ B, FIB, FVIII and PAI-1 in the rat serum (P  < 0.05). The expression of ET-1, VWF and ICAM-1 in CIH group were higher than CCH group (P  < 0.05), however, the expression of CD62p was increased in CCH group but not in CIH group. The expression of t-PA in CIH group were lower than CCH group (P  < 0.05), but there were no significant differences in CCH group and NC group (P  > 0.05). Using transmission electron microscope, we found that the mitochondrial ultrastructure of thoracic aorta endothelial cells in CIH and CCH group were damaged. Moreover, the myocardial contractility in CIH and CCH group were significantly decreased compared with NC group. CONCLUSION: Our results suggested that CIH and CCH could cause endothelial dysfunction, dysfunction of the coagulation-fibrinolysis system and decreasing of myocardial contractility. Compared with CCH, CIH has greater effect on vasoconstriction and adhesion of vascular endothelial cells, and stronger procoagulant effect. Show more

Keywords: Chronic intermittent hypoxia, chronic continuous hypoxia, vascular endothelial function, myocardial contractility

DOI: 10.3233/CH-190706

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

Authors: Sun, Xianlei | Tung, Wingtai | Zou, Jie | Wang, Weiwei | Kratz, Karl | Ma, Nan | Lendlein, Andreas

Article Type: Research Article

Abstract: BACKGROUND: The behavior of endothelial cell is remarkably influenced by the physical and biochemical signals from their surrounding microenvironments. OBJECTIVE: Here, the elasticity of fiber meshes was studied as a design parameter of substrates for endothelial cells in order to modulate angiogenesis. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured on electrospun fiber meshes made from polyetheresterurethane (PEEU), differing in their elasticity. Cell morphology, proliferation, migration and angiogenesis of endothelial cells on the degradable substrates meshes were characterized. RESULTS: The aspect ratio of HUVECs cultured on the fiber meshes from PEEU materials increased …with increasing stiffness of the materials. HUVECs cultured on fiber meshes with high stiffness (Young’s modulus E  = 4.5±0.8 MPa) presented a higher proliferation rate and significantly faster migration velocity, as well as higher tube formation capability than the cells cultured on fiber meshes with low stiffness (E  = 2.6±0.8 MPa). CONCLUSIONS: These results suggested that tuning the fiber meshes’ elasticity might be a potential strategy for modulating of the formation or regeneration of blood vessels. Show more

Keywords: Tensile E-modulus, HUVECs, electrospun fiber meshes, multiblock copolymers

DOI: 10.3233/CH-190696

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

Authors: Qiu, Yijie | Yang, Daohui | Zhang, Qi | Chen, Kailing | Dong, Yi | Wang, WenPing

Article Type: Research Article

Abstract: OBJECTIVE: To evaluate the feasibility of vector flow imaging technique (V Flow) in measurement of wall shear stress (WSS) of common carotid arteries (CCA) in healthy adults and to provide the normal WSS values assessed by V Flow. METHODS & MATERIALS: This prospective study was approved by the Ethics Committee of our University. Eighty healthy adult volunteers were included (mean age 43.3 y, 47 females, 33 males). The volunteers were classified into three groups according to their age: group I (age 20 - 39 y), group II (age 40 - 59 y) and group III (age 60 - …80 y). Mindray Resona 8 ultrasound machine and a linear array transducer (3–9 MHz) was used, equipped with the updated V Flow function. Common carotid arteries of both sides were evaluated in three segments (initial segment, middle segment and near bifurcation segment). The WSS values of CCA were measured by two independent radiologists. The intraclass correlation coefficient (ICC) of observer reliability in WSS measurement was calculated. Inter-observer reproducibility was also evaluated with the 95% Bland-Altman limits of agreement (LOA). RESULTS: V Flow measurements were performed successfully in 79 volunteers (98.8 %, 79/80). The mean value of WSS in right CCA was (0.66±0.24) Pa, in left CCA was (0.66±0.18) Pa (P  > 0.05). Mean WSS value had a moderately negative correlation with age group (P  < 0.05). The mean WSS value of group I(mean±SD, 0.75±0.25 Pa) is larger than group II (mean±SD, 0.62±0.13 Pa) and group III (mean±SD, 0.49±0.11 Pa) (P  < 0.05). The ICC of observer reliability of group I, II and III was 0.96 (95% confidence interval (95% CI) 0.92–0.98), 0.94 (95% CI 0.88–0.97), 0.93 (95% CI 0.76–0.98) respectively. The Bland-Altman plots showed that the 95% LOA were –0.17–0.12 (Pa) for group I, –0.09–0.13 (Pa) for group II and –0.08–0.10 (Pa) for group III. CONCLUSION: V Flow measurement is a simple, rapid and feasible imaging method for the WSS assessment of CCA in healthy volunteers, which will probably be an important tool for assessing CCA function. Show more

Keywords: Vector flow imaging (V Flow), wall shear stress (WSS), common carotid artery (CCA), feasibility, normal value

DOI: 10.3233/CH-190719

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2019

Authors: Kiss, Rudolf | Farkas, Nelli | Jancso, Gabor | Kovacs, Krisztina | Lenard, Laszlo

