Clinical Hemorheology and Microcirculation - Volume 69, issue 1-2

Authors: Negrão de Figueiredo, G. | Mueller-Peltzer, K. | Zengel, P. | Armbruster, M. | Rübenthaler, J. | Clevert, D.A.

Article Type: Research Article

Abstract: BACKGROUND: Contrast-enhanced ultrasound (CEUS) has been used as an additional imaging technique to conventional ultrasound in order to clarify gallbladder findings, CEUS is easy and fast to perform, overcomes the limitations of gray-scale ultrasonography and is a safe tool. OBJECTIVE: The aim of this retrospective mono-center analysis study is to evaluate the diagnostic performance of CEUS in the assessment of gallbladder disease by comparing its results with additional CT findings. METHODS: A total of 24 patients between 2009 and 2017 with unclear gallbladder appearance were retrospectively analysed. The contrast agent administered was a second-generation blood pool …agent (SonoVue® , Bracco, Milan, Italy). Examinations were performed and interpreted by a single experienced radiologist with more than fifteen years’ experience. RESULTS: 24 patients were successfully examined without any adverse reaction. CEUS presented a sensitivity of 75%, a specificity of 100.0%, a positive predictive value of 100.0% and a negative predictive value of 95%. CONCLUSIONS: In conclusion, the excellent results in this study acknowledged that CEUS is a feasible alternative tool to differentiate gallbladder pathologic alterations. Show more

Keywords: CEUS, gallbladder, pathologic alterations

DOI: 10.3233/CH-189116

Citation: Clinical Hemorheology and Microcirculation, vol. 69, no. 1-2, pp. 83-91, 2018

Authors: Apfelbeck, M. | Clevert, D.-A. | Ricke, J. | Stief, C. | Schlenker, B.

Article Type: Research Article

Abstract: INTRODUCTION: Reduced acceptance of radical prostatectomy in patients with low risk or intermediate risk prostate cancer has significantly changed treatment strategies in prostate cancer (PCa) during the last years. Focal therapy of the prostate with high intensity focused ultrasound (HIFU) is an organ-preserving treatment for prostate cancer with less impairment of health-related quality of life. Follow-up after HIFU therapy by imaging modalities remains a major problem as eg. MRI performs poorly. Contrast enhanced ultrasound (CEUS) allows to monitor the vascular architecture of organs non-invasively. However, only limited data are available using CEUS to define successful and complete HIFU treatment of …the prostate. In this study, we aimed to evaluate short-term image findings using CEUS and image fusion before and after HIFU treatment. MATERIALS AND METHODS: Prospective single arm study in patients with uni- or bilateral, low or intermediate risk prostate cancer or recurrent cancer after radiotherapy treated with HIFU at our institution between October 2016 and November 2017. HIFU hemiablation or whole gland treatment was performed using the Focal One® device. PCa was diagnosed either by multiparametric magnetic resonance imaging (mpMRI) followed by MRI fusion based targeted biopsy combined with 12 core transrectal ultrasound (TRUS) guided biopsy or 12 core random biopsy only. Monitoring of the target region before, immediately and 24 hours after the ablation was done by CEUS in combination with image fusion using an axial T2-weighted MRI sequence. RESULTS: 6 consecutive patients with Gleason score (GS) 6, 5 patients with GS 7a prostate cancer and one patient with biochemical recurrence after radiotherapy were included in the study. Three patients underwent whole gland treatment due to histological proven bilateral PCa or recurrent PCa after radiotherapy. Hemiablation was performed in 9 patients with unilateral tumor and no PIRADS 4 or 5 lesion in the contralateral lobe. Median patient age was 69.8 years and median PSA (prostate-specific antigen) level was 8.4 ng/ml. CEUS showed markedly reduced microbubbles in the ablated area, the prostate capsule still showed signs of perfusion. The study is limited by the short follow up and small number of patients. CONCLUSIONS: CEUS examination showed a reduction of microcirculation in the treated area immediately after the treatment and 24 hours later. The combination of CEUS and image fusion seems to be helpful for detecting the PCa target lesion and monitor the success of HIFU ablation treatment. Evidence for image findings after HIFU-therapy are rare. Further studies on this topic are needed. Show more

Keywords: High intensity focused ultrasound therapy, image fusion, prostate, CEUS, contrast enhanced ultrasound

DOI: 10.3233/CH-189123

Citation: Clinical Hemorheology and Microcirculation, vol. 69, no. 1-2, pp. 93-100, 2018

