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: Wu, Zhihua | Zhao, De | Duan, Yourong | Dong, Yi | Li, Yaogang

Article Type: Research Article

Abstract:  Cell metabolism decides the state of cells in division, differentiation and growth, maintaining intracellular balance. Monitoring the metabolic behavior of cells is of great significance to study the development of diseases in cell levels. Surface-enhanced Raman spectroscopy (SERS) is a powerful technique to detect and quantify analytes in extremely low concentration. Combined with SRES technology, we can monitor the concentration of metabolites in live cells and thus study the biological behavior of cells. In this work, Raman-tag labelled [email protected] nanoparticles were used to monitor the distribution of reactive oxygen species (ROS) in SKOV3 cells. With the help of the ultrasensitive …Raman enhancement material, the distribution of ROS in SKOV3 cells was mapped, the results were further confirmed in the fluorescent images. The SERS platform provides an ultrasensitive monitoring method of ROS distribution, which may offer an opportunity for real-time monitoring the cell metabolism in the cell biology applications. Show more

Keywords: Reactive oxygen species, cell metabolism, SERS, detection, Raman mapping

DOI: 10.3233/CH-200861

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

Authors: Amoroso, Matteo | Apelgren, Peter | Elander, Anna | Säljö, Karin | Kölby, Lars

Article Type: Research Article

Abstract: BACKGROUND: Acute normovolemic hemodilution (ANH) has been proposed as a microsurgical technique to improve blood flow in free flaps. OBJECTIVE: Here, we present the first systematic review of clinical and experimental studies on the effect of ANH. METHODS: We performed a systematic literature search of PubMed, Medline, the Cochrane Library, Google Scholar, and ClinicalTrials.gov using search strategies and a review process in agreement with the PRISMA statement and the Cochrane Handbook for systematic reviews of interventions. PICO criteria were defined before bibliometric processing of the retrieved articles, which were analyzed with the SYRCLE RoB tool for …risk of bias and the GRADE scale for level of evidence. RESULTS: We retrieved 74 articles from the literature search, and after processing according to PICO criteria, only four articles remained, all of which were experimental. The rating for risk of bias was uncertain according to SYRCLE RoB results, and the level of evidence was low according to GRADE evaluation. CONCLUSIONS: There is no clinical evidence for the effect of ANH on microcirculation in free flaps, and experimental studies provide weak evidence supporting the use of hemodilution in reconstructive microsurgery. Show more

Keywords: Acute normovolemic hemodilution, free flap, blood flow, systematic review, reconstructive surgery

DOI: 10.3233/CH-200832

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

Authors: Meissner, Florian | Plötze, Katrin | Matschke, Klaus | Waldow, Thomas

Article Type: Research Article

Abstract: BACKGROUND: Tranexamic acid (TXA) reduces perioperative bleeding among patients undergoing heart surgery. It is uncertain whether its postoperative administration, after prior administration before cardiopulmonary bypass (CPB), has an additional benefit. OBJECTIVE: Our study aimed to evaluate whether the postoperative administration of TXA reduces the blood loss after heart surgery. METHODS: In a retrospective cohort study at the University Heart Center Dresden, patients who underwent on-pump open-heart surgery and received 1 g TXA before CPB were included. Patients with postoperative administration of 1 g TXA were compared to patients without. Primary endpoint was the postoperative blood loss …within 24 hours. RESULTS: Among 2,179 patients undergoing heart surgery between 1 July 2013 and 31 October 2014, 92 (4.2%) received TXA postoperatively. After matching, 71 patients with postoperative administration of TXA were compared to 71 without (n  = 142). Postoperative administration of TXA did not result in decreased blood loss (MD 146.7 mL; p  = 0.064). There was no evidence of an increased risk for thromboembolic complications. CONCLUSIONS: The postoperative administration of TXA did not reduce blood loss. The use of TXA was shown to be safe in terms of thromboembolic events and hospital mortality. Unless there is no clear evidence, the postoperative administration of TXA should be restricted to patients with massive blood loss and signs of hyperfibrinolysis only. Show more

Keywords: Tranexamic acid, antifibrinolytics, hyperfibrinolysis, blood loss, open-heart surgery, cardiac surgery

DOI: 10.3233/CH-200836

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

Authors: Bruno, Raphael Romano | Masyuk, Maryna | Muessig, Johanna M. | Binneboessel, Stephan | Bernhard, Michael | Bäz, Laura | Franz, Marcus | Kelm, Malte | Jung, Christian

