Clinical Hemorheology and Microcirculation - Volume 75, issue 2

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 Plasma withdrawn at later time points did not affect endothelial barrier function (p  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. 75, no. 2, pp. 121-133, 2020

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. 75, no. 2, pp. 135-142, 2020

Authors: Lee, Ja Young | 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. 75, no. 2, pp. 143-149, 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. 75, no. 2, pp. 151-162, 2020

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. 75, no. 2, pp. 163-176, 2020

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. 75, no. 2, pp. 177-188, 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

Keywords: Lipolytic injectables, nano PPC, inflammation, apoptosis

DOI: 10.3233/CH-190715

Citation: Clinical Hemorheology and Microcirculation, vol. 75, no. 2, pp. 189-199, 2020

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. 75, no. 2, pp. 201-217, 2020

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. 75, no. 2, pp. 219-232, 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. 75, no. 2, pp. 233-241, 2020