Low Shear Blood Viscosity Research Articles

Hemorheologic changes in patients with chronic hepatitis B

To study the variation of the hemorheology in patients with chronic hepatitis B and study its relations with HBV DNA, liver function and oxidative stress markers. Indices for hemorheology, oxidative stress markers, liver function, and HBV DNA were measured in 55 patients with chronic hepatitis B and correlative analysis was made. The low-shear whole blood viscosity (BV), RBC aggregation index were significantly higher in hepatitis B group than those in the control group (P < 0.05), Hematocrit (HCT), the low-shear BV, RBC aggregation index were significantly higher in the patients whose ALT was higher than the patients whose ALT was normal and the controls. No significant difference was found in HBV DNA and indices of hemorheology (P > 0.05), nor in indices of hemorheology and oxidative stress markers (P > 0.05). There is disturbance of microcirculation and oxidative stress in the body of patients with chronic hepatitis B. The hemorheology and oxidative stress markers should be regarded as useful indexes in patients with chronic hepatitis B in addition to HBV markers.

Covalent binding of poly(ethylene glycol) (PEG) to the surface of red blood cells inhibits aggregation and reduces low shear blood viscosity

Covalent binding of poly(ethylene glycol) (PEG) to the surface of red blood cells inhibits aggregation and reduces low shear blood viscosity

Covalent binding of poly(ethylene glycol) (PEG) to the surface of red blood cells inhibits aggregation and reduces low shear blood viscosity.

A simple method to coat human red blood cells (RBC) with PEG is described. Using a reactive derivative, monomethoxy-PEG (mPEG) was covalently attached to the surface of RBC in aqueous media under mild conditions. The PEG coating dramatically reduced aggregation and low shear viscosity of RBC resuspended in autologous plasma, and inhibited RBC agglutination by blood group-specific antibodies. Morphology and deformability of the PEG-treated cells were unaltered. The PEG coating of the RBC surface may be of significant benefit in the treatment of a variety of diseases characterized by vasoocclusion or impaired blood flow, e.g., myocardial infarction, sickle cell disease.

Cellular determinants of low-shear blood viscosity

Low-shear viscometry is one of the methods commonly used to estimate the degree of red blood cell (RBC) aggregation in various bloods and RBC suspensions. However, it has been previously shown that alterations in RBC morphology and mechanical behavior can affect the low-shear apparent viscosity of RBC suspensions; RBC aggregation is also sensitive to these cellular factors. This study used heat treatment (48°C, 5 min), glutaraldehyde (0.005–0.02%) and hydrogen peroxide (1 mM) to modify cell geometry and deformability. Red blood cell aggregation was assessed via a Myrenne Aggregometer (“M” and “Ml” indexes), RBC suspension viscosity was measured using a Contraves LS-30 viscometer, and RBC shape response to fluid shear stresses ( i.e., deformability) was determined by ektacytometry (LORCA system). Our results indicate that low-shear apparent viscosity and related indexes may not always reflect changes of RBC aggregation if cellular properties are altered: for situations where RBC aggregation has been only moderately affected, cellular mechanical factors may be the major determinant of low-shear viscosity. These findings thus imply that in situations which may be associated alterations of RBC geometry and/or deformability, low-shear viscometry should not be the sole measurement technique used to assess RBC aggregation.

A mathematical analysis of haemorheologic factors during cardiopulmonary bypass for congenital heart disease.

Rheologic properties of blood are impaired by cardiac surgery using cardiopulmonary bypass. This study was set out to establish a mathematical model in order to assess seven known haemorheologic factors and evaluate their degrees of influence on blood rheology in cardiopulmonary bypass. Sixteen patients undergoing elective congenital cardiac surgery were studied. High shear blood viscosity, low shear blood viscosity, haematocrit, red blood cell filtration rate, red blood cell electrophoresis time, plasma viscosity and fibrinogen were monitored. The method for mathematical calculation was the stepwise regression analysis. The results showed that both high shear and low shear blood viscosity were mainly influenced by haematocrit and plasma viscosity. Red blood cell filterability contributed more than red blood cell electrophoresis time for low shear blood viscosity. The mathematical model was re-tested statistically and demonstrated that the selected factors in the model represented approximately 75% of rheologic changes during the surgery. Therefore, this mathematical analysis can be used to estimate the role of various possible haemorheologic factors and evaluate cardiopulmonary bypass techniques and therapeutic interventions.

