Clinical Hemorheology and Microcirculation - Volume 15, issue 2

Authors: Li, Anlan | Sahm, Ursel | Artmann, G.M.

Article Type: Research Article

Abstract: The positive effects of Ergopeptide Alkaloids, particularly Dihydroergotoxine with Dihydroergocryptine (DHEC) as one of the components, on cerebral functions has been known for about three decades. DHEC in particular has multiple biological effects: It is an α-adrenoreceptor blocking agent and an agonist of dopamine receptors and is known as a peripheral and cerebral vasodilator. An anti-aggregative activity has been shown on platelet aggregation induced by adrenaline and collagen as well as on erythrocyte aggregation induced by dextran. It also is a metabolic enhancer, protecting against metabolic stress due to hypoxia and ischemia and it increases the uptake of deoxyglucose and …oxygen utilisation in the brain. We studied the protective effect of DHEC (concentration range 10 nM to 100 μM) on human red blood cell (RBC) rheology in acidotic and hyperosmolar solutions (AHS) modelling the hypoxic and ischemic microcirculation. The microscopic photometric monolayer technique was used to quantify alterations of RBC resting shape, stiffness and relaxation time automatically and time dependently (Elias-c-analyser). The technique is based on changes in light transmission through a RBC monolayer in a flow chamber at controlled shear stresses. A HEPES buffer solution was used as control buffer and an acidotic/hyperosmotic buffer solution (pH 6.8, 380 mosmol/kg) to simulate the metabolic challenge in ischemia. AHS itself hardly altered the RBC discocytic shape. However, it significantly increased RBC stiffness and relaxation time (p<0.001). Both RBC in control buffer and RBC pre-stressed in AHS for 20 minutes were incubated with DHEC at different concentrations within the flow chamber. DHEC-induced stomatocytes appeared dose-dependently in both, control buffer and AHS, within less than 2 minutes. The shape change was reversible after re-incubating in control buffer solution or in AHS not containing DHEC. The AHS induced stiffness and relaxation time increases were partially inhibited when DHEC was added to AHS (p<0.05). Although there was a slight effect of DHEC on RBC in buffer, DHEC was significantly more effective when RBCs were exposed to AHS (p<0.01). From a biophysical point of view the stomatocytic shape change observed might indicate a slight expansion of the cytosolic side of the RBC membrane. This in consequence partially maintain undisturbed spectrin/protein spatial distribution. Inhibition of spectrin-cytosolic interactions, which are altered due to pH shifts in the AHS, leads to maintenance of RBC fluidity. In conclusion DHEC might preserve RBC fluidity in vivo especially in the ischemic and hypoxic region of the pathologic microcirculation. The direction, but not the extent of in vivo effects should be predictable from the in vitro results, since metabolic and physiological effects in in vivo conditions could further enhance the in vitro effects. The RBC stomatocytic shape change observed could be positively correlated with the known vasoactive DHEC effect, acting to improve the blood flow in ischemic regions. Show more

Keywords: Ergopeptide alkaloids, The microscopic photometric monolayer technique, Rheology, Erythrocyte fluidity, Stomatocyte, Hypoxic and ischemic microcirculation

DOI: 10.3233/CH-1995-15201

Citation: Clinical Hemorheology and Microcirculation, vol. 15, no. 2, pp. 133-146, 1995

Authors: Brun, J.F. | Monnier, J.F. | Charpiat, A. | Orsetti, A.