Authors: Tsikouras, Panagiotis | Niesigk, Barbara | von Tempelhoff, Georg-Friedrich | Rath, Werner | Schelkunov, Olga | Daragó, Peter | Csorba, Roland

Article Type: Research Article

Abstract: INTRODUCTION: Recent studies have shown increased RBC aggregation and no difference in plasma viscosity in the presence of markedly lower hematocrit in women at term compared to non-pregnant women. Little is known about the outcome of blood rheological parameters and red blood cell (RBC) deformability particularly in the course of normal pregnancy. METHODS: During a 36 months interval 1.913 blood samples were randomly collected from a total of 945 pregnant women in the course of their pregnancy (n  = 1.259) and during puerperium (upto 1 week; n  = 654). Next to the blood count, hemorheological parameters including red blood cell …(RBC) -aggregation (stasis E0; low shear E1), -deformability (low, moderate and high shear conditions) and plasma viscosity (pv) were assessed. Plasma viscosity (pv) was examined using KSPV 1 Fresenius, RBC aggregation (stasis: E0 and low shear: E1) using MA1-Aggregometer; Myrenne and RBC deformability (def) was determined by Rheodyn SSD Diffractometer, Myrenne, Roetgen, Germany were tested. In some of these women laboratory results prior to pregnancy (n  = 145) were available which were compared with those during pregnancy. RESULTS: Mean maternal pv remained unchanged within each trimester and compared to the values before pregnancy and during early puerperium (Range of means: 1.18–1.20 mPa S). In contrast, RBC agg (E0 and E1) was markedly higher in the 2nd (21.8 ± 7.0 and 28.9 ± 9.4; p  < 0.001) and 3rd trimester (18.74 ± 8.4 and 28.2 ± 9.4; p  < 0.01) compared to the values before pregnancy (16.4 ± 6.4 and 20 ± 7.5) and during 1st trimester (17.49 ± 6.5 and 22.4 ± 7.4). There was a stat. significant temporary reduction in RBC def. under all shear rate conditions during 2nd trimester compared to the values before pregnancy which remained significantly lower during 3rd trimester only under high shear rates. An increase RBC agg was stat. significantly inversely correlated with reduced RBC def being most pronounced under low shear rate conditions. While RBC rigidity was stat. significantly correlated with higher hematocrit values there was only a weak correlation between RBC agg and haematocrit (E0: r  = –0.084; p  = 0.03; E1: r  = –0.06; p  = 0.1). Pv was not correlated with haematocrit or RBC def but stat. significantly correlated with RBC agg. CONCLUSIONS: Blood rheological changes manifest during 1st trimester, and fairly remain unchanged during 2nd trimester until term. Physiologic hemodilution and increasing hypercoagulability is accompanied by high RBC -aggregation and – rigidity during 2nd trimester while plasma viscosity remains nearly unaffected throughout normal pregnancy. Show more

Keywords: Normal pregnancy, haemorheology, red blood cell aggregation, red blood cell deformability

DOI: 10.3233/CH-189104

Citation: Clinical Hemorheology and Microcirculation, vol. 69, no. 1-2, pp. 101-114, 2018

Authors: Oelert, Anja | Kittel, Manuela | Hahn, Martin | Haase, Hermann | Jünger, Michael

Article Type: Research Article

Abstract: In five patients who suffered from chronic venous insufficiency clinical stage C4 (n  = 3) and C6 (n  = 2) the capillary blood pressure was measured twice by means of invasive direct cannulation of nailfold capillaries of the toe. During one measurement course the patients wore below knee medical compression stockings (40 mmHg) during the other they did not have compression therapy. With the patient in supine position, the CP was investigated by the servo-nulling technique under resting conditions and under dynamic conditions: the calf-muscle/ankle joint venous pump was simulated by means of inflating a blood pressure cuff, which surrounded the mid …lower leg, to 60 mmHg for 60 s. Results: The simulated calf-muscle contraction induced a steep increase of CP with 5.65 mmHg/s (Q1 5.27 mmHg/s, Q3 5.92 mmHg/s), which was significantly (p  = 0.013) reduced by MCS to 2.47 mmHg/s (Q1 1.65 mmHg/s, Q3 3.0 mmHg/s). Time needed to reach the max. CP was 11.35 s, which was lengthened by MCS to 23.4 s (p  = 0.134). Conclusion: Compression therapy prevents capillary hypertension, the major hemodynamic reason for the development of advanced stages of chronic venous insufficiency which are defined by skin disease like hyperpigmentation, lipodermatosclerosis and ulcer. Show more