Effect of perfluorochemical emulsion on blood trauma and hemorheology.

One of the major problems of development and improvement of heart assist devices is the reduction of blood cell damage. The extremely high levels of shear stress, turbulence, prolonged contact between blood and foreign surfaces, and other abnormal hydrodynamic circumstances have been shown to cause hemolysis, activation of platelets, and changes in mechanical properties of red blood cells. Hemolysis, in turn, can drastically increase red blood cell aggregation at low shear conditions. A new pharmacologic approach to reduce blood trauma and improve rheologic properties of blood subjected to mechanical stress was investigated. These experiments showed that the replacement of 20% of the plasma volume with Fluosol (Alpha Therapeutic Corp., Los Angeles, CA), a perfluorochemical that transports oxygen, reduced mechanical fragility of human (P < 0.01) and ovine (P = 0.054) red blood cells by approximately 30%. The same replacement of plasma with Fluosol reduced hemolysis (plasma free Hb) by approximately 40% compared to control (P < 0.05) during in vitro pumping of blood with a centrifugal pump. A 20% replacement of plasma volume with Fluosol remarkably reduced low shear blood viscosity (from 31.9 +/- 6.1 to 18.2 +/- 4.8 cP, for shear rate gamma = 0.277 sec-1) and erythrocyte sedimentation rate (from 16.7 +/- 9.2 to 3.1 +/- 3.1) mm/hr) in human blood. Decrease of these parameters indicates the reduction of red blood cell aggregation. Results of this study demonstrate the potential feasibility of Fluosol to improve mechanical properties of blood in patients with heart assist devices.

Heparin effect on red blood cell aggregation.

We studied the effect of relatively high dosages of heparin (25-150 U/ml) on some rheological parameters of donor blood. It was found that heparin increased the erythrocyte sedimentation rate (ESR) and low shear blood viscosity at all concentrations studied. The increase of these parameters indicates an elevation in RBC aggregation. In all samples with a heparin concentration of 100 U/ml, the average ESR was increased by approximately 75% (p < 0.001); whole blood viscosity increased under shear rate, gamma = 0.277 sec-1, by approximately 30% (p < 0.001). Since bolus injection of heparin may result in transient high local concentration, these results suggest a possible additional adverse effect to the well known heparin effect on platelet aggregation.

Hematologic correlates of spontaneous echo contrast in patients with atrial fibrillation and implications for thromboembolic risk

Spontaneous echo contrast has been observed in conditions of low blood flow velocity, such as rheumatic mitral stenosis and & trial fibrillation (AF). The phenomenon has been attributed to increased echogenicity due to aggregation of blood cells at low shear rates. The aim of this study was to determine whether abnormalities of blood composition also might contribute to spontaneous echo contrast formation by promoting cellular aggregation. Transesophageal echo-cardiography was performed in 185 patients with AF (31 with valvular and 154 with nonvalvular AF). The left atrium was examined for thrombus and spontaneous echo contrast, which was graded from 0 (nil) to 4+ (severe) by 2 independent observers. Forty milliliters of venous blood was obtained from each patient for hematologic analysis. Spontaneous echo contrast was observed in 46% of patients (74% with valvular and 41% with nonvalvular AF). In linear regression analysis, positive correlations were found between grade of spontaneous echo contrast and erythrocyte sedimentation rate (p < 0.001), lowshear blood viscosity (p < 0.001) and anticardiolipin antibody (p = 0.02) in the total study population, and in patients with nonvalvular AF. Spontaneous echo contrast correlated with mitral valve area (p < 0.01) and gradient (p = 0.03), but not with hematologic parameters in patients with valvular AF. Left atrial thrombus was present in 6 patients, all of whom had spontaneous echo contrast. Age (p < 0.01), spontaneous echo contrast (p = 0.03) and the fibrinogen concentration (p = 0.03) correlated with previous embolic events. These results suggest that, in addition to flow disturbance associated with structural carrdiac abnormalities and AF, blood composition may also be important in spontaneous echo contrast formation, particularly in patients with nonvalvular AF. The association between spontaneous echo contrast and both the erythrocyte sedimentation rate and low-shear blood viscosity supports a role for red cell aggregation in the pathogenesis of this phenomenon.

