Clinical Hemorheology and Microcirculation - Volume 56, issue 3

Authors: Kasperczyk, Aleksandra | Słowińska-Łożyńska, Ludmiła | Dobrakowski, Michał | Zalejska-Fiolka, Jolanta | Kasperczyk, Sławomir

Article Type: Research Article

Abstract: Lead-induced oxidative stress has been identified as the essential factor in lead poisoning pathogenesis. Therefore, the present study examined the association between occupational lead exposure and blood rheological parameters with respect to malondialdehyde (a lipid peroxidation product), lipofuscin, and glutathione concentrations in erythrocytes. The examined group included 283 healthy male employees of lead-zinc works. In brief, 129 workers were classified as the low-exposure group, while the high-exposure group was composed of 154 workers. The mean blood levels of lead and zinc-protoporphyrin and the mean urine concentrations of delta-aminolevulinic acid were used as exposure markers. The control group consisted of 73 …healthy male administrative workers. Whole blood viscosity was elevated in both exposure subgroups compared with the control group. Erythrocyte aggregability increased significantly; although the increase was greater in the low exposure group. Erythrocyte deformability decreased in both subgroups. The levels of malondialdehyde and lipofuscin were significantly elevated, whereas the glutathione content decreased. In conclusion, occupational exposure to lead may induce oxidative stress in erythrocytes. This stress elevates whole blood viscosity and disturbs erythrocyte aggregability and deformability. There is a dose-effect relationship between lead levels and blood rheological parameters. Show more

Keywords: LORCA, lead poisoning, oxidative stress, blood viscosity, erythrocyte deformability, erythrocyte aggregation

DOI: 10.3233/CH-131678

Citation: Clinical Hemorheology and Microcirculation, vol. 56, no. 3, pp. 187-195, 2014

Authors: Toth, A. | Papp, J. | Rabai, M. | Kenyeres, P. | Marton, Zs. | Kesmarky, G. | Juricskay, I. | Meiselman, H.J. | Toth, K.

Article Type: Research Article

Abstract: Cardiovascular diseases (CVD) are the most frequent cause of death throughout the world. The coronary vessel system is a special part of the circulation since there is a continuous change in blood flow, perfusion pressure and shear rate during each cardiac cycle. It is also the place of the narrowest capillaries in the human body, therefore the role of rheological alterations may be of greater importance than in the other parts of the circulatory system. During the past decades, our group has investigated hemorheological parameters (HP) in over 1,000 patients diagnosed with various forms of ischemic heart disease (IHD). In …one prospective study, we measured the HP of patients with acute coronary syndrome (ACS). On admission, all examined variables were significantly worse than those of control subjects. During the hospital phase, some of the HP showed further deterioration, and HP remained in the pathologic range during the follow-up period. In another study, we showed that HP are in close correlation with the severity of coronary artery disease. In patients treated with percutaneous coronary intervention, changes in HP were very similar to those observed in subjects with ACS. In a recent study, we analyzed HP in patients undergoing CABG surgery. Our data suggest a hemorheological advantage of off-pump surgery. In another study low Hct/WBV ratio can be regarded as a risk factor of cardiac death in IHD. Our data indicate that rheological parameters are significantly altered in patients with IHD: the extent of the alterations is in excellent correlation with the clinical severity of the disease. Our findings prove that HP play a critical role in the pathogenesis of myocardial ischemia. In recent in vitro and in vivo studies we have investigated the effects of red wine on hemorheological parameters. Our results show that moderate red wine consumption has beneficial effects on hemorheological parameters which may contribute to the French paradox. Show more

Keywords: Ischemic heart disease, acute coronary syndrome, percutaneous coronary intervention, coronary artery bypass grafting, red wine, ethanol, hematocrit per blood viscosity ratio

DOI: 10.3233/CH-131685

Citation: Clinical Hemorheology and Microcirculation, vol. 56, no. 3, pp. 197-204, 2014

Authors: You, Yun | Wang, Jinyu | Tong, Yan | Hao, Qingxiu | Li, Yujie | Yang, Hongjun | Huang, Luqi | Liao, Fulong