Article Type: Research Article

Abstract: INTRODUCTION: With the aging of the population, the screening of frail patients, especially before high-risk surgery, come to the fore. The background of the frail state is not totally clear, most likely inflammatory processes are involved in the development. METHODS: Our survey of patients over age of 65 who were on cardiac surgery were performed with Edmonton Frail Scale (EFS). Patients’ demographic, perioperative data, incidence of complications and correlations of inflammatory laboratory parameters were studied with the severity of the frail state. RESULTS: On the basis of EFS, 313 patients were divided into non-frail (NF,163,52%), pre-frail …(PF,89,28.5%) and frail (F,61,19.5%) groups. Number of complications in the three groups were different (NF:0.67/patient, PF:0.76/patient, F:1.08/patient). We showed significant difference between NF and F in both intensive care and hospital stay, but there was no statistical difference between the groups in hospital deaths (NF:5/163, PF:3/89, F:5/61). We also found a significant difference between NF and F patients in preoperative fibrinogen-, CRP- and white blood cell count levels. CONCLUSIONS: We first present the incidence of frailty in patients with heart surgery in a Central-European population. According to our results, inflammatory processes are likely to play a role in the development of the frail state. Show more

Keywords: Frailty, frail state, CRP, fibrinogen, cardiac surgery

DOI: 10.3233/CH-190681

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2019

Authors: Zhang, Shupin | Wan, Jing | Wu, Rong | Fang, Ya

Article Type: Research Article

Abstract: OBJECTIVE: To evaluate the efficacies of conventional ultrasound (US), US elasticity imaging (EI), and acoustic radiation force impulse (ARFI) elastography in breast malignancy diagnosis. METHODS: We included 315 women (mean age, 44 years; range, 18–81 years) with 336 pathologically proven breast lesions in this retrospective study. All lesions underwent conventional US, EI, and ARFI (including virtual touch tissue imaging [VTI], virtual touch tissue quantification [VTQ], and virtual touch tissue imaging and quantification [VTIQ]) elastography. Multivariate logistic regression analysis was performed to assess 12 independent variables for malignancy prediction. Diagnostic performance was evaluated with receiver operating characteristic (ROC) curve …analysis. RESULTS: Irregular lesion shape was the strongest independent predictor for breast malignancy, followed by poorly defined margins, taller than wide dimensions, posterior echo attention, VTIQ, and VTI boundaries (P  < 0.05). Area under the ROC curve (AUC) for VTIQ was higher than other significant independent variables. With the best cut-off value of 3.74 m/s, the AUC, sensitivity, and specificity were 0.93 (95% CI: 0.90, 0.96), 90.1%, and 91.1%, respectively. CONCLUSIONS: ARFI elastography is a promising method in breast malignancy prediction, with good diagnostic performance. For patients requiring surgery, the combination of various methods can provide better diagnostic results and may help to reduce unnecessary biopsy or surgery. Show more

DOI: 10.3233/CH-180527

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2019

Authors: Astapenko, David | Ticha, Alena | Tomasova, Adela | Hyspler, Radomir | Zadak, Zdenek | Lehmann, Christian | Cerny, Vladimir

Article Type: Research Article

Abstract: BACKGROUND: Endothelial glycocalyx (EG) is a carbohydrate-rich gel-like mesh covering the apical surface of endothelial cells. It has been linked to the microvascular pathophysiology and tissue metabolism. However, little is known about its condition in young healthy adults. OBJECTIVE: We aimed to describe the condition of EG in young healthy adults by in vivo EG imaging and measurement of syndecan-1, a plasma marker of EG integrity in order to obtain references values. METHODS: For in vivo EG studies we used Side-stream Dark Field imaging of the sublingual microcirculation. Recordings were analysed automatically by GlycoCheck …software providing the Perfused Boundary Region (PBR) as a marker of EG thickness. Levels of syndecan-1 were analysed in plasma samples by ELISA. RESULTS: 21 volunteers were included in the study. Median of the PBR value was 1.82 μm (interquartile range 1.69–2.01, 95% CI 1.79–1.97). Median concentration of syndecan-1 was 0.3 ng/ml (interquartile range 0.23–0.39, 95% CI 0.27–0.49). CONCLUSION: This study provides a comparison for cohorts of patients with a particular disease where the EG is presumably damaged. Our findings do not entirely comply with already published data in healthy individuals. Show more

Keywords: Endothelial glycocalyx, syndecan-1, healthy volunteers

DOI: 10.3233/CH-190581

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2019

Authors: Wu, Qiong | Li, Yi | Liu, Yilun | Shen, Jian | Wang, Yan | Yi, Xiaolei | Hu, Bing

Article Type: Research Article

Abstract: PURPOSE: The aim of this study was to evaluate the diagnostic value of conventional sonography and ultrasound elastography for thyroid nodules of each Bethesda category and to analyze their potential role in the corresponding management decision. METHODS: This retrospective study included 557 thyroid nodules diagnosed by conventional ultrasound (US) and real-time ultrasound elastography (RTE) before fine-needle aspiration (FNA) from 458 patients. The US, RTE, and cytological results were collected and analyzed according to different Bethesda categories. Differences in the distribution of sonographic features between groups were evaluated by the Chi-square test or Fisher exact test. The sensitivity, specificity, …positive predictive value, negative predictive value, and accuracy of conventional US and RTE for the diagnosis of malignant nodules in each category were then calculated and analyzed. RESULTS: The diagnostic accuracy of the comprehensive US diagnosis in all categories stayed at a relatively high level from 78.4% to 88.6%, and good specificities ranging from 77.3% to 100% were revealed in all Bethesda categories. As to RTE, the diagnostic accuracies in categories I–IV stayed at a relatively low level ranging from 44.6% to 65.6% except for better performance in categories V and VI (85.2%, 89.1%). Besides, the accuracies of comprehensive US (85.2%, 88.6%) and RTE (85.2%, 89.1%) is relatively low compared to the corresponding cytological diagnoses in categories V and VI. CONCLUSIONS: Conventional US is complementary to FNA for providing additional hints especially in categories I–IV for further clinical managements, while RTE failed to provide useful diagnostic information in general. Show more