Blood viscosity and plasma proteins influencing it are increased in Type I diabetes in the DCCT

The Diabetes Control and Complications Trial (DCCT), an NIH-sponsored study at 29 institutions in the U.S. and Canada, was designed to examine the effects of intensive management in type I diabetes. Between 1983 and 1989, 1441 patients with and without mild retinopathy (primary and secondary) were randomized into two major treatment groups, intensively and conventionally treated patients. Retinopathy, nephropathy, and neuropathy were assessed periodically in each patient. In this study, levels of fibrinogen, haptoglobin, albumin and total protein were measured and viscosity of fresh blood was simultaneously evaluated in 45 local DCCT patients. Viscosity was measured at 17 rotation rates arranged logarithmically from .03 to 300 inverse seconds shear rate on blood adjusted to 41 % hematocrit by the addition or removal of its own plasma. Blood's time-based flow properties --- transient resistance and viscoelasticity --- were also assessed. Blood viscosity showed the greatest elevation (10 to 19%) in the 0.08-2.0 inverse second shear rate range. Increased low shear rate blood viscosity was found to be linked to fibrinogen and hemoglobin Alc levels. In addition to steady flow blood viscosity measurement, blood's time-based flow properties were also assessed at 15 inverse seconds shear rate. Transient resistance was increased 30% in diabetes; its elevation was found to be linked to both fibrinogen level and low shear blood viscosity. Diabetic blood's viscoelasticity at this high shear rate was much less strikingly increased than its transient resistance. Viscoelastic strain energy was correlated with fibrinogen, low shear viscosity, haptoglobin, and albumin level. Interleukin-6 (IL-6), a potent stimulator of fibrinogen and haptoglobin synthesis in hepatocytes in culture, was found to be elevated in diabetes, indicating that it is the likely mediator of the observed plasma protein changes. The altered blood flow properties observed in this well-characterized group of type 1 diabetes mellitus patients may playa role in development of diabetic complications.

Blood and plasma viscometry – A comparison between three viscometers

Plasma viscosity and the viscous component of blood viscosity were measured in an oscillatory capillary viscometer (OCR-D) and compared to the blood viscosity determined in the Contraves LS-30 machine at identical nominal shear rates and to plasma viscosity readings obtained in the Coulter Harkness capillary viscometer. The OCR-D system yields lower reproducibility compared to the other methods. It also gives lower absolute viscositY readings for blood at low shear rates. Hemoconcentra­ tion, as induced in vivo by a standard ergometer exercise, is less strongly reflected in the low shear blood viscosity data from the OCR-D system compared to the analogue results obtained in the LS-30. These findings suggest, that the OCR-D method is less reproducible and not directly comparable with the conventional methods. Possibly the latter are best for routine while oscillatory methods may give a more detailed analysis of specific questions.

Whole blood viscosity during normal pregnancy.

In a serial study the changes in whole blood viscosity at different shear rates and its major determinants were determined in 24 healthy women with normal pregnancies. Whole blood viscosity and plasma viscosity were measured with a rotational viscometer. Red cell aggregation was measured by syllectometry. During normal pregnancy we found a decrease in whole blood viscosity at all shear rates until 29 weeks gestation, followed by a smaller increase between 30 and 37 weeks, which was most pronounced at higher shear rates, especially in nulliparae. The changes in whole blood viscosity were to a great extent determined by the changes in haematocrit and plasma viscosity. Haematocrit was more important for whole blood viscosity at lower shear rates, while plasma viscosity had more influence on high shear blood viscosity. The continuous increase in red cell aggregation had no demonstrable influence on low shear blood viscosity as measured in vitro in a rotational viscometer.

