Clinical Hemorheology and Microcirculation - Volume Preprint, issue Preprint
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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: This in vitro study was designed to examine the effect of some newly synthesized aminoalcanolic derivatives of xanthone (I, II) and aroxyalkyl derivatives of 2-methoxyphenylpiperazine (III, IV) having cardiovascular activity on the haemorheological parameters of RBCs from healthy individuals and patients with chronic venous disease. Additionally, the influence of compounds I-IV on some RBCs associated enzymes such as acetylcholinesterase (Ache), glucose-6-phosphate dehydrogenase (G6PD) and glutathione reductase (GR) as well as glutathione (GSH) content were determined in vitro in RBCs from healthy subjects. The study showed that compounds I, III and IV significantly increased RBCs deformability. Moreover, both xanthone…derivatives reduced RBCs aggregation and diminished RBCs aggregates strength in all RBCs groups. Compounds II and III significantly improved Ache activity, whereas compounds I and II increased G6PD and GR activity and GSH level. In conclusion, compounds I, III and IV, which significantly improved RBCs deformability in vitro , may facilitate the passage of blood in the vascular system. Additionally, compounds I and II which inhibit RBCs aggregates formation in vitro may contribute to more rapid degradation of red blood cell aggregates in circulating blood.
Abstract: BACKGROUND: Little is known about the effect of mean arterial blood pressure (MAP) augmentation on the microcirculation in cardiogenic-shock patients with peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) support. We investigated the effect of increasing MAP on the microcirculation in cardiogenic-shock patients with ECMO support. METHODS: A single-center prospective observational study under taken in ICU patients undergoing ECMO support for post-cardiotomy cardiogenic shock was carried out. Patients with MAP <60 mmHg treated with ECMO support were the study cohort. Inotropic and vasopressor agents (dopamine, dobutamine, norepinephrine or epinephrine) were administered to maintain the MAP at 60–90 mmHg. Hemodynamic and…microcirculatory data were obtained at a baseline MAP of <60 mmHg and 1 h after target MAP was reached. As parameters of microcirculation, we measured thenar eminence tissue oxygenation (StO2 ) and its change during the vessel obstruction test and cerebral tissue oxygenation (rSO2 ) with near-infrared spectroscopy. RESULTS: Seventeen patients were enrolled in the study. MAP of all patients increased and reached predefined therapeutic targets (52 [50–54.5] vs.74 [70–78.5] mmHg; p < 0.001). To obtain these targets, doses of inotropic agents were increased (inotrope score increased from 14 [15.5–28] μg/kg/min; p < 0.001). No obvious changes were observed in thenarmuscleStO2 and cerebral rSO2 . Thenar muscle StO2 desaturation slope and resaturation slopes during the vessel obstruction test were also unchanged. CONCLUSIONS: Increasing MAP from <60 mmHg to 60–90 mmHg did not affect microcirculation variables in cardiogenic-shock patients with ECMO support.
Abstract: In this ESCHM 2016 conference talk report, we summarise two recently published original articles Franco et al. PLoS Biology 2015 and Franco et al. eLIFE 2016. The vascular network undergoes extensive vessel remodelling to become fully functional. Is it well established that blood flow is a main driver for vascular remodelling. It has also been proposed that vessel pruning is a central process within physiological vessel remodelling. However, despite its central function, the cellular and molecular mechanisms regulating vessel regression, and their interaction with blood flow patterns, remain largely unexplained. We investigated the cellular process governing developmental vascular remodelling in…mouse and zebrafish. We established that polarised reorganization of endothelial cells is at the core of vessel regression, representing vessel anastomosis in reverse. Moreover, we established for the first time an axial polarity map for all endothelial cells together with an in silico method for the computation of the haemodynamic forces in the murine retinal vasculature. Using network-level analysis and microfluidics, we show that endothelial non-canonical Wnt signalling regulates endothelial sensitivity to shear forces. Loss of Wnt5a/11 renders endothelial cells more sensitive to shear, resulting in axial polarisation at lower shear stress levels. Collectively our data suggest that non-canonical Wnt signalling stabilizes forming vascular networks by reducing endothelial shear sensitivity, thus keeping vessels open under low flow conditions that prevail in the primitive plexus.
