Clinical Hemorheology and Microcirculation - Volume 50, issue 1-2
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Clinical Hemorheology and Microcirculation, a peer-reviewed international scientific journal, serves as an aid to understanding the flow properties of blood and the relationship to normal and abnormal physiology. The rapidly expanding science of hemorheology concerns blood, its components and the blood vessels with which blood interacts. It includes perihemorheology, i.e., the rheology of fluid and structures in the perivascular and interstitial spaces as well as the lymphatic system. The clinical aspects include pathogenesis, symptomatology and diagnostic methods, and the fields of prophylaxis and therapy in all branches of medicine and surgery, pharmacology and drug research.
The endeavour of the Editors-in-Chief and publishers of
Clinical Hemorheology and Microcirculation is to bring together contributions from those working in various fields related to blood flow all over the world. The editors of
Clinical Hemorheology and Microcirculation are from those countries in Europe, Asia, Australia and America where appreciable work in clinical hemorheology and microcirculation is being carried out. Each editor takes responsibility to decide on the acceptance of a manuscript. He is required to have the manuscript appraised by two referees and may be one of them himself. The executive editorial office, to which the manuscripts have been submitted, is responsible for rapid handling of the reviewing process.
Clinical Hemorheology and Microcirculation accepts original papers, brief communications, mini-reports and letters to the Editors-in-Chief. Review articles, providing general views and new insights into related subjects, are regularly invited by the Editors-in-Chief. Proceedings of international and national conferences on clinical hemorheology (in original form or as abstracts) complete the range of editorial features.
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Clinical Hemorheology and Microcirculation: medical practitioners in all fields including hematology, cardiology, geriatrics, angiology, surgery, obstetrics and gynecology, ophthalmology, otology, and neurology. Pharmacologists, clinical laboratories, blood transfusion centres, manufacturing firms producing diagnostic instruments, and the pharmaceutical industry will also benefit.
Important new topics will increasingly claim more pages of
Clinical Hemorheology and Microcirculation: the role of hemorheological and microcirculatory disturbances for epidemiology and prognosis, in particular regarding cardiovascular disorders, as well as its significance in the field of geriatrics. Authors and readers are invited to contact the editors for specific information or to make suggestions.
Abstract: Objective: Purpose of this study was to monitor changes of microcirculation in acute compartment syndrome using contrast enhanced ultrasound (CEUS) and to assess the modified perfusion with a special quantification software. Methods: 8 patients with trauma of the lower limb or the upper extremity were enrolled after acute compartment syndrome was diagnosed clinically and by intracompartmental pressure measurement. The qualitative analysis of the corresponding compartment was assessed using B-scan mode and CEUS simultaneously. CEUS was performed using a multifrequence probe (6–9 MHz, LOGIQ E9 GE) after a i.v. bolus injection of 2 × 2.4 ml contrast agent (SonoVue® , Bracco,…Italy). Digital raw data were stored as cine loops up to 2 minutes. Retrospectively semiquantitative perfusion analysis was performed using time intensity curve analysis and the quantification software QONTRAST® . Results: 6 out of 8 patients had to be operated due to clinical symptoms and to a pressure perfusion gradient lower than 30 mm Hg. 2 out of 8 were treated conservatively. In all patients haematomas were seen in B-scan mode. No necrosis could be detected. In the TIC analysis low levels of time to peak (20.0 ± 12.1) and area under the curve (118.4 ± 87.8) were observed in acute compartment syndrome. Similarly results have been obtained using the perfusions parameter PEAK (11.1 ± 5.7), time to PEAK (14.7 ± 9.7), regional blood volume (257.1 ± 192.6), and regional blood flow (12.1 ± 6.5) in QONTRAST® perfusion software. Conclusion: CEUS may be capable of differing between acute compartment syndrome and imminent compartment syndrome.