Article Type: Research Article

Abstract: Increased red cell aggregation appears to experimentally impair muscular microcirculation and thus O2 supply to muscles. In sportsmen, we reported in three different cross-sectional studies a correlation between RBC aggregation and lactate release during exercise, which could be explained by this mechanism. This study aimed at confirming this finding in a follow up study of young gymnasts submitted to a 6 months training session. 11 gymnasts (age 12–14.5 yr; 7 girls and 4 boys; weight 33–60.5 kg; height 1.44–1.7m) underwent a 15 min submaximal incremental exercise-test on cycloergometer before and after the training session, as part of a check-up …for detecting adverse effects of training on growth and puberty. The difference between RBC aggregation (measured with the Myrenne erythroaggregometer) before and after training was correlated to the difference in blood lactate area under the curve during exercise before and after training (‘M’ index which measures aggregation during stasis after disaggregation at 600 s−1 : r=0.727 p<0.02; ‘M1’ index which measures RBC aggregation at low shear rate after disaggregation: r=0.832 p<0.01). Changes in plasma viscosity during the same period are also positively correlated to changes in lactate area: r=0.717 p<0.02. Since changes in aggregation and changes plasma viscosity are not correlated, they appear to be independent determinants of lactate response during exercise. Thus, decreases in RBC aggregation and/or plasma viscosity after training in young gymnasts are associated with an improvement in aerobic metabolism during exercise. Although a causal relationship remains to be demonstrated, this study, in agreement with previous ones showing a correlation between RBC aggregation and lactate response, suggests a possible involvement of RBC aggregation in O2 transfer to exercising muscles. Show more

Keywords: Blood viscosity, hematocrit, exercise, gymnasts, hemorheology, erythrocyte deformability, erythrocyte aggregation, blood lactate

DOI: 10.3233/CH-1995-15202

Citation: Clinical Hemorheology and Microcirculation, vol. 15, no. 2, pp. 147-156, 1995

Authors: Iijima, S. | Otsuka, F. | Ohba, H. | Itoga, H. | Kikuchi, Y.

Article Type: Research Article

Abstract: Micropore (diameter, 5 μm) passage of neutrophils under constant suction was studied in Behçet's disease by a modification of the Nuclepore filtration method. Filtration times for neutrophils (5000/μl) in neutrophil-erythrocyte suspensions in plasma were determined from suspension filtration times (filtered volume, 0.5 ml; suction pressure, 10 cmH2 O; temperature, 37°C) subtracted by those of neutrophil-poor erythrocyte suspensions in plasma of the same hematocrit values. Filtration times determined were significantly higher (p<0.01) in patients (10.9±5.4 sec; mean±S.D.; n=10) than in healthy subjects (4.9±1.2 sec; n=10). Filtration times for leukocytes of 5000/μl in whole blood were similarly determined to examine the effect …of the preparation; the values were also significantly higher (p<0.001) in patients (8.8±5.3 sec; n=17) than in control (3.4±1.0 sec; n=17). The addition of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP; 5 nM) to the neutrophil-erythrocyte suspensions resulted in immediate increases of the neutrophil filtration times to 165±100 sec in the patients which were significantly higher (p<0.01) than those to 39±18 sec in the control. These results suggest that neutrophils in Behçet's disease are in an active state, possibly with an increased resistance to flow through microvessels as well as with an increased response to chemotactic stimulations. Show more

Keywords: Behçet's disease, neutrophil activity, neutrophil rheology, neutrophil filterability, chemotactic stimulation

DOI: 10.3233/CH-1995-15203

Citation: Clinical Hemorheology and Microcirculation, vol. 15, no. 2, pp. 157-165, 1995

Authors: Soler, C. | Caillot, A. | Amoussou Guenou, K. | Gamand, S. | Girtanner, C. | Benichou, A.C. | Herrmann, T. | Juge, J. | Voutay, M. | Rusch, P. | Delomier, Y. | Healy, J.C.

Article Type: Research Article

Abstract: Impaired oxygenation due to microcirculatory changes within the cerebral parenchyma may contribute to deterioration of intellectual function in vascular senile dementia (Hachinski score ≥ 7). The action of naftidrofuryl, used for treating elderly patients with senile dementia, was evaluated objectively in two groups of patients given naftidrofuryl either as a single intravenous dose or by chronic oral administration for three months. Their cerebral, microcirculatory flow rate was assessed before and after treatment by in vivo cineangioscintigraphy following an i.v. bolus of Tc-99m labelled erythrocytes. The deformability of erythrocytes from orally treated patients was also measured using an in vitro cellular …transit time analyser (CTA) technique. A further experiment assessed the rheology of a rigid sub-population of erythrocytes in pathological samples when exposed to naftidrofuryl at concentrations appropriate to clinical use. Cerebral flow rates increased by about 20% and 30% after intravenous or chronic oral naftidrofuryl, respectively and these differences were statistically significant. In 10 orally treated patients, mean transit times by CTA decreased from 3.12 ms (day 0) to 2.70 ms (day 87 of treatment) (p<0.01). In the presence of naftidrofuryl, the proportion of the least deformable erythrocytes in pathological samples decreased by at least 50%. Clinical effects of naftidrofuryl on the cerebral microcirculation were not restricted to acute exposure. Naftidrofuryl may enhance the deformability of individual erythrocytes. Show more