Abstract: The formation of a functionally-confluent and shear-resistant endothelial cell monolayer on cardiovascular implants is a promising strategy to prevent thrombogenic processes after implantation. On the basis of existing studies with arterial endothelial cells adhering after two hours on gelatin-based hydrogels in marked higher numbers compared to tissue culture plates, we hypothesize that also venous endothelial cells (HUVEC) should be able to adhere and form an endothelial monolayer on these hydrogels after days. Furthermore, variation of the hydrogel composition, which slightly influences the materials elasticity and even more the degradation behaviour, should have no considerable effect on HUVEC. Therefore, the monolayer…formation and shear resistance of HUVEC were explored on two gelatin-based hydrogels differing in their elasticity (Young’s moduli between 35 and 55 kPa) in comparison to a positive control (HUVEC on glass cover slips) and a negative control (HUVEC on glass cover slips activated with interleukin-1β) after 9 days of culturing. HUVEC density after 9 days of culturing under static conditions was lower on the hydrogels compared to both controls (p < 0.05 each). On G10_LNCO8 slightly more EC adhered than on G10_LNCO5. Staining of the actin cytoskeleton and VE-cadherin revealed a pronounced cell-substrate interaction while the cell-cell interaction was comparable to the controls (HUVEC on glass). The secretion of vasoactive and inflammatory mediators did not differ between the hydrogels and the controls. Adherent HUVEC seeded on the hydrogels were able to resist physiological shear forces and the release of cyto- and chemokines in response to the shear forces did not differ from controls (HUVEC on glass). Therefore, both gelatin-based hydrogels are a suitable substrate for EC and a promising candidate for cardiovascular applications.
Abstract: BACKGROUND: Sickle cell anemia (SCA) is an inherited blood disorder. SCA patients present clinical and hematologic variability that cannot be only explained by the single mutation in the beta-globin gene. Others genetic modifiers and environmental effects are important for the clinical phenotype. SCA patients present arginine deficiency that contributes to a lower nitric oxide (NO) bioactivity. OBJECTIVE: The aim of this work is to determine the association between hematological and biochemical parameters and genetic variants from eNOS gene, in pediatric SCA patients. METHODS: 26 pediatric SCA patients were genotyped using polymerase chain reaction (PCR)…and restriction fragment length polymorphism (RFLP) techniques in three important eNOS gene polymorphisms - rs2070744, rs1799983 and intron 4. RESULTS: Results from this study show a significant statistical association between some parameters and genetic variants: an increased reticulocyte count and high serum lactate dehydrogenase levels were associated with both the rs2070744_TT and the rs1799983_GG genotypes at eNOS gene and high levels of neutrophils were associated with the eNOS4a allele. CONCLUSIONS: Our results reinforce the importance of NO bioactivity in SCA. We presume that NO, and its precursors might be used as therapy to improve the quality of life of SCA patients.
Abstract: BACKGROUND: Surgical flaps have become reliable tools in the microsurgical armamentarium, but are still faced with tissue loss due to impaired perfusion which can lead to complete flap failure. Remote Ischemic Conditioning (RIC) has been demonstrated to be an effective way to improve microcirculation in surgical flaps in humans. However, little is known about the optimal amount and length of RIC cycles. OBJECTIVE: Determination of a superior protocol for RIC of cutaneous microcirculation in humans. METHODS: 60 healthy volunteers were randomized into different groups and received a RIC protocol, consisting of three cycles of either…1 second, 1, 5, or 10 minutes of ischemia followed by ten minutes of reperfusion. RIC was applied with a inflatable tourniquet placed on the upper arm. Changes in microcirculation were assessed via combined laser doppler/spectroscopy (O2C device) at the anterior lateral thigh. Relative increase at the end of conditioning vs. baseline measurements was calculated and compared between groups. RESULTS: RIC caused significant changes in cutaneous microcirculation (p < 0.05) which were more pronounced in groups with longer ischemia intervals. The ten minutes group was significantly superior. CONCLUSION: A conditioning protocol containing three cycles of ten minutes of ischemia is superior to protocols with shorter ischemia intervals for RIC of cutaneous microcirculation.
Abstract: BACKGROUND: Diabetic foot ulcers (DFU) are a major complication in diabetics. Impaired microvascular reactivity is a major contributor to the development of DFU and has been traditionally quantified by time-domain or frequency-domain measures of skin blood flow (SBF). These measures, however, are unable to characterize the changes of nonlinear dynamics of SBF associated with diabetes and peripheral neuropathy. OBJECTIVE: The objective of this study was to investigate altered nonlinear dynamics of skin blood flow in the plantar foot of diabetics with peripheral neuropathy. METHODS: 18 type 2 diabetics with peripheral neuropathy and 8 healthy controls…were recruited. SBF at the first metatarsal head in response to a loading pressure of 300 mmHg and a local heating was measured using laser Doppler flowmetry. A sample entropy approach was used to quantify the degree of regularity of SBF. RESULTS: Our results showed that the regularity degree of SBF in the diabetic foot underwent only small changes during post-occlusive reactive hyperemia and thermally induced biphasic response compared to non-diabetics. SBF of the diabetic foot has higher degree of irregularity during reactive hyperemia because of attenuated myogenic activity, and demonstrated higher regularity during the biphasic response largely due to significantly enhanced cardiac activities. CONCLUSIONS: This study suggests that the regularity degree of SBF at the first metatarsal head could be used to assess impaired microvascular reactivity and thus may be used to assess the risk for DFU in diabetics with peripheralneuropathy.