Abstract: Background: Free tissue transfer in head and neck reconstructions has a very high success rate, but thrombotic vessel occlusion is still a serious complication occurring in up to 10% of all cases. Thus, a simple, fast and reliable monitoring system for free flaps would be of advantage. Objective: The aim of this study was to investigate whether free flap monitoring by measuring perfusion-dependent parameters is a suitable method for discovering vessel thrombosis in free flaps. Methods: 10 patients requiring tissue reconstruction after tumour surgery or because of chronic wounds were included in this study. 10 microvascular flaps were harvested and…transplanted. Perfusion was determined by measuring a fluorescent oxygen sensor foil covering the flap's skin surface by means of a USB-handheld fluorescence microscope prototype. The sensor contained an oxygen reservoir which was consumed by the tissue corresponding to the perfusion status of the flap. Measurements were done before explantation, after successful anastomosis and 1 day after surgery. Results: Clinically well-perfused grafts showed slope values between 0.07 and 0.27 (mean: 0.18 ± 0.07), and clinically poorly perfused grafts showed slope values between 0.35 and 0.75 (mean: 0.52 ± 0.19). In the present study, we used a threshold slope value of 0.3 for differentiating between well-perfused and poorly perfused flaps. Conclusion: Flap monitoring via oxygen imaging by means of fluorescent sensor foils appears to be a fast, non-invasive, cost-effective and thus suitable method for analyzing flap perfusion with the additional advantage of aiding decision making on flap revision.
Abstract: Background: The protective effect of acetylsalicylic acid (aspirin) in primary and secondary prophylaxis of cardiovascular events is attributed to the inhibition of platelet cyclooxygenase (COX). However, a recent animal study found a vasodilating and blood pressure lowering effect of aspirin independent of COX, but mediated by inhibition of the RhoA/Rho kinase signaling pathway. Method: Prospective, randomized, double-blind, placebo-controlled cross-over study. In each instance 5 healthy volunteers received either aspirin 500 mg/d or placebo for 7 days. Capillary red blood cell velocity (vRBC) at rest and after postischemic hyperemia was determined on day 1 and 7 by means of nailfold capillary…microscopy. Results: In the aspirin group after 7 days a significant increase of vRBC was found at rest and during hyperemia. In the placebo group vRBC did not change. The finding was confirmed by the cross-over design of the study. Conclusion: Aspirin at a dosage of 500 mg/d has an impact on vasoregulation in the microcirculation. At present, the underlying mode of action in humans is unknown.
Abstract: Echinocyte formation is associated with a rigidification of the cells that may affect capillary perfusion and, consequently, the tissue oxygen supply. This study examines how many echinocytes appeared after the addition of radiographic contrast media (RCM) (Iodixanol320, Ioversol300, Iopamidol300, and Iomeprol400) compared to red blood cells in autologous plasma and in isotonic saline solution. Isotonic saline solution, Iodixanol, Ioversol, Iopamidol and Iomeprol in concentrations of 10 vol%, 20 vol%, and 40 vol% were added to the plasma of seven healthy subjects. Subsequently, the erythrocytes were resuspended in these plasma/RCM mixtures, incubated for 5 minutes and then examined under the microscope.…The concentrations and the RCM in the mixture had a significant effect on the number of discocytes (factor concentration: p < 0.0001; factor RCM: p < 0.0001). The percentage of discocytes for all concentrations depended significantly on the RCM/plasma mixture (concentration × RCM: p < 0.002). Of all RCM/plasma mixtures used, the Iodixanol/plasma mixture showed the most similar discocyte fraction compared to red blood cells in the autologous plasma. Importantly, while Iodixanol differed from all other RCMs, the other RCMs did not differ from one another with respect to the discocyte fraction.