Article Type: Research Article

Abstract: BACKGROUND: Dehydration occurs frequently in older patients and constitutes a significant clinical problem. OBJECTIVE: This proof-of-concept study examines whether 1) sublingual measurement in dehydrated old patients is feasible, 2) frailty and incompliance in old, awake patients affects video-quality, 3) dehydration impacts microcirculation METHODS: This prospective observational study included clinically dehydrated patients aged ≥65 years immediately after admission. Dehydration was assessed clinically. A sidestream dark field camera (SDF) was used for measurement. Video-quality was evaluated with MIQS (microcirculation image quality score). Both AVA 4.3C- and AVA POEM-software analyzed the videos. Seventeen patients ≥65 years not showing dehydration …served as control. RESULTS: Thirteen patients (8 female) were included. The average age was 83±8 years. The mini-mental test was 17±15 points, the Clinical Frailty Scale 4±3, the Barthel-Index 59±39. None of these parameters correlated with MIQS (3.4±4.2 SD (“acceptable”)). Dehydrated patients had a slightly impaired microcirculation, with a significantly lower percentage of perfused small vessels compared to control (83.1±7.7% versus 88.0±6.0%, P  < 0.05). After rehydration, there was acute improvement in the microcirculation. CONCLUSIONS: Sublingual microcirculatory SDF-measurement is both, safe and valid for dehydrated old patients - regardless of frailty, age or cognitive performance. Dehydration leads to an impaired microcirculation. Show more

Keywords: Microcirculation, elderly, dehydration, older, rehydration, cognitive impairment, SDF-measurement.

DOI: 10.3233/CH-200859

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

Authors: Bahrami, Saeed | Norouzi, Mahmood

Article Type: Research Article

Abstract: Cardiovascular disease is now under the influence of several factors that encourage researchers to investigate the flow of these vessels. Oscillation influences the blood circulation in the volume of red blood cells (RBC) strongly. Therefore, in this study, its effects have been considered on hemodynamic parameters in the elastic wall and coronary bifurcation. In this study, a 3D geometry of non-Newtonian and pulsatile blood circulation is considered in the left coronary artery bifurcation. The Casson model with various hematocrits is analyzed in elastic and rigid walls. The wall shear stress (WSS) cannot show the stenosis artery alone, therefore, the oscillatory …shear index (OSI) is represented as a hemodynamic parameter of WSS individually of time. The results are determined using two-way fluid-structure interaction (FSI) coupling method using an arbitrary Lagrangian-Eulerian method. The most prominent difference in velocity happened in the bifurcation and at hematocrit 30 with yield stress 6.59E-04 Pa. The backflow and vortex flow in the LCx branch grown with increasing shear rates. The likelihood of plaque generation at the ending of the LM branch is observed in hematocrits 10 and 20, while the WSS magnitude is normal in the hematocrit 60 with the greatest yield stress in the bifurcation. The shear stress among the rigid and elastic models is the highest at the ending of the LM branch. The wall shear stress magnitude among the models decreased at most of 24.49% by dividing the flow. Time-independent results for models showed that there is the highest value of OSI at the bifurcation, which then quickly dropped. Show more

Keywords: Fluid solid interaction, blood flow, hematocrit, Casson model, hemodynamic parameter

DOI: 10.3233/CH-200854

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-18, 2020

Authors: Maruyama, Toru | Arita, Takeshi | Yokoyama, Taku | Hieda, Michinari | Fukata, Mitsuhiro | Fujino, Takehiko | Mawatari, Shiro | Akashi, Koichi

Article Type: Research Article

Abstract: BACKGROUND: Disturbed microcirculation is related to diabetic complications, and erythrocyte deformability is a critical factor regulating microcirculation. OBJECTIVES: To know the relationship between the impaired deformability and density profile in diabetic erythrocytes. METHODS: We recruited patients with type 2 diabetes (n  = 15, diabetic group) and age- and sex-matched non-diabetic subjects (n  = 15, control group). Erythrocyte density (ED) profile was obtained by the phthalate ester separation technique. ED distribution was fitted by sigmoidal curve, yielding SG of phthalate ester allowing passage of half erythrocytes population (ED50 ) and slope factor. Erythrocyte deformability was estimated by our specific …filtration technique. RESULTS: Diabetic group showed significantly (p  < 0.001) higher HbA1c and fasting blood glucose concentration. Erythrocyte deformability in diabetic group was impaired as compared with that in control group (p  < 0.001) and proportional to HbA1c (p  = 0.009). However, ED50 and the slope factor in diabetic group did not differ from respective parameters in control group. CONCLUSIONS: This study demonstrated that erythrocyte deformability was impaired in diabetic patients even under treatment. HbA1c up to 7.5% is concluded not to alter the erythrocyte density but to impair the deformability, which might be a warning to clinicians for prevention of diabetic complications. Show more

Keywords: Deformability, density, diabetes, erythrocyte, hemoglobin

DOI: 10.3233/CH-200873

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

Authors: Jung, F. | Krieger, V. | Hufert, F.T. | Küpper, J.-H.

