Clinical Hemorheology and Microcirculation - Volume 35, issue 1-2

Authors: Késmárky, Gábor | Fehér, Gergely | Koltai, Katalin | Horváth, Beáta | Tóth, Kálmán

Article Type: Research Article

Abstract: Background: In atherosclerotic diseases vascular reserve is impaired and pressure gradient is decreased, therefore the reduced blood fluidity can lead to tissue ischemia more rapidly. In previous investigations we demonstrated the deterioration of plasma and whole blood viscosities in patients with acute ischemic coronary syndromes, chronic coronary artery disease, and percutaneous transluminal coronary angioplasty. Methods: Hemorheological variables (plasma and whole blood viscosities, hematocrit, red blood cell aggregation), hemostaseological parameters (plasma fibrinogen and von Willebrand factor (vWf)), and platelet aggregation were detected in more recent studies in cardio- and cerebrovascular diseases, and diabetes mellitus. Common risk factors (lipid profile, smoking, glucose …level, previous diseases) and medication were also recorded. Results: High portion of vascular patients were demonstrated to have poor ex vivo platelet inhibition. Effective antiplatelet treatment detected by aggregometry was related to lower plasma fibrinogen concentration and red blood cell aggregation and was also associated with less recurrent vascular events during the follow-up (p<0.001). Beside the impaired hemorheological characteristics, the diabetic patients showed elevated vWf activity, which turned to correlate with hemoglobin A1c concentration (p<0.01) rather than the fasting glucose. Summary: Our studies indicate the active role and interaction of hemorheological and hemostaseological factors in atherosclerotic heart diseases. Show more

Keywords: Viscosity, hemostasis, ischemic heart disease

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 67-73, 2006

Authors: Pongrácz, Endre | Andrikovics, Hajnalka | Csornai, Márta | Bernát, Iván S. | Nagy, Zoltán

Article Type: Research Article

Abstract: The concentration of plasma fibrinogen (FIB) is an important factor in the coagulation cascade and also in the determination of blood and plasma viscosity depending on both genetic and acquired factors. The -455G/A polymorphism of the β-FIB gene is connected to the plasma concentration of FIB but the effect of Leiden mutation on hemorheological parameters is unclear. The two genetic polymorphisms were studied by polymerase chain reaction in healthy subjects and ischemic stroke cohort and the effects on the concentration of plasma FIB, whole blood and plasma viscosity of patients as well. A total of 278 ischemic stroke patients and …173 control subjects were enrolled. Marcro-rheological parameters as plasma FIB concentration, whole blood viscosity (90 sec−1 shear rate) and plasma viscosity have been measured also in the subgroup of young (age<50 years) and in a subgroup of non-smoker patients. Results: No significant difference was found in the prevalency of H1/H2 genotype between controls and cases in pooled stroke group OR 0.95 (95% CI: 0.47–1.27), however H2/H2 genotype frequency was increased in young subgroup of patients (OR: 1.66 95% CI: 0.52–5.25). Plasma FIB concentration was increased both in the total cohort (p<0.05) and in the non-smoker subgroup (p<0.03) of patients carried H2/H2 as compared to H1/H1 genotype and the prevalence was increased in the group of patients having plasma FIB concentration >4 g/l (p<0.05). The whole blood viscosity was elevated in the H2/H2 group as compared to the group carrying wild type (p<0.03). A tendency of increased plasma viscosity in the group of patients with H2/H2 genotype as compared to wild type was found (p=0.07). Leiden mutation prevalence showed an increased risk OR: 1.67 (95% CI: 0.75–3.70) in the young patients group as compared to controls. In patients who have had the highest plasma viscosity, higher frequency of Leiden mutation was detected as compared to wild type, in total group (p=0.01), in young patients (p=0.03) and in subgroup of non-smoker patients (p=0.05). Conclusions: Our findings support the notion that the homozigous variant of β-FIB gene can raise both plasma FIB concentration and whole blood viscosity. Leiden mutation connected to the elevation of plasma viscosity could demonstrate a new pathway of increased thrombophylic potential in ischemic stroke patients. Show more

Keywords: Ischemic stroke, genetic polymorphisms, -445 β-fibrinogen, Leiden mutation, blood viscosity, plasma viscosity, hemorheology

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 75-82, 2006

Authors: Kovács, Ágnes | Szikszai, Zita | Várady, Éva | Imre, Sándor

Article Type: Research Article

Abstract: The aim of this study was to assess social and health status of residents older than 90 years in an East-Hungarian city. The investigation involved 70 subjects, measuring routine laboratory parameters and plasma viscosity. Mean cholesterol, erythrocyte sedimentation rate (ESR), collagen cross links and plasma viscosity values exceeded the reference range, but mean red blood cell count, hematocrit and hemoglobin were below it. Plasma viscosity was found pathologically elevated in 51% of cases. We compared these results with an earlier laboratory screening test performed on the same population with the age range of 60 to 90 years. In this cohort …the mean fibrinogen concentration, ESR, HDL-cholesterol and collagen cross links values were higher, but mean cholesterol, triglyceride, total protein, hemoglobin and hematocrit values were lower than the reference range. Show more

Keywords: Oldest-old, laboratory parameters, plasma viscosity, aging

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 83-88, 2006

Authors: Feher, Gergely | Koltai, Katalin | Kesmarky, Gabor | Szapary, Laszlo | Juricskay, Istvan | Toth, Kalman

Article Type: Research Article

Abstract: Background: There is increasing evidence that impaired hemorheological parameters are associated with increased risk of cardio- and cerebrovascular events. The aim of our present study was to examine the relationship of these parameters to the advancing age. Methods: The data of 6236 cardio- and cerebrovascular patients (3774 males, mean age 59.8±13.2 years and 2462 females, mean age 60.9±12.8 years) were included into this analysis. Males and females were divided into three groups, A < 45 years of age (young), B 45–65 years (middle-aged), C > 65 years (old). To exclude the effect of risk profile, previous diseases and medication, 623 …patients (397 males, mean age 60.2±12.7 yrs and 226 females, mean age 60.5±12.4 yrs) were selected from the examined group with matching parameters. Blood was collected after an overnight fasting. Hematocrit, fibrinogen, red blood cell aggregation, plasma and whole blood viscosity were determined. Results: All the measured parameters correlated significantly with advancing age in the whole population (p<0.01), however the values of the correlation coefficients were very low. On the other hand, examining the different age-groups we found that these parameters did not consequently correlate with age, in fact hematocrit, red blood cell aggregation and whole blood viscosity values were negatively correlated with age in old males (p<0.05). In the selected population these parameters did not correlate with advancing age. Conclusions: In the whole population the correlation of hemorheological parameters and advancing age may be just of statistical, but not clinical significance because of the high number of subjects. In the selected population these parameters did not correlate with advancing age. Our results suggest that these parameters are mostly independent of aging, increased values are not associated with older age but the more frequently occurring diseases. Show more

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 89-98, 2006

Authors: Bogar, L. | Juricskay, I. | Kesmarky, G. | Feher, G. | Kenyeres, P. | Toth, K.

Article Type: Research Article

Abstract: Plasma fibrinogen concentration, plasma and whole blood viscosity (WBV) are independent risk factors of coronary artery disease (CAD). Fibrinogen seems to be a relatively stronger risk factor for women than for men, but men are more endangered by higher hematocrit (Hct) and WBV than women are. We have previously reported that a theoretically optimal Hct value can be determined using Hct/WBV ratio in healthy subjects, hyperlipidemic and Raynaud's disease patients. Our aim was to examine whether Hct/WBV ratio is differently correlated with Hct in men and women with proven CAD. In a retrospective study we analysed the hemorheological data of …162 CAD outpatients (107 men and 55 women). Coronary angiography, echocardiography and impedance cardiography were performed. Hemorheological parameters (Hct, fibrinogen level, plasma viscosity, WBV), blood picture, serum lipid concentrations were determined and Hct/WBV ratio was calculated. Mean ages of male and female patients were similar (54.9 and 55.4 years, respectively), but men had significantly higher coronary angiography score than women. Mean left ventricular ejection fraction, stroke volume index and cardiac index showed no significant differences in men and women. Similarly, lipid concentrations, fibrinogen levels and plasma viscosities demonstrated no statistical differences. However, Hct, WBV and Hct/WBV ratios were significantly higher in male than in female patients (p<0.00001; p<0.00001 and p<0.005, respectively). The most striking gender difference was found in the correlation between Hct/WBV ratio and cardiac index. Men older than 56 years showed negative, women positive correlation (r=−0.485, p=0.01; r=0.468, p=0.006, respectively). This study demonstrates that Hct/WBV ratio as a rheological oxygen carrying capacity parameter is positively correlated with the cardiac index as it can be expected. However, the correlation is negative in elder men indicating an unhealthy relation between hemodynamic and hemorheologic parameters. Show more

Keywords: Coronary angiography, cardiac index, hemodynamics, hematocrit, blood viscosity, hemorheology

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 99-103, 2006

Authors: Matschke, K. | Tugtekin, S.M. | Knaut, M. | Mrowietz, C. | Park, J.-W. | Jung, F.

