Clinical Hemorheology and Microcirculation - Volume 56, issue 4

Authors: Lang, Sven A. | Moser, Christian | Gehmert, Sebastian | Pfister, Karin | Hackl, Christina | Schnitzbauer, Andreas A. | Stroszczynski, Christian | Schlitt, Hans J. | Geissler, Edward K. | Jung, Ernst M.

Article Type: Research Article

Abstract: OBJECTIVE: To assess the effects of vascular-disrupting agent (VDA)-based therapy including monitoring of therapeutic efficacy with contrast-enhanced ultrasound (CEUS) in a gastric cancer model. MATERIALS & METHODS: Gastric cancer cell lines and endothelial cells were used. Effects of the VDA ASA404 on cells were determined by MTT assays and Western blotting in vitro. Therapeutic efficacy of ASA404 was assessed in vivo in a subcutaneous mouse model in combination with paclitaxel. CEUS with TIC (time intensity curve) analyses was employed to measure tumor perfusion. Finally, tumor tissue was harvested and processed for histological work-up. RESULTS: In vitro, ASA404 impaired growth of …ECs upon stimulation with conditioned media from gastric cancer cells. No direct effects on tumor cells were observed. In vivo treatment with ASA404 in combination with paclitaxel led to significant decrease of tumor microvascularization as determined by CEUS. Furthermore, combination of ASA404 with paclitaxel showed a significant inhibition of tumor growth which was paralleled by strong reduction of tumor cell proliferation and vessel area. CONCLUSION: VDA-based therapy in combination with paclitaxel, and therapy monitoring by CEUS, appears to be a promising strategy for gastric cancer. Show more

DOI: 10.3233/CH-121658

Citation: Clinical Hemorheology and Microcirculation, vol. 56, no. 4, pp. 287-299, 2014

Authors: Guerci, Philippe | Tran, Nguyen | Menu, Patrick | Losser, Marie-Reine | Meistelman, Claude | Longrois, Dan

Article Type: Research Article

Abstract: The choice of volume expander for fluid resuscitation in hemorrhagic shock is still debated. Changes in plasma viscosity (PV) are barely investigated while PV modulates functional capillary density, microcirculation and organ function. The present study evaluated the impact of 2 strategies of fluid resuscitation in hemorrhagic shock in pigs. Ten pigs were subjected to hemorrhagic shock and randomly assigned to a low viscosity fluid regimen (Lactated Ringer's, LR) group or a high viscosity regimen (hypertonic-hydroxyethyl starch, HES) for volume resuscitation. Sublingual microcirculatory flow and tissue oxygen tension were assessed together with macro- and microcirculatory, biochemical and rheological variables at baseline, …30 minutes after hemorrhagic shock, immediately after reaching resuscitation endpoints (R-0), and 60 minutes after resuscitation (R-60). PV decreased similarly in both groups following resuscitation (from 1.36 [1.32–1.38] to 1.21 [1.21–1.23] for LR, and from 1.32 [1.31–1.32] to 1.20 [1.17–1.21] mPa.s for HES). No differences were found between the groups for other rheological variables, microcirculatory flow or tissue oxygen tension at R-0 and R-60. Despite a 6-fold difference in the volumes required to achieve blood flow endpoints, commercially available volume expanders had similar effects on rheological and microcirculatory variables, irrespective of their viscosity. Our findings are consistent with the absence of clinically relevant differences between crystalloid and colloid resuscitation of hemorrhagic shock. Show more

Keywords: Hemorrhagic shock, volume expander, plasma viscosity, microcirculation, pigs, functional capillary density

DOI: 10.3233/CH-141663

Citation: Clinical Hemorheology and Microcirculation, vol. 56, no. 4, pp. 301-317, 2014

Authors: Vayá, Amparo | Rivera, Leonor | Todolí, José | Hernandez, Jose Luis | Laiz, Begoña | Ricart, José M.

Article Type: Research Article

Abstract: Red blood cell distribution width (RDW) has been shown to be associated with disease activity in several inflammatory disorders. However only one study to show this has been conducted in patients with Behçet's disease (BD). The aim of the present study was to analyse the association of RDW with BD and its main complications; i.e.; thrombosis and posterior uveitis. A second aim was to analyse the possible correlation between RDW and both haematological and inflammatory parameters. Eighty-nine patients with BD (48 males/41 females) and 94 controls (49 males/45 females) were included in the study. Patients were in an inactive phase …of the disease, showing only minimum activity. RDW was statistically higher in patients than in controls (14.02 ± 1.32 vs. 13.15 ± 0.75; p < 0.001) as were CRP, fibrinogen, leucocytes and neutrophils (p < 0.001). No differences in haematimetric indices (MCV, MCH, MCHC) were observed (p > 0.05). RDW correlated negatively with haemoglobin, MCH and MCHC (p < 0.05), and directly with homocysteine (p < 0.01). No correlation was found between RDW and the several inflammatory parameters analysed (p > 0.05). The multivariate regression analysis revealed that haemoglobin and homocysteine were independent predictors of RDW (beta coefficient: −0.310; p = 0.003, beta coefficient: 0.379; p < 0.001, respectively). RDW >14 was associated with neither thrombosis nor uveitis (p = 0.935; p = 0.553, respectively). Our results indicate that BD patients show increased RDW when compared with controls. This increase seems to be related with haematimetric indices and with homocysteine levels. Lack of correlation with inflammatory markers may be due to the fact that patients were in an inactive phase of the disease. Show more