Abstract: After intra-arterial administration of several radiographic contrast media (RCM) a disorder of the downstream microcirculation with regard to blood flow velocity in microvessels and to tissue oxygen partial pressure in the myocardium of the pig heart was described. Iodixanol did not induce such a microcirculatory disorder in the myocardium of the beating heart of pigs. Whether the morphological changes reported in venous endothelial cells after incubation in culture media supplemented with RCM in vitro coincide with a serious endothelial cell dysfunction is not known. In this study we wanted to get information on possible states of dysfunction or perturbation of…venous and arterial ECs through the release of prostacyclin, which was shown to follow the perturbation of ECs. Functionally confluent venous endothelial cells on extracellular matrix secreted great amounts of prostacyclin in reaction to the RCMs indicating a clear perturbation of the ECs. This was not the case in arterial EC cultures. The prostacyclin release from arterial ECs exposed to Iodixanol was more than 10-fold higher than that from arterial ECs exposed to Iomeprol. This could be one of the important factors contributing to the undisturbed myocardial microcirculation after injection of Iodixanol despite a slight echinocyte formation.
Abstract: Gelatins functionalized with desaminotyrosine or desaminotyrosyl tyrosine form physically crosslinked polymer networks due to the interactions between the introduced aromatic moeties. In the swollen state, their mechanical properties can be tailored in a range similar to the elasticity of soft tissues. The aim of this study was to evaluate their potential as biomaterials by determining whether these materials – in comparison to plain gelatin – induce bleedings, thrombotic processes, or angiogenesis. These investigations were performed using the hen's egg chorioallantoic membrane (HETCAM) assay. These results indicate that the gelatin-based hydrogels did not possess angiogenic effects and also did not induce…bleedings, thrombotic processes or vessel destruction (avascular zones). The biocompatibility of the materials in vitro motivates the exploration of their application as matrix in local drug-release systems with short half-life times (1 hour up to several days).
Keywords: HETCAM, gelatin, angiogenesis, thrombosis, biomaterial, implant material
Abstract: Objective: The aim of this study was to evaluate the value of linear contrast enhanced intraoperative ultrasound (CE-IOUS) to improve detection of malign liver tumors lesions before surgery or radiofrequency ablation (RFA). Materials and Methods: 50 patients were included for surgery of malignant liver tumors (mean age 61 years (19–80); male n = 35, female n = 15), suffering from HCC (n = 15), colorectal liver-metastasis (n = 28), CCC (n = 2) or other malign liver lesions (n = 5). Preoperative CE-CT (n = 38), CE-MRI (n = 23) or PET-CT (n = 8) confirmed hepatic tumor manifestation. Before…undergoing surgery, intraoperative conventional (IOUS) as well as CE-IOUS were performed by one experienced examiner in all cases using multifrequency linear probes (6–9 MHz, 6–15 MHz; LOGIQ E9; GE Healthcare, Milwaukee, WI, USA). CE-IOUS was performed after bolus injection of 5 ml up to 15 ml SonoVue® (Bracco Imaging SpA, Milan, Italy). Digitally stored images of CE-IOUS were compared with fundamental B-Scan and preoperative imaging (CE-CT, CE-MRI and PET-CET). Results: In 28 of 50 patients (56%), additional lesions were found using CE-IOUS (mean tumor size 8 mm, range 4–12 mm). This resulted in a change of surgical strategy or the intraoperative application of RFA in 27 patients (54%). Modification of therapy due to additionally found liver lesions was statistically significant (p < 0.05). Comparing conventional IOUS and CE-IOUS, 14 additional lesions in 10 patients were seen by CE-IOUS. All lesions seen in B-scan could also be detected with CE-IOUS. Summary: This is the first study using contrast-enhanced ultrasound with high resolution linear probes for intraoperative detection of malignant liver lesions. Compared to preoperative imaging and also conventional IOUS more than 50% additional lesions were found leading to therapeutic consequences of patients. A recently started prospective study has to show whether these changes in the surgical or interventional therapy will influence morbidity, mortality and especially the recurrence rate.
