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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-190731

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-190717

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-190736

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

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

Article Type: Research Article

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

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

DOI: 10.3233/CH-190723

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