Clinical hemorheology and microcirculation (CLIN HEMORHEOL MICRO)

Publications in this journal

• Article: Red blood cell distribution width and erythrocyte deformability in patients with acute myocardial infarction.

  Amparo Vayá, Leonor Rivera, Rafael de la Espriella, Fernando Sanchez, Marta Suescun, José Luis Hernandez, Lorenzo Fácila
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  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.
  Clinical hemorheology and microcirculation 06/2013;
• Article: Association of red blood cell distribution width, inflammation markers and morphological as well as rheological erythrocyte parameters with target organ damage in hypertension.

  Maria Fornal, Barbara Wizner, Marcin Cwynar, Jarosław Królczyk, Aleksander Kwater, Renata A Korbut, Tomasz Grodzicki
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  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.
  Clinical hemorheology and microcirculation 05/2013;
• Article: The effect of ischemia- reperfusion injury on measures of vascular function.

  Wesam Alhejily, Alda Aleksi, Billie-Jean Martin, Todd J Anderson
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  ABSTRACT: BACKGROUND: Ischemia-reperfusion injury results in conduit vessel endothelial dysfunction as assessed by flow-mediated dilatation (FMD). The effect on the potentially more important microvascular circulation has not been well studied. The objective of our study was to assess the effect of ischemia-reperfusion injury on microvascular function including peripheral arterial tonometry (PAT) hyperemic index. METHODS: 45 healthy volunteers free of cardiovascular disease were recruited (mean age 35 ± 14 yrs, 29 men). Using ultrasound, the flow-mediated dilation (FMD) and hyperemic velocity (VTI) of the brachial artery were measured following a 5-minute forearm cuff occlusion. Simultaneously, the PAT hyperemic index was measured. Ischemia was then induced by a 15-minute upper arm occlusion and within 15 minutes of recovery the vascular measures were repeated. RESULTS: Ischemia caused a significant reduction in FMD (7.9 ± 4.0 to 4.7 ± 3.5, p = 0.0001). The hyperemic VTI, a measure of microvascular function, was unaffected following ischemia-reperfusion (92 ± 30 vs. 97 ± 37 cm, p = 0.236). Finally, PAT index was also unchanged by the intervention (2.07 ± 0.8 vs. 2.04 ± 0.7, p = 0.742). CONCLUSIONS AND DISCUSSIONS: Ischemia-reperfusion caused conduit and not resistance vessel endothelial dysfunction. The PAT-index was unchanged suggesting that this measure is more closely aligned with resistance than conduit vessel function. This has implications for its use as a measure of vascular function in clinical research.
  Clinical hemorheology and microcirculation 05/2013;
• Article: Protein oxidation in chronic kidney disease.

  Gregorio Caimi, Caterina Carollo, Eugenia Hopps, Maria Montana, Rosalia Lo Presti
  Clinical hemorheology and microcirculation 05/2013;
• Article: Haematological, biochemical and inflammatory parameters in inactive Behçet's disease. Its association with red blood cell distribution width.

  Amparo Vayá, Leonor Rivera, José Todolí, Jose Luis Hernandez, Begoña Laiz, José M Ricart
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  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.
  Clinical hemorheology and microcirculation 05/2013;
• Article: Hypoxia/reoxygenation stress increases markers of vaso-occlusive crisis in sickle SAD mice.

  Emeline Aufradet, Geneviève Desouza, Vanessa Bourgeaux, Amine Bessaad, Yannick Campion, Emmanuelle Canet-Soulas, Vincent Pialoux, Erica N Chirico, Anne-Marie Chevrier, Yann Godfrin, Cyril Martin
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  ABSTRACT: In sickle cell disease, the factors involved in vasoocclusive crisis (VOC) include the sickling of red blood cells (RBC), abnormal blood rheology, inflammation, vascular adhesion, oxidative stress, coagulation, and vascular tone modulation. The aim of this study was to further characterize the molecular response of some factors involved in VOC by inducing a hypoxia/reoxygenation stress in sickle SAD mice. Results show that a hypoxia/reoxygenation stress in SAD mice can induce: (i) a decrease in reticulocytes count, and mean corpuscular volume along with an increase in lactate dehydrogenase (p = 0.07) and sickled cell proportion; (ii) a significant increase in lung VCAM-1, ICAM-1, IL-1β, ET-1, eNOS, and TF mRNA associated with an increase in VCAM-1 expression on lung endothelium; (iii) a rise in cardiac oxidative stress with increased lipid oxidation and decreased anti-oxidant enzyme activities, and (iv) an increase in plasma TNF-α and IL-6 and a decrease in plasma ET-1. In SAD mice, hypoxia/reoxygenation stress induces hemolysis that, together with oxidative stress, inflammation, vascular adhesion, and coagulation, may induce vascular occlusion and consequently RBC sickling. The present results give the kinetics of VOC molecular markers in SAD mice which may aid in testing the efficiency of new therapeutic processes against VOC.
  Clinical hemorheology and microcirculation 05/2013;
• Article: Non-invasive pressure measurement of the great saphenous vein in healthy controls and patients with venous insufficiency.