Article Type: Research Article

Abstract: Background: Experimental data have shown the potential risk of cellular damage of the myocardium during extra corporeal circulation (ECC). The influence of ECC on myocardial oxygen tension however remained unclear. Therefore, the influence of ECC on the oxygen tension in a beating heart was investigated. Methods: In a pig animal model flexible pO2 microcatheters were positioned in the midmyocardium of the left ventricle and the skeletal muscle and tissue oxygen tension during ECC were monitored and compared with data of a control group without ECC. Results: ECC and unload of the heart caused a significantly higher increase of myocardial …pO2 than in a non-ECC control group. Conclusion: Our findings show the beneficial effect of ECC on myocardial pO2 . This may support the use of ECC in coronary artery bypass grafting because the potential myocardial injury due to ECC is not related to myocardial ischemia. On the contrary, myocardial pO2 was even increased during extracorporeal circulation in this study. Show more

Keywords: Extra corporeal circulation, microcirculation, myocardium, left ventrical, tissue oxygen tension

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 105-111, 2006

Authors: Aloulou, Ikram | Varlet-Marie, Emmanuelle | Mercier, Jacques | Brun, Jean-Frédéric

Article Type: Research Article

Abstract: The metabolic syndrome which is at high risk for diabetes and atherothrombosis is associated with hemorheologic abnormalities. Initially, insulin resistance was considered as the core of the syndrome. However, it becomes clear that the syndrome is a cluster in which the combined effects of obesity, insulin resistance, and hyperinsulinemia can be inconstantly associated, contributing to a various extent to a global impairment of blood rheology. We previously reported in 157 nondiabetic subjects that both obesity and insulin resistance increase red cell rigidity (Dintenfass's Tk) and plasma viscosity (ηp ), and that whole blood viscosity at high shear rate (ηb …1000 s−1 ) reflects rather obesity than insulin resistance. In this study we aimed at defining the specific hemorheologic profile of insulin resistance and hyperinsulinemia by separating a sample of 81 subjects into 4 subgroups according to quartiles of insulin sensitivity (SI) (measured with the minimal model of an intravenous glucose tolerance test) and baseline insulin. Results show that (1) values of SI within the upper quartile are associated with low ηb due to low ηp ; (2) low SI regardless insulinemia is associated with increased aggregation indexes; (3) when low SI is associated with hyperinsulinemia (insulin the upper quartile and SI in the lower) there is a further increase in ηb due to an increase in ηp ; (4) neither SI nor insulinemia modify Hct. Thus hyperinsulinemia and insulin resistance induce hyperviscosity syndromes which are somewhat different, although they are associated most of the time. Low SI increases RBC aggregation while hyperinsulinemia increases ηp . Show more

Keywords: Insulin resistance, insulin sensitivity, minimal model, metabolic syndrome, hemorheology, plasma viscosity, erythrocyte aggregability

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 113-119, 2006

Authors: Williams, P.R. | Hawkins, K. | Wright, C. | Evans, A. | Simpkin, H. | Barrow, M.S. | Williams, R.L.

Article Type: Research Article

Abstract: The rheological behaviour of coagulating human blood has been measured using multiple strain wave frequencies. The results indicate that coagulating blood, prior to the point of incipient clot formation, can be modelled by a modified form of the Gross–Marvin ‘ladder’ model, and the benefits of such modeling for blood coagulation are discussed.

Keywords: Rheology, blood coagulation, discrete relaxation spectra

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 123-127, 2006

Authors: Savov, Y. | Antonova, N. | Zvetkova, E. | Gluhcheva, Y. | Ivanov, I. | Sainova, I.

Article Type: Research Article

Abstract: Whole blood viscosity (WBV) and hematometric indices of erythrocytes as red blood cell count (RBC), mean erythrocyte volume (MCV), hemoglobin (HGB), hematocrit (HCT), mean hemoglobin content of erythrocytes (MCH), HGB/HCT values (MCHC) and red blood cell distribution width (RDW) have been studied in a group of 15 chronic opioid addicts under methadone maintenance therapy with mean age 26.53±7.34 years. WBV elevation and changes in MCV, HGB, HCT, RDW were found in intravenous drug users compared to healthy individuals. As well, RBC was decreased leading to an increase in MCH and MCHC values. Correlation analysis suggested that the correlation among the …RBC, HGB, HCT and WBV was the closest. Heroin macrocytosis (heroin macrocytic anemia) was established, related with the increased RDW in chronic heroin abusers. The results are in accordance with data revealing abnormal effects of alcohol and other drugs on whole blood rheology and hematometric/morphometric characteristics of erythrocytes. Show more

Keywords: Whole blood viscosity, erythrocyte hematometric indices, chronic heroin abusers, heroin macrocytosis (heroin macrocytic anemia)

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 129-133, 2006

Authors: Konstantinova, Elena | Ivanova, Lilia | Tolstaya, Tatiyana | Mironova, Elena

Article Type: Research Article

Abstract: The results of some researches specify the important role of blood rheological properties changes in arterial hypertension (AH) pathogenesis. The goal of our study is to investigate the parameters of hemorheology and platelet aggregation in patients with various grade of AH. The study was carried out on 27 patients with grade 1 AH (group 1), 24 patients with grade 2 AH (group 2) and 29 healthy subjects (group 3). In patients of these groups, we evaluated erythrocytes deformability, red blood cells and platelets aggregation, blood and plasma viscosity. Using intra-vital computer-associated microscopic system we investigated microcirculation of bulbar conjunctiva. We …observed that the rate of ADP-induced platelets aggregation is higher in group 1 as compared to groups 2 and 3. In groups 1 and 3, red blood cells rigidity index is significantly lower as compared to group 2. Erythrocyte aggregability is higher in group 2 in comparison with groups 1 and 3. The results obtained demonstrate that mild hypertension is associated with the rise of platelets aggregability, moderate hypertension is accompanied by the reduction of red blood cells deformability and increase of erythrocyte aggregability. These data may reflect differences in conditions for the formation of microcirculation disorders in AH of various grade. Show more

Keywords: Arterial hypertension, platelets, erythrocytes, deformability, aggregation, microcirculation

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 135-138, 2006

Authors: Pais, Eszter | Alexy, Tamas | Holsworth, Jr., Ralph E. | Meiselman, Herbert J.

Article Type: Research Article

Abstract: The vegetable cheese-like food, natto, is extremely popular in Japan with a history extending back over 1000 years. A fibrinolytic enzyme, termed nattokinase, can be extracted from natto; the enzyme is a subtilisin-like serine protease composed of 275 amino acid residues and has a molecular weight of 27.7 kDa. In vitro and in vivo studies have consistently demonstrated the potent pro-fibrinolytic effect of the enzyme. However, no studies to date have evaluated the effects of nattokinase on various hemorheological parameters and thus we have begun to assess the effects of the enzyme on RBC aggregation and blood viscosity. Blood samples …were incubated with nattokinase (final activities of 0, 15.6, 31.3, 62.5 and 125 units/ml) for 30 minutes at 37°C. RBC aggregation was measured using a Myrenne MA-1 aggregometer and blood viscosity assessed over 1–1000 s−1 with a computer controlled scanning capillary rheometer (Rheolog® ). Our in vitro results showed a significant, dose-dependent decrease of RBC aggregation and low-shear viscosity, with these beneficial effects evident at concentrations similar to those achieved in previous in vivo animal trials. Our preliminary data thus indicate positive in vitro hemorheological effects of nattokinase, and suggest its potential value as a therapeutic agent and the need for additional studies and clinical trials. Show more

Keywords: Nattokinase, red blood cell, aggregation, hemorheology

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 139-142, 2006

Authors: Yerer, M. Betül | Aydoğan, Sami

Article Type: Research Article

Abstract: The hormone melatonin, secreted from the pineal gland at night and suppressed during the day, provides a circadian and seasonal signal to the organism. The impact of pharmacological doses of melatonin on erythrocyte deformability was investigated by our group in several studies in both in vitro and in vivo conditions. The aim of this study was to investigate the effects of alterations in the physiological melatonin levels via the circadian rhythm on erythrocyte deformability. 50 male rats weighing 250–300 g were divided in 5 groups. The rats were subjected to 12/12, 24/0, 0/24, 16/8 and 8/16 h of Light/Dark (L/D) …cycle, respectively. The elongation indexes (EI) of the erythrocytes were measured by a laser diffractometer (Myrenne Rheodyne SSD) by using 30 μl of whole blood suspended in 2 ml of Dextran 60. There was no significant difference in the EI of the 24/0 h L/D group compared to the control (12/12), whereas the decrease of EI was statistically important in the 0/24 h L/D group (p=0.009). This decrease in EI was also significant when this group was compared to the 24/0 h L/D group (p=0.05). Furthermore, the EI was affected significantly by alterations in the circadian rhythm, compared to control (16/8, 8/16 h L/D; p=0.05 and p=0.007, respectively). As a result, the alterations in physiological melatonin levels via different circadian rhythms have significant impacts on the deformability of erythrocytes, which therefore may cause important cardiovascular implications in the people who are exposed to different light dark cycles. Furthermore, these data represents a new and a quite crucial open-field to be investigated and taken into account in in vivo hemorheological studies. Show more