Keywords: Chronic venous insufficiency, dermal capillary blood pressure, cutaneous microcirculation, dermal capillary hypertension, pathophysiology of chronic venous insufficiency, servo nulling pressure measurement

DOI: 10.3233/CH-189122

Citation: Clinical Hemorheology and Microcirculation, vol. 69, no. 1-2, pp. 115-121, 2018

Authors: Wernly, Bernhard | Lichtenauer, Michael | Vellinga, Namkje A.R. | Boerma, E. Christiaan | Ince, Can | Kelm, Malte | Jung, Christian

Article Type: Research Article

Abstract: BACKGROUND AND PURPOSE: The Microcirculatory Shock Occurrence in Acutely Ill Patients (micro-SOAP) study investigated associations of microcirculation and mortality. Risk stratification in critically ill patients is of utmost interest. Established score such as APACHE2 (Acute Physiology And Chronic Health Evaluation 2) are relatively complex and might therefore be of limited use. Blood urea nitrogen (BUN) was described to be associated with mortality in various diseases. We therefore aimed (i) to evaluate BUN for prediction of mortality in a cohort of critically ill patients and (ii) to investigate associations of BUN with microcirculation. METHODS: 412 patients were included in …our post-hoc analysis of the prospective multicenter microSOAP study. Assesment of the sublingual microcirculation (Sidestream Dark Field (SDF) imaging) and collection of laboratory values were performed on the same day in this point prevalence study. Evaluation of associations with mortality was done by logistic regression analysis. An optimal BUN cut-off was calculated by means of the Youden Index. RESULTS: Median BUN was 9.0 mmol/L. BUN was associated with in-hospital-mortality in a logistic regression analysis (HR 1.03; 95% CI 1.01–1.05; p  < 0.001). Per quartile (BUN 0–5.4 mmol/L, 5.4–9.0 mmol/L, 9.0–15.9 mmol/L and above 15.9 mmol/L) in-hospital mortality increased by as much as 51% (HR 1.51; 95% CI 1.23–1.85; p  < 0.001). ROC analysis was done (AUC 0.63 95% CI 0.58–0.67) and the statistically optimal cut-off calculated by means of the Youden Index: 9.7 mmol/L. This cut-off was associated with a significant 3-fold increase in mortality (HR 2.97 95% CI 1.88–4.70; p  < 0.001) and remained robustly associated with adverse outcome after correction for APACHE2 (HR 2.71 95% CI 1.61–4.59; p  < 0.001), renal function as expressed by creatinine (HR 2.63 95% CI 1.59–4.33; p  = 0.001), as well in an integrative model (MAP<60 mmHg, tachycardia (heart rate >90/min), lactate above 1.5 mmol/L, age above 80 years; HR 2.43 95% CI 1.50–3.92; p  < 0.001). Parameters of microvascular perfusion were associated neither with BUN nor mortality. CONCLUSIONS: BUN is associated with hospital mortality and a combination of BUN and clinical signs might constitute a powerful but easy-to-use tool for risk stratification in critically ill patients and help improve their outcome. BUN was not associated with parameters of microcirculation which were not associated with mortality. Show more

Keywords: Critically ill, BUN, ICU, risk stratification, risk score, microcirculation

DOI: 10.3233/CH-189111

Citation: Clinical Hemorheology and Microcirculation, vol. 69, no. 1-2, pp. 123-131, 2018

Authors: Nemeth, Norbert | Deak, Adam | Szentkereszty, Zsolt | Peto, Katalin

Article Type: Research Article

Abstract: In surgical pathophysiology ischemia-reperfusion, inflammatory processes, sepsis, vascular interventions, tissue trauma, shock, all mean conditions in which hemorheological parameters show alterations. Despite of numerous clinical and experimental studies, the in vivo hemorheology is not completely understood yet, and several fundamental questions still need to be answered. Investigating these issues, experimental surgical models are important, in point of view of the translational research as well. In this paper we aimed to make an attempt on summarizing the possible factors and conditions that might have an effect on hemorheological results in experimental surgical studies. Hemorheological parameters show alterations in surgical pathophysiological …processes in a complex way. However, the changes are dominantly non-specific. Standardized experimental conditions, related to the experimental animal (species, animal welfare) anesthesia-medications, operation, sampling and, if applicable, conditions of the postoperative period, are inevitable for a safe assessment of valuable (hemorheological) results. Parallel investigations – such as microcirculatory monitoring, imaging techniques, other laboratory methods, histomorphology– have great importance, together with individual analysis of changes, for a better understanding of the changes and for comparability with clinical results. Show more