Abstract: OBJECTIVE: In a fulminant porcine sepsis model, we determined the kinetics of hypoxia induced changes in relation to sepsis parameters and markers of organ damage. METHODS: Female pigs were challenged by live Escherichia coli and samples were analysed up to 4 hours. Bone marrow reactions were determined by analysing immature forms of peripheral blood cells by a hematology analyser and light microscopy. Platelet mitochondrial membrane depolarisation was determined by flow cytometry. RESULTS: Core temperature, modified shock index and lactate levels all became significantly elevated compared to baseline values at 4 hours in septic animals.…At 2 hours already the reticulocyte count, nucleated red blood cell count and the absolute number of dysplastic platelets became significantly elevated. The platelet mitochondrial membrane depolarisation was significantly decreased by 2 hours in septic animals compared to the baseline values and to control animals. No massive organ damage was evident during the 4-hour observation period, but uric acid levels in septic animals became significantly elevated already by 2 hours. CONCLUSIONS: In this Escherichia coli induced porcine model, severe sepsis was evident by conventional criteria at 4 hours while several - mostly hypoxemia induced - biomarkers were already altered by 2 hours.
Keywords: Immature red blood cells and platelets, platelet apoptosis, sepsis
Abstract: OBJECTIVE: To determine the value of combining conventional ultrasonography with virtual touch tissue imaging quantification (VTIQ) for differential diagnosis of breast lesions smaller than 10 mm. METHODS: A total of 98 breast lesions smaller than 10 mm were examined by conventional ultrasound and VTIQ using a Siemens ACUSON S3000 ultrasound machine. Pathologic diagnosis was established after surgery or fine needle biopsy. RESULTS: Malignant lesions were characterized by taller-than-wide shape, poorly circumscribed margin, and marked hypoechogenicity. The mean VTIQ shear wave velocity (SWV) value of malignant lesions was 4.88±1.87 m/s (range, 1.75–9.34 m/s), significantly higher than that of benign lesions…(2.68±1.02 m/s; range, 1.18–4.67 m/s). The optimal cutoff SWV value was 3.27 m/s, with sensitivity, specificity, diagnostic accuracy, positive predictive value (PPV), and negative predictive value (NPV) of 86.20%, 95.65%, 92.86%, 89.29%, and 94.29%, respectively. The combination of SWV >3.27 m/s plus the US feature of poorly circumscribed margin had the highest sensitivity (93.33%) and specificity (100%) for diagnosis of malignant breast lesions. CONCLUSION: Features such as taller-than-wide shape, poorly circumscribed margin, and marked hypoechogenicity on conventional US, and SWV >3.27 m/s on VTIQ, are indicators of malignancy in breast lesions with diameter <10 mm. The combination of poorly circumscribed margin and SWV >3.27 m/s provides the highest specificity and diagnostic accuracy.
Keywords: Conventional ultrasonography, virtual touch tissue imaging quantification, breast lesions
Abstract: BACKGROUND: Tetrahydrobiopterin (BH4), an endogenous nucleic acid derivative, acts as an important cofactor for several enzymes found within the vascular endothelium, which is deranged in sepsis. OBJECTIVE: We hypothesized that BH4 would improve capillary density and decrease inflammation within the intestinal microcirculation of septic rats. METHODS: We conducted a randomized, controlled trial using two previously validated models of sepsis in rats: 1) A fecal peritonitis model using a stent perforating the ascending colon, and 2) An endotoxemia model using lipopolysaccharide (LPS) toxin from E. coli . Experimental groups receiving BH4 (60 mg/kg) were compared to otherwise…healthy controls and to untreated groups with sepsis-like physiology. RESULTS: BH4 decreased leukocyte-endothelial adhesion by 55% and 58% (P < 0.05) in the peritonitis model and endotoxemia models, respectively. In the endotoxemia model but not the peritonitis model, BH4 improved functional capillary density in capillary beds within the intestine (141.3 vs. 106.7 mm/cm2 , p < 0.05). Macrohemodynamic parameters were no different between placebo treatment and BH4-treated groups. CONCLUSIONS: This study demonstrates that BH4 improves capillary density and inflammation in two separate models of sepsis. BH4 may represent a novel adjunct in the treatment of sepsis and septic shock in clinical practice. Further dose-finding studies and clinical trials are warranted.
Keywords: Tetrahydrobiopterin, endotoxemia, peritonitis, sepsis, microcirculation, rat