Article Type: Research Article

Abstract: Background: In the early phase of the COVID-19 pandemic Germany missed to set up efficient containment measures. Consequently, the number of cases increased exponentially until a lockdown was implemented to suppress the spread of SARS-CoV-2. Fortunately, Germany has a high capability for coronavirus lab testing and more than 30,000 ICU beds. These capabilities and the lockdown turned out to be an advantage to combat the pandemic and to prevent a health-system overload. Aim: The aim was to predict the plateau day of SARS-CoV-2 infections or deaths. Results: The effect on the viral spread of the German …measures taken and the impact on the peak of new infection cases is shown. By normalizing daily case numbers, the plateau day of the current outbreak in Germany could be calculated to be reached at April 12, 2020 (day 103 of 2020). Conclusion: Normalized case number curves are helpful to predict the time point at which no further new infections will occur. Upon reaching the plateau day during a lockdown phase, a residual time-period of about 2-3 weeks can be utilized to prepare a safe unlocking period. As can be learned from Asian countries such as South Korea and Taiwan there must be strict rules to keep the risk of infection low. Those include social distancing, face mask wearing in combination with digital contact tracing and serosurveillance studies. Following those rules, a safe dance around the infection curve allows to keep the population at a reduced infection rate. Show more

Keywords: Corona virus, SARS-CoV-2, COVID-19, herd immunity, hammer and dance strategy

DOI: 10.3233/CH-209004

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

Authors: Windberger, U. | Dibiasi, Ch. | Lotz, E.M. | Scharbert, G. | Reinbacher-Koestinger, A. | Ivanov, I. | Ploszczanski, L. | Antonova, N. | Lichtenegger, H.

Article Type: Research Article

Abstract: BACKGROUND: Dynamic mechanical analysis of blood clots can be used to detect the coagulability of blood. OBJECTIVE: We investigated the kinetics of clot formation by changing several blood components, and we looked into the clot “signature” at its equilibrium state by using viscoelastic and dielectric protocols. METHODS: Oscillating shear rheometry, ROTEM, and a dielectro-rheological device was used. RESULTS: In fibrinogen- spiked samples we found the classical high clotting ability: shortened onset, faster rate of clotting, and higher plateau stiffness. Electron microscopy explained the gain of stiffness. Incorporated RBCs weakened the clots. Reduction of temperature …during the clotting process supported the development of high moduli by providing more time for fiber assembly. But at low HCT, clot firmness could be increased by elevating the temperature from 32 to 37°C. In contrast, when the fibrinogen concentration was modified, acceleration of clotting via temperature always reduced clot stiffness, whatever the initial fibrinogen concentration. Electrical resistance increased continuously during clotting; loss tangent (D) (relaxation frequency 249 kHz) decreased when clots became denser: fewer dipoles contributed to the relaxation process. The relaxation peak (Dmax) shifted to lower frequencies at higher platelet count. CONCLUSION: Increasing temperature accelerates clot formation but weakens clots. Rheometry and ROTEM correlate well. Show more

Keywords: Clot stiffness, kinetic, temperature, erythrocytes, fibrinogen, rheometry, thrombelastometry, dielectric test

DOI: 10.3233/CH-190799

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 2020

Authors: Al-Hindwan, H.S.A. | Silbernagel, G. | Curio, J. | Abulgasim, K. | Schröder, M. | Wuerdemann, I. | Kasner, M. | Landmesser, U. | Reinthaler, M.