Keywords: Thyroid nodules, fine-needle aspiration, conventional US, real-time ultrasound elastography, Bethesda category

DOI: 10.3233/CH-180533

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Shi, You-Zhen | Jin, Yan | Zheng, Li

Article Type: Research Article

Abstract: OBJECTIVES: To identify the associated factors for malignancy in partially cystic thyroid nodules (PCTNs) on ultrasound (US). MATERIALS AND METHODS: This is a retrospective study. 338 PCTNs confirmed by surgery was included in this study. The US features of the nodules were reviewed and their significance in differential diagnosis was analyzed. RESULTS: In the 338 PCTNs, 50 were malignant and 288 were benign. Univariate analyses revealed that a taller-than-wide shape and spiculated or microlobulated margin were significantly associated with malignancy while the spongy form, an ovoid to round shape and smooth margin were significantly associated with …benign nature. In terms of the internal solid portion of the nodule, eccentric configuration, non-smooth margin, hypoechogenicity, and microcalcification were more frequently demonstrated in malignant nodules than in benign ones. In the multivariate logistic regression analysis, a taller than wide shape (OR: 13.357; 95% CIs: 3.457–28.797) was revealed to be the strongest independent predictor for malignancy, followed by microcalcification (OR: 11.578; 95% CIs: 3.142–29.563), spiculated or microlobulated margin (OR: 6.331; 95% CIs: 1.425–9.457), eccentric configuration (OR: 5.456; 95% CIs: 1.358–8.774), non-smooth rim of the internal solid portion (OR: 4.897; 95% CIs: 0.754–7.021), and hypoechogenicity of the internal solid portion (OR: 4.651; 95% CIs: 0.712–8.245). CONCLUSIONS: Understanding the ultrasound characteristics of malignant PCTNs is important to make a precise diagnosis of thyroid nodules. Show more

Keywords: Partially cystic thyroid nodules, conventional ultrasound

DOI: 10.3233/CH-190582

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2019

Authors: Auer, Timo Alexander | Fischer, Thomas | Garcia, Stephan Rodrigo Marticorena | Penzkofer, Tobias | Jung, Ernst-Michael | Hamm, Bernd | Lerchbaumer, Markus Herbert

Article Type: Research Article

Abstract: BACKGROUND: Contrast-enhanced ultrasound (CEUS) has been used as an additional imaging technique in order to evaluate focal liver lesions. CEUS is easy and fast to perform, overcomes the limitations of B-mode US. OBJECTIVE: To evaluate the diagnostic potential of contrast-enhanced ultrasound (CEUS) in focal liver lesions (FLL) with unclear findings on computed tomography (CT) or magnetic resonance imaging (MRI). METHODS: In this single-center retrospective study, 146 patients with at least one FLL underwent additional CEUS of the liver to clarify inconclusive cross-sectional imaging findings. Ultrasonography was performed using B-mode imaging and CEUS after injection of sulphur …hexafluoride microbubbles (second-generation contrast agent) within two months after ceMRI or ceCT and interpreted by an experienced radiologist (EFSUMB level 3). Histopathological reports, long-term follow-up or clinical course served as reference standard. RESULTS: Thirty-eight of the 146 patients had malignant and 108 benign FLL. Overall, CEUS had 92% sensitivity (95% -CI, 79–97) and 98% specificity (95% -CI, 93–99) with an AUC of 0.95 in correctly characterizing the lesion as malignant or benign. Sensitivity increased to 98% (95% -CI, 96–100) for benign lesions and decreased to 92% (95% -CI, 78–98) for malignant lesions. CEUS showed the highest diagnostical accuracy in lesion <1 cm with an AUC of 1.000, while the lowest accuracy was achieved in lesions >2 cm with an AUC of 0.924 due to a decreasing specificity of 86% (95% -CI, 87–100). CONCLUSION: CEUS correctly distinguished malignant from benign FLL in cases with inconclusive cross-sectional imaging findings and achieved high levels of diagnostic accuracy. CEUS has added diagnostic value especially in small lesions ≤1 cm while specificity remains limited in larger lesions. Show more

Keywords: CEUS, focal liver lesions, sonography, contrast-enhanced ultrasound, liver ultrasound

DOI: 10.3233/CH-190718

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2019

Authors: Bakker, Nathalie | Schoorl, Marianne | Stoutjesdijk, Eline | Houdijk, Alexander P.J.

