Red Cell Filterability Research Articles

THE INFLUENCE OF PRETERM DELIVERY ON RED CELL FILTER-ABILITY IN NEONATES - INFERENCES AS TO PATHOGENESIS OF CLINICAL COMPLICATIONS OF PREMATURITY

Short gestation correlates with impairments in red cell filterability at birth. We used Nuclepore blood cell suspension filtration (Jones et al, 1985). There was no correlation between pore occupation time and mean red cell volume or leukocyte count. Irrespective of the cellular pathological cause(s) for this prematurity-related impairment of red cell filterability, this finding may reflect important in vivo phenomena: the pathogenesis of haemolysis, jaundice and circulatory stagnation, thrombosis and haemorrhage in neonatal life may depend in part on this malfunction of the fetal red cell after birth. J.G. Jones et al (1985) Br. J. Haem. 59, 541-546.

Initial filtration rate and initial clogging in the Hemorheometre.

The role of different factors contributing to red cell filterability in the Hemorheometre has been investigated. Although the original method uses a small volume of suspension to determine red cell filterability, the present experiments showed that the results obtained are still significantly affected by filter clogging. Consequently a change in filterability could be due to a change in filter clogging possibly by residual leucocytes. An adaptation of filter chamber and filling method is described, resulting in a simpler and faster measuring procedure. The inaccuracy in measuring low haematocrits contributes significantly to experimental errors. Therefore a definition of red cell filterability based on the red cell count (instead of haematocrit) of the suspension is suggested.

Effects of verapamil on calcium-induced rigidity and on filterability of red blood cells from healthy volunteers and patients with progressive systemic sclerosis.

The effects of verapamil on calcium-induced decrease deformability of red blood cells (RBCs) and on the filterability of RBCs from healthy volunteers and patients with progressive systemic sclerosis (PSS) were investigated in vitro using a gravity driven filtration technique. The filterability of RBCs was increased by verapamil 1 microgram/ml (P less than 0.01) in healthy volunteers (P less than 0.05) and in patients with PSS (P less than 0.05). A high concentration of verapamil (200 micrograms/ml) caused an 80% reduction (P less than 0.05) in the filterability of RBCs from healthy volunteers. The filterability of RBCs stored at 4 degrees C for 24 h was increased by 1 microgram/ml verapamil (P less than 0.05). Verapamil (1 microgram/ml) prevented the decrease in deformability of RBCs due to an increase in either extracellular or intracellular calcium concentrations (P less than 0.05). By increasing red cell filterability verapamil may be useful in the treatment of PSS and other peripheral vascular diseases where decreased red cell deformability may play an important role in the pathogenesis.

Roles of cell geometry and cellular viscosity in red cell passage through narrow pores.

The relative roles of two fundamental determinants of red cell deformability, namely cell size and cellular viscosity, in affecting red cell passage through narrow channels have been assessed by determining the filterability of red cells subjected to osmotic variations. Suspensions of red cells (10(6) cells/microliter) in eight different osmolalities ranging from 172 +/- 3 (mean +/- SD) to 665 +/- 28 mosmol/kg H2O were filtered through polycarbonate sieves with three different pore diameters (2.6 +/- 0.2, 4.5 +/- 0.6, and 6.9 +/- 0.8 micron). The mean corpuscular volume varied inversely with osmolality and ranged from 149 +/- 9 to 67 +/- 10 fl; the mean corpuscular hemoglobin concentration varied directly with osmolality and ranged from 23.7 +/- 0.8 to 55.9 +/- 3.9 g/dl. The filtration data were analyzed with a theoretical model to derive the parameter beta, which is the ratio of resistance in a pore bearing a red blood cell to that in a pore filled with the suspending medium alone. For each pore size, beta showed a V-shaped relationship with osmolality; the optimum osmolality for minimum beta varied inversely with the pore size. For the small 2.6-micron pores, the minimum beta was attained following hyperosmotic shrinkage of the red cells at 400 mosmol/kg H2O, whereas passage through the large 6.9-micron pores was facilitated by hypoosmotic swelling of the red cells in about 200 mosmol/kg H2O. Red cell filtration through small pores is more sensitive to alterations in cell volume, whereas that through large pores is primarily determined by changes in cellular viscosity.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Properties and Walking Performance in Chronic Arterial Occlusive Disease