  M Koster, B R Amann-Vesti, M Husmann, V Jacomella, T O Meier, C Jeanneret, J Hafner, C Thalhammer
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  ABSTRACT: OBJECTIVES: Venous pressure measurement using an intravenous catheter is the sole method for the diagnosis of venous hypertension in patients with chronic venous insufficiency. A noninvasive tool to quantify increased venous pressure is essential for studying venous pathophysiology. Aim of the study was to investigate the value of controlled compression ultrasound (CCU) for noninvasive assessment of venous pressure (VP) of the great saphenous vein (GSV) in healthy persons and patients with venous insufficiency to quantify venous hypertension. METHODS: An optimal visible part of the GSV directly above the ankle was marked on the skin and compressed under ultrasound control and pressure needed for complete compression of the vein was recorded using a pressure manometer with a translucent silicone membrane. Complete insufficiency of the GSV (Hach IV) was documented by duplex ultrasound by an independent investigator before start of the study. VP measurement was performed while normal breathing, deep inspiration and expiration and during a standardized Valsalva maneuver. RESULTS: Twenty controls and 19 patients with complete insufficiency of the GSV were included. Valsalva maneuver induced a slight increase in VP in controls (20.1 ± 4.5 vs 25.1 ± 6.6 mbar) but a significant higher increase in patients from 26 to 37 mbar (IQR 18.5-28.0 vs 31.5-43.0; p < 0.001). CONCLUSION: Noninvasive venous pressure measurement of the great saphenous vein using CCU is feasible and documents an increased pressure during Valsalva maneuver in Hach IV patients compared to healthy controls.
  Clinical hemorheology and microcirculation 05/2013;
• Article: RDW in patients with systemic lupus erythematosus. Influence of anaemia and inflammatory markers.

  Amparo Vayá, Rafael Alis, Jose L Hernández, Javier Calvo, Luisa Micó, Marco Romagnoli, Jose M Ricarte
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  ABSTRACT: Red blood cell distribution width (RDW) is a routine parameter that reflects size variations in erythrocytes. High RDW has been associated with cardiovascular events and inflammatory diseases. However, no studies evaluating the association of RDW with systemic lupus erythematosus (SLE) have been published. We aimed to explore the association of RDW with inflammatory markers in SLE. As SLE is often associated with anaemia, we considered this factor in order to know whether RDW is related with inflammation, anaemia or both in SLE. The study included 105 SLE patients (7 men, 98 women; aged 15-73 years) and 105 controls (9 men, 96 women; aged 18-71 years). Patients were divided according to anaemia status (26 with, 79 without). Biochemical, hematological and inflammatory parameters (C-reactive protein (CRP), fibrinogen and erythrocyte aggregation (EA1)) were analyzed. SLE patients showed increased RDW, CRP and EA1 (p < 0.001), and decreased hemoglobin levels (p < 0.001) when compared with controls. RDW was higher in SLE patients with anaemia (a-SLE) as compared with those without anaemia (na-SLE) (p < 0.01) or controls (p < 0.001). CRP in a-SLE was higher than in controls (p < 0.01) but lower than in na-SLE (p < 0.05). In na-SLE RDW correlated directly with fibrinogen and CRP (p < 0.001), but not in a-SLE. Our results indicate that SLE patients show higher RDW irrespectively of anaemia status, and that RDW is influenced by both anaemia and inflammation, but the influence of anaemia is stronger.
  Clinical hemorheology and microcirculation 05/2013;
• Article: Half-dose enoxaparin vs. full-dose enoxaparin for postoperative bridging therapy in patients after cardiac surgery: Which dose regimen should be preferred?