Keywords: Hemorheology, experimental surgery, experimental design, inter-species differences

DOI: 10.3233/CH-189105

Citation: Clinical Hemorheology and Microcirculation, vol. 69, no. 1-2, pp. 133-140, 2018

Authors: Felthaus, Oliver | Schön, Teresa | Schiltz, Daniel | Aung, Thiha | Kühlmann, Britta | Jung, Friedrich | Anker, Alexandra | Klein, Silvan | Prantl, Lukas

Article Type: Research Article

Abstract: BACKGROUND: Multiple symmetric lipomatosis is a rare disease characterized by the excessive growth of uncapsulated masses of adipose tissue. Although the etiology has yet to be elucidated, a connection to brown adipose tissue has been proposed recently. The mTOR pathway which is found to be regulated in lipomatous tissue as well as associated with brown adipose tissue can be inhibited by a compound called rapamycin. METHODS: We isolated adipose tissue derived stem cells from both affected and unaffected tissue and treated these cells with different concentrations of rapamycin. RESULTS: The differences in both proliferation and differentiation …between adipose tissue derived stem cells (ASCs) from lipomatous and normal tissue decreased after mTOR pathway inhibition. In some patients regulation of mTOR genes was opposed in the ASCs from the two different tissues. CONCLUSIONS: Treatment with rapamycin might be a novel therapeutical approach for patients suffering from multiple symmetric lipomatosis. Show more

Keywords: Multiple symmetric lipomatosis, rare disease, mTOR pathway, rapamycin

DOI: 10.3233/CH-189107

Citation: Clinical Hemorheology and Microcirculation, vol. 69, no. 1-2, pp. 141-151, 2018

Authors: Arora, N. | Caldwell, A. | Wafa, K. | Szczesniak, A. | Caldwell, M. | Al-Banna, N. | Sharawy, N. | Islam, S. | Zhou, J. | Holbein, B.E. | Kelly, M.E.M. | Lehmann, Ch.

Article Type: Research Article

Abstract: BACKGROUND/OBJECTIVE: Non-infectious uveitis is an inflammatory disease of the eye commonly treated by corticosteroids, though important side effects may result. A main mediator of inflammation are oxygen free radicals generated in iron-dependent pathways. As such, we investigated the efficacy of a novel iron chelator, DIBI, as an anti-inflammatory agent in local and systemic models of endotoxin induced uveitis (EIU). METHODS: Firstly, the effects of DIBI in systemic EIU in Lewis rats were established. 2 hours post intravenous LPS or LPS/DIBI injections, leukocyte activation and functional capillary density (FCD) were examined using intravital microscopy (IVM) of the iridial microcirculation. …Secondly, the toxicity of DIBI was evaluated in BALB/C mice for both acute and chronic dosages through gross ocular examination, intraocular pressure measurements and hematoxylin-eosin staining of ocular tissue. Lastly, three groups of BALB/C mice, control, LPS or DIBI + LPS, were studied to evaluate the effectiveness of DIBI in treating local EIU. Five hours post-local intravitreal (i.v) injection, leukocyte activation and capillary density were examined via IVM. RESULTS: Treatment of systemic EIU with DIBI resulted in a reduction of leukocyte activation and FCD improvement within the iridial microcirculation. Toxicity studies suggested that acute and chronic DIBI administration had no adverse effects in the eye. In the local EIU model, DIBI was shown to reduce leukocyte activation and restored the FCD/DCD ratio, providing evidence for its anti-inflammatory properties. CONCLUSIONS: Our study has provided evidence that DIBI has anti-inflammatory effects in experimental uveitis. Additionally, no local ocular toxicity was observed. Show more

Keywords: Iron chelation, ocular inflammation, endotoxin, intravital microscopy, microcirculation

DOI: 10.3233/CH-189109

Citation: Clinical Hemorheology and Microcirculation, vol. 69, no. 1-2, pp. 153-164, 2018