Article Type: Research Article

Abstract: BACKGROUND: An adequate erythrocyte function is vital for tissue oxygenation and wound healing. The erythrocyte membrane phospholipid composition plays an important role in erythrocyte function and administration of omega-3 fatty acids may provide a means to improve it. OBJECTIVE: To investigate peri-operative erythrocyte function and effects of omega-3 fatty acids METHODS: Forty-four patients undergoing elective laparoscopic colon resection for non-metastasized cancer were randomized between intravenous omega-3 poly-unsaturated fatty acids (n-3 PUFAs) or placebo (saline). Peri-operative blood samples were analyzed with a Lorrca MaxSIS Ektacytometer and erythrocyte membrane phospholipids were determined with gas chromatography. RESULTS: …Patient and operation characteristics were equal between groups. There was a significant increase in erythrocyte membrane eicosapentaenoic acid (EPA) but not docosahexaenoic acid (DHA) in the n-PUFA group. There were no significant differences in erythrocyte deformability but the aggregation index (AI) was significantly lower and the aggregation half time (T½) was significantly higher in the n-3 PUFA group. CONCLUSION: This study confirms rapid changes in erythrocyte membrane phospholipid composition after administration of intravenous n-3 PUFAs. Erythrocyte deformability parameters were not affected but erythrocyte aggregability was decreased in the n-3 PUFA group. Further investigation is necessary to gain more insights in the effects of n-3 PUFA and the postoperative inflammatory response on erythrocyte function. Show more

Keywords: Erythrocytes, deformability, aggregability, colon cancer surgery, omega-3 fatty acids

DOI: 10.3233/CH-190687

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

Authors: Ding, Xiaohu | Lu, Lin | Yang, Jing | Chen, Yijiao | Ma, Jin

Article Type: Research Article

Abstract: PURPOSE: To explore the peripapillary capillary density distribution and its correlation with nerve fibre layer in superficial and deep retinal layers of healthy Chinese. METHODS: Images of superficial and deep retinal capillary networks were obtained by optical coherence tomography angiography (OCTA) using a CIRRUS TM HD-OCT Model 5000 system and analyzed by Image-Pro Plus (Medical Cybernetics, Version 6.0). Peripapillary capillary density was defined as the mean optical density of the annular region between two concentric circles of 3.085 mm and 3.835 mm diameter. Parafoveal capillary density was defined as the mean optical density between the foveal avascular zone (FAZ) boarder …and a 2.5 mm diameter circle. Retinal nerve fibre layer (RNFL) thickness was also measured and the correlation with capillary density determined. RESULTS: Mean peripapillary capillary density was 4.16±1.06 in the superficial and 2.92±0.80 in the deep layer. Corresponding mean parafoveal densities were 2.65±0.55 and 2.51±0.55. Capillary densities were higher in the superficial layer of all quadrants for both peripapillary and parafoveal regions (P  <  0.001). A significant correlation between peripapillary capillary density and RNFL thickness was found in the superficial layer (r  = 0.305, P  <  0.05). A negative correlation between age and capillary density was found in both peripapillary and parafoveal regions (P  <  0.001). CONCLUSIONS: Peripapillary capillary density in the superficial layer highly correlated with RNFL thickness. Regional and age-related differences in peripapillary and parafoveal capillary density should be considered when diagnosing and monitoring individuals with diseases affecting retinal capillary density. Show more

Keywords: Capillary density, Optical coherence tomography angiography (OCTA) angiogram, Retinal nerve fibre layer

DOI: 10.3233/CH-180453

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2019

Authors: Koch, Christoph | Taeger, Christian | Geis, Sebastian | Lonic, Daniel | Heidekrueger, Paul | Dolderer, Juergen | Bitzinger, Diane | Hirche, Christoph | Prantl, Lukas | Kehrer, Andreas

Article Type: Research Article

Abstract: BACKGROUND: Purpura fulminans (PF) is a distinct form of rare meningococcal septicaemia mostly in childhood which is characterized by high lethality, extensive necroses and mutilations of extremities. Other ethiologies are idiopathic forms or purpura neonatorum, which is marked by deficiency of Protein-C. PF is caused by micro-embolism of the vascular system, followed by quickly spreading necroses of skin and different organs. Modern concepts of intensive care treatment of the acute phase of this disease and early surgical intervention lead to a rising number of surviving patients requiring limb salvage. Aim of this study is to evaluate a possible lower morbidity …and the grade of lower loss of function because of early surgical intervention. PATIENTS AND METHODS: Between the years 1998 and 2017 cases of PF at two large centers for critical wound care, the department of plastic-, hand- and reconstructive surgery of the university hospital of Regensburg and the department of plastic-, hand- and reconstructive surgery of the BG-clinic Ludwigshafen patients were included into our study. We retrospectively examined patients with PF who were stabilized by intensive care medicine and received surgical interventions. After survival of the acute phase (10 days), patients received plastic surgical reconstructions. RESULTS: A total number of eight patients could be included into our study. All patients survived the initial phase (10 days). All patients required plastic-surgical interventions to address extensive skin and soft tissue defects. Flap operations were judged necessary in five cases. Hereby four defects could be reconstructed by free tissue transfer, one with a local flap. Flap survival was 100 percent. One flap required revision of the arterial anastomosis of the flap arteria. Another flap got partial necrosis. One patient died due to multiorgan failure. Early debridements with consequent fasciotomies and secondary plastic-surgical reconstruction achieved good functional results. Limb salvage was accomplished in three patients. One patient died due to fulminant progress of the disease. CONCLUSION: Management of PF requires a multidisciplinary approach and close communication between the different subspecialties. Early debridements with consequent fasciotomies showed good results in salvaging subfascial muscle tissue in the extremities with satisfying functional results. Early surgical intervention is an important factor for improved limb salvage and survival. Show more

