Clinical Hemorheology and Microcirculation - Volume 59, issue 2

Authors: Vitorino de Almeida, V. | Silva-Herdade, A. | Calado, A. | Rosário, H.S. | Saldanha, C.

Article Type: Research Article

Abstract: Besides playing an important role in blood hemostases, fibrinogen also regulates leukocyte function in inflammation. Our previous in vitro studies showed that the adhesive behaviour of the neutrophil is modulated by soluble fibrinogen when present at a physiological concentration. This led us to propose that this plasma glycoprotein might further influence leukocyte recruitment in vivo and thus contribute to the inflammatory response. To address this in vivo, leukocyte recruitment was here investigated under acute inflammatory conditions in the absence of soluble fibrinogen in the blood circulation. For such, intravital microscopy on mesentery post-capillary venules was performed on homozygous fibrinogen α …chain-deficient mice ((α−/− ) mice). Acute inflammatory states were induced by perfusing platelet activating factor (PAF) over the exposed tissue. As control animals, two groups of mice expressing soluble fibrinogen in circulation were used, namely, C57BL/6 wild type animals and heterozygous fibrinogen α chain-deficient mice ((α+/− ) mice). Under acute inflammatory conditions, an abnormal pattern of recruitment was observed for leukocytes in homozygous (α−/− ) mice in comparison to both control groups. In fact, the former exhibited a significantly decreased number of rolling leukocytes that nevertheless, migrated with increased rolling velocities when compared to leukocytes from control animals. Consistently, homozygous mice further displayed a diminished number of adherent leukocytes than the other groups. Altogether our observations led us to conclude that leukocyte recruitment in homozygous (α−/− ) mice is compromised what strongly suggests a role for soluble fibrinogen in leukocyte recruitment in inflammation. Show more

Keywords: Neutrophil recruitment, fibrinogen, intravital microscopy, Inflammation

DOI: 10.3233/CH-121660

Citation: Clinical Hemorheology and Microcirculation, vol. 59, no. 2, pp. 97-106, 2015

Authors: Vayá, Amparo | Rivera, Leonor | de la Espriella, Rafael | Sanchez, Fernando | Suescun, Marta | Hernandez, José Luis | Fácila, Lorenzo

Article Type: Research Article

Abstract: Increased RDW has been found to be a marker of adverse outcomes in cardiovascular disease (CVD), although the exact mechanism remains unclear. Recently, several authors have found that higher RDW is associated with decreased erythrocyte deformability, which can impair blood flow through microcirculation, a fact which may explain the increased risk for CVD events associated with elevated RDW. The aim of the present study was to investigate the association between RDW and erythrocyte deformability in patients with acute myocardial infarction (AMI). The study group comprised 60 AMI patients and 72 gender- and age-matched controls, in whom erythrocyte deformability was determined …by means of the elongation index (EI) in a Rheodyn SSD, along with haematological, biochemical and inflammatory parameters. Patients showed higher RDW (p = 0.012) and lower EI (p < 0.05) than controls. When anaemic patients were removed from the study, AMI showed still lower EI than controls (p < 0.05), but no differences in RDW were observed (p = 0.141). RDW correlated inversely with haematimetric indices (p < 0.001), but not with inflammatory and biochemical parameters (p > 0.05). EI correlated inversely with Hb, MCHC (p < 0.001) and directly with MCV (p < 0.05). EI also correlated inversely with glucose (p < 0.05) and directly with HDL-cholesterol (p < 0.05). The multivariate regression model showed that only MCV and Hb were independent predictors of RDW (beta coefficients: −0.383, −0.208; p < 0.001, p = 0.050, respectively). In addition, MCV, MCHC and hyperlipidaemia were independent predictors of EI (beta coefficients: 0.366, −0.533, −0.192; p < 0.001, p < 0.001, p = 0.019 respectively). In AMI patients, increased RDW is not related with EI, so this mechanism does not seem to be responsible for an increased CDV risk in these patients. Show more

Keywords: Red blood cell distribution width, erythrocyte deformability, acute myocardial infarction

DOI: 10.3233/CH-131751

Citation: Clinical Hemorheology and Microcirculation, vol. 59, no. 2, pp. 107-114, 2015

Authors: Vent-Schmidt, Jens | Waltz, Xavier | Pichon, Aurélien | Hardy-Dessources, Marie-Dominique | Romana, Marc | Connes, Philippe