  Andreas Weiss, Stefan Brose, Katrin Ploetze, Klaus Matschke
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  ABSTRACT: BACKGROUND: Patients who require oral anticoagulation (OAC) after cardiac surgery due to an increased risk for thromboembolic events should receive bridging therapy with heparin until the INR is in a therapeutic range. For this purpose, unfractionated heparin (UFH) or low molecular weight heparin (LMWH) can be used. Recently published studies have demonstrated the safety and efficiency of therapeutic dose LMWH as bridging anticoagulant in cardiac surgery. The present study compares a full-therapeutic dose regimen with a half-therapeutic dose regimen of LMWH looking for safety and efficiency. PATIENTS AND METHODS: This study represents a retrospective, single-center cohort study. In a period of 19 months all patients in whom a postoperative bridging therapy after cardiac surgery was necessary (atrial fibrillation, mechanical heart valve replacement, tricuspid valve repair, intracardiac patch implantation, excision of intracardiac tumors) were selected. In the first part of the study, patients received full-dose (FD = 1 mg/kg bodyweight twice daily) LMWH (Enoxaparin). Analogously, patients in the second part of the study were treated with half-dose (HD = 0.5 mg/kg bodyweight twice daily) LMWH. In case of renal insufficiency (GFR <30 ml/min) the dose was adjusted to one daily application. The duration of follow-up was the patients' entire stay in hospital. Main outcome parameters were bleeding, thromboembolic events, and death. The first dose of LMWH was given on the morning of the first postoperative day, considered that the bleeding risk was acceptable. OAC (Phenprocoumon) was started on the evening of the first postoperative day. RESULTS: Altogether 402 out of 3133 patients met the inclusion criteria (201 patients in each group). Despite a reduced renal function in the HD-group (p = 0.002) both groups were well matched. Mortality was significantly higher in the HD-group than in the FD-group (5.5% vs. 0.5%, p = 0.003) but not related to the anticoagulation regimen. We observed more bleeding events in the FD-group (11 vs. 5, p = 0.126) but vice versa more thromboembolic events in the HD-group (9 vs. 5, p = 0.277). In the HD-group postoperative dialysis was required more often (29 vs. 12, p = 0.011) and there was a higher incidence of patients who were psychic disorientated (42 vs. 26, p = 0.033). The hospital stay was longer in the FD-group (FD: 15.1 ± 9.3 days, HD 12.5 ± 8.1 days, p = 0.003). CONCLUSION: This study shows that a bridging therapy with LMWH is feasible and safe no matter which dose-regimen is used. The differences observed seem not to be related to the anticoagulation. The decision of using a full-dose or half-dose LMWH bridging regimen should be determined by the individual risk of the patient and the general bleeding risk of the procedure.
  Clinical hemorheology and microcirculation 05/2013;
• Article: Evaluation of microvascularization in focal salivary gland lesions by contrast-enhanced ultrasonography (CEUS) and Color Doppler sonography.

  Xi Wei, Ying Li, Sheng Zhang, Xubin Li, Hailing Wang, Xu Yong, Xiaoqing Wang, Xing Li, Ming Gao
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  ABSTRACT: OBJECTIVE: To evaluate the dynamic microvascularization of focal salivary gland lesions by contrast-enhanced ultrasound (CEUS) and Color Doppler sonography. MATERIALS AND METHODS: One hundred and sixty-eight patients with 183 major salivary gland lesions (mean age, 56 years; age range, 12-83 years) underwent gray-scale ultrasonography (US), Color Doppler (CD) and CEUS. The CD and CEUS patterns were classified into three types (scores 0-3). Combined score grades were calculated based on the CD and CEUS pattern scores. The time-intensity curve (TIC) parameters of CEUS were then analyzed. Sensitivity, specificity, negative predictive value and positive predictive value of combined score grades were also calculated. RESULTS: Among all the lesions, there were 161 in parotid gland, 22 in submandibular gland and 157 lesions were benign and 26 were malignant. For score grades (combined CEUS patterns with CD types), scores 1-2 were graded as benign; scores 3-4 were graded as indetermination-suspicious benign or malignant and scores 5-6 were graded as malignant.score 5-6 and score 1-2 indicated 24 (92.3%) and 135 (85.9%) malignant and benign lesions confirmed pathologically, respectively. The sensitivity and negative predicted value of combined score grades for malignant lesions were 92.3% and 98.5%, respectively. In addition, TIC analysis indicates that PI and AUC in malignant lesions were higher than those in benign lesions (p = 0.04 and 0.02, respectively). CONCLUSION: The combined score grade could be a useful method to assess the macro-and micro-vascularization and to differentiated diagnose benign and malignant lesions in major salivary glands.
  Clinical hemorheology and microcirculation 05/2013;
• Article: Crosstalk between inflammation, iron metabolism and endotelial function in Behçet's disease.