Keywords: Purpura fulminans, symptoms, surgical management, intensive care management, Idiopathic Thrombocytopenic Purpura, Disseminated Intravascular Coagulation, Acquired Protein C Deficiency, Sepsis, Neisseria meningitidis, Menigococcal sepsis, streptococcus pyogenes, herpes simplex virus

DOI: 10.3233/CH-190588

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Yi, Dong | Benhua, Xu | Qiong, Cao | Qi, Zhang | Yijie, Qiu | Daohui, Yang | Lingyun, Yu | Wen-Ping, Wang

Article Type: Research Article

Abstract: AIM: To investigate the value of contrast enhanced ultrasound with high resolution linear transducers (HF-CEUS) for differential diagnosis of focal fundal gallbladder (GB) wall thickening. METHODS: A total of 32 patients with incidentally detected focal fundal GB wall thickening were included. After conventional B mode ultrasound (BMUS) examinations, HF-CEUS were performed with a 7.5–12 MHz 9L4 linear transducer (S2000 HELX OXANA unit, Siemens). Two radiologists independently reviewed the HF-CEUS enhancement patterns to determine the differential features between malignancy and benignity with a five-point confidence scale. The diagnostic accuracy of BMUS and HF-CEUS for GB wall thickening was compared. The …final gold standard was surgery with histological examination. RESULTS: Final diagnoses included GB adenocarcinoma (n  = 16), adenomyomatosis (n  = 12), Xanthogranulomatous (n  = 2) and cholecystitis (n  = 2). HF-CEUS features associated with GB adenocarcinoma including arterial phase inhomogeneous hyperenhancement, venous phase hypoenhancement and disruption of GB wall layer structure (P  <  0.05). Two small (5 mm) liver metastasis were confirmed by HF-CEUS during the late phase liver sweep as hypoenhanced lesions. Nonenhanced Rokitansky-Aschoff sinuses were clearly observed in 83.3% focal adenomyomatosis. Overall sensitivity, specificity and accuracy for differentiation between malignant and benign focal fundal GB wall thickening of HF-CEUS and BMUS were 84.3% vs 53.1%, 90.6% vs 59.3% and 87.5% vs 56.2% (P  <  0.005). CONCLUSIONS: CEUS performed with high frequency linear transducers could be a useful alternative in the differential diagnosis of focal fundal GB wall thickening on conventional ultrasound. Show more

Keywords: Gallbladder, contrast enhanced ultrasound (CEUS), linear transducer, differential diagnosis, focal wall thickening

DOI: 10.3233/CH-190697

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

Authors: Wang, S. | Li, B. | Yin, T. | Hong, J. | Gu, J. | Wei, L.

Article Type: Research Article

Abstract: BACKGROUND: The aneurysmal subarachnoid hemorrhage (aSAH) is an acute severe hemorrhagic stroke with high morbidity and mortality with poor prognosis. OBJECTIVE: This study aims to analyze the changes of cerebral venous circulation in patients with aneurysmal subarachnoid hemorrhage by digital subtraction angiography (DSA). MATERIALS AND METHODS: Totally, 57 patients with aSAH, 48 patients with unruptured aneurysms, and 45 patients without aneurysms (control group) were enrolled. The microvascular cerebral circulation time (mCCT), venous cerebral circulation time (vCCT), cerebral arterioles and cortical veins were analyzed by DSA. RESULTS: There were changes of cerebral microvessels and cortical …veins in patients with aSAH. The mCCT (6.15±1.37 s) and vCCT (2.79±0.34 s) of aSAH patients significantly increased compared with control patients (3.74±0.50 s; 2.64±0.32 s) (P  <  0.05). However, the mCCT increased more compared with vCCT in aSAH patients (P  <  0.001), while the vCCT increased more compared with mCCT in severe aSAH cases (P  <  0.01). There was no significant difference in mCCT and vCCT between patients with unruptured aneurysms and controls (P  = 0.131; P  = 0.621). CONCLUSIONS: The mCCT increases in acute aSAH patients within 72 hours and vCCT increases in severe aSAH cases. Show more

Keywords: Aneurysmal subarachnoid hemorrhage, cerebral vein, digital subtraction angiography, microvascular cerebral circulation time, venous cerebral circulation time

DOI: 10.3233/CH-190573

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Chayer, Boris | Allard, Louise | Qin, Zhao | Garcia-Duitama, Julian | Roger, Laurence | Destrempes, François | Cailhier, Jean-François | Denault, André | Cloutier, Guy

Article Type: Research Article

Abstract: BACKGROUND: An enhanced inflammatory response is a trigger to the production of blood macromolecules involved in abnormally high levels of erythrocyte aggregation. OBJECTIVE: This study aimed at demonstrating for the first time the clinical feasibility of a non-invasive ultrasound-based erythrocyte aggregation quantitative measurement method for potential application in critical care medicine. METHODS: Erythrocyte aggregation was evaluated using modeling of the backscatter coefficient with the Structure Factor Size and Attenuation Estimator (SFSAE). SFSAE spectral parameters W (packing factor) and D (mean aggregate diameter) were measured within the antebrachial vein of the forearm and tibial vein …of the leg in 50 healthy participants at natural flow and reduced flow controlled by a pressurized bracelet. Blood samples were also collected to measure erythrocyte aggregation ex vivo with an erythroaggregometer (parameter S 10 ). RESULTS: W and D in vivo measurements were positively correlated with the ex vivo S 10 index for both measurement sites and shear rates (correlations between 0.35–0.81, p  <  0.05). Measurement at low shear rate was found to increase the sensitivity and reliability of this non-invasive measurement method. CONCLUSIONS: We behold that the SFSAE method presents systemic measures of the erythrocyte aggregation level, since results on upper and lower limbs were highly correlated. Show more