Article Type: Research Article

Abstract: BACKGROUND: High surgical risk patients presenting with severe mitral valve regurgitation (MR) and concomitant aortic valve disease are frequently a challenge for the interdisciplinary heart team meeting. If open-heart surgery for severe MR is performed, aortic stenosis (AS) or regurgitation (AR) is corrected during the same procedure if at least moderate severity of AS or AR has been confirmed. In patients with prohibitive surgical risk, optimal management strategies in the light of available transcatheter interventions still needs to be established. METHODS AND RESULTS: In this retrospective single center Study, we aimed to investigate the impact of coincident moderate …aortic valve disease on the outcome of patients undergoing MitraClip for severe MR. In 286 MitraClip procedures performed in our institution, 21 patients (7,3%) were identified to suffer from concomitant moderate AS and 28 patients had moderate AR (9,8%). Patients with AS were found to have a higher incidence of >moderate MR following the procedure when compared to patients without aortic valve disease (14,3% vs. 8,9%, p  = 0.001). No differences between the groups were found regarding a combined endpoint of all cause deaths and heart failure hospitalizations after 1 year follow up (no aortic-valve disease vs. moderate AS: 19% vs 18%; p  = 0,881 and no aortic valve disease vs moderate AR: 19% vs. 25%; p  = 0.477). However, mortality was significantly higher in patients with coincidental moderate AR (3.8% patients without aortic valve disease, 5% in patients with AS, 17,9% in patients with AR; p  = 0.006). CONCLUSION: According to our analysis coincidental Aortic valve stenosis may be associated with worse technical results regarding residual MR after MitraClip. Although our results regarding a combined endpoint of all-cause mortality and heart failure hospitalizations within one year of follow up were comparable between the groups, patients with moderate AR had significantly higher mortality rates. Due to the limited number of patients, our study is only hypothesis generating. Larger trials are necessary to confirm our result. Show more

DOI: 10.3233/CH-200818

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

Authors: Strumwasser, Aaron | Cohan, Caitlin | Beattie, Genna | Chong, Vincent | Victorino, Gregory

Article Type: Research Article

Abstract: BACKGROUND: Autotaxin (ATX-secretory lysophospholipase D) is the primary lysophosphatidic acid (LPA) producing enzyme. LPA promotes endothelial hyper-permeability and microvascular dysfunction following cellular stress. OBJECTIVE: We sought to assess whether ATX inhibition would attenuate endothelial monolayer permeability after anoxia-reoxygenation (A-R) in vitro and attenuate the increase in hydraulic permeability observed after ischemia-reperfusion injury (IRI) in vivo . METHODS: A permeability assay assessed bovine endothelial monolayer permeability during anoxia-reoxygenation with/without administration of pipedimic acid, a specific inhibitor of ATX, administered either pre-anoxia or post-anoxia. Hydraulic permeability (Lp ) of rat mesenteric post-capillary venules was evaluated after IRI, …with and without ATX inhibition. Lastly, Lp was evaluated after the administration of ATX alone. RESULTS: Anoxia-reoxygenation increased monolayer permeability 4-fold (p  < 0.01). Monolayer permeability was reduced to baseline similarly in both the pre-anoxia and post-anoxia ATX inhibition groups (each p  < 0.01, respectively). Lp was attenuated by 24% with ATX inhibition (p  < 0.01). ATX increased Lp from baseline in a dose dependent manner (p  < 0.05). CONCLUSIONS: Autotaxin inhibition attenuated increases in endothelial monolayer permeability during A-R in vitro and hydraulic permeability during IRI in vivo . Targeting ATX may be especially beneficial by limiting its downstream mediators that contribute to mechanisms associated with endothelial permeability. ATX inhibitors may therefore have potential for pharmacotherapy during IRI. Show more

Keywords: Autotaxin, anoxia-reoxygenation, ischemia-reperfusion, hydraulic permeability

DOI: 10.3233/CH-190732

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

Authors: Ahmadizad, Sajad | Rahmani, Hiwa | Khosravi, Nikoo | Falakdin, Zahra | Connes, Philippe | Daraei, Ali

Article Type: Research Article

Abstract: BACKGROUND: Platelet activation is associated with abdominal obesity and exercise training is an important modulator of body weight. OBJECTIVE: We investigated the effects of two high intensity interval exercise (HIIE) protocols of different intensity and duration on platelet indices and platelet aggregation in overweight men. METHODS: Ten overweight men performed 6 intervals of 30s exercise at 110% of peak power output (PPO) interspersed by 3 : 30 min active recovery (1/7 protocol) at 40% of PPO and 6 intervals of 2 min exercise at 85% of PPO interspersed by 2 min active recovery (1/1 protocol) at 30% of …PPO in two separate sessions. Platelet indices and platelet aggregation were measured before and immediately after both HIIEs. RESULTS: Platelet indices increased significantly following HIIE (P  < 0.05), though, significant differences between the two protocols were only detected for platelet count, which was markedly increased following 1/1 protocol. Platelet aggregation increased significantly (P  < 0.05) in response to the two HIIE protocols, with no significant difference being observed between the two protocols (P  > 0.05). CONCLUSIONS: It is concluded that HIIE leads to transient increases in markers of thrombus formation and that work to rest ratio is an important factor when investigating the changes in thrombocytosis following HIIE. Show more

Keywords: Interval exercise, exercise intensity, platelet function, thrombocytosis, thrombus

DOI: 10.3233/CH-200848

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

Authors: Jung, F.