  Rita Oliveira, Patricia Napoleão, João Banha, Eleonora Paixão, Andreia Bettencourt, Berta Martins da Silva, Dina Pereira, Filipe Barcelos, Ana Teixeira, José Vaz Patto, Ana Maria Viegas-Crespo, Luciana Costa
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  ABSTRACT: Behçet's disease (BD) is a rare chronic vasculitis of unclear etiology. It has been suggested that inflammatory response has an important role in BD pathophysiology. Herein, we aimed to study the interplay between inflammation, iron metabolism and endothelial function in BD and search for its putative association with disease activity. Twenty five patients clinically diagnosed with BD were selected and twenty four healthy age-sex matched individuals participated as controls. Results showed an increase of total number of circulating white blood cells and neutrophils, serum transferrin, total iron binding capacity, mieloperoxidase (MPO), ceruloplasmin (Cp), C reactive protein, β2 microglobulin and Cp surface expression in peripheral blood monocytes in BD patients comparatively to healthy individuals (p < 0,05). Of notice, the alterations observed were associated to disease activity status. No significant differences between the two groups were found in serum nitric oxide concentration. The results obtained suggest an important contribution from innate immunity in the pathogenesis of this disease. In particular, surface expression of leukocyte-derived Cp may constitute a new and relevant biomarker to understand BD etiology.
  Clinical hemorheology and microcirculation 04/2013;
• Article: Hemorheological profile in primary and secondary Raynaud's phenomenon. Influence of microangiopathy.

  Amparo Vayá, Rafael Alis, Marco Romagnoli, Jose Todolí, Javier Calvo, Jose M Ricart
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  ABSTRACT: Raynaud's phenomenon (RP) is an episodic peripheral circulatory disorder characterized by local artery spams in subjects exposed to cold or emotional stress. It is not well-established whether RP patients show an altered rheological profile, mostly due to patient classification and clinical severity. We aimed to compare the hemorheological profile in patients with primary and secondary RP with a healthy control group. Eighteen primary RP, 22 secondary RP and 22 healthy controls, were included in the study. RP patients were also divided according to the presence of digital ulcers (7 with, 33 without). Biochemical and hemorheological variables were analyzed, including glucose, triglycerides, total-cholesterol, immunoglobulins, fibrinogen, plasma viscosity, erythrocyte aggregation, erythrocyte deformability and blood viscosity. Age was higher in secondary RP as compared with primary (p = 0.049), while glucose, triglycerides IgA, IgG and plasma viscosity were higher in secondary RP than in healthy subjects (p < 0.05). RP patients with digital ulcers presented higher IgA (p = 0.012), lower erythrocyte aggregation time (p = 0.008) and a trend for higher fibrinogen levels and plasma viscosity (p = 0.064, p = 0.069, respectively). The results of the present study indicate that secondary RP patients show a mild impairment of the rheological profile that aggravates with microangiopathy severity.
  Clinical hemorheology and microcirculation 04/2013;
• Article: Endothelialized and preconditioned natural umbilical arteries with long term patency open the route for future human uses.