Abstract: Objectives: To assess the benefit of ultrasound (US) image fusion in the identifiability and assessment of the dignity of renal lesions. Materials and methods: 25 patients with 29 renal lesions were investigated using standard US and CEUS (contrast enhanced US) with image fusion (CT or MRI). Identifiability and assessment of dignity was evaluated using cross-sectional images and US separately as well as using both US-techniques with additional image fusion. The respective modality was rated by two experienced radiologists (10 and 5 years of experience) using a (subjective) 5 point rank scale (1 = best). Results: Using CEUS, image fusion resulted…in improved identifiability (score: 1.1 ± 0.4) and improved assessment of dignity (score 1.0 ± 0) of renal lesions than using cross sectional images (score 1.8 ± 1.2 and 3.8 ± 1.2 respectively) separately. Conclusion: Image fusion improved the identifiability and the assessment of the dignity of renal lesions compared to using the respective modalities separately.
Abstract: Purpose: Obstructive diseases of the salivary glands, a common problem in the ENT field, are often based on sialolithiasis but can also result from rare circumstances. Due to recent technical innovations, there has been significant development in the treatment of obstructive diseases of the salivary glands such that minimally invasive glandula-sustaining therapy has now become standard. However, there is still no effective technique to assess and monitor the recovery of the parenchyma of the gland. As a result, recurrent infections often lead to modification of the gland in which fibrosis increases and the gland becomes coarse. After treatment, the parenchyma…of the gland is able to recover. Thus, to more effectively monitor and promote the success of treatment, we have developed a new method to measure and quantify the stiffness of the glandula tissue using elastography (Virtual Touch TM Application) to assess the degree of recovery. Materials and methods: First, we collected elastography data from 30 healthy volunteers as part of a conventional ultrasound (Siemens, ACUSON, S 2000, Germany) with a multi-frequency linear 9 MHz transducer in order to determine if normal findings are sufficiently quantifiable. We subsequently measured patients with sialolithiasis of the submandibular gland. Results: For healthy volunteers, the average value was 1.96 ± 0.48 m/s for the glandula submandibularis and 2.66+/- 0.89 for the parotid gland, a statistically significant difference. For patients with sialolithiasis of the submandibular gland, the average value was 2.98 ± 0.4 m/s, a highly significant difference in comparison to the healthy side of the patient. Conclusion: Elastography is an easy to use diagnostic method that shows promise to become a valuable tool for the assessment of disease severity as it provides the possibility to quantify the level of treatment benefit for the patient.
Abstract: A major clinical problem of high relevance in the cardiovascular field is late stent thrombosis after implantation of drug eluting stents (DES). Clinical widely used DES currently utilize durable polymer coatings, which can induce persistent arterial wall inflammation and delayed vascular healing resulting in an impaired endothelialization. In this study we explored the interaction of smooth muscle cells (SMC) and human umbilical vein endothelial cells (HUVEC) with electrospun scaffolds prepared from resorbable polyetheresterurethane (PDC) and poly(p-dioxanone) (PPDO), as well as polyetherimide (PEI), which can be surface modified, in comparison to poly(vinylidene fluoride-co-hexafluoropropene) (PVDF) as reference material, which is established as…coating material of DES in clinical applications. Our results show that adhesion could be improved for HUVEC on PDC, PPDO and PEI compared to PVDF, whereas almost no SMC attached to the scaffolds indicating a cell-specific response of HUVEC towards the different fibrous structures. Proliferation and apoptosis results revealed that PPDO and PEI have no significant negative influence on vitality and cell cycle behaviour compared to PVDF. Hence, they represent promising candidates for temporary blood vessel support that induce HUVEC attachment and prevent SMC proliferation.