Keywords: Erythrocyte aggregation, quantitative ultrasound, shear rate control, human, clinical measurements

DOI: 10.3233/CH-180541

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-18, 2019

Authors: Li, Guanhua | Zhang, Yu | Tang, Wei | Zheng, Junmeng

Article Type: Research Article

Abstract: BACKGROUND: Polyamidoamine (PAMAM) dendrimers have been investigated for decades and currently applied in various areas throughout nanomedicine, including gene therapy, drug delivery, anti-bacteria and imaging. It is therefore necessary to assess cytotoxicity of PAMAM dendrimers systematically. Because blood components are usually the initial step of contact with any therapeutic agent, comprehensive hemocompatibility study is needed. MATERIAL S AND METHODS: The triblock dendrimer: polyamidoamine-polyethylene glycol-cyclic RGD (PAMAM-PEG-cRGD), was successfully synthesized. Various in vitro assays to characterize hemocompatibility of both PAMAM (Generation 4.0) and PAMAM-PEG-cRGD were performed, including hemolytic assay, platelet activation examination, platelet counting, assessment of coagulating pathways …and evaluation of complement system activation. RESULTS: The hemolytic ratio of PAMAM-PEG-cRGD maintained below 5%. Surface engineering of PEG and cRGD to PAMAM attenuated hemolysis and RBC aggregation as compared with unmodified PAMAM. PAMAM (Generation 4.0) reduced platelet counting in a dose-dependent manner, and the platelet number dropped dramatically at a relatively low incubating dose (1 μ M). Such surface modifications also alleviated platelet activation and platelet reduction mediated by PAMAM polycationicity. Finally, high concentration (10μ M) of PAMAM interfered the coagulation system, prolonging prothrombin time significantly. CONCLUSION: Surface modification of PEG and cRGD to PAMAM (Generation 4.0) improves hemocompatibility. Introduction of PEG and cRGD significantly mitigates hemolytic and RBC aggregation effects as compared with unmodified PAMAM. Similarly, these modifications alleviate platelet activation and platelet reduction mediated by PAMAM polycationicity. Show more

Keywords: Polyamidoamine (PAMAM), dendrimer, nanoparticle, hemocompatibility, surface modification

DOI: 10.3233/CH-190641

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2019

Authors: Raberin, Antoine | Nader, Elie | Ayerbe, Jorge Lopez | Mucci, Patrick | Connes, Philippe | Durand, Fabienne

Article Type: Research Article

Abstract: Blood rheology and hemodynamic parameters have never been explored together during acclimatization to altitude. This study aimed to investigate changes in blood rheology parameters and pulmonary hemodynamics during the first days of real moderate altitude exposure. Seventeen athletes were tested at sea-level, 20 hours after their arrival at 2,400 meters of altitude (H1) and five days later (H2). Blood was sampled to analyze red blood cell (RBC) aggregation, blood viscosity and hematocrit. Pulmonary arterial pressure (PAP), pulmonary capillary pressure (Pcap) and pulmonary vascular resistance (PVR) were assessed by echocardiography. We observed a rise in hematocrit, blood viscosity, RBC …aggregation, PAP, Pcap and PVR between sea-level and H1. In H2, RBC aggregation, hematocrit, PAP, Pcap and PVR remained different compared to SL and no difference was observed between H1 and H2. Blood viscosity decreased in H2 and returned to sea-level values. Our results suggest that hemoconcentration occurring within the first hours of altitude exposure increased blood viscosity, which contributed to the changes in pulmonary hemodynamic. When blood viscosity decreased in H2, no change occurred in pulmonary hemodynamic parameters suggesting that hypoxic pulmonary vasoconstriction was still present. The elevated RBC aggregation observed after in H2 could participate in the increase of Pcap. Show more

Keywords: Moderate altitude, pulmonary arterial pressure, pulmonary vascular resistance, blood viscosity, red blood cell aggregation

DOI: 10.3233/CH-190671

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2019

Authors: Xie, Juan

Article Type: Research Article

Abstract: PURPOSE: To evaluate the diagnostic value of quantitative shear wave elastography (SWE) for the differential diagnosis of solid pancreatic tumors. MATERIALS AND METHODS: A total of 66 solid pancreatic masses were enrolled in this study and all the lesions underwent quantitative SWE. The stiffness of the masses was expressed in shear wave velocity (SWV, m/s). The receiver operating characteristic (ROC) curve was plotted to assess the diagnostic performance of quantitative SWE. The optimal cutoff value for SWV in the differentiation of benign from malignant masses was determined. RESULTS: The final diagnoses were 26 benign and 40 …malignant masses. The SWVs were statistically higher for pancreatic malignant masses compared with those for benign masses (3.30±1.22 m/s versus 1.31±0.64 m/s; P  <  0.001). The area under the curve (AUC, 0.93) was obtained. When the best cut-off point was 1.77 m/s, the accuracy, sensitivity, and specificity were 92.4%, 90.0%, and 96.2%, respectively. CONCLUSIONS: Quantitative SWE is a novel technique that can be considered as a quantitative and objective diagnostic tool for prediction of pancreas malignancy. Show more