  Estelle Paternotte, Halima Kerdjoudj, Tunay Kokten, Jean-Francois Stoltz, Anna Kearney-Schwartz, Jean-Claude Voegel, Patrick Menu
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  ABSTRACT: The major challenge of vascular tissue engineering is to develop a small calibre vascular graft with a high patency rate. In native vessels, the thrombosis is prevented by the endothelium located at the luminal site of the vessel. The aim of this study was to develop a resistant endothelial lining on the inner surface of vascular graft using a polyelectrolyte multilayers (PEM) film. Umbilical arteries were de-endothelialized, coated with 3.5 bilayers of poly(styrene sulfonate) (PSS)/poly(allylamine hydrochloride) (PAH) and then cellularized with endothelial cells. The grafts were cultured for a week in static condition and preconditioned by exposure to a shear stress of at 1 Pa for three hours before implantation on the rabbit carotid site. Histological and confocal microscopy in vitro investigations showed that PEMs films improve cell adhesion and retention on the luminal surface after shear stress preconditioning. In vivo Doppler data showed that graft preconditioning is a crucial factor for graft patency. Indeed, preconditioned grafts remained over the whole experimental period, whereas unpreconditioned grafts were obstructed after only one week of implantation. These results open the route toward the development of a new generation of vascular substitutes having a long term patency.
  Clinical hemorheology and microcirculation 04/2013;
• Article: Erythrocyte deformability and aggregation in homozygous sickle cell disease.

  Amparo Vayá, Susana Collado, Ma Angeles Dasí, Ma Luz Pérez, Jose Luis Hernandez, Eva Barragán
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  ABSTRACT: Rheological properties of homozygous sickle cell anaemia (SCA) show marked heterogeneity, which may be explained in part by the concomitance of alpha genotypes or beta haplotypes, along with hydroxurea (HU) treatment. To further clarify this issue, in 11 homozygous patients with SCA in the steady state and in 16 healthy controls, we analysed erythrocyte deformability (ED) in a Rheodyn SSD by means of the Elongation Index (EI) at 12, 30 and 60 Pa, and erythrocyte aggregation at stasis (EA0) and at 3 sec-1 (EA1) in a Myrenne aggregometer along with fibrinogen, biochemical and haematological parameters. When compared with controls, homozygous (SS) patients showed a lower EI at all the shear stresses tested (p < 0.01) and higher EA0 (p < 0.014), but not higher EA1 (p = 0.076). Fibrinogen did not show statistical differences (p = 0.642). In the Spearman's correlation IE60 correlated inversely with Hb S (p < 0.05) and directly with MCV, MCH and Hb F levels (p < 0.01). EA0 correlated inversely with MCV, MCH, Hb F (p < 0.01) and directly with Hb S (p < 0.05). HU treatment improved EI and EA0, but not EA1. This paradoxical behaviour of HU on erythrocyte aggregation merits further research to be clarified.
  Clinical hemorheology and microcirculation 04/2013;
• Article: Quantifying morphological alteration of RBC population from light scattering data.

  Raghwendra Mishra, Debasish Sarkar, Sourav Bhattacharya, Sanjaya Mallick, Mousumi Chakraborty, Debarati Mukherjee, Manoj Kar, Roshnara Mishra
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  ABSTRACT: Studies of RBC morphological alterations, despite their potential clinical and experimental application, are compromised due to lack of simple and rapid techniques. As a complementary approach toward quantitative microscopy, we have reconstituted morphological information from light scattering data obtained from flow cytometer. Normal and poikilocytic agent treated samples were analyzed by microscopy and respective morphological index (MI) was calculated from the morphology based scores assigned to RBC. The samples were simultaneously analyzed by flowcytometer and the scatter data were obtained. Accordingly, the best correlated parameters of both forward scatter and side scatter were chosen to formulate a suitable regression model with MI as response. Flow cytometry data was also verified with another instrument (BD FACS Verse) and the equation obtained was validated with separate set of samples. The multivariate regression analysis yields a quadratic model with MI as response (R2 = 0.96, p < 0.001). The flow cytometric data from both instruments were in good agreement (Intra class correlation 0.9, p < 0.001). The model was found to simulate the sample MI with high accuracy (R2 = 0.97, p < 0.001). This proposed method was verified to be simple, rapid, quantitative and cost effective for the measurement of morphological alteration of RBC.
  Clinical hemorheology and microcirculation 04/2013;
• Article: The Nebivolol action on vascular tone is dependent on actin cytoskeleton polymerization and Rho-A activity into ECs and SMCs.