Keywords: Erythrocyte deformability, shear stress, melatonin, circadian rhythm

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 143-147, 2006

Authors: Cicco, Giuseppe | Vetrugno, Michele | Rotelli, Maria Teresa | Sborgia, Giancarlo | Pennetta, Massimiliano | Vico, Pier Paolo | Memeo, Vincenzo | Nitti, Luigi | Sborgia, Carlo

Article Type: Research Article

Abstract: Background: Glaucoma is currently attributed to two different possible pathogenetic mechanisms: mechanical (the ocular damage is induced by physical injury), and vascular (the ocular damage is sustained by ischemia of the optic nerve head). Aim: We considered the possibility that several anti-glaucoma drugs (β-blockers, carbonic anhydrase inhibitors and prostaglandins) could have an influence on optic nerve head hemorheology and oxygen supply. Materials and method: We studied 4 groups of 10 subjects each: a control group, and 3 primary open angle glaucoma (POAG) groups, treated with topical β-blockers, (10 patients), carbonic anhydrase inhibitors (CAI), and prostaglandin analogs (PG), respectively. In these …4 groups we investigated the RBC surface AchE and cytosolic calcium levels in order to assess their possible influence on the hemorheology and microcirculation in optic nerve head blood perfusion. Results: A significant correlation (p<0.048) was found between the RBC surface acetylcholinesterase and RBC intracytosolic calcium values in patients with POAG treated with β-blockers. We found no significant correlation (p=n.s.) between the same patterns in the other Groups or in Controls. Conclusion: These data indicate that CAI and PG drugs do not interfere with AchE in POAG patients, whereas β-blockers negatively affect the RBC deformability. Show more

Keywords: Hemorheology, glaucoma, β-blockers, carbonic anhydrase inhibitors, prostaglandins

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 149-154, 2006

Authors: Velcheva, Irena | Antonova, Nadia | Dimitrova, Valentina | Dimitrov, Nikolay | Ivanov, Ivan

Article Type: Research Article

Abstract: It is known that plasma lipids could increase the cerebrovascular risk through alteration of the hemorheological profile. The aim of the study was to evaluate the relationship between blood viscosity parameters and plasma lipids in patients with cerebrovascular disease (CVD). The study included 43 patients with transient ischemic attacks (TIAs), 53 patients with chronic unilateral cerebral infarctions (UCI) and 57 patients with risk factors (RF) for CVD. Whole blood viscosity (WBV) at different shear rates by Couette rotational viscometer Contraves Low Shear 30, plasma viscosity (PV) with capillary viscometer, hematocrit (Hct), fibrinogen (Fib), Cholesterol (Chol), triglycerides (Tg) and high-density lipoproteins …(HDL) were examined in all patients and in a control group of 56 presumed healthy subjects. The hemorheological results showed increase of Hct, Fib, WBV and PV in the patients with TIAs and UCI; it was more pronounced in the UCI patients. Significant increase of Hct and WBV in the group with RF for CVD was also found. The elevation of Chol and Tg predominated in the patients with UCI and in the subjects with RF for CVD. These lipid variables correlated significantly with PV in the TIAs and RF for CVD groups. Conclusion is drawn about the significance of plasma Tg for decrease of blood fluidity and for impairment of the cerebral circulation in CVD. Show more

Keywords: Cerebrovascular disease, plasma lipids, blood and plasma viscosity

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 155-157, 2006

Authors: Ahmadizad, Sajad | El-Sayed, Mahmoud S. | MacLaren, Donald P.M.

Article Type: Research Article

Abstract: The present study was designed to investigate the effects of resistance exercise and recovery on platelet activation and function. Twenty one healthy male subjects (27.9±4.8 years) completed three sets of five to seven repetitions of six exercises at an intensity corresponding to 80% of one repetition maximum (1RM), which was followed by 30 minutes recovery. Venous blood samples (20 ml) were obtained before, immediately after exercise and at the end of recovery and were analysed for platelet indices, platelet aggregation using collagen and various final concentrations of adenosine-5′-diphosphate (ADP), and beta thromboglobulin (B-TG). Resistance exercise was followed by a significant …increase in corrected platelet count, corrected plateletcrit, and B-TG. These increases were transient and decreased to pre-exercise level at the end of recovery. When plasma samples were not corrected for changes in platelet count, exercise was followed by a significant increase (P<0.05) in platelet aggregation using high concentration of ADP. With corrected samples, platelet aggregation and B-TG were not altered after exercise and recovery. It was concluded that heavy resistance exercise induces in vivo activation of platelets as manifested by an increase in platelet aggregation and a rise in B-TG and that these changes could be explained partially by changes in plasma volume and platelet count induced by exercise. Show more

Keywords: Resistance exercise, recovery, platelet function, B-TG, platelet count

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 159-168, 2006

Authors: Gori, Tommaso | Di Stolfo, Giuseppe | Sicuro, Silvia | Dragoni, Saverio | Parker, John D. | Forconi, Sandro

Article Type: Research Article

Abstract: Although microvascular dysfunction is of critical importance in the pathophysiology of myocardial ischemic syndromes, no study has investigated whether there are differences in the sensitivity to ischemia and reperfusion injury between microvessels and conduit arteries. Ten healthy young nonsmoking male volunteers (age range 24–45) were enrolled. Parameters measured included radial (conduit) artery (endothelium-dependent) flow-mediated dilation, microvascular cutaneous reactive hyperemia (using laser Doppler) and acetylcholine-induced microvascular vasodilation (laser Doppler iontophoresis). Data were acquired before and after ischemic injury (15 minutes of ischemia of the brachial artery followed by 15 minutes reperfusion) and analyzed in a randomized, blinded fashion. Conduit artery FMD …was significantly blunted after ischemia (before: 7.5±1.1%; after: 2.9±1.0%, P<0.05). Conversely, ischemia had no effect on microvascular reactive hyperemia (P=ns) and acetylcholine-induced vasodilation (P=ns). Using a human in vivo model, we demonstrate that microvessels are more resistant to ischemic injury as compared to conduit arteries. Show more

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 169-173, 2006

Authors: Mannini, Lucia | Marcucci, Rossella | Paniccia, Rita | Antonucci, Emilia | Giglioli, Cristina | Valente, Serafina | Gori, Anna Maria | Prisco, Domenico | Gensini, Gian Franco | Abbate, Rosanna

Article Type: Research Article

Abstract: Recently the phenomenon of aspirin resistance has been object of several studies, but no data are available on the possible role of the haemorheologic parameters in affecting platelet function and resistance to antiplatelet agents. Aim of our study was to evaluate platelet function and haemorheology in patients with acute coronary syndromes (ACS), receiving double antiplatelet therapy with aspirin and clopidogrel. The study population included 301 (231M/70F; age: 66±13 yrs) consecutive adult patients admitted to the Coronary Care Unit of the Azienda Ospedaliero-Universitaria Careggi, with diagnosis of acute myocardial infarction or unstable angina. We assessed: whole blood viscosity (WBV) at shear …rates of 0.512 s−1 and 94.5 s−1 , plasma viscosity (PLV) at 94.5 s−1 shear rate, erythrocyte deformability index (DI) and PFA-100 closure times with ADP (PFA/ADP) and epinephrine (PFA/EPI). We considered any PFA-100-EPI result <203 sec (95th percentile of control distribution) to be indicative of aspirin resistance. 104/301 patients (34.5%) had PFA/EPI CTs in the reference range (group 1) whereas the remaining had values higher than 203 sec (group 2). WBV at 94.5 sec −1 s.r. was similar in group 1 and 2 (WBV: 4.43±0.25 vs 4.45±0.61 mPa·sec, respectively). PLV and WBV at 0.512 sec −1 s.r. were slightly higher, but not significantly, in group 1 than in group 2 (PLV: 1.47±0.13 vs 1.44±0.15 mPa·sec; p=0.08 and WBV: 23.37±4.6 vs 22.54±3.90 mPa·sec; p=0.07). DI was significantly lower in group 1 with respect to group 2 (4.05±2.93 vs 5.71±3.30, p<0.0001). White blood count (WBC) was significantly higher in group 1 than in group 2 (11464±3504 vs 7867±2162, p<0.0001). In conclusion, these results demonstrate that in patients with acute coronary syndromes the antiaggregant effect of aspirin is modulated not only by the direct action on platelets, but also by erythrocyte deformability and white blood cell count. Show more

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 175-181, 2006

Authors: Cortinovis, A. | Crippa, A. | Cavalli, R. | Corti, M. | Cattaneo, L.