Article Type: Research Article

Abstract: This research was aimed to investigate the anti-inflammatory mechanism of acetylharpagide extracted from Ajuga decumbens Thunb. Human umbilical vein endothelial cells (HUVECs) and human monocytic leukemia cell line THP-1 were employed as experimental materials. The MTT assay (3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) was used to determine the safe dose range of acetylharpagide. TNF-α (20 ng/ml) was used to model THP-HUVECs adhesion/transmigration and trypsin was used to model wounding of HUVECs under controlled shear stress of 0.1 Pa and 0.2 Pa (5 h) by Bioflux1000 assays accordingly. Effects of acetylharpagide were dynamically monitored by microscopic time-lapse photography. Acetylharpagide within the concentration of 0-200 …μM showed no sign of toxicity to HUVECs and THP-1. Acetylharpagide dose-dependently inhibited THP-1 adhesion to TNF-α activated HUVECs monolayer with an IC50 of 171 μM under static conditions. Acetylharpagide at 200 μM inhibited leukocyte adhesion and transmigration to HUVECs monolayer activated by TNF-α under 0.1 Pa shear stress (P < 0.05). The compound at 200 μM also inhibited HUVECs migration under 0.2 Pa in the wound healing model compared with the control group (P < 0.05). In conclusion, the anti-inflammatory effects of acetylharpagide are possibly related to inhibiting leukocytes adhesion and transmigration. Moreover, acetylharpagide also inhibits the endothelial cells migration notably, which might be the additional action responsible for its effect in reliving-chronic inflammatory progress. Show more

Keywords: Acetylharpagide, biomechanopharmacology, endothelial cells, inflammation, shear stress

DOI: 10.3233/CH-131704

Citation: Clinical Hemorheology and Microcirculation, vol. 56, no. 3, pp. 205-217, 2014

Authors: Erdogan, Dogan | Uysal, Bayram Ali | Aksoy, Fatih | Kaya, Selcuk | Icli, Atilla | Ceyhan, Betul Mermi | Ozaydin, Mehmet

Article Type: Research Article

Abstract: BACKGROUND: The underlying mechanisms of increased risk of thrombo-embolism in atrial fibrillation (AF) are not completely understood; however, substantial evidence supports that AF is associated with a prothrombotic state. Accordingly, we hypothesized that strict rate control could attenuate platelet activity and thrombotic state in patients with non-valvular AF. METHODS: Seventy-five patients with non-valvular AF were divided into 2 groups based on heart rate: (1) normal ventricular rate (n = 34, 18 female) and (2) high ventricular rate (n = 39). Thirty-three sex- and age-matched subjects in sinus rhythm were included as control. Thirty patients with high ventricular rate (16 female) …were successfully followed. Markers of platelet function were measured at baseline and repeated 1-month after adequate rate control in high ventricular rate group. RESULTS: Serum fibrinogen levels were significantly higher in AF patients with high ventricular rate than that in controls. Mean platelet volume, soluble CD40L and β-Thromboglobulin were significantly higher in AF patients with high ventricular rate than those in both AF patients with normal ventricular rate and controls. Soluble CD40L and β-Thromboglobulin were significantly higher in AF patients with normal ventricular rate than those in controls. One-month after adequate rate control, serum fibrinogen, soluble CD40L and β-Thromboglobulin levels significantly decreased (from 2.26 ± 1.02, 85.01 ± 37.05, 3.10 ± 0.90 to 1.55 ± 1.08, 66.34 ± 33.72, 2.71 ± 0.53; p < 0.001, p = 0.002, p = 0.03, respectively) in high ventricular rate group. CONCLUSIONS: AF patients with high ventricular rate had increased indices of platelet activity and thrombotic state. Furthermore, strict rate control significantly decreased indices of thrombotic state and platelet activity in those patients. Show more

Keywords: Atrial fibrillation, platelet activity, strict rate control, hypercoagulability

DOI: 10.3233/CH-131710

Citation: Clinical Hemorheology and Microcirculation, vol. 56, no. 3, pp. 219-229, 2014

Authors: Kadi, A. | de Isla, N. | Moby, V. | Lacolley, P. | Labrude, P. | Stoltz, J.F. | Menu, P.