Recent investigations suggest an interdependence between blood fluidity and walking performance in patients with peripheral arterial occlusive disease (PAOD). Therefore, various blood fluidity variables (erythrocyte aggregation, erythrocyte flexibility, plasma viscosity, plasma proteins) were studied in groups of healthy subjects and claudicants with severe PAOD (exhausted perfusion reserve) receiving intravenous treatment with Trental (600 mg Pentoxifylline b.i.d., 21 days). Erythrocyte flexibility (expressed by filterability through micropore filters), red cell aggregation and plasma viscosity deteriorate with progression of disease especially in Stage IIb and III Fontaine classification, with walking distance below 150 m. Trental treatment resulted in patients with advanced POAD stages in improvement of red cell filterability, red cell aggregation, decrease of plasma viscosity, increase in absolute walking distance and relief from rest pain, suggesting that such patients are accessible to conservative treatment with hemorheologically active agents.

Bupivacaine alters red blood cell properties: a possible explanation for neonatal jaundice associated with maternal anesthesia.

Cord blood was incubated with lidocaine, mepivacaine, bupivacaine, or buffer and red blood cell filterability was determined. Only bupivacaine at either 1 or 2 micrograms/ml prolonged filterability by an average of 58 to 65% over red cells treated with buffer alone. Tritiated bupivacaine was bound to a greater extent to red cell ghosts from cord blood (24.6 +/- 5.8%) than to adult red cell ghosts (14.6 +/- 2.6%). Finally, we determined red cell survival in 13-day-old rats injected with bupivacaine or buffer. At 2 h after injection, buffer-treated animals had a red cell survival of 96.9 +/- 3.3%, whereas 2-h survival was reduced to 82.6 +/- 8.7% for the animals injected with bupivacaine. Our results suggest that the neonatal jaundice associated with maternal anesthesia, especially bupivacaine, may be related to the observations that these agents cross the placenta, bind to the red cell membrane and reduce its filterability, resulting in shortened red cell survival.

Erythrocytes from ozone-exposed mice exhibit decreased deformability

Injury from short-term exposure to ozone (O 3) was detected by a simple test of red blood cell (RBC) filterability. This test measures changes in the ability of the RBC to deform—as occurs during passage through small capillaries. Male CD-1 mice were exposed to 1.0, 0.7, or 0.3 ppm O 3 for 4 hr, and blood samples were obtained by heart puncture. RBCs were suspended in Tris-HCl buffer, pH 7.4, containing 10 mg/dl glucose. After incubation in air for up to 6 hr, the time required for 2 ml RBC suspension to pass through a 3-μm-pore-size polycarbonate filter was determined. A significant increase in the 6-hr filtration time for O 3-exposed (1.0 ppm) mice over unexposed mice and a lack of protection by vitamin E were shown. The increases in RBC filtration times for O 3-exposed mice appeared to be dose related. Ozone exposure (1.0 ppm) caused a significant increase in the hematocrit of both vitamin E-deficient and -supplemented mice. Vitamin E supplementation appeared to partially prevent this increase in hematocrit. Measurement of lipid peroxidation by the thiobarbituric acid (TBA) test revealed no detectable levels of TBA-reactive material in RBC from O 3-exposed mice. These results suggest that measurement of RBC filterability may be feasible as a clinical test for short-term injury from exposure to oxidant gases.

Effects of Ketanserin on Platelet Function and Red Cell Filterability in Hypertension and Peripheral Vascular Disease

Serotonin is a vasoactive substance that acts on blood vessels and platelets but whose primary action lies in its role as an amplifier for other agents. The aim of this work was to study the effects on blood platelets and erythrocytes of the S2-serotonergic receptor antagonist ketanserin. Twenty-seven patients with untreated hypertension and/or intermittent claudication received a bolus intravenous (i.v.) injection of 10 mg ketanserin followed by 2 mg/h during 3 h i.v. infusion. Platelet function and erythrocyte filterability were studied before and 30 min, 3 h, and 24 h after the bolus injection. The results showed decreases of plasma beta-thromboglobulin and platelet factor 4 levels (p less than 0.001) and platelet aggregation induced by epinephrine plus serotonin (p less than 0.001), whereas ADP-induced aggregation remained unchanged 30 min and 3 h after ketanserin administration. Red cell filterability was decreased (p less than 0.01). There was a tendency toward lower mean arterial blood pressure but heart rate remained unchanged. The dual effect of ketanserin on platelet function and erythrocyte filterability might be of great clinical value in hypertension and peripheral vascular disease in which microcirculatory flow is altered.