Article Type: Research Article

Abstract: As known, at the arteriolar level there is the highest resistance to the flow due to the section and to the velocity with an average pressure fall of 50 mmHg (from 85 to 35 mmHg). This resistance is expressed in sec−1 by the ratio W/2r. This ratio is very high with an average value of 332 sec−1 and viscosity at this high shear-rate is negligible. At the capillary level the pressure fall is 11.5 mmHg but the vascular resistance W/2r is much lower, on average 32 sec−1 . We can say that if a resistance of 333 sec−1 …corresponds with a pressure fall of 50 mmHg, then a resistance of 32 sec−1 should correspond with a pressure fall of 4.8 mmHg. The highest pressure fall is due to another kind of resistance which we can define as “Capillary Blood Viscosity” because it depends on the rheological and structural characteristics of the blood. Our instrument reproduces the structure of the capillary district in an experimental model and measures the General Blood Viscosity (GBV) and the Capillary Blood Viscosity (CBV) at the same shear-rate and in particular at the low shear-rate when in non-Newtonian fluids the highest increase in viscosity appears. Consequently, at the capillary, viscosity is dominant with respect to the other geometric and physical resistances. Moreover, the percentage ratio between the GBV and the CBV gives a physical measure of erythrocyte deformability. Knowing viscosity at shear-rate present in the circulatory system, we can obtain the size of RBCs aggregates in the different circulatory districts and their characteristics expressed like “aggregation bond”. Changes in CBV are the only possibility in clinical practice to improve the circulatory flow in the capillary district because it is not sure that changes in the arteriolar section can improve the capillary flow or rather open arterio-venous anastomosis. Moreover, in the systemic circulation the aggregate size allows us to point out the phenomenon of cell adhesion because the presence of several receptors involves also the other blood cells. Finally the size and the stability of the RBCs aggregates can modify the endothelial thrombo-resistance. Show more

Keywords: General blood viscosity, capillary blood viscosity, erythrocyte deformability, erythrocyte aggregation, microcirculation

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 183-192, 2006

Authors: Velcheva, Irena | Antonova, Nadia | Titianova, Ekaterina | Damianov, Petar | Dimitrov, Nikolay | Ivanov, Ivan

Article Type: Research Article

Abstract: The study aimed to follow the relationship between some hemorheological variables and the main risk factors (RF) for carotid atherosclerosis (CA). Carotid atherosclerosis was evaluated by color duplex sonography of the carotid arteries in 18 patients with RF for CA, 31 patients with transient ischemic attacks (TIAs), 21 patients with chronic unilateral cerebral infarctions (UCI) and 11 healthy subjects without RF for CA. The examined hemorheological variables were whole blood and plasma viscosity, hematocrit and fibrinogen. They were correlated with intima-media thickness (IMT) of the common carotid and the internal carotid arteries and with other main RF for CA: hypertension, …diabetes mellitus, coronary heart disease, and hyperlipidemia. The hemorheological investigation showed an increase in blood and plasma viscosity at different shear rates and it was more expressed in the group with UCI. The neurosonographic investigation revealed an increase in the IMT and carotid artery stenoses in the patients' groups with CVD. These were also more frequent in the patients with UCI. Different correlations were established between the hemorheological parameters, the IMT of the carotid arteries and other RF for CA. In the group with UCI, the hematocrit and the whole blood viscosity correlated significantly with the IMT, arterial blood pressure and cholesterol values. These data confirm the influence of the hemorheological parameters on carotid blood vessel walls and on blood flow in patients with CVD. Show more

Keywords: Blood and plasma viscosity, risk factors, carotid atherosclerosis, carotid intima media thickness

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 195-198, 2006

Authors: Lo Presti, Rosalia | Tozzi Ciancarelli, Maria Giuliana | Canino, Baldassare | Carollo, Caterina | Lucido, Daniela | Amodeo, Gabriella | Romano, Adele | Caimi, Gregorio

Article Type: Research Article

Abstract: An abnormal activation state of polymorphonuclear leukocytes (PMN) plays a key role in organ injury induced by vascular atherosclerotic disease (VAD) and diabetes mellitus (DM). PMN membrane fluidity and cytosolic Ca2+ content can be considered markers of PMN activation. In this research we evaluated the PMN membrane fluidity and cytosolic Ca2+ content in VAD subjects with and without type 2 DM and examined the association between these parameters and the mono- or polyvascular localization. We enrolled 155 VAD subjects, including 92 non-diabetic (group A: mean age 63.6±9.2 years) and 63 diabetic patients (group B: mean age 65.4±7.8 years). …Among group A 63 patients had monovascular and 29 polyvascular disease; among group B 30 patients had monovascular and 22 polyvascular disease. In each patient we evaluated the PMN membrane fluidity labelling the cells with the fluorescent probe 1,4-(trimethylamino)-phenyl-4-phenylhexatriene (TMA-DPH) and the PMN cytosolic Ca2+ content marking the cells with the fluorescent probe Fura 2-AM. PMN membrane fluidity did not discriminate normal subjects from diabetic and non-diabetic VAD subjects, while cytosolic Ca2+ content was increased in both groups. PMN membrane fluidity did not distinguish normal subjects from mono- or polyvascular VAD patients with and without type 2 DM. PMN cytosolic Ca2+ content was increased especially in monovascular VAD patients; both mono- and polyvascular VAD subjects with DM had a PMN cytosolic Ca2+ content higher than normals. Our results show the presence of an increased PMN cytosolic Ca2+ content in diabetic and non-diabetic VAD subjects but no association was observed between this increase and the mono- or polyvascular localization. Show more

Keywords: Vascular atherosclerotic disease, type 2 diabetes mellitus, polymorphonuclear leukocyte membrane fluidity, polymorphonuclear leukocyte Ca$^{2+}$ content

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 199-201, 2006

Authors: Cicha, Iwona | Yilmaz, Atilla | Suzuki, Yoji | Maeda, Nobuji | Daniel, Werner G. | Goppelt-Struebe, Margarete | Garlichs, Christoph D.

Article Type: Research Article

Abstract: Connective tissue growth factor (CTGF) is overexpressed in atherosclerotic blood vessels. To further investigate the role of CTGF in atherosclerosis, we examined whether CTGF is released from platelets by high shear stress, and whether the expression of CTGF along the atherosclerotic lesions depends on local hemodynamic conditions. Human platelets were subjected to 10 dyn/cm2 or 120 dyn/cm2 and analysed by Western blotting. Furthermore, longitudinal sections of 25 carotid plaques were immunohistochemically analysed for the endothelial expression of CTGF. A very low CTGF amount was secreted from platelets at low shear stress (11.4±3.9% of total CTGF in platelets). On …the contrary, high shear stress caused a markedly increased CTGF release from platelets (29±13.8%, p=0.07 vs low shear stress, n=4). Immunohistochemical analyses showed that the mean numbers of CTGF-positive endothelial cells were significantly higher up-stream as compared with down-stream regions of the luminal surface of atherosclerotic vessels (21.3±3.6 vs 13.9±2.8 down-stream, p<0.001). Moreover, in plaques undergoing intimal neovascularization, newly formed vessels accumulated particularly in up-stream parts of the lesions. In conclusion, this study demonstrated that CTGF is released from platelets by high shear stress. Furthermore, disturbed flow along atherosclerotic vessels may induce endothelial CTGF expression and contribute to the progress of atherosclerotic lesions. Show more

Keywords: CTGF, platelets, atherosclerosis, hemodynamics

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 203-206, 2006

Authors: Aloulou, Ikram | Varlet-Marie, Emmanuelle | Mercier, Jacques | Brun, Jean-Frédéric

Article Type: Research Article

Abstract: The metabolic syndrome, which is associated with an high risk for diabetes and atherothrombosis, is associated with hemorheologic abnormalities. These abnormalities seem more and more to be explained by its various symptoms than by insulin resistance which represents theoretically the core of the syndrome. In this study we aimed at defining the specific hemorheologic profile of insulin resistance and hyperinsulinemia by separating a sample of 90 subjects into 4 subgroups according to the clinical score “NCEP-ATPIII” which is the best recognized standardized definition of the syndrome. Results show no significant changes of blood rheology across classes of NCEP score despite …a borderline rank correlation between RBC aggregability “M1” and the score. Whole blood viscosity was mostly correlated to HDL-cholesterol (r=−0.353, p=0.007) and triglycerides (r=0.574, p=0.0001). Plasma viscosity was correlated with total cholesterol (r=0.3359, p=0.02) and with LDL-cholesterol (r=0.357, p=0.03). Red blood cell rigidity “Tk” was negatively correlated to HDL-cholesterol (r=−0.430, p=0.007). Aggregability “M” was correlated to total cholesterol (r=0.356, p=0.01) and “M1” to HDL-cholesterol (r=−0.406, p=0.006). Thus, despite previously described correlations with glucose disposal parameters, the hyperviscosity syndrome of the metabolic syndrome is not proportional to its clinical scoring and is strongly dependent upon the lipid profile. Show more