Keywords: Endothelialization, drug eluting stent, degradable polymer, electrospinning, cell selectivity
Abstract: In the ovary with its cyclically developing and regressing functional bodies and the associated intense neovascularisation and remodelling, alpha-smooth muscle actin (SMA) immunolocalisation has been frequently used as a marker to establish vessel hierarchy, in angiogenesis studies, or in studies characterising ovarian neoplasms in various species. The present study aims at detection of alpha-SMA-immunolocalisation within all structural components of the cycling bovine ovary in order to complement the hitherto available data. 27 ovaries, mainly of dairy cows ranging from 23 to 118 months of age and displaying all major stages of follicle and corpora lutea development, were collected at the…abattoir and subjected to routine HE and trichrome staining as well as alpha-SMA immunohistochemistry. For this purpose, the specimens were pooled to form groups of the respective stage of corpus luteum development. The ovarian stroma displayed a notable alpha-SMA-reactivity, particularly surrounding the functional bodies. The study revealed specialised vascular modifications such as multi-directionally arranged vascular smooth muscle layers, vascular sphincters and distinct epitheloid modifications of the media in ovarian arteries. Alpha-SMA-reactivity of the microcirculation within corpora lutea of various stages allowed inferences on respective angiogenic properties. The findings were discussed focussing on functional interpretations.
Abstract: The need for engineered devices to treat cardiovascular diseases is increasing due to an aging population and a changing lifestyle. Soft poly(n-butyl acrylate) (cPnBA) networks were recently described as polymer networks with adjustable mechanical properties and suggested as soft substrates for cells, which could potentially be used for cardiovascular implants. Vascular prostheses designed to be implanted in arteries should have an elasticity similar to blood vessels (elastic modulus at body temperature between 100 and 1200 kPa). Therefore, cPnBA networks with E-moduli of 250 kPa (cPnBA0250) and 1100 kPa (cPnBA1100) were developed. Recently, it was shown that both materials were non-cytotoxic…for murin fibroblasts, human primary endothelial cells and human monocytes. However, before such newly developed polymers can be used in vivo, it has to be assured that the sterilized materials have a very low endotoxin load to avoid an unspecific activation of the immune system, which otherwise might cause local or systemic inflammatory responses and could lead to severe pathologies. In this study we investigated the immuno-compatibility of sterilized cPnBA0250 and cPnBA1100 with the help of an immuno-competent macrophage cell line as well as with whole human blood.
Abstract: Background: Atherosclerotic plaques are initiated by pro-inflammatory endothelial activation at arterial regions subjected to non-uniform shear stress. We applied the in vitro flow-through cell culture slides to investigate whether different patterns of shear stress affect the secreted cytokine and chemokine profile in endothelial cells. Methods: Human umbilical vein endothelial cells (ECs) were exposed to 24 h of flow in straight or bifurcating flow-through slides, in some experiments followed by 6 h stimulation with 2.5 ng/mL TNF-α. IL-1β, IL-6, IL-8, IL-12p70, MIP-1α, MCP-1and sICAM-1 were measured in conditioned medium samples by flow cytometry using antibodies conjugated with fluorescent beads. Results: The…release of IL-1β, IL-12p70 and MIP-1α from endothelial cells exposed to shear stress was below detectable levels. Strongly increased level of sICAM and significantly increased IL-8 concentration were detected in conditioned medium from endothelial cells exposed to flow in bifurcating slides as compared with cells grown under laminar flow in straight channels. The release of IL-6 and MCP-1 was not significantly induced in bifurcating slides. Treatment with TNF-α for 6 h induced 2–3 fold increase in secreted chemokines and cytokines. In particular, significantly increased MCP-1 and increased IL-8 levels were released from endothelial cells grown in bifurcating slides. This release was partly prevented in cells grown in straight channels, i.e. under exposure to laminar flow only. Conclusions: Although the endothelial monolayer areas exposed to non-uniform shear stress are relatively small, the activation of cells in these regions is strong enough to produce a detectable change in cytokine and chemokine profile, which represents the earliest step in atherogenic endothelial dysfunction.