Keywords: Red blood cell distribution width, Behçet's disease, thrombosis, posterior uveitis

DOI: 10.3233/CH-131744

Citation: Clinical Hemorheology and Microcirculation, vol. 56, no. 4, pp. 319-324, 2014

Authors: Fornal, Maria | Wizner, Barbara | Cwynar, Marcin | Królczyk, Jarosław | Kwater, Aleksander | Korbut, Renata A. | Grodzicki, Tomasz

Article Type: Research Article

Abstract: OBJECTIVES: To assess the relationships of red blood cell distribution width (RDW), mean corpuscular hemoglobin concentration (MCHC) and erythrocyte deformability with pathological changes of selected target organs, and with inflammation markers interleukin-6 (IL-6) and fibrinogen, in a group of newly diagnosed, never-treated and otherwise healthy hypertensive patients. METHODS: The study group consisted of 101 adults divided into three sub-groups: 37 diagnosed arterial hypertension, 29 with hypercholesterolemia, and 35 healthy. The individuals with hypertension or hypercholesterolemia were otherwise healthy and were not on any therapy prior to entering the study. For each individual, data were obtained on: systolic and diastolic blood …pressure (SBP, DBP), pulse wave velocity (PWV), carotid intima media thickness (IMT), left ventricle geometry, blood morphology, lipids profile, fibrinogen, CRP, IL-6 and red blood cell deformability index (DI). RESULTS: In the group of hypertensives, the multivariate regression analysis showed significant relationship of RDW with PWV, IL6 and fibrinogen. Also, RDW was found to be correlated with MCHC and DI, and MCHC was significantly related to IMT and IL-6. CONCLUSIONS: A hypothesis has been formulated that the development of target organ damage in hypertension is accompanied by the increasing impairment of erythropoiesis. This process may be mediated by inflammation. Show more

Keywords: Essential hypertension, red blood cell distribution width, mean corpuscular hemoglobin concentration, erythrocyte deformability, interleukin-6, fibrinogen

DOI: 10.3233/CH-131745

Citation: Clinical Hemorheology and Microcirculation, vol. 56, no. 4, pp. 325-335, 2014

Authors: Daly, Amanda | Raval, Jay S. | Waters, Jonathan H. | Yazer, Mark H. | Kameneva, Marina V.

Article Type: Research Article

Abstract: It was previously demonstrated that red blood cell (RBC) deformability progressively decreases during storage along with other changes in RBC mechanical properties. Recently, we reported that the magnitude of changes in RBC mechanical fragility associated with blood bank storage in a variety of additive solutions was strongly dependent on the donor gender [15]. Yet, the potential dependence of changes in the deformability and relaxation time of stored blood bank RBCs on donor gender is not known. The objective of this study was to determine the effects of donor gender and blood bank storage on RBC deformability and relaxation time through …the measurement of RBC suspension viscoelasticity. Packed RBC units preserved in AS-5 solution from 12 male and 12 female donors (three from each ABO group) were obtained from the local blood center and tested at 1, 4 and 7 weeks of storage at 1–6°C. At each time point, samples were aseptically removed from RBC units and hematocrit was adjusted to 40% before assessment of cell suspension viscoelasticity. RBC suspensions from both genders demonstrated progressive increases (p < 0.05) in viscosity, elasticity and relaxation time at equivalent shear rates over seven weeks of storage indicating a decrease in RBC deformability. No statistically significant differences in RBC deformability or relaxation time were observed between male and female RBCs at any storage time. The decrease in RBC deformability during blood bank storage may reduce tissue perfusion and RBC lifespan in patients receiving blood bank RBCs. Show more

Keywords: Donor RBCs, storage lesions, male and premenopausal female, RBC elasticity/deformability, mechanical fragility

DOI: 10.3233/CH-131754

Citation: Clinical Hemorheology and Microcirculation, vol. 56, no. 4, pp. 337-345, 2014

Authors: Martini, Romeo | Ticcinelli, Valentina | Bagno, Andrea

Article Type: Research Article

Abstract: The skin flowmotion of 13 patients suffering from critical limb ischemia (CLI) was studied with wavelet analysis (WA) of the laser Doppler signals (LDS). The WA selects six different frequency components (FCs), each relating to a specific cardiovascular system structures activities; FC I 1–2 Hz heart, FC II 0.2 Hz respiratory, FC III 0.1 Hz myogenic, FC IV 0.04 Hz, sympathetic, FC V 0.01 Hz, and FC VI 0.007 Hz endothelial. The aim of the study was to observe which FC changed after the limb revascularization. The LDS was measured at the dorsum of the foot, one week before and …no later than 30 days after revascularisation. The absolute and relative amplitude and energy of the flowmotion WA FCs, the ankle brachial pressure index (ABI) and the transcutaneous pressure of oxygen (TcpO2) were assessed before and after revascularization. The results showed that after successful revascularization ABI and TcpO2 increased from 0.34 ± 0.10 to 0.54 ± 0.09 (p 0.0003) and from 20.3 ± 13.4 to 43.8 ± 18.7 mmHg (p 0.0002) whereas only the absolute amplitude and energy of the cardiac FC I increased from 0.57 ± 0.44 to 1.07 ± 0.69 (P 0.002) AU and 1.14 ± 1.78 AU2 to 3.54 ± 3.78 AU2 (p 0.004). In conclusion after limb revascularization the cardiac component of the flowmotion increased maybe because the cardiac stroke volume had more influence over the skin arterioles. Show more