Keywords: Elasticity imaging techniques, pancreatic neoplasms, ultrasonography

DOI: 10.3233/CH-190665

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2019

Authors: Wang, Yali | Wu, Feng | Hu, Feng | Wu, Yunjiang | Zhou, Jun | Xu, Yan | Shao, Xiangrong | Hu, Tao

Article Type: Research Article

Abstract: Drag-reducing polymers (DRPs) was previously demonstrated to increase blood flow, tissue perfusion, and reduce vascular resistance. The purpose of this study was to investigate the effect of DRPs on pulmonary vascular remodeling and right ventricular dysfunction in a rat model of chronic hypoxia-induced pulmonary hypertension (HPH). A total of forty male Wistar rats were randomly and equally assigned into four experimental groups (Group I: normoxia + saline, Group II: normoxia + PEO, Group III: hypoxia + saline, Group IV: hypoxia + PEO) and maintained in normoxia (21% O2 ) or hypobaric hypoxia (10% O2 ). After four weeks, comparisons were …made of the following aspects: the mean pulmonary arterial pressure (mPAP), right ventricular systolic pressure (RVSP), right ventricular hypertrophy, wall thickness of pulmonary trunk and arteries, internal diameter of pulmonary arteries, cardiomyocyte cross-sectional area (CM CSA), and ultrastructure of right ventricular. Treatment with PEO in Group IV attenuated the increases in RVSP and mPAP (40.5±7.2 and 34.7±7.0 mmHg, respectively, both P  <  0.05), compared with Group III. Distal vascular remodeling was visible as a significant increase in medial wall thickness (64.2±12.3% vs. 43.95±7.0%, P  <  0.01) and a remarkable decrease in internal diameter of small pulmonary arteries (35.2±9.7μ m vs. 50.4±14.7μ m, P  <  0.01) in Group III, to a greater extent than that detected in Group IV. Nevertheless, no significant histopathological differences in medial wall thickness was observed in pulmonary trunk between Group III and Group IV (P  >  0.05), denoting that PEO chiefly attenuated the remodeling of small pulmonary arteries rather than main arteries in hypoxic environment. Infusion of DRPs (intravenous injection twice weekly) also attenuated the index of right ventricular hypertrophy, protected against the increase of cardiomyocyte cross-sectional area, and provided protection for cardiac ultrastructure. DRP treatment with intravenous injection elicited a protective effect against pulmonary vascular remodeling and right ventricular dysfunction in the rat model of HPH. DRPs may offer a new potential approach for the treatment of HPH, which may have theoretical significance and application value to society. Show more

Keywords: Drag-reducing polymers, vascular remodeling, right ventricular, chronic hypoxia, pulmonary hypertension

DOI: 10.3233/CH-190668

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Sirufo, Maria Maddalena | Ginaldi, Lia | de Martinis, Massimo

Article Type: Research Article

Abstract: Volleyball players are exposed to the possibility of several well recognized injuries, among which microvascular abnormalities are the less described and studied, although they could diminish their ability and performance. Capillaroscopy is a simple, non-invasive method to diagnose vascular abnormalities in athletes suffering for the consequences of repeated application of pressure by local trauma on the fingertips. The detected capillaroscopic picture will be the base for the follow-up and will indicate the possible need for further investigations aimed at excluding other occulted conditions. At our knowledge, this is the first report describing and documenting the related microvascular abnormalities in a …volleyball player. This case emphasizes the fact that volleyball players among other athletes, whose hands are exposed to repeated fingertips trauma may suffer from microcirculation damage, for which reason they should be able to access an effective health surveillance program able to detect the first signs and offer the most appropriate clinical support. Show more

Keywords: Volleyball, athletes, sport, capillaroscopy, hand, injury, microcirculation, translational medicine

DOI: 10.3233/CH-190667

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-5, 2019

Authors: Vosseler, Markus | El Shazly, Ahmed | Parker, John D | Münzel, Thomas | Gori, Tommaso

Article Type: Research Article

Abstract: BACKGROUND: Evidence of a circadian rhythm in endothelium-dependent vasomotor function, with a nadir in Flow-Mediated Dilation (FMD) in the early morning hours, has been previously reported. These changes have been proposed to be one of the mechanisms explaining the circadian pattern in the incidence of cardiovascular events. We set out to investigate the circadian rhythm of FMD, low-flow mediated dilation (L-FMC) and sympathetic vascular tone. METHODS AND RESULTS: 10 young healthy male volunteers (mean age, 28.9±3.7 years) underwent measurements of radial artery endothelium-dependent FMD and L-FMC at 8AM, 2PM and 8PM on the same day. Sympathetic vascular tone …was assessed with laser Doppler and Fourier transform analysis. Compared with 2PM and 8PM, FMD decreased markedly in the early morning (2.9±3.4%; 6.2±2.9%; 6.0±4.0%; P  = 0.007). In contrast, L-FMC was maximal at 8AM, decreased significantly at 2PM, and returned to higher values at 8PM (–5.1±1.3%; –2.7±2.0%; –4.6±2.2%; P  = 0.030), such that the composite endpoint of endothelial function (sum of FMD+L-FMC) was not significantly different among timepoints. Vascular sympathetic tone was maximal early in the morning and lowest in the evening (P  = 0.014) without a correlation with the changes in FMD or L-FMC. CONCLUSIONS: Endothelial responsiveness (FMD) and basal tone (L-FMC) appear to follow different circadian rhythms, with an impaired responsiveness in the early morning and a nadir in baseline tone in the early afternoon. Show more

Keywords: Endothelial function, circadian rhythm, vascular physiology

DOI: 10.3233/CH-190587

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2019

Authors: Ederer, I.A. | Goertz, O. | Bosselmann, T. | Sogorski, A. | Zahn, P.K. | Lehnhardt, M. | Daigeler, A. | Kolbenschlag, J.