Keywords: Insulin resistance, insulin sensitivity, minimal model, metabolic syndrome, hemorheology, plasma viscosity, erythrocyte aggregability

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 207-212, 2006

Authors: Yerer, Mükerrem Betül | Aydoğan, Sami | Çomu, Faruk Metin | Arslan, Mustafa | Güneş-Ekinci, Işın | Kurtipek, Omer | Unal, Yusuf

Article Type: Research Article

Abstract: General anesthesia, either with inhalation or through nonvolatile anesthetics, is known to affect the overall cardiovascular function as well as the microcirculatory hemodynamics. In this study, the effects of desfluran anesthesia on the red blood cell deformability of young and old rats are investigated. 33 male rats were used in the study and the rats were divided into two groups according to their age (young and old) comprising of two subgroups in each. First group was the young control (n=5), the second was the young group treated with desfluran (n=7), the third group was the old control (n=7) and the …last group was the old group treated with desfluran (n=7). %6 of desfluran was applied to the rats with inhalation in an adjustable cage for one hour. The elongation indexes of the erythrocytes were measured by a laser diffractometer (Myrenne Rheodyne SSD). Deformability indexes of red blood cells were significantly increased with desfluran in young rats (p=0.042) whereas they were significantly decreased in old rats (p=0.004) with desfluran application compared with their controls. When we compared the young and old control groups, the deformability indexes were significantly higher in old ones (p<0.001). However, there was no significant difference between the old and the young desfluran applied groups. The volatile anesthetic agent desfluran impairs the deformability of erythrocytes in old rats compared to their controls, whereas it has the opposite effects on young ones. This may be due to the alterations in membrane structure with age. These results reveal that the inhalation of anesthetics like desfluran may cause more serious problems in the elder people during the surgery and may influence their hemodynamic parameters. Show more

Keywords: Desflurane, erythrocyte deformability, anesthesia, rat

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 213-216, 2006

Authors: Tatarishvili, J. | Sordia, T. | Mchedlishvili, G.

Article Type: Research Article

Abstract: Objective: The aim of the present study was the analysis of the specific hemorheological disorders during the middle stages of experimental traumatic and hemorrhagic shock. Methods: The following hemorheological properties were investigated: Red Blood Cell (RBC) aggregability, their deformability, and systemic hematocrit. The RBC aggregability was assessed by using the “Georgian technique”. The RBC deformability was determined with the nuclepore membrane filter method of Reid. The hematocrit was measured by blood centrifugation. The results obtained were treated statistically by using the “Two sample T-test”. Results: We found that in the animals with traumatic shock the erythrocyte aggregability index increased by …mean 181%, while in the hemorrhagic group this index on contrary decreased by mean 68% as compared to control group; The RBC deformability underwent a significant decrease during both traumatic and hemorrhagic shock: by a mean of 52% during the first and 62% during the second one. The systemic hematocrit decreased by a mean of 45% during the traumatic shock and by a mean of 50% during the hemorrhagic shock. Conclusion: The data obtained provide evidence that the hemorheological disorders are among the most significant microcirculatory disturbances in the pathogenesis of both the traumatic and the hemorrhagic shock. Show more

Keywords: Traumatic shock, hemorrhage, erythrocyte aggregability

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 217-221, 2006

Authors: Sordia, Tea | Tatarishvili, Jemal | Mchedlishvili, George

Article Type: Research Article

Abstract: Objectives: The aim of the present study was the experimental analysis of blood rheological disorders in the microcirculation during endotoxic shock. Methods: Experiments were carried out on 30 white laboratory rats of both sexes weighing about 200 g. The experimental animals were divided in two groups: the control group and the group undergoing experimental endotoxic shock. The following specific hemorheological properties were investigated in all animals during the experiments: red blood cells (RBC) aggregability, their deformability and the systemic hematocrit. Results: We found that all the investigated hemorheological parameters appreciably changed underconditions of endotoxic shock. The RBC aggregability index was …increased by a mean of 136%. As to the RBC deformability index was found to be decreased by 71%, and the systemic hematocrit lowered by 31%, as compared to the same parameters in the control group. Conclusion: The data obtained provide us with evidence that the hemorheological derangements associated with the development of the heavy microcirculatory disorders during endotoxic shock, are most significant factors. Show more

Keywords: LPS induced endotoxic shock, hemorheological disorders, mesenterial microcirculation in rat experiments

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 223-226, 2006

Authors: Lo Presti, Rosalia | Tozzi Ciancarelli, Maria Giuliana | Hoffmann, Enrico | Incalcaterra, Egle | Canino, Baldassare | Montana, Maria | D'Amico, Teresa | Catania, Anna | Caimi, Gregorio

Article Type: Research Article

Abstract: Acute myocardial infarction (AMI) is associated with an elevated polymorphonuclear leukocyte (PMN) count and a PMN rheological impairment. In this study we evaluated two major rheological aspects (membrane fluidity and cytosolic Ca2+ concentration) in a group of young adults with AMI. We enrolled 41 AMI patients (39 men and 2 women; mean age 41.0±4.0 years), who were examined 5–10 days after AMI (T1) and 12 months later (T2). The membrane fluidity was obtained labelling granulocytes with the fluorescent probe 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) and considering the degree of fluorescence polarization, inversely correlated to the membrane lipid fluidity. The cytosolic Ca2+ …content was obtained marking PMN cells with the fluorescent probe Fura-2AM and considering the ratio between the Fura 2-Ca2+ complex and the unchelated Fura 2 fluorescence intensity. Both parameters were evaluated at baseline and after in vitro activation with 4-phorbol 12-myristate 13-acetate (PMA) at the concentration of 4.5 μM, prolonged for 5 and 15 minutes. At T1 the PMN membrane fluidity and cytosolic Ca2+ content in AMI patients were respectively decreased and increased in comparison with control group. At T2 the membrane fluidity was not any more different from control subjects, but there was also a further increase in cytosolic Ca2+ content. In vitro, PMN activation caused no significant variation of these parameters in the control group, while in AMI patients membrane fluidity significantly decreased and cytosolic Ca2+ content increased not only during the initial stage, but also after 12 months. The long-term functional alteration of PMN cells observed in young adults with AMI confirms the role of these cells in the inflammatory response following AMI. In the light of these data, the use of molecules able to modulate granulocyte activity, such as calcium channel blockers or pentoxifylline, should be reconsidered in myocardial infarction, together with the usual pharmacological treatment. Show more

Keywords: Acute myocardial infarction in young people, polymorphonuclear leukocyte membrane fluidity, polymorphonuclear leukocyte Ca$^{2+}$ content

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 227-230, 2006

Authors: Di Massimo, C. | Lo Presti, R. | Corbacelli, C. | Pompei, A. | Scarpelli, P. | De Amicis, D. | Caimi, G. | Tozzi Ciancarelli, M.G.

Article Type: Research Article

Abstract: To verify the potential involvement of the age-dependent modifications of EC-SOD activity in the impairment of plasma NO availability with advancing age, 40 healthy men divided into 4 age groups for the purpose of comparison (young: 27.4±1.5 years; middle: 50.8±2.2, years; old: 70.0±1.8 years; very old: 86.1±1.1 years) were enrolled in this study. Plasma samples were used for measurements of the stable end-product nitrite/nitrate (NOx ), as an expression of NO availability, EC-SOD activity, thiobarbituric acid reactive substances (TBARS) as a marker of lipid peroxidation, low density lipoprotein (LDL) copper-mediated oxidation in vitro and total antioxidant capacity (TEAC). Our results …indicated a significant age-related progressive decrease of plasma NOx content and EC-SOD activity and their values were positively correlated (r=0.713, p<0.001). Increased TBARS amount together with reduced lag time for in vitro oxidation of LDL and decreased content of TEAC were observed with advancing age. Finally, EC-SOD values were negatively correlated with plasma TBARS values (r=−0.855, p<0.001). Findings of the present study suggest that the decrease of antioxidant defence strategies play a primary role by compromising NO availability in normally aged individuals, particularly through a progressive decrease of EC-SOD activity. Show more

Keywords: Elderly, nitric oxide, extracellular superoxide dismutase

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 231-237, 2006

Authors: Manetta, Jérôme | Aloulou, Ikram | Varlet-Marie, Emmanuelle | Mercier, Jacques | Brun, Jean-Frédéric

Article Type: Research Article

Abstract: Aging impairs blood rheology while various training protocols improve it. The purpose of this study was to delineate the respective role of aging and endurance training on blood rheology. Thirty-two subjects [16 middle-aged men: 8 cyclists (MAcy) and 8 sedentary men (MAsed) and 16 young men: 8 cyclists (Ycy) and 8 sedentary men (Ysed)] were compared in this study. Results showed higher red blood cell (RBC) rigidity and aggregability (AFFIBIO), lower RBC disaggregability (AFFIBIO) at middle age than at 25 yr, regardless of training status. However there was no age-related difference in whole blood viscosity at either native or corrected …hematocrit, plasma viscosity, hematocrit, and Myrenne aggregation indexes M and M1. Training was associated with a reduced hematocrit in middle age subjects but not in 25 yr old ones. We evidenced no effect of training on red cell rigidity (Dintenfass's Tk index), in whole blood viscosity at either native or corrected hematocrit, and plasma viscosity. Thus, regular cycling at middle age maintains a low hematocrit but does not prevent aging-related increase in red cell rigidity and aggregability. Specific effects of cycling among other sports may explain this specific pattern. Show more

Keywords: Exercise training, hemorheology, aging, viscosity, hematocrit, erythrocyte aggregability, cyclism

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 239-244, 2006

Authors: Silva, A.S. | Saldanha, C. | Martins-Silva, J.