A HAEMORHEOLOGICAL STUDY OF LIGNOCAINE

Eight volunteers received lignocaine 75 mg i.m. Peak plasma lignocaine concentrations (mean 0.80 microgram ml-1; range 0.31-1.86 micrograms ml-1) were attained at 30 min. Haematocrit and red cell deformability remained unchanged. Lignocaine caused small but significant decreases in plasma viscosity and whole blood viscosity at both high and low shear rates (94 and 0.94 s-1). The small reductions in plasma viscosity and high shear blood viscosity observed ex vivo may be the result of alterations in plasma proteins. The reductions in low shear blood viscosity are considered to result from decreased red cell aggregation.

BLOOD VISCOSITY AS A FACTOR IN SENSORINEURAL HEARING IMPAIRMENT

The cause of sensorineural hearing impairment is unknown in a high proportion of patients. Since ischaemia is a possible factor, the relation between hearing threshold and blood viscosity, plasma viscosity, and haematocrit was investigated in 49 patients with idiopathic hearing loss, taking into account age, sex, smoking, and socioeconomic group. Hearing thresholds were unrelated to haematocrit or low-shear blood viscosity. Hearing impairment at high frequencies was directly related to high-shear blood viscosity and inversely related to plasma viscosity. The derived measure of red-cell rigidity was significantly related at all frequencies to hearing thresholds. A second study of 92 subjects from a population sample confirmed the inverse relation with plasma viscosity and lack of relation with haematocrit. Increased pure-tone thresholds appear to be related to increased red-cell rigidity; this may be an important factor in sensorineural hearing impairment with implications for diagnosis and prevention.

The effect of propranolol on blood viscosity changes induced by experimental coronary occlusion.

The effect of propranolol treatment was investigated in the myocardial ischemia-induced hyperviscosity state in anesthetized dogs. In untreated control dogs, low shear blood viscosity rose progressively, following an acute occlusion of the left anterior descending coronary artery; this effect was partially but significantly reduced by intravenously administered propranolol (0.2 mg/kg). The effect of the in vitro addition of propranolol was also determined upon viscosity of blood samples obtained at hourly intervals from dogs subjected to similar coronary ligation. The in vitro addition of propranolol did not produce a similar reversal of the hyperviscosity state observed in the blood obtained from dogs after coronary ligation.

Blood Viscosity, Glycaemic Control and Retinopathy in Insulin-Dependent Diabetes

1. In a cross-sectional study, 32 insulin-treated diabetic patients had elevated low shear (27.1 vs 22.1 mPa s, P less than 0.05) and high shear blood compared with 10 non-diabetic controls. After correction to 45% packed cell volume, the abnormality had a tendency to be greater in patients with proliferative (mean low shear viscosity, 30.8 mPa s) than background (29.2 mPa s) or nil/minimal retinopathy (27.6 mPa s, 0.05 less than P less than 0.97, permutational trend test). 2. The fibrinogen levels were higher in the diabetic group (P less than 0.05) and correlated with the low shear blood viscosity (rs = 0.38, P less than 0.05). 3. In a prospective study, 74 insulin-treated diabetic patients with background retinopathy were randomized into two groups. Thirty-six patients were on attempted improved therapy (A group); in these the mean glycosylated haemoglobin (Hb A1c) fell within 1 year (11.6 to 10.1%, P less than 0.001). both the corrected low shear blood and plasma viscosity fell similarly (P less than 0.001). The fall was greater than in those patients who were kept on usual therapy (U group) and whose glycosylated haemoglobin did not change significantly (11.7 to 11.4% over the year. 4. The effect of diabetes on blood viscosity may not be a direct pathological factor, as the same increased viscosity would be produced by a mean increase of 1.7% in packed cell volume, compared with a population range of 14% packed cell volume.

An assessment of red cell deformability using a simple filtration method.

We assessed the simple method of measuring red cell deformability described by Reid et al. The technique was found to be reproducible. The validity of the method as a measure of red cell deformation was confirmed by (a) marked reduction of the deformability index after fixation of red cells with glutaraldehyde, and (b) an inverse correlation of deformability index with high-shear blood viscosity (r = 0.4; P < 0.001). There was no correlation of deformability index with low-shear blood viscosity, plasma viscosity, fibrinogen, or the white cell count. In normal subjects, deformability index was similar in males and females, and in smokers and non-smokers. Patients with acute myocardial infarction, or intermittent claudication, had reduced deformability compared to controls (P < 0.01).