Article Type: Editorial

DOI: 10.3233/CH-209001

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-2, 2020

Authors: Jung, E.M. | Stroszczynski, C. | Jung, F.

Article Type: Research Article

Abstract: In the hands of experienced examiners, the contrast enhanced sonography (CEUS) offers the possibility to analyze dynamic microcirculatory disturbances in real time dynamically without any risk for kidneys and thyroid gland even in severe progressing disease bedside. Based on severe COVID-19 infections, first experiences with abdominal CEUS examinations are presented. In the stage of an imminent organ failure with significantly reduced kidney and liver function, CEUS can be used to show a narrowing of the organ-supplying arteries, as well as a delayed capillary filling of vessels near the capsule, a regional reduced parenchymal perfusion or an inflammatory hyperemia with capillary …hypercirculation. It is possible to quickly rule out organ infarction and to dynamically record the mesenteric arterial and venous blood flow. Show more

Keywords: Corona virus, contrast enhanced ultrasound sonography (CEUS), COVID-19, liver, kidney

DOI: 10.3233/CH-209003

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

Authors: Wenzel, Folker

Article Type: Other

DOI: 10.3233/CH-209002

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

Authors: Liu, Bo-Ji | Zhang, Yi-Feng | Zhao, Chong-Ke | Wang, Han-Xiang | Li, Ming-Xu | Xu, Hui-Xiong

Article Type: Research Article

Abstract: The purpose of the study was to explore the differences of conventional ultrasound characteristics, thyroid imaging reporting and data system (TI-RADS) category and shear wave speed (SWS) measurement between follicular adenoma (FA) and follicular thyroid carcinoma (FTC). Twenty-eight FTCs and 67 FAs proven by surgery were retrospectively included for analysis. Conventional ultrasound and point-shear wave elastography (p-SWE) were performed in all of the included patients. The ultrasound features, American Thyroid Association (ATA) TI-RADS category and American College of Radiology (ACR) TI-RADS category, SWS measurement were compared between the two groups. Receiver operating characteristic (ROC) curve was performed and area under …ROC curve (AUC) was obtained for significant features. There were no statistical differences in mean age (46.9±15.7years vs. 48.6±13.6years, P  = 0.639), gender (9 males, 32.1% vs. 18 males, 29.0%, P  = 0.766) and mean diameter (28.3±16.2 mm vs. 33.8±11.9 mm, P  = 0.077) between FTCs and FAs. Hypoechogenicity, lobulated or irregular margin, macrocalcification were more common in FTCs than FAs (all P  < 0.05). Mean SWS of FTCs (2.29±0.64 m/s) was slightly higher than that of FAs (1.94±0.68 m/s) (P  = 0.023). The AUCs were 0.655, 0.744, and 0.744 with the cut-off SWS≥1.89 m/s, ACR TI-RADS category 4 and intermediate suspicion of ATA TI-RADS category. The sensitivity and AUC were 82.1% and 0.812 with combined ultrasound features of hypoechogenicity, lobulated or irregular margin and macrocalcification. In Conclusion, SWS measurement and TI-RADS categories were useful for the identification of FTCs from FAs. Show more

Keywords: Follicular thyroid carcinoma (FTC), follicular adenoma (FA), ultrasound, TI-RADS category, Shear wave speed

DOI: 10.3233/CH-190750

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

Authors: Hu, Wenjie | Dong, Yi | Zhang, Xuemei | Zhang, Huiping | Li, Fan | Bai, Min