  A Kadi, N de Isla, V Moby, P Lacolley, P Labrude, J F Stoltz, P Menu
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  ABSTRACT: Nitric oxide is implicated in the target action of Nebivolol, a selective β1 adrenoceptor blocker used in hypertension treatment. As the NO production and the actin cytoskeleton are linked, the aim of this work was to study the involvement of actin cytoskeleton on Nebivolol action mechanism in cultured endothelial cells. We studied the effect of Nebivolol (200μM) on actin filaments remodeling and its impact on NO production and eNOS activation. Results showed that Nebivolol perturbs actin filaments polymerization, increases NO production and eNOS activity between 30 minutes and 1 h. Stabilization of actin filaments with phalloïdine (50μM) abolishes Nebivolol effects on eNOS activation and NO production. Furthermore, Rho-kinase activity decreased during the first hour of Nebivolol treatment, then increased after 3 h, while actin filaments repolymerized, eNOS activation and NO production decreased. In SMCs, Nebivolol induced a decrease in the Rho-kinase activity from 1 h until 24 h of incubation. In conclusion, we suggest that Nebivolol induced NO production in ECs via complementary actions between actin cytoskeleton remodeling inducing eNOS activation and Rho-kinase implication. The effect of Nebivolol on ECs occurs during the first hour, this effect on SMCs seems to be maintained until 24 h, explaining persisted action of Nebivolol observed in vivo.
  Clinical hemorheology and microcirculation 04/2013;
• Article: Effect of heat stress on blood rheology in different pigs breeds.

  Xavier Waltz, Michelle Baillot, Philippe Connes, Jean-Luc Gourdine, Lucien Philibert, Eric Beltan, Tawfik Chalabi, David Renaudeau
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  ABSTRACT: The main objectives of the present work were to test the effects of heat stress on blood rheology and to determine whether the responses can change according to the pigs breeds. Thirty-six pigs from three pig's lines (n = 12 for each line) with assumed different tolerance to heat stress were compared: Large White (LW, little tolerance), Creole (CR, good tolerance) and LW × CR pigs (produced from a cross between LW and CR lines). In a first period, all pigs were exposed to a 9-d period of thermo-neutral environment (24°C; d-9 to d-1; P0). At the end of P0, six pigs from each line were slaughtered (n = 18). Then in a second period, the remaining pigs (6/breed; n = 18) were exposed to a 5-d period of heat stress (32°C; d + 1 -d + 5; P1) and thereafter slaughtered at d + 5. Rectal and skin temperatures, as well as respiratory rate, were recorded on d-1 and d + 5. At slaughter, blood was sampled for hematological and hemorheological measurements. Heat stress caused a rise of the skin temperature and respiratory rate without any changes in the rectal temperature or on the hematological and hemorheological parameters when all pigs' lines were considered. We observed a pig line effect on blood viscosity at high shear rate (375 s-1) and red blood cell deformability at 30 Pa with CR pigs having lower blood viscosity and higher red blood cell deformability than LW pigs. While the changes of blood viscosity under heat stress did not reach statistical significance in LW and CR lines, blood viscosity (at 375 s-1) increased above the temperate values in the LW × CR line. Red blood cell deformability at 30 Pa was higher in CR pigs exposed to heat stress compared to LW pigs in the same condition. In conclusion, thermal loading caused physiological stress but did not widely change the hematological and hemorheological profiles. Although some blood rheological parameters seem to vary with the pigs breeds, the responses to heat stress are very similar.
  Clinical hemorheology and microcirculation 04/2013;
• Article: Protein carbonyl groups in trained subjects before and after a cardiopulmonary test.

  R Lo Presti, B Canino, P Cilluffo, V Calandrino, E Hopps, G Caimi
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  ABSTRACT: Physical exercise influences the body's oxidative status. The modifications can involve lipids, proteins and nucleic acids, and different effects seem to be induced by regular and acute exercise respectively. We examined protein oxidation, expressed as concentration of protein carbonyl groups (PC), in trained subjects before (time 0), 10 min (time 1) and 24 hours (time 2) after a cardiopulmonary test performed on a cycloergometer. We enrolled 38 trained subjects (26 men and 12 women), subdivided in two groups (A1 and B1) of 19 subjects each, according to the median value of VO2max, and in two groups (A2 and B2) of 19 subjects each, according to the median value of PC at baseline. PC concentration was measured by an enzyme-linked immunosorbent assay (ELISA). The groups A1 and B1 did not differ from each other as regards the basal PC level and groups A2 and B2 were not different as regards the VO2max. At time 1 PC showed a significant increase in comparison with baseline in trained subjects as a whole group, as well as in each subgroup. At time 2, PC were decreased in comparison with both times 0 and 1 in the whole group and in subgroups A1 and B2, whereas in subgroups A2 and B1 the PC value at time 2 was not different compared to time 0. The percentage increase of PC at time 1 vs time 0, as well as the percentage decrease at time 2 vs time 1 and time 0 respectively, were not different between subgroups A1 and B1. On the contrary, the percentage variations observed at each interval were significantly different between subgroups A2 and B2. The results suggest a reaction of antioxidant systems to acute exercise in trained subjects, influenced by basal PC levels more than by aerobic fitness.
  Clinical hemorheology and microcirculation 04/2013;
• Article: Predictive value of brachial reactive hyperemia and flow-mediated dilation in stable coronary artery disease.