Article Type: Research Article

Abstract: The aim of this study was to test the accuracy of viscosimetric method to estimate the red blood cell (RBC) deformability properties. Thirty-three subjects were enrolled in this study: 6 healthy subjects (AA), 11 patients with sickle cell-hemoglobin C disease (SC) and 16 patients with sickle cell anemia (SS). Two methods were used to assess RBC deformability: 1) indirect viscosimetric method and 2) ektacytometry. The indirect viscosimetric method was based on the Dintenfass equation where blood viscosity, plasma viscosity and hematocrit are measured and used to calculate an index of RBC rigidity (Tk index). The RBC deformability/rigidity of the three …groups was compared using the two methods. Tk index was not different between SS and SC patients and the two groups had higher values than AA group. When ektacytometry was used, RBC deformability was lower in SS and SC groups compared to the AA group and SS and SC patients were different. Although the two measures of RBC deformability were correlated, the association was not very high. Bland and Altman analysis demonstrated a 3.25 bias suggesting a slight difference between the two methods. In addition, the limit of agreement represented 28% (>15%) of the mean values of RBC deformability, showing no interchangeability between the two methods. In conclusion, measuring RBC deformability by indirect viscosimetry is less accurate than by ektacytometry, which is considered the gold standard. Show more

Keywords: Ektacytometry, blood viscosity, red blood cell deformability, methodology

DOI: 10.3233/CH-131727

Citation: Clinical Hemorheology and Microcirculation, vol. 59, no. 2, pp. 115-121, 2015

Authors: Li, Mingxing | Luo, Zhijian | Chen, Xiaomei | Xuan, Jiqing | Ye, Fan | Liu, Hui | Chen, Kewen

Article Type: Research Article

Abstract: BACKGROUND: Renal ischemia-reperfusion injury (IRI) is common in renal transplantation, shock, and nephrolithotomy. OBJECTIVE: To quantitatively assess rabbit renal IRI with contrast-enhanced ultrasound (CEUS) and investigate associations between renal cortical time-intensity curve (TIC) parameters and intracellular adhesion molecule-1 (ICAM-1) expression. METHODS: Eighteen white rabbits were randomly assigned into control and IRI groups (n = 9 each), and CEUS examination was performed 24 h after modeling. TIC parameters including arrival time (AT), time to peak intensity (TTP), changes in peak intensity, area under the curve (AUC), and slope of the ascending TIC, and correlations between these parameters and ICAM-1 expression were …evaluated with linear correlation analyses. RESULTS: AT, TTP, and AUC were significantly increased in the IRI group (P < 0.05), and the slope of the ascending TIC was significantly lower than that in the control group (P < 0.05). ICAM-1 content in the renal cortex was significantly increased in the IRI group (P < 0.05). In addition, the slope of the ascending TIC negatively correlated with renal ICAM-1 expression (r = −0.923, P < 0.01), whereas AT and TTP positively correlated with ICAM-1 expression (r = 0.697 and 0.892, both P < 0.01). CONCLUSIONS: TIC parameters including the slope of the ascending TIC, AT, and TTP closely correlated with ICAM-1 in the renal cortex, and it is considered that the TIC can be used to quantitatively monitoring renal cortex blood perfusion and CEUS can be used to indirectly evaluate the degree of inflammatory reaction associated with renal IRI. CEUS may be a useful non-invasive method to identify inflammation caused by renal IRI-associated diseases. Show more

Keywords: Renal ischemia-reperfusion injury, contrast-enhanced ultrasound, time-intensity curve, intracellular adhesion molecule-1, rabbit

DOI: 10.3233/CH-131768

Citation: Clinical Hemorheology and Microcirculation, vol. 59, no. 2, pp. 123-131, 2015

Authors: Manfredi, Andreina | Sebastiani, Marco | Carraro, Valeria | Iudici, Michele | Bocci, Mario | Vukatana, Gentiana | Gerli, Roberto | De Angelis, Rossella | Del Medico, Patrizia | Praino, Emanuela | Lo Monaco, Andrea | D'Amico, Roberto | Del Giovane, Cinzia | Mazzuca, Salvatore | Colaci, Michele | Giuggioli, Dilia | Ferri, Clodoveo