Article Type: Research Article

Abstract: OBJECTIVES: To evaluate the clinical value of Arrival-time Parametric Imaging (At-PI) in the differentiation of benign and malignant breast lesions. METHODS: For this ethics committee-approved retrospective study, a total of 184 breast lesions in 176 women were included and gray-scale ultrasound (gray-scale US), contrast-enhanced ultrasound (CEUS) and At-PI were performed. In CEUS and At-PI, perfusion patterns, perfusion uniformity and color spatial distribution for lesions were analyzed qualitatively and the maximal diameter ratio of the lesion in accumulated parametric images and that in gray-scale images (MDRAI/GI ) and area ratio of the lesion in accumuated parametric images and that …in gray-scale images (ARAI/GI ) were calculated quantitatively. Kappa and Intraclass Correlation Coefficient (ICC) were used to evaluate the interobserver reproducibility for CEUS and At-PI and the intraobserver reproducibility for At-PI, respectively. The area under receiver operating characteristic (AUC), sensitivity, specificity, accuracy and positive and negative likelihood ratios (PPV, NPV) were calculated for MDRAI/GI and ARAI/GI . RESULTS: Good interobserver and intraobserver reproducibility for At-PI were identified. In At-PI, there were statistically significant differences in perfusion patterns, color spatial distribution, MDRAI/GI and ARAI/GI between benign and malignant breast lesions (P  < 0.05). The AUCs of MDRAI/GI and ARAI/GI were 0.895 and 0.954, respectively, with no significant difference between them (Z = 1.84, P  > 0.05). By using the thresholds of 1.125 for MDRAI/GI and 1.21 for ARAI/GI , the sensitivity, specificity, accuracy, PPV and NPV of At-PI were 84.48%, 88.24%, 85.57%, 92.45% and 76.92%, respectively, for MDRAI/GI and 93.10%, 91.18%, 92.39%, 94.74% and 88.57%, respectively, for ARAI/GI . CONCLUSIONS: At-PI is helpful to distinguish benign from malignant breast lesions. And MDRAI/GI and ARAI/GI are useful and efficient features for differential diagnosis. Show more

Keywords: Contrast-enhanced ultrasound, arrival-time parametric imaging, benign and malignant breast lesions

DOI: 10.3233/CH-200826

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

Authors: Kim, Yu Kyung | Lim, Young Tae | Suh, Jang Soo | Hah, Jeong Ok | Lee, Jae Min

Article Type: Research Article

Abstract: BACKGROUND: Previously, hemorheology studies using Rheoscan mainly focused on chronic kidney disease, cardiovascular disease, and endocrine disease in adults. The study using LORCA focused on erythrocyte disease. There were no studies using Rheoscan in children. OBJECTIVE: We aimed to investigate erythrocyte deformability among various hematologic diseases occurring in children, namely, iron deficiency anemia (IDA), hereditary spherocytosis (HS), immune thrombocytopenia (ITP), and aplastic anemia (AA). METHODS: Differences between those with HS, IDA, ITP, AA and healthy controls were compared among 43 patients, comprising 7 patients with HS, 8 patients with IDA, 6 patients with AA, 9 patients …with ITP, and 13 healthy controls. Erythrocyte deformability was measured using a microfluidic ektacytometer (RheoScan-D, RheoMeditech, Seoul, Korea). The erythrocyte elongation index (EI) was defined as (L – W)/(L  + W), where L and W are the major and minor axes of the ellipse, respectively. RESULTS: The EI values of IDA, HS and AA were significantly decreased compared with healthy controls, but those of ITP were similar to healthy controls. CONCLUSIONS: This study showed that erythrocyte deformability differed among various hematologic diseases. Further study concerning correlation in relation to the diagnostic and prognostic significance of erythrocyte deformability in hematologic disease is needed. Show more

Keywords: RBC deformability, children, hereditary spherocytosis, iron deficiency anemia, aplastic anemia, immune thrombocytopenia

DOI: 10.3233/CH-200817

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

Authors: Bakker, Nathalie | Schoorl, Marianne | Demirkiran, Ahmet | Cense, Huib A. | 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 oral omega-3 fatty acids in morbidly obese women undergoing gastric bypass surgery METHODS: Fifty-six morbidly obese women undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery were randomized between a low calorie diet (LCD) during 2 weeks or oral omega-3 poly-unsaturated fatty acids (n-3 PUFAs) and a normal diet during 4 …weeks. Peri-operative blood samples were analyzed with the Lorrca MaxSIS Ektacytometer for erythrocyte deformability and aggregability. RESULTS: There were no significant differences in erythrocyte function between the groups at any time point. Only erythrocyte aggregability parameters were affected by surgery. At six month follow-up, aggregation index (AI) and cholesterol, glucose and insulin were significantly improved. CONCLUSIONS: In this study, oral Omega-3 supplementation did not affect erythrocyte function compared to a LCD. Six months after surgery a significant improvement in AI and metabolic parameters was observed in both groups, contributing to a reduction in the risk at thromboembolic and cardiovascular complications. Show more

