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

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

Keywords: Carotid plaque, contrast-enhanced ultrasound perfusion patterns, stenosis, free fatty acid, stroke

DOI: 10.3233/CH-190804

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

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