Article Type: Research Article

Abstract: BACKGROUND: Mechanism of remote ischemic conditioning (RIC) remain not fully understood yet. Thus, we performed a clinical trial to assess the neuronal influence on its signal induction. METHODS: RIC was conducted on 45 patients who were randomized into 3 groups. Group A and B underwent brachial plexus anesthesia while RIC was performed on the blocked (A) and non-blocked side (B), respectively. In group C, RIC was conducted before regional anesthesia, thus serving as control group. All measurements were taken contralateral to RIC. The relative increase of microcirculatory parameters compared to baseline was evaluated and compared between the groups. …RESULTS: Superficial blood flow (sBF) significantly increased in group A and C but values were higher among group C. Compared to group A, group C showed a significant increase of sBF during the initial 5 minutes of reperfusion (1.75; CI 1.139 – 2.361 vs . 0.97, CI 0.864 – 1.076, p  <  0.05). Deep blood flow, tissue oxygen saturation and relative hemoglobin content were marginally influenced by RIC irrespectively of the presence of regional anesthesia. CONCLUSION: Despite regional anesthesia a significant RIC stimulus can be induced although its microcirculatory response is attenuated compared to control. Hence, RIC induction does not merely depend on neuronal signaling. Show more

Keywords: Remote ischemic conditioning, neuronal signaling, plexus anesthesia, microsurgery, reperfusion

DOI: 10.3233/CH-190626

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Dong, Yi | Liu, Lingxiao | Cao, Qiong | Zhang, Qi | Qiu, Yijie | Yang, Daohui | Yu, Lingyun | Wang, Wen-Ping

Article Type: Research Article

Abstract: BACKGROUND AND AIM: To evaluate the benefits of contrast-enhanced ultrasound (CEUS) with high frequency transducers in characterization of focal gallbladder lesions (FGL). MATERIAL AND METHODS: From January 2017 to April 2019, 59 FGL detected by B mode ultrasound (BMUS) were examined, first with the low frequency convex transducer (1–5 MHz) and afterwards with high frequency transducer (7.5–12 MHz). High frequency dynamic CEUS were applied after bolus injection of 4.8 ml Sulphur hexafluoride microbubbles (SonoVue® , Milan). The BMUS and CEUS imaging features were recorded and compared. All lesions were confirmed by surgical resection and histopathologic results. RESULTS: The final …diagnoses of 59 FGL included gallbladder adenocarcinoma (n  = 15), gallbladder polyps (n  = 11), gallbladder adenomas (n  = 18), focal adenomyomatosis (n  = 9), and gallbladder Ascariasis debris (n  = 6). The mean diameter of FGL was 24.5±11.4 mm, and mean depth to the abdominal wall was 21.2±7.3 mm. While applying CEUS with high frequency transducer, specific diagnostic features, including arterial phase irregular intralesional vascularity (10/15, 66.7%), late phase hypoenhancement (12/15, 80%), destruction of gallbladder wall (8/15, 53.3%), infiltration to the adjacent liver (6/15, 40.0%) were significantly higher in malignant FGL. The overall sensitivity, specificity and diagnostic accuracy for the correct characterization of malignant FGL were significantly improved by CEUS with high frequency transducer (sensitivity 93.3%, specificity 88.5%, accuracy 100%). CONCLUSION: With its superior contrast resolution, CEUS performed with high frequency transducers is helpful to achieve better visualization of gallbladder fundus and make differential diagnosis of gallbladder lesions, which might greatly improve diagnostic confidence between malignant and benign FGL. Show more

Keywords: Contrast enhanced ultrasound (CEUS), focal gallbladder lesion, high frequency, diagnosis, differentiation

DOI: 10.3233/CH-190639

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Liu, Haifang | Zhu, Yuping | Jiao, Jie | Yuan, Jia | Pu, Tianning | Yong, Qiang

Article Type: Research Article

Abstract: The aim of this study was to assess the elasticity of Hashimoto’s thyroiditis in the different processes via supersonic ShearWave™ Elastography (SWE™). Quantitative information is delivered as Young’s modulus value expressed in kilo-Pascal (kPa). 30 healthy female and 30 healthy male individuals aging at 40±20 y had undergone conventional ultrasonography and SWE to determine the influence of gender on elasticity of thyroid. Also 60 female and 60 male patients (mean age, 40±20 y) with Hashimoto’s thyroiditis in different processes underwent conventional ultrasonography and SWE to determine the elasticity of thyroid in Hashimoto’s thyroiditis. Furthermore, the relationship between elasticity values and …thyroid peroxidase antibody (TPOAB) in the patients was investigated. We found significant impact of gender on elasticity values of healthy thyroids. Our study showed that increased elasticity values with statistical significance in hyperthyroidism stage, normal thyroid function stage and hypothyroidism were shown. Low degree relationship between elasticity values and TPOAB was found in 60 male patients. However, there was no such correlation in female patients. Show more

Keywords: ShearWave™ elastography, hashimoto’s thyroiditis, ultrasound imaging, elasticity

DOI: 10.3233/CH-170347

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2018