DOI: 10.3233/CH-1995-15204

Citation: Clinical Hemorheology and Microcirculation, vol. 15, no. 2, pp. 167-176, 1995

Authors: Rasia, Rodolfo José

Article Type: Research Article

Abstract: A numerical process is proposed to evaluate viscoelastic properties of mammalian erythrocyte membranes from diffractometric data obtained with the Erythrodeformeter (1). The numerical process is based on an idealized model of the cell response to the applied fluid shear stress assuming that the tank treading motion start lags the start of the shear stress field by several milliseconds. Photometric readings performed on the elliptical diffraction pattern generated by the shear elongated cells and photometrically recorded curves of creep and recovery of cells, are used in the calculations of rheological properties, averaged over several millions of cells. Results obtained from different …hematological disorders are presented and compared with those obtained from healthy donors, showing significative differences that are in accordance with the type and the state of the corresponding disease. Computed values representative of the elastic modulus of normal cells agree very well with those ones determined with the micropipette technique (2) while retardation time, and consequently values of surface viscosity, obtained by the diffractometric technique are somewhat smaller than the ones obtained by the shape recovery in micropipettes. Show more

Keywords: Diffractometry, Erythrocyte viscoelastic properties, Hemorheology, Hereditary spherocytosis, Hemoglobinopathy, Thalassemia

DOI: 10.3233/CH-1995-15205

Citation: Clinical Hemorheology and Microcirculation, vol. 15, no. 2, pp. 177-189, 1995

Authors: Dupuy-Fons, C. | Brun, J.F. | Pellerin, F. | Laborde, J.C. | Bardet, L. | Orsetti, A. | Janbon, C.

Article Type: Research Article

Abstract: Increased blood viscosity has been shown to experimentally reduce blood flow. In lower limb ischaemia, haemorheologic abnormalities have been repeatedly described but their pathophysiologic importance remains unclear. In this study, we investigated the possible influence of blood rheology on oxygen transfer (as measured by transcutaneous oxygen pressure: TcPO2 ) in 121 nondiabetic patients suffering from P.O.A.D. (age: 46–91 year-old, 88 men and 33 women) with Leriche and Fontaine stage: II (n=61); III (n=35); IV (n=25), compared to 39 controls. Blood viscosity was higher (p<0.001) in patients, due to increased plasma viscosity (p<0.01) and red cell rigidity which was significantly (p<0.01) …higher. Red blood cell aggregation (Myrenne aggregometer) was significantly higher (p<0.05) in P.O.A.D. and was negatively correlated with TcPO2 after one minute standing and after three minutes standing (p<0.001). In stage III, patients TcPO2 is negatively correlated with haematocrit/viscosity ratio (a proposed index of the influence of blood rheology on oxygen transfer; p<0.01). The correlation between TcPO2 and red blood cell rigidity (Tk index; p<0.01) suggest that blood rheology may influence oxygen transfer to tissues in patients with P.O.A.D.. The factors of blood viscosity which may be involved in worsening the ischaemic process may be (a) red cell rigidity (in stage III); (b) red cell aggregation (in the whole sample of patients). Show more

Keywords: Erythrocyte aggregation, Peripheral occlusive arterial disease, Transcutaneous oxygen pressure

DOI: 10.3233/CH-1995-15206

Citation: Clinical Hemorheology and Microcirculation, vol. 15, no. 2, pp. 191-199, 1995

Authors: Brun, J.F. | Micallef, J.P. | Supparo, I. | Rama, D. | Benezis, C. | Orsetti, A.