Authors: Saldanha, Carlota | Freitas, Teresa | Silva-Herdade, Ana Santos

Article Type: Research Article

Abstract: Timolol maleate is a compound used in treatment for reducing increased intra-ocular pressure by limiting aqueous humor production. Decreased erythrocyte deformability (ED), increased activity of erythrocyte acetylcholinesterase (AChE), increased values of nitrosoglutathione (GSNO) and nitic oxide (NO) and decreased plasma levels of NO metabolites, were described in primary open angle glaucoma patients. In healthy human red blood cells (RBCs), timolol is an inhibitor of AChE and induces NO efflux and GSNO efflux from that blood component in lower concentration than those obtained in presence of the natural AChE substrate, acetylcholine (ACh). The signal transduction pathway in RBCs described for NO …in dependence of AChE-ACh active complex involves Gi protein, protein tyrosine kinase (PTK like Syk and p53/56Lyn), protein tyrosine phosphatase (PTP) and adenylyl cyclase (AC). The aim of this in vitro study was to verify the effect of timolol maleate in ED, NO efflux and NO derivatives molecules (NOx) like nitrite (NO2 – ), nitrate (NO3 – , peroxynitrite (– ONOO) and GSNO under the presence of PTK, PTP, AC and guanylyl cyclase (GC) enzyme proteins inhibitors. Blood samples from healthy donors were each one divided and were performed aliquots in absence (control aliquots) and presence of timolol or timolol plus each inhibitor and Gi protein uncoupling. No significant differences in erythrocyte NO efflux, GSNO, peroxynitrite, nitrite and nitrate concentrations in response to timolol when compared with the untreated blood samples aliquots were obtained. It was observed an increase in erythrocyte deformability at high shear stresses induced by the simultaneous presence of timolol and band 3 protein dephosphorylation by PTK syk inhibitor. No significant differences where verified in peroxynitrite levels in the blood aliquots in presence of timolol plus each enzyme inhibitor and Gi protein uncoupling in relation to the control aliquots. No variation of GSNO concentration occurs under the presence of timolol and AMGT (PTK lyn inhibitor) besides the significant higher values observed with each one of the other inhibitors. Nitrate concentration increases significantly in all aliquots with timolol plus each one of the inhibitors. The same was observe with nitrite levels with exception of the aliquots with timolol plus AMGT or timolol plus Gi protein uncoupling showing no significant values in relation to the control aliquots. Besides the changes in NO derivative molecules and NO efflux from RBCs obtained in this study with blood samples of healthy donors under the effect of timolol plus each inhibitor of the proteins participants in NO signal transduction mechanism, further analogue studies must be promoted with blood samples of patients with glaucoma or any other inflammatory vascular disease. Show more

Keywords: Erythrocyte deformability, nitric oxide, acetylcholinesterase, timolol

DOI: 10.3233/CH-189110

Citation: Clinical Hemorheology and Microcirculation, vol. 69, no. 1-2, pp. 165-173, 2018

Authors: Kumar, Reddi K. | Heuchel, Matthias | Kratz, Karl | Lendlein, Andreas | Jankowski, Joachim | Tetali, Sarada D.

Article Type: Research Article

Abstract: Remaining uremic toxins in the blood of chronic renal failure patients represent one central challenge in hemodialysis therapies. Highly porous poly(ether imide) (PEI) microparticles have been recently introduced as candidate absorber materials, which show a high absorption capacity for uremic toxins and allow hydrophilic surface modification suitable for minimization of serum protein absorption. In this work, the effects of extracts prepared from PEI microparticles modified by nucleophilic reaction with low molecular weight polyethylene imine (Pei) or potassium hydroxide (KOH), on human monocytic (THP-1) cells are studied. The obtained results suggested that the extracts of Pei and KOH modified PEI absorbers …have no negative effect on THP-1 cell viability and do not initiate the critical differentiation towards macrophages. The extracts did not enhance transcript or protein levels of investigated proinflammatory markers in THP-1 cells, namely, TNFμ, MCP1, IL6 and IL8. Based on these findings such modified PEI microparticles should be qualified for further pre-clinical evaluation i.e. in an in vivo animal experiment. Show more

Keywords: Chronic kidney disease, hemodialysis, Inflammation, Porous poly(ether imide) microparticulate absorbers, THP-1 cells, Uremic toxins

DOI: 10.3233/CH-189112

Citation: Clinical Hemorheology and Microcirculation, vol. 69, no. 1-2, pp. 175-185, 2018