Keywords: Critical limb ischemia, revascularisation, flowmotion

DOI: 10.3233/CH-131755

Citation: Clinical Hemorheology and Microcirculation, vol. 56, no. 4, pp. 347-358, 2014

Authors: Caimi, G. | Hopps, E. | Montana, M. | Carollo, C. | Calandrino, V. | Incalcaterra, E. | Canino, B. | Lo Presti, R.

Article Type: Research Article

Abstract: We determined the concentration of nitric oxide metabolites (NO2 − +NO3 − ), expressed as NOx, in several clinical conditions. Regarding this, we have examined 25 subjects with arterial hypertension, 41 subjects with chronic kidney disease in conservative treatment, 106 subjects with metabolic syndrome subdivided according to the presence (n = 43) or not (n = 63) of diabetes mellitus, 48 subjects with obstructive sleep apnea syndrome (OSAS), 14 women with systemic sclerosis complicated with Raynaud's phenomenon, 42 dialyzed subjects and 105 young subjects with acute myocardial infarction (AMI). In subjects with arterial hypertension, chronic kidney disease, metabolic syndrome, systemic …sclerosis, as well as, in dialyzed and AMI subjects, we found at baseline a NOx increase. In dyalized subjects after a standard dialysis session, we observed a decrease in NOx. The increase in NOx in juvenile AMI was significantly influenced by cigarette smoking and less by cardiovascular risk factors and the extent of coronary lesions; at 3 and 12 months later than the initial event, we observed a decrease of NOx that remains significantly higher than the control group. In subjects with OSAS no difference in NOx was noted in comparison with normal controls, although their subdivision according to the apnea/hypopnea index operates a clear distinction regarding NOx concentration. Show more

Keywords: NOx, hypertension, kidney disease, metabolic syndrome, OSAS, sistemic sclerosis, dialysis, AMI

DOI: 10.3233/CH-131758

Citation: Clinical Hemorheology and Microcirculation, vol. 56, no. 4, pp. 359-369, 2014

Authors: Arbel, Yaron | Szekely, Yishay | Berliner, Shlomo | Hallevi, Hen | Halkin, Amir | Herz, Itzhak | Keren, Gad | Bazan, Shmuel | Bornstein, Natan | Banai, Shmuel | Finkelstein, Ariel

Article Type: Research Article

Abstract: BACKGROUND: The phenomenon of slow coronary flow (SCF) in the presence of normal coronary arteries may indicate endothelial dysfunction, which is characteristic of an early stage in the development of atherosclerosis. Measurement of the Carotid Intima-Media Thickness (CIMT) allows identification of early stages of atherosclerosis. CIMT might offer a non-invasive method of diagnosing SCF patients. Previous studies demonstrated conflicting results regarding the relationship between these two phenomena. In the present study, we examined the association between coronary flow velocity and the degree of CIMT in patients with angiographically normal coronary arteries. METHODS: Coronary arterial blood flow velocity was measured using …two methods - Corrected Thrombolysis in Myocardial Infarction (TIMI) Frame Count (CTFC) and Coronary Clearance Frame Count (CCFC). In addition, we measured the level of the CIMT using a special automated computerized software. RESULTS: Seventy Five consecutive patients were prospectively recruited. No correlation was found between CIMT and mean CTFC (r = −0.08, p = NS) or mean CCFC (r = −0.07, p = NS). In addition, CIMT values did not differ between the SCF and the Normal coronary flow (NCF) groups (0.796 mm vs. 0.805 mm, respectively, p = 0.733). Patients with SCF had higher levels of hematocrit (39.9% vs. 36.1%, p < 0.001), LDL cholesterol (101.1 mg/dl vs. 85.8 mg/dl, p = 0.01) and higher rate of current smokers (28.9% vs. 10.8%, p = 0.05). CONCLUSIONS: Patients with angiographically normal coronary arteries and SCF do not have increased CIMT values. However, current smoking, higher LDL cholesterol and hematocrit levels are all related to slower coronary blood flow. Show more

Keywords: Normal coronary arteries, coronary flow, TIMI frame count, carotid intima-media thickness, smoking, slow flow

DOI: 10.3233/CH-141808

Citation: Clinical Hemorheology and Microcirculation, vol. 56, no. 4, pp. 371-381, 2014

Article Type: Other

Citation: Clinical Hemorheology and Microcirculation, vol. 56, no. 4, pp. 383-389, 2014