  Mir Abolfazl Ostad, Philipp S Wild, Boris Schnorbus, Andreas Schulz, Thomas Munzel, Ascan Warnholtz
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  ABSTRACT: BACKGROUND: The purpose of this study was to determine the predictive value of a single measurement of reactive hyperemia (RH) and brachial flow-mediated dilation (FMD) in patients with established stable coronary artery disease (CAD). METHODS: RH and brachial artery FMD were ultrasonographically measured in 325 patients with stable CAD. Patients were followed for cerebro-cardiovascular events. The median follow-up was 3.7 years (range 0.01-5.7 years). RESULTS: Sixty-seven patients (20.6%) had an cerebro-cardiovascular event. Patients with subsequent events had lower FMD (4.9 ± 3.3% versus 6.3 ± 3.5%, p = 0.003), higher brachial artery resting diameter (5.1 ± 0.7 mm versus 4.8 ± 0.7 mm, p = 0.002) and lower NMD (11.2 ± 5.1% versus 12.8 ± 5.4%, p = 0.02), while the mean hyperemic flow velocity and shear stress did not differ from patients without cerebro-cardiovascular events. Cox proportional hazard model adjusted for sex, age, BMI, and traditional cardiovascular risk factors revealed a hazard ratio of 0.84 for lower FMD (p = 0.01). CONCLUSIONS: We conclude that single spot measurements of peak RH do not provide long-term prognostic information, but evaluation of conduit artery FMD predicts long-term cerebro-cardiovascular events in patients with stable CAD. The prognostic value of FMD is incremental to traditional cardiovascular risk factors and may therefore be of clinical importance.
  Clinical hemorheology and microcirculation 04/2013;
• Article: Simultaneous investigation of hemodynamic, microcirculatory and arterio-venous micro-rheological parameters in infrarenal or suprarenal aortic cross-clamping model in the rat.

  Norbert Nemeth, Ferenc Kiss, Zoltan Klarik, Eniko Toth, Anita Mester, Istvan Furka, Iren Miko
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  ABSTRACT: We aimed to investigate hemodynamic, microcirculatory and hemorheological consequence of infrarenal or suprarenal aortic cross-clamping (IRAXC, SRAXC) in the rat. We hypothesized that the magnitude of the changes are different. Twenty-one male rats were randomized into Control, IRAXC or SRAXC groups. Under anesthesia the right carotid artery was cannulated for monitoring heart rate and mean arterial pressure, then median laparotomy was performed. In AXC groups the abdominal aorta and the caudal caval vein were atraumatically clamped for 60 minutes below or above the renal vessels. Before and just after the ischemia, in the 30th and 60th minutes of the reperfusion besides hemodynamic test, laser Doppler flowmetry was used on the liver's, small-intestine's and the kidney's surface, then arterial (cannulated carotid artery) and venous (lateral tail vein) blood samples were taken for determining hematological, acid-base, erythrocytes' deformability, osmoscan and aggregation parameters. We found that when hemodynamic changes were prominent, microcirculatory or hemorheological parameters did not show such large differences. However, every parameter changed in various manners, showing more or less differences between IRAXC and SRAXC groups. Although the largest deviations were observable in SRAXC group, the acid-base and hemodynamic alterations were much more expressed than the micro-rheological ones. Further investigations of in vivo relations-correlations of changes in hemodynamic, microcirculatory, metabolic and hemorheological factors need further studies providing simultaneous monitoring possibilities.
  Clinical hemorheology and microcirculation 04/2013;