Article Type: Research Article

Abstract: Clinical and experimental studies have shown that the use of phytosterol esters as a food ingredient reduces the plasma concentrations of cholesterol and LDL cholesterol, not affecting the HDL cholesterol levels. Based on the use of phytosterols as a food ingredient, we have conducted a 30-day feeding study with Wistar rats, drinking low-fat milk containing phytosterols, in order to evaluate the plasma cholesterol concentrations and the hemorheological parameters. Throughout the study, clinical observations, body weights and food and milk consumption were measured and at the end of the feeding period, blood samples were collected for biochemical and hemorheological determinations. There …were no clinical changes, alterations in growth, food or milk consumption. In the plasma cholesterol and HDL concentrations there were no significant differences, but LDL levels decreased about 70%. In the hemorheological parameters, significant changes were observed in plasma viscosity and in membrane fluidity in all experimental groups. The blood viscosity and the erythrocyte deformability show significant improvements with the ingestion of the phytosterols enriched milk. With these results we conclude that phytosterols maintain their cholesterol lowering properties when incorporated in milk and can be considered a hypolipemic food component. Show more

Keywords: Phytosterols, cholesterol, LDL-cholesterol, HDL-cholesterol, milk, hemorheology

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 245-250, 2006

Authors: Gonçalves, Sonia | Maria, A. Vasco | Silva, A.S. | Martins-Silva, J. | Saldanha, C.

Article Type: Research Article

Abstract: Plant sterols have been reported to decrease plasma concentrations of cholesterol without any side effects. To evaluate the effects on plasma cholesterol concentrations and the hemorheological parameters, we performed a study with hypercholesterolemic patients (n=19) treated with phytosterol-enriched milk (2 g/day). Hypercholesterolemic patients (n=15) of matched age drinking equal type of milk but without phytosterols were used as control group. Concentrations of total cholesterol, HDL-C, LDL-C and hemorheological parameters were measured in the beginning, after 15 and 30 days of milk intake. After 15 days of beverage intake, hypercholesterolemic subjects treated with phytosterol-enriched milk showed a significant decrease in plasma …concentrations of total cholesterol and LDL-C by 9.62% (p<0.05) and 12.20% (p<0.05), respectively. After 30 days, a little increase in the total cholesterol and LDL-C concentrations were observed. In the hypercholesterolemic control group there were nonsignificant changes between plasma concentrations of total cholesterol, HDL-C and LDL-C during the study. The evaluation of plasma viscosity and erythrocyte aggregation shows no changes statistically significant during the study for both groups studied. The results obtained during the study show a positive effect with the phytosterol-enriched milk as plasma cholesterol-lowering as combined treatment for hypercholesterolemia. Show more

Keywords: Hypercholesterolemia, phytosterols, LDL-C, HDL-C, functional food, plasma viscosity, erythrocyte aggregation

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 251-255, 2006

Authors: Kobayashi, Takao | Nakamura, Mashio | Sakuma, Masahito | Yamada, Norikazu | Sakon, Masato | Fujita, Satoru | Seo, Norimasa

Article Type: Research Article

Abstract: Incidence of venous thromboembolism (VTE), which had been considered a relatively rare disease in Japan, has been on the increase in recent years as eating habits have become more similar to those of the West. We have investigated the recent incidence data of perioperative pulmonary thromboembolism (PTE) in Japan and have established guidelines for the prevention of VTE. Recommended thromboprophylaxis is early ambulation for low risk group, elastic stocking (ES) or intermittent pneumatic compression (IPC) for moderate risk group, IPC or low dose unfractionated heparin (LDUH) for high risk group, and LDUH + IPC or LDUH + ES for highest …risk group. The management fee for PTE prophylaxis was established and covered by health insurance in April 2004. Surprisingly, the incidence of perioperative PTE decreased just after this guideline was issued. After accumulation of further evidence and application of pharmacological agents, such as low molecular weight heparin, we will establish the advanced guidelines in the future. Show more

Keywords: Venous thromboembolism, pulmonary thromboembolism, thromboprophylaxis, elastic stocking, intermittent pneumatic compression, heparin

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 257-259, 2006

Authors: Momtselidze, Nana | Mantskava, Maia | Mchedlishvili, George

Article Type: Research Article

Abstract: The aim of the present study was the comparative analysis of the role of specific hemorheological derangements in the pathogenesis of ischemic brain infarcts with and without diabetes mellitus. Blood plasma viscosity, as well as red blood cells (RBC) aggregability were quantitatively investigated in all patients during the study. Both of the above mentioned indices of hemorheological disorders were significantly higher in the patients with brain infarcts and diabetes mellitus as compared to the control and the group of ischemic brain infarcts without diabetes. During the ischemic stroke, blood plasma viscosity was increased by a mean of 9.2 per cent …in the first and by a mean of 17.6 per cent in the second group of patients. As to the erythrocyte aggregability index, it was changed considerably more – by a mean of 113.8 per cent during stroke without diabetes, while in the diabetic patients the RBC aggregability index was found to be increased by a mean of 147.3 per cent. Ischemic brain infarcts in patients with diabetes mellitus were associated with a significant increase of the patients' blood rheological disorders in all the investigated cases. Show more

Keywords: Erythrocyte aggregability, blood plasma viscosity, ischemic brain infarct with and without diabetes mellitus

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 261-264, 2006

Authors: Bolokadze, N. | Lobjanidze, I. | Momtselidze, N. | Shakarishvili, R. | Mchedlishvili, G.

Article Type: Research Article

Abstract: The aim of this work was to perform a comparative investigation of erythrocyte aggregability changes in the peripheral and cerebral circulation during ischemic and hemorrhagic stroke. Subjects of the present study were patients with ischemic brain infarcts (14 patients) and with hemorrhagic stroke (21 patients) from the Intensive Care Unit of the Institute of Neurology and Neurosurgery. The blood samples were obtained from the following blood vessels: the common carotid artery carrying blood to the primarily damaged brain hemisphere, both jugular veins carrying blood from the primarily damaged and the contralateral hemispheres, as well as from the cubital vein to …obtain specimens of the systemically circulating blood. Erythrocyte aggregation was evaluated by using the “Georgian technique”. We found that the RBC aggregation indices increased in both the regional as well as the systemic circulation of the hemorrhagic stroke patients as compared to ischemic stroke patients. The results of the present study demonstrate different changes of erythrocyte aggregation in ischemic and hemorrhagic stroke patients. Therefore, the role of blood rheological properties in their pathogenesis seems also to be different. Show more

Keywords: Erythrocyte aggregation, ischemic stroke, hemorrhagic stroke

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 265-267, 2006

Authors: Bianciardi, Giorgio | Tanganelli, Italo | Totagiancaspro, Dorotea | Brogi, Marco | Carducci, Antonietta | De Santi, Maria Margherita

Article Type: Research Article

Abstract: Fractal dimension of pericellular membrane of monocytes was evaluated in diabetic patients and in control subjects. Monocytes were collected from normal healthy volunteers (n=6) and from diabetic (type 1 and type 2) patients (n=9). Monocytes from healthy volunteers were also stimulated in vitro with the ionophore A23187 or with the oligopeptide FMLP. Monocytes, obtained by Ficoll-Hypaque, were examined with a Philips 300 transmission electron microscope. The cell contour was extracted, resized to a standard dimension and converted to a single pixel outline. Box-counting method was then applied to determine the fractal dimension. Fractal dimensions of monocytes appeared statistically increased in …diabetic patients (type 1 and type 2), compared with sex- and age-matched controls (p<0.01, p<0.01). The mechanism underlying the observed increased complexity of pericellular membrane may be explained by the in vivo activation of the circulating monocyte in diabetes. In effect, fractal analysis of stimulated in vitro monocytes showed a significant increase of complexity of pericellular membrane, compared with their controls (p<0.001). Our approach was able to assess and quantitatively evaluate in diabetic patients morphological modifications of the monocyte linked to its activation, offering new parameters useful to follow the effects of therapeutical procedures. Show more

Keywords: Fractals, morphometry, monocytes, diabetes

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 269-272, 2006

Authors: Fornal, Maria | Lekka, Małgorzata | Pyka-Fościak, Grażyna | Lebed, Kateryna | Grodzicki, Tomasz | Wizner, Barbara | Styczeń, Jan