Article Type: Research Article

Abstract: BACKGROUND: Digital ulcers (DU) affect 50% of systemic sclerosis (SSc) patients, representing a challenging clinical problem. Despite a high negative predictive value, capillaroscopic scores proposed to select patients at risk for DU show an inadequate positive predictive value, especially in patients without previous DU. AIM OF THIS STUDY: To increase the predictive value for DU development of capillaroscopy, through a predictive risk chart taking into account capillaroscopic, demographic, and clinico-serological parameters. PATIENTS AND METHODS: Two hundred and nineteen unselected SSc patients from 8 Italian Rheumatology Centers were consecutively enrolled during a 6-month period. Demographic, clinical, serological and instrumental data and …capillaroscopy skin ulcers risk index (CSURI) were collected. RESULTS: A multivariate logistic regression analysis showed a significant positive association between DU appearance and male gender, DU history, altered CSURI, and ESR. A prediction risk chart of the development of DU within 6 months were built on the basis of the above parameters. According to the risk level, four risk classes were identified: low (≤19.3%); medium (>19.3%, ≤58.6%); high (>58.6%, ≤89.2%), and very high risk (>89.2%). CONCLUSIONS: The systematic evaluation of the above parameters can be helpful to identify patients at risk to develop DU optimizing preventive vasoactive therapy. Show more

Keywords: capillaroscopy, digital ulcers, systemic sclerosis, predictive risk chart

DOI: 10.3233/CH-141809

Citation: Clinical Hemorheology and Microcirculation, vol. 59, no. 2, pp. 133-143, 2015

Authors: Hammer, Alexandra | Koppensteiner, Renate | Steiner, Sabine | Niessner, Alexander | Goliasch, Georg | Gschwandtner, Michael | Hoke, Matthias

Article Type: Research Article

Abstract: Flavonoid-rich dark chocolate has positive effects on vascular function in healthy subjects and in patients at risk of atherosclerosis. The impact of dark chocolate on endothelial and microvascular function in patients with symptomatic peripheral artery disease (PAD) has not been investigated so far. In an investigator blinded, randomized, controlled, cross-over trial we assessed the effect of flavonoid-rich dark chocolate and cocoa-free control chocolate on flow-mediated dilatation (FMD) of the brachial artery and on microvascular function (assessed by Laser Doppler fluxmetry) in 21 patients with symptomatic (Fontaine stage II) PAD. Measurements were done in each patient on 2 single days, with …an interval of 7 days, at baseline and at 2 hours after ingestion of 50 g dark chocolate or 50 g white chocolate, respectively. FMD remained unchanged after intake of dark chocolate (baseline and 2 hours after ingestion, %: 5.1 [IQR 4.4 to 7.3] and 5.5 [IQR 3.9 to 10.4]; p = 0.57, and after intake of white chocolate (baseline and 2 hours after ingestion, %: 6.4 [IQR 4.5 to 11.4] and 4.4 [IQR 2.6 to 8.7]; p = 0.14. Similarly, microcirculatory parameters were not significantly altered after intake of any chocolate compared with the respective baseline values. In conclusion, a single consumption of 50 g dark chocolate has no effect on endothelial and microvascular function in patients with symptomatic PAD. Show more

Keywords: Dark chocolate, vascular function, peripheral artery disease, flow-mediated dilatation, laser Doppler fluxmetry

DOI: 10.3233/CH-141817

Citation: Clinical Hemorheology and Microcirculation, vol. 59, no. 2, pp. 145-153, 2015

Authors: Silva-Herdade, A.S. | Freitas, T. | Almeida, J. Pedro | Saldanha, C.

Article Type: Research Article

Abstract: The erythrocyte adenosine triphosphate (ATP) is utilised for protein phosphorylation and exported through the pannexin 1 hemichannel (Px1) in the microcirculation. The physiological stimuli for ATP release are dependent of blood shear rate level and of the tissue oxygen content. The deoxygenated and oxygenated states of haemoglobin are respectively bound and unbound to N terminal domain of the protein band 3 of the erythrocyte membrane in dependence of its degree of phosphorylation. The protein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP) contribute to the phosphorylation degree of band 3 and are modulated by protein kinase C (PKC). Chelerythrine (Che) …is a competitive inhibitor of ATP for PKC and a negative modulator of erythrocyte deformability. The aim of this study was to assess the mobilization of nitric oxide (NO) in erythrocyte in absence and presence of Che and Px1 inhibitor (carbenoxolone). Erythrocyte deformability was evaluated in presence of carbenoxolone (Carb). Regarding the effects observed in the erythrocyte by presence of Che or Carb, the values of efflux of NO and the concentration of nitrosogluthatione are similar and with no changes in relation to their absence. Px1inhibition by Carb 10 μM ameliorates the erythrocyte deformability at a shear force of 0.6 and 1.2 Pa. The PKC inhibitor shows similar effects to the Carb on the mobilization of nitric oxide in erythrocyte. The blockage of ATP release by Carb from erythrocytes suggests a possible benefit to develop in ischemia reperfusion or in inflammatory response where will be needed to rescue the excess of NO present and ameliorate the red blood cell deformability at low shear rates. Show more