Keywords: Erythrocytes, deformability, aggregability, morbid obesity, laparoscopic gastric bypass surgery, omega-3 fatty acids

DOI: 10.3233/CH-190777

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

Authors: Wei, Linlin | Zeng, Kexue | Gai, Juanjuan | Zhou, Feixiong | Wei, Zhenglin | Bao, Qinghui

Article Type: Research Article

Abstract: OBJECTIVE: To study the effect of acupuncture on neurovascular units after cerebral infarction (CI) in rats through the phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/AKT) signaling pathway. METHODS: A total of 36 Sprague-Dawley rats were randomly divided into sham group (n  = 12), model group (n  = 12) and acupuncture group (n  = 12). The external carotid artery was only exposed in model group, while the post-CI ischemia-reperfusion model was established using the suture method in the other 2 groups. After modeling, the rats in sham group and model group were fixed and sampled, while those in acupuncture group were treated with …acupuncture intervention for 2 weeks and sampled. The neurological deficits of rats were evaluated using the Zea-Longa score, and the spatial learning and memory of rats were detected via water maze test. Moreover, the expressions of vascular endothelial growth factor (VEGF), growth associated protein-43 (GAP-43) and synuclein (SYN) in brain tissues were detected via immunohistochemistry, and the relative protein expressions of PI3K p85, PI3K p110 and p-AKT were detected via Western blotting. The messenger ribonucleic acid (mRNA) expressions of VEGF, GAP-43 and SYN were detected via quantitative polymerase chain reaction (qPCR). RESULTS: The Zea-Longa score was significantly increased in model group and acupuncture group compared with that in sham group (p  < 0.05), while it significantly declined in acupuncture group compared with that in model group (p  < 0.05). The escape latency was significantly prolonged and the times of crossing platform were significantly reduced in model group and acupuncture group compared with those in sham group (p  < 0.05), while the escape latency was significantly shortened and the times of crossing platform were significantly increased in acupuncture group compared with those in model group (p  < 0.05). The positive expressions of VEGF, GAP-43 and SYN were obviously increased in model group and acupuncture group compared with those in sham group (p  < 0.05), while they were obviously increased in acupuncture group compared with those in model group (p  < 0.05). Besides, model group and acupuncture group had significantly higher relative protein expressions of PI3K p85, PI3K p110 and p-AKT than sham group (p  < 0.05), while acupuncture group also had significantly higher relative protein expressions of PI3K p85, PI3K p110 and p-AKT than model group (p  < 0.05). The relative mRNA expressions of VEGF, GAP-43 and SYN were remarkably increased in model group and acupuncture group compared with those in sham group (p  < 0.05), while they were remarkably increased in acupuncture group compared with those in model group (p  < 0.05). CONCLUSION: Acupuncture promotes the repair of neurovascular units after CI in rats through activating the PI3K/AKT signaling pathway, thereby exerting a protective effect on neurovascular units. Show more

Keywords: Acupuncture, cerebral infarction, PI3K/AKT signaling pathway, neurovascular units

DOI: 10.3233/CH-190659

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

Authors: Liu, Ying | Huang, Zhen-Li | Zhang, Zhen | Gong, Lin | Zhang, Shuang-Chuan | Zhou, Yu-Xin

Article Type: Research Article

Abstract: Background: N-terminal pro-B-type natriuretic peptide (NTproBNP) appears to be a useful tool for diagnosing hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. However, a consensus for its application has not been reached. Objective: The present study aims to evaluate the role of NTproBNP in predicting hsPDA in preterm infants, and explore the optimal cutoff value and testing-time. Methods: A prospective blind study of 120 preterm infants with birth weights of < 1,500 g was conducted at the NICU of Peking University Shenzhen Hospital. Blood samples were successively collected on the first three days after birth for NTproBNP analysis. …Echocardiographies were performed on day three of life to confirm the status of the ductus arteriosus. A receiver operating characteristic curve (ROC) analysis was performed to determine the ability of NTproBNP to recognize hsPDA. Results: NTproBNP was significantly higher in infants with hsPDA, than in infants in the control group, on both day two (P  < 0.001) and day three (P  < 0.001). On day two, a NTproBNP cutoff value of 3,689.0 pmol/L offered an optimal predictive value for hsPDA, while on day three, the optimal cut-off value for hsPDA was 2,331.5 pmol/L. The investigators proposes day three of life (48–72 hours) as the optimal testing time. Conclusion: The NTproBNP biomarker during the early neonatal period can be a useful tool for screening and assessing hsPDA in premature infants, especially on day three of life. Show more