Article Type: Research Article

Abstract: The mechanical properties of erythrocyte membrane have been studied using an atomic force microscope. Measurements were carried out on blood samples taken from 7 diabetes mellitus patients and 8 healthy individuals. For each blood sample a distribution of a Young's modulus was constructed. It has been found that both the mean value and the width of the distribution in diabetic patients exceed the corresponding results for healthy persons by a factor greater than 3. The high sensitivity of the atomic force microscopy and the ability to measure the full distribution of the erythrocyte membrane Young's modulus makes it a unique, …powerful and promising tool in studies of the membrane stiffness of red blood cells. Show more

Keywords: Atomic force microscopy, erythrocyte deformability, erythrocyte stiffness, diabetes mellitus

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 273-276, 2006

Authors: Riquelme, Bibiana | Foresto, Patricia | D'Arrigo, Mabel | Filippini, Fernando | Valverde, Juana

Article Type: Research Article

Abstract: Hypertension (HTA) and dyslipidemia (DLP) represent major risk factors for cardiovascular and cerebral-vascular ischemic disease. The mechanisms through which they can induce vascular damage are both metabolic and mechanical. Hemorheological alterations in HTA are result of changes affecting both red cell intrinsic structure and their interactions with the plasmatic components. Several hemorheological determinants (biochemical, ionic, metabolic and rheologic) could influence and produce an impaired erythrocyte deformability determining an increased flow resistance in the microcirculation. The “Erythrodeformeter” allows obtaining the stationary and dynamical linear parameters of erythrocyte membrane by laser diffractometry. Stationary and oscillatory shear-induced elongation of cells leads to an …elliptical diffraction pattern, its geometric characteristics being directly related to those of deformed RBC. Erythrocyte stationary parameters (Deformability Index, surface viscosity and elastic modulus) were obtained in stationary regime. Complex viscoelastic parameters (dynamic elasticity, dynamic loss, viscous and elastic components of the complex viscosity) were obtained when operating in oscillating mode. The diffractometric method is sensitive to detect pathological or induced alterations on RBC membrane, which can affect blood flow in vivo. The rheological parameters obtained give important information about the erythrocyte membrane and allow to detect and characterize erythrocyte alterations in vascular pathologies. Show more

Keywords: Diffractometry, erythrocyte viscoelastic properties, hemorheology, hypertension

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 277-281, 2006

Authors: Travagli, Valter | Zanardi, Iacopo | Boschi, Letizia | Turchetti, Vera | Forconi, Sandro

Article Type: Research Article

Abstract: Clinical measurement of blood viscosity is an important parameter in the diagnosis of different diseases (e.g., diabetes, hypertension, cardiovascular diseases). The significance of blood viscosity in the microcirculatory flow is also of great importance. Thus, a simple and accurate evaluation of hemorheological properties could be an important challenge in clinical practice. Nowadays, validated measurements of plasma viscosity are commonly carried out with rotational viscometers by means of the various geometric configurations. However, red blood cells deform under mechanical force and this aspect could lead to an artificial variation in the apparent viscosity. In this work, an evaluation of a new …technique for the viscosity determination is focused. In particular, a torsional oscillation viscometer was adopted (VM10AL, CBC Europe) in the presence and in the absence of stirring conditions at thermostated conditions. The profile of the rheological behaviour as a function of time was recorded and compared with that obtained using a cone-plate rotational viscometer (AR300, TA Instrument). Show more

Keywords: Blood viscosity, torsional oscillation viscometer

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 283-289, 2006

Authors: Athanassiou, G. | Moutzouri, A. | Kourakli, A. | Zoumbos, N.

Article Type: Research Article

Abstract: Sickle cell disease is characterized by vaso-occlusive episodes, mainly in the small vessels, resulting in tissue ischemia, multi-organ failure, and, occasionally, death. Hydroxyurea (HU) is an agent with important and effective role in the treatment of patients suffering from this disease. The purpose of this study was to estimate the effect of HU on the deformability of the red blood cell's membrane (RBCM) in an effort to possibly improve the rheological properties of the RBCs of patients with sickle cell anemia (SCA), as well as to investigate the mechanical and rheological properties of these cells using micropipette and filtration techniques. …The rigidity index, IR, which is a measure of cell rigidity and the elastic shear modulus, μ, which is a measure of cell's membrane deformability (CMd), of the RBCs from normal subjects, used as normal controls, were found significantly lower as compared to those of patients with SCA, regardless the treatment with HU. Patients under treatment with HU exhibited values better than those of untreated patients, in both, IR as well as μ, although still worse than the values of normal controls. Show more

Keywords: Red blood cell deformability, filterability, sickle cell disease, micropipette

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 291-295, 2006

Authors: Aydoğan, Sami | Yerer, Mükerrem Betül | Çomu, Faruk Metin | Arslan, Mustafa | Güneş-Ekinci, Işın | Unal, Yusuf | Kurtipek, Omer

Article Type: Research Article

Abstract: Alterations in blood rheology under the influence of anesthesia have been observed and discussed among the responsible factors for the deterioration of tissue and organ perfusion related to anesthetic procedures. Sevoflurane is one of the volatil anesthetics which is being used very common in surgery. In this study, the effects of sevoflurane anesthesia were investigated in different age groups of rats. 22 male rats were used in the study and the rats were divided into two groups according to their age (young and old) comprising of two subgroups in each. First group was the young control (n=5), the second was …the young group treated with sevoflurane (n=5), the third group was the old control (n=7) and the last group was the old group treated with sevoflurane (n=5). %2 of sevoflurane was applied to the rats with inhalation in a adjustable cage for one hour. The deformability indexes of the erythrocytes were measured by a laser diffractometer (Myrenne Rheodyne SSD). Deformability indexes of red blood cells were significantly decreased with sevoflurane in old rats (p=0.028) whereas it had not any significant effect in young group compared with their controls. When we compared the young and old control groups, the deformability indexes were significantly higher in old ones (p<0.001). However, there were not any significant difference between the old and the young sevoflurane applied groups. A volatil anesthetic agent sevoflurane has impaired the deformability of erythrocytes in old rats compared to their controls, whereas it had not any significant effect in young ones which may be due to the flexibility of the young erythrocytes leading them to tolerate to the environmental changes. These results reveal that the inhalation anesthetics like sevoflurane may cause more serious problems in the elder people and their hemodynamic parameters should be checked more seriously during the surgery. Show more

Keywords: Sevoflurane, erythrocyte deformability, anesthesia, rat

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 297-300, 2006

Authors: Musielak, Malgorzata | Kościelak, Jerzy

Article Type: Research Article

Abstract: Human fibrinogen (TF) has been separated into two fractions: F1 – homodimers with respect to the γ chain, and F2 – heterodimers composed of γA and γ′ polypeptides. Their rouleaux-inducing properties were as follows: (1) both, at the same concentration of 0.8%, were less effective than TF; (2) F1 produced larger rouleaux even under static conditions of a hemocytometer where F2 was silent; (3) F2 induced the process when a suspension was gently sheared between microscopic slides. Since the synthetic peptide γ′(414–427) inhibited the rouleau formation in a mixture with F2, the C-terminal amino acids of the γ′ polypeptide …probably bind the molecule to the cell. The inhibition was feebly visible in the native ratio of F1/F2, implicating a compensatory effect of F1. Show more

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 301-303, 2006

Authors: Startseva, Julia | Sulimova, Natali | Cherkassov, Vladimir | Kon, Kat | Lysov, Andrej

Article Type: Research Article

Abstract: We have made the diagnosis of transcapillary flow disturbances in the lungs of lung cancer patients with the available noninvasive method of videobiomicroscopy of eye conjunctiva with further morphometric processing of obtained data using PC. 77 patients with lung cancer have been studied. Using videobiomicroscopy we calculated the size of venous capillary sacculations, the square of capillary glomerules (Sg ), the amplitude (A), the ‘length’ of the twisted part of a microvessel (Lt ), the amplitude-length coefficient (Ca ), the frequency-length coefficient (Cf ), the size of venous capillaries (V), intravascular conglomeration of aggregated erythrocytes (conglomerate), RBC aggregation coefficient (Cs …) and the degree of sludge. To evaluate the data obtained, a comparative morphologic investigation of histologic samples taken from the intact areas of the lung parenchyma has been carried out. We diagnosed moderate or determined disturbances in the capillary flow that were confirmed by microscopy. Show more

Keywords: Lung cancer, capillary flow, videobiomicroscopy

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 305-306, 2006

Authors: Mantskava, Maia | Momtselidze, Nana | Pargalava, Nugzar | Mchedlishvili, George

Article Type: Research Article

Abstract: The aim of the present study was to evaluate blood rheological disorders, in particular RBC enhanced aggregation, and compare changes in these parameters in patients with type 1 and 2 diabetes mellitus. For evaluation of RBC aggregability in the present study we applied the “Georgian technique”, which was developed and applied for several years in our laboratory. Its advantage is that it is a direct and quantitative method. In all the investigated patients, diabetes mellitus was complicated with the foot gangrenes. The patients were divided into two groups: (a) with type 1 and (b) with type 2 diabetes mellitus. We …matched the RBC aggregability indices in both groups of diabetic patients and compared the obtained results with those in the healthy control group. We found that rheological disorders were considerably pronounced. The RBC aggregability index increased by 62 percent (p<0.001) in type 1 and by 57 percent (p<0.001) in type 2 diabetic patients as compared to the control group. However, there were insignificant differences of the RBC aggregability changes between the two groups of patients. Therefore we conclude that blood rheological disorders are similar in both types of diabetes mellitus. The disturbed blood fluidity related to the increased RBC aggregability in the microcirculation promotes, in particular, the development of legs gangrene in both types of diabetes mellitus. Show more

Keywords: Blood rheological disorders, the erythrocyte aggregability index, 1st types and 2nd types of diabetes mellitus

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 307-310, 2006

Authors: Pérez, S.M. | Riquelme, B. | Acosta, I. | Valverde, J. | Milani, A.