Article Type: Research Article

Abstract: Nitric oxide is implicated in the target action of Nebivolol, a selective β1 adrenoceptor blocker used in hypertension treatment. As the Nitric Oxide (NO) production and the actin cytoskeleton are linked, the aim of this work was to study the involvement of actin cytoskeleton on mechanism of action of Nebivolol 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 Endothelial Cells (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. Show more

Keywords: Nebivolol, β blocker, actin cytoskeleton, eNOS, nitric oxide, Rho-kinase, endothelial cell

DOI: 10.3233/CH-131718

Citation: Clinical Hemorheology and Microcirculation, vol. 56, no. 3, pp. 231-246, 2014

Authors: Ostad, Mir Abolfazl | Wild, Philipp S. | Schnorbus, Boris | Schulz, Andreas | Munzel, Thomas | Warnholtz, Ascan

Article Type: Research Article

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. Show more

Keywords: Endothelium, flow-mediated dilation, coronary artery disease, reactive hyperemia, shear stress

DOI: 10.3233/CH-131720

Citation: Clinical Hemorheology and Microcirculation, vol. 56, no. 3, pp. 247-257, 2014

Authors: Vayá, Amparo | Alis, Rafael | Romagnoli, Marco | Todolí, Jose | Calvo, Javier | Ricart, Jose M.

Article Type: Research Article

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. Show more

Keywords: Raynaud's phenomenon, hemorheology, digital ulcers

DOI: 10.3233/CH-131723

Citation: Clinical Hemorheology and Microcirculation, vol. 56, no. 3, pp. 259-264, 2014

Authors: Alhejily, Wesam | Aleksi, Alda | Martin, Billie-Jean | Anderson, Todd J.

Article Type: Research Article

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. Show more

Keywords: Endothelial dysfunction, Ischemic reperfusion injury (IR), flow-mediated dilation (FMD), and microvascular

DOI: 10.3233/CH-131741

Citation: Clinical Hemorheology and Microcirculation, vol. 56, no. 3, pp. 265-271, 2014

Authors: Zhou, Juan | Pavlovic, Dragan | Rüb, Johanna | Masur, Stefan | Spassov, Alexander | Whynot, Sara | Hung, Orlando | Kern, Hartmut | Saleh Abdo, Islam | Shukla, Romesh | Cerny, Vladimir | Lehmann, Christian

Article Type: Research Article

Abstract: Intestinal microcirculatory disturbances play an important role in the pathophysiology of sepsis. A neural anti-inflammatory pathway has been suggested as a potential target for therapy that may dampen systemic inflammation. The aim of this study is to investigate the effects of physostigmine, a cholinesterase inhibitor, on the intestinal microcirculation and vascular contractility in experimental endotoxemia. Endotoxemia was induced in Lewis rats by intravenous lipopolysaccharide (LPS) administration. Animals were treated with either physostigmine or saline (control) following LPS challenge. The intestinal microcirculation, including leukocyte-endothelial interaction, functional capillary density (FCD) and non-perfused capillary density (NCD), was examined by intravital microscopy (IVM) 2 …hours after LPS administration. The impact of physostigmine on vascular contractility of rat aortic rings was examined by in vitro myography. Physostigmine significantly reduced the number of adhering leukocytes in intestinal submucosal venules (V1 venules: −61%, V3 venules: −36%) of LPS animals. FCD was significantly increased by physostigmine treatment (circular muscle layer: +180%, longitudinal muscle layer: +162%, mucosa: +149%). Low concentrations of physostigmine produced significant contraction of aortic ring preparations, whereas high concentrations produced relaxation. In conclusion, physostigmine treatment significantly improved the intestinal microcirculation in experimental endotoxemia by reducing leukocyte adhesion and increasing FCD. Show more

Keywords: Physostigmine, microcirculation, sepsis, endotoxemia, intravital microscopy

DOI: 10.3233/CH-131743

Citation: Clinical Hemorheology and Microcirculation, vol. 56, no. 3, pp. 273-284, 2014

Article Type: Correction

DOI: 10.3233/CH-141835

Citation: Clinical Hemorheology and Microcirculation, vol. 56, no. 3, pp. 285-286, 2014