Keywords: Erythrocyte, protein kinase C, pannexin 1, carbenoxolone nitric oxide

DOI: 10.3233/CH-141833

Citation: Clinical Hemorheology and Microcirculation, vol. 59, no. 2, pp. 155-162, 2015

Authors: Cho, Seungkwan | Namgung, Bumseok | Kim, Han Sung | Leo, Hwa Liang | Kim, Sangho

Article Type: Research Article

Abstract: This study examined the effects of red blood cell (RBC) aggregation at pathological levels on NO/O2 transport in small arterioles. Transient gas diffusion simulations were performed with in vivo cell-free layer (CFL) widths data obtained from arteriolar flows in the rat cremaster muscle. The CFL data were measured at physiological and pathological levels of aggregation under reduced flow conditions (pseudoshear rate = 31.4 ± 10.5 s−1 ). Our results showed that the mean peak NO concentration significantly decreased with increasing the aggregation level from non-aggregating to normal-aggregating (P < 0.05) and to hyper-aggregating (P < 0.01) conditions. In contrast, …the partial O2 pressure (PO2 ) in pathological aggregating conditions significantly increased from those under non-aggregating (P < 0.001) and normal-aggregating (P < 0.05) conditions. Although the NO scavenging by RBCs could be impaired with a thicker CFL at higher levels of aggregation, the overall decrease in NO production due to reduction of wall shear stress with the thicker CFL dominantly limited the NO availability in tissue. On the other hand, the O2 availability in tissue increased due to the relatively high core hematocrit in the blood lumen with the thicker CFL. Show more

Keywords: Hemodynamics, plasma layer, microcirculation, gas diffusion

DOI: 10.3233/CH-141837

Citation: Clinical Hemorheology and Microcirculation, vol. 59, no. 2, pp. 163-175, 2015

Authors: Gayda, Mathieu | Gremeaux, Vincent | Drigny, Joffrey | Juneau, Martin | Nigam, Anil

Article Type: Research Article

Abstract: This study aims were: 1) to assess forearm blood flow (FBF) and muscle oxygen consumption (mVO2 ) repeatability assessed with near-infra red spectroscopy (NIRS) during venous occlusions (VO) in middle aged healthy subjects and patients with stable coronary heart disease (CHD), 2) to assess the agreement between mVO2 calculated from NIRS signals during VO and arterial occlusion (AO) in 18 middle aged healthy subjects and 12 patients with CHD. FBF and mVO2 were measured using NIRS during 2 successive VO (1-min duration), followed by a 5-min AO. Repeatability for FBF and mVO2 during VO was assessed with …intra class correlation (ICC), coefficient of variation (CV %) and agreement between VO and AO mVO2 was assessed with a Bland and Altman analysis. FBF and mVO2 during VO were highly reproducible in healthy (FBF: ICC 0.73, CV% 9.75; mVO2 : ICC 0.89, CV% 12.6) and CHD subjects (FBF: ICC 0.95, CV% 10.26; mVO2 : ICC 0.98, CV% 7.92). VO and AO mVO2 were in agreement in healthy (mean bias: 0.002 mL O2 .min−1 .100g−1 ) and CHD subjects (mean bias: 0.014 mL O2 .min−1 .100g−1 ). FBF and mVO2 measured with NIRS during VO and/or AO are highly reproducible methods to assess microvascular function in healthy subjects and stable CHD patients. Show more

Keywords: Near-infra red spectroscopy, repeatability, agreement, vascular occlusions, healthy middle aged subjects, patients with coronary heart disease

DOI: 10.3233/CH-141836

Citation: Clinical Hemorheology and Microcirculation, vol. 59, no. 2, pp. 177-183, 2015