Article Type: Research Article

Abstract: β-thalassaemia is a hereditary hemolytic disease, in which each clinic phenotype encompasses a heterogenic group of genetic alterations resulting in β-globin chain synthesis decrease or absence in red blood cells. Studies on β-thalassaemia carriers suggest the existence of decreased red cell deformability. The erythrocyte deformability in the blood stream is a well-known fact regarding blood circulation efficiency. Red blood cells may be considered to be viscoelastic and their behavior may be described according to complex viscoelastic parameters when they undergo oscillatory stresses. This dynamic behavior is physiologically important due to the in vivo pulsatile blood flow. The aim of the …present work was to evaluate complex erythrocyte viscoelastic parameters in patients suffering from heterozygous β-thalassaemia in comparison with healthy individuals. Our results reveal that even though thalassaemia erythrocytes show a decreased deformability in the stationary state, in a dynamic state, hemorheological alterations are only evident at low oscillatory frequencies, i.e., at lower frequencies in contrast with the normal heart rate (60 cycles/min = 1 Hz), producing no significant alterations at increased heart rate. Show more

Keywords: β-thalassaemia minor, erythrocyte rheology, dynamic viscoelasticity

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 311-316, 2006

Authors: Ahmadizad, Sajad | El-Sayed, Mahmoud S. | MacLaren, Donald P.M.

Article Type: Research Article

Abstract: To examine the effects of drinking an amount of water equal to weight loss on the responses of blood rheological variables, eleven healthy male subjects performed three resistance exercise trials. The aim of the first session was to determine the amount of weight loss following a resistance exercise trial at 80% of one repletion maximum (1RM). In the second and third sessions subjects performed the same resistance exercise protocol without and with drinking an amount of water equal to that recorded for body weight loss. Three venous blood samples were taken before exercise, immediately after exercise, and at the end …of 30-min recovery and were analysed for haematocrit (Hct), haemoglobin (Hb), blood cells count and the main determinant of blood rheology. Haematocrit, plasma viscosity, fibrinogen, albumin, and total protein were significantly increased in response to resistance exercise and returned to pre-exercise level following 30-min of recovery. The changes in blood rheological variables in response to resistance exercise occurred similarly in both control and water trials with no significant difference being observed between trials. Plasma volume loss through sweating and respiratory tract during resistance exercise could have contributed to the decrease in plasma volume, though, this contribution was negligible. Therefore, it is concluded that the increases in blood rheological variables in response to resistance exercise are mainly due to plasma shifts from intravascular space to extravascular spaces rather than plasma volume loss through sweating and respiratory tract. Show more

Keywords: Water intake, resistance exercise, fibrinogen, plasma viscosity, haemoconcentration

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 317-327, 2006

Authors: Varlet-Marie, Emmanuelle | Mercier, Jacques | Brun, Jean-Frédéric

Article Type: Research Article

Abstract: There is a lack of consensus about the biological diagnosis of the overtraining syndrome (OTS). Recently, efforts have been made to standardize its clinical diagnosis (e.g., standardized questionnaires like that of the French consensus group on overtraining of the Société Française de Médecine du Sport–SFMS). We previously reported that the early signs of overtraining (= “overreaching”) in elite sportsmen are associated with a hemorheologic pattern (raised hematocrit and plasma viscosity ηp ) that suggests some degree of reversal of the “autohemodilution” which characterizes fitness, and that the feeling of heavy legs in overtrained athletes is related to higher ηp …and higher red cell aggregation. We thus investigated on a sample of 48 athletes (age 24±1 yr), referred for possible diagnosis of overtraining to what extent plasma viscosity is a predictor of OTS. From those 48 athletes 10 had a value of ηp in the highest quartile (ηp >1.44 pPa.s) and 8 of them had a diagnosis of overreaching, while in the 38 whose ηp was <1.44 mPa.s there were 20 cases of overreachings. Overt cases of OTS were found in 1 subject of the highest quintile and two in the lowest. Thus the predictive value of ηp for early stages (overreaching) or chronicized stages (overtraining syndrome) is as follows: (a) prediction of overreaching: sensitivity 28.57%; specificity 90%; positive predictive value 80%; negative predictive value 47.37%; (b) prediction of chronicized overtraining: sensitivity 2.70%; specificity 18.18%; positive predictive value; 10.00%; negative predictive value 5.26%. These results show that ηp is a rather specific, although poorly sensitive predictor of overreaching but has no interest in the diagnosis of the overtraining syndrome itself. Show more

Keywords: Overtraining, overreaching, plasma viscosity, hemorheology

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 329-332, 2006

Authors: Aloulou, Ikram | Varlet-Marie, Emmanuelle | Mercier, Jacques | Brun, Jean-Frederic

Article Type: Research Article

Abstract: Hemorheologic effects of exercise training (“hemorheologic fitness”) are very different according to the mode and the intensity of this training. We previously reported that low intensity endurance training in sedentary patients suffering from the metabolic syndrome sumultaneously improved blood rheology, body composition and lipid oxidation at exercise. We aimed at analyzing the link among these improvements in 24 patients submitted to a 2 months targeted training designed for increasing exercise lipid oxidation. Variations of whole blood viscosity at high shear rate (ηb 1000 s−1 ) were explained here by two statistically independent determinants: hematocrit and red cell rigidity. ηb …decreased in 16 subjects, but increased in 8, due to a rise in hematocrit. Changes in RBC rigidity appeared to reflect weight loss and decrease in LDL cholesterol. Plasma viscosity was related to cholesterol and its training-induced changes are related to those of VO2 max  but not to lipid oxidation. Red cell aggregability (Myrenne) reflected both the circulating lipids (Chol, HDL and LDL) and the ability to oxidize lipids at exercise. Factors associated to a post-training decrease in aggregability (M1) were weight loss and more precisely decrease in fat mass, improvement in lipid oxidation, rise in HDL-Chol, and decrease in fibrinogen. On the whole the major determinant of hemorheologic improvement was an increase in cardiorespiratory fitness (VO2 max  ), correlated with a decrease in plasma viscosity, rather than an improvement in lipid metabolism, although RBC aggregability and deformability exhibited clear relationships with lipid metabolism. For which reason Hct increased in 30% of the patients during this kind of training remains unclear. Show more

Keywords: Blood viscosity, plasma viscosity, hemorheology, erythrocyte deformability, erythrocyte aggregability, insulin sensitivity, insulin resistance, minimal model

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 333-339, 2006

Authors: Carvalho, F.A. | Maria, A.V. | Braz Nogueira, J.M. | Guerra, J. | Martins-Silva, J. | Saldanha, C.

Article Type: Research Article

Abstract: We stimulated human erythrocytes obtained from patients with hypercholesterolemia (HC; n=42), renal transplantation (RT; n=18) and hypertension (HT; n=10) with acetylcholine (ACh 10 μM) and measured the amperometric NO production, comparing with the NO levels achieved on erythrocytes of healthy persons (n=27). We also measured the hemoglobin, hematocrit, erythrocyte aggregation, erythrocyte deformability, plasma viscosity and fibrinogen concentration from human blood samples. The erythrocytes NO levels were of 2.5±0.7 nM (P=0.038, HC), 2.4±1.1 nM (RT) and 2.2±0.8 nM (HT) against the 2.0±0.8 nM for the control groups. For each group and at each shear stress value, the erythrocytes deformability decreases with …the increase of the NO concentration after ACh stimulation. We observed a significant increase of the control values on the erythrocyte aggregation results on each patient group. Besides the lower erythrocyte deformability obtained on HC, RT and HT blood samples, the erythrocytes produced higher NO levels after ACh stimulation than the healthy ones. The power of erythrocyte hemorheological behaviour could be compensated by the NO production at the presence of acetylcholine. We can hypothesises that cholinergic drugs could be used as co-adjuvants of specific therapeutics compounds on these studied diseases. Show more

Keywords: Nitric oxide, hemorheology, acetylcholine, hypertension, hypercholesterolemia, renal transplantation

Citation: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 341-347, 2006