Article Type: Research Article

Abstract: Correlations among values at rest of blood viscosity (MT 90, high shear rate), RBC Aggregation (Myrenne) and four markers of fitness were investigated in 21 professional football players during a triangular maximal exercise test. Maximal O2 uptake ($\dot{\mathrm{V}}$ O2 max, directly measured) was correlated with resting plasma viscosity (r=−0.666 p<0.01) and blood viscosity at corrected hematocrit 45% (r=−0.426 p<0.05). The physical working capacity $\dot{\mathrm{W}}$ 170 was correlated with $\dot{\mathrm{V}}$ O2max (r=0.645 p<0.01) and with both resting plasma viscosity (r=−0.524 p<0.02) and hematocrit (r=−0.524 p<0.05). Two determinants of the 4 mmol lactate threshold were found: …red cell aggregation ‘M’ (r=−0.529 p<0.02) and ‘M1’ (r=0.477 p<0.05). Thus, markers of aerobic working capacity are negatively correlated with plasma viscosity and hematocrit, while the 4 mmol.l−1 lactate threshold which measures the ability to avoid blood lactate increase is negatively correlated to RBC aggregation. Show more

Keywords: Blood viscosity, hematocrit, exercise, football, $\dot{\mathrm{V}}\mathrm{O}_{2}$ max hemorheology, erythrocyte deformability, erythrocyte aggregation, blood lactate

DOI: 10.3233/CH-1995-15207

Citation: Clinical Hemorheology and Microcirculation, vol. 15, no. 2, pp. 201-212, 1995

Authors: Brun, J.F. | Micallef, J.P. | Supparo, I. | Orsetti, A.

Article Type: Research Article

Abstract: The effect of breakfast on blood rheology during exercise was studied. 5 subjects (23–27 yr weight 60–84 kg, height 1,72–1,84 m) performed in random order two 25 min submaximal exercise sessions including a final step at 85% of theoretical maximal heart rate during 15 min. This was done fasting and again after eating a 495 kcal breakfast (8,9% proteins, 27,3% lipids; 63.9% glucids). The rheologic response to exercise was measured at high shear rate with the MT90 viscometer. Changes in whole blood viscosity and hematocrit were similar, but fasting subjects underwent an increase in RBC rigidify (Tk index) while plasma …viscosity was higher after breakfast and exhibited a stronger increase during cycling. This breakfast modifies the rheologic response to exercise, by preventing a reduction in RBC deformability and increasing plasma viscosity as well as its rise during cycling. Show more

Keywords: Blood viscosity, exercise, hemorheology, erythrocyte deformability, nutrition

DOI: 10.3233/CH-1995-15208

Citation: Clinical Hemorheology and Microcirculation, vol. 15, no. 2, pp. 213-220, 1995

Authors: Capecchi, P.L. | Ceccatelli, L. | Petri, S. | De Lalla, A. | Acciavatti, A. | Provvedi, T. | Laghi Pasini, F. | Di Perri, T.

Article Type: Research Article

Abstract: In patients affected with peripheral obliterative arterial disease, the intravenous infusion of 50 mg buflomedil prevented ischaemia-dependent impairment of whole blood viscosity (WBV) and filterability (WBF) in the course of isotonic ischaemic exercise of an upper limb. The drug was also able to reduce the effects of ischaemia on some functional parameters of polymorphonuclear leukocytes (PMNs), such as superoxide anion generation induced by the formylated oligopeptide fMLP, and cytosolic free calcium level modifications in resting and fMLP-stimulated cells. An enhancement of ischaemia-dependent increase in adenosine plasma levels was also observed as associated with the effects of buflomedil. Treatment with the …adenosine receptor antagonist theophylline was able to partially remove the effects of buflomedil. Thus, the possibility is suggested that some pharmacological properties of buflomedil could depend, at least in part, on an interference with the adenosine system. Show more

Keywords: Buflomedil, ischaemia, haemorheology, neutrophils, adenosine, theophylline

DOI: 10.3233/CH-1995-15209

Citation: Clinical Hemorheology and Microcirculation, vol. 15, no. 2, pp. 221-233, 1995

Article Type: Abstract

DOI: 10.3233/CH-1995-15210

Citation: Clinical Hemorheology and Microcirculation, vol. 15, no. 2, pp. 235-260, 1995