Keywords: HsPDA, NTproBNP, Preterm infants, Very low birth weight infants

DOI: 10.3233/CH-190803

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

Authors: Pang, Mengru | Lei, Xiaoxuan | Yao, Zexin | Chen, Caihong | Cheng, Biao

Article Type: Research Article

Abstract: It has been reported that the beta-adrenergic receptor blocker (propranolol) and the a-adrenergic receptor (AR) blocker (phentolamine) both can inhibit human endothelial cell (EC) angiogenesis in vitro . However, it is unknown whether this inhibition also acts on pericytes. The present study aimed to determine how pericytes react to treatment with an a-/β- AR blocker. In the study, cell proliferation assays and scratch assay were performed to assess the effect of phentolamine or propranolol on cell proliferation and migration. Western blot and ELISA were employed to determine changes in VEGF-A and Ang-1 expression levels. The results indicated that the nonselective …a-/β- AR blocker inhibited the proliferation, migration, and secretion of pericytes. The use of the nonselective a-/β- AR blocker might have an impact on vascularization and vascular maturation. Our research suggests the rational use of nonselective a-/β- AR blockers to treat angiogenesis-dependent diseases. Show more

Keywords: Adrenergic receptor blocker, phentolamine, propranolol, pericytes, angiogenesis

DOI: 10.3233/CH-190780

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

Authors: Liu, Xuanwei | Zhao, Na’na | Zeng, Kexue | Xiao, Peng | Sheng, Pengjie | Luo, Xun | Wang, Yulong

Article Type: Research Article

Abstract: OBJECTIVE: This study aims to investigate the effect of nimodipine combined with betahistine on the levels of CRP and other inflammatory cytokines, as well as vascular endothelial function in patients with hypertensive cerebral vasospasm. METHODS: A total of 80 patients with hypertensive cerebral vasospasm from March 2016 to September 2018 were enrolled and randomly equally divided into two groups. At 1 week before enrollment, the application of all antihypertensive drugs was stopped. Then amlodipine tablets were used in control group, based on which nimodipine tablets were applied in observation group. All the patients included were followed up for …1 month. The changes in the cerebral vasospasm index in the course of treatment as well as inflammatory cytokines and indicators related to vascular endothelial function at 1 month after treatment were measured and compared between the two groups. The correlations of the cerebral vasospasm index with the changes in inflammatory cytokines and vascular endothelial function-related factors in the body were analyzed. Finally, the effective rates of blood pressure regulation and cerebral vasospasm treatment were compared, while the adverse reactions and the overall clinical treatment effect of the two groups were evaluated. RESULTS: The cerebral vasospasm indexes in observation group were significantly lower than those in control group at 3 d, 1 week and 1 month after treatment (p  < 0.05). At 1 month after treatment, the levels of inflammatory cytokines such as high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α ) in observation group were significantly reduced compared to those in control group (p  < 0.05). As for vascular endothelial function-related indicators, the endothelin-1 (ET-1) level in observation group was markedly lower than that in control group, whereas the level of nitric oxide (NO) was statistically higher than that in control group (p  < 0.05). The cerebral vasospasm index was statistically positively correlated with changes in hs-CRP, IL-6, TNF-α and ET-1 (p  < 0.05), but negatively correlated with changes in NO (p  < 0.05). Besides, the effective rates of blood pressure regulation and cerebral vasospasm treatment in observation group were significantly higher than those in control group (p  < 0.05). The overall treatment effective rate in observation group was markedly higher than that in control group (p  < 0.05), and there were no significant differences of adverse reactions between the two groups (p  > 0.05). CONCLUSION: For the treatment of hypertensive cerebral vasospasm, combined application of betahistine on the basis of nimodipine can effectively reduce the body’s aseptic inflammatory responses, improve vascular endothelial function and increase the cerebral circulation blood flow, which offers a favorable strategy for clinical therapy. Show more

Keywords: Key words: Betahistine, hypertension, cerebral vasospasm, inflammatory cytokine, vascular endothelial function, nimodipine

DOI: 10.3233/CH-190589

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

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: 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

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: 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: 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: 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: 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: 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: 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: 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: 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: 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