Erythrometer: A new device for measuring erythrocyte filterability and plasma viscosity

The Erythrometer is a new device capable of determining both red blood cell filterability and plasma viscosity. In the case of filterability measurements, a suspension of washed red blood cells is filtered at a steady flow rate through a 3 or 5 microns pore-diameter membrane. Pressure drop across the membrane is recorded and a red blood cell filterability index can be calculated according to the change in pressure. The authors describe the instrument's operating principle and performance and present some of the results obtained.

Evaluation of the contribution of red and white cells to the flow of suspensions of washed blood cells through 3 micron Nuclepore membranes.

This study was designed to investigate a method of analysis which can quantitate the contribution of white cells to the flow of washed suspensions of blood cells. Such an analysis would obviate the need to remove white cells when studying the filterability of normal and abnormal red cells. The flow of suspensions of washed blood cells through a 3 micron Nuclepore membrane declines continually due to the occlusion of pores and the degree of pore occlusion is reduced significantly by the removal of the 'buffy coat' during the preparation of the suspension. These findings are in complete agreement with many other reports. However, a detailed kinetic analysis of the results suggests strongly that the white cell population makes a small contribution to the degree of pore occlusion which is caused largely by approximately 1% of the total red cell population. Despite the phenomenon and extent of pore occlusion, a kinetic analysis of the complete non-linear flow profile allows a measure of the deformability of red cells from filtration studies of washed but unfractionated blood cells.

Prostacyclin increases filterability of normal and rigidified human red blood cells in vitro.

Red blood cell (RBC) deformability is a critical determinant of capillary flow. In a previous study we found decreased deformability (filterability) of red cells of patients with clinical symptoms of peripheral ischaemia associated with systemic sclerosis and prostacyclin (PGI2) infusion had beneficial effect on both the clinical symptoms and red cell filterability. The present study was therefore designed to investigate the effect of PGI2 on RBC deformability in vitro, by measuring the filterability of RBCs suspended in saline. The results demonstrate that PGI2 increases filterability of normal RBCs and significantly improves the impaired deformability of cells due to storage or calcium influx.

Effect of contrast media on red cell filtrability and morphology.

The effects of radiological contrast media on red cell morphology and rigidity have been studied. It has been shown that all the contrast agents studied, even when iso-osmolar with plasma, produce changes in red cell morphology, revealing the intrinsic chemotoxicity of contrast medium molecules. The changes are greatest with the most strongly protein-bound medium investigated--meglumine ioglycamide. The effects on red cell rigidity, on the other hand, appear purely a function of osmolality, being entirely reproducible with hyperosmolar solutions of saline. At concentrations iso-osmolar with plasma no effect on deformability is observed. Since the increased rigidity of red cells induced by contrast medium adversely affects blood flow, the use of the new low-osmolality contrast media is particularly recommended in pulmonary angiography and renal arteriography.

Decrease of red blood cell filterability seen in intensive care I. The correlation of low erythrocyte filterability with mortality and its return to normal values in critically ill patients under parenteral nutrition.

Damage to the internal viscosity of red cell is correlated with changes in the surface area to volume ratio and to prelytic phenomena. Considerable changes in shape were noticed in red cells from shocked dogs and some critically ill patients in blood smear or fresh preparation, or after in vitro treatment with colloidal plasma substitutes or glucose, and so erythrocyte filterability was investigated in critically ill patients, given or not given parenteral nutrition. The results revealed an increase of the erythrocyte filtration time (EFT 1/2) in more than 50% of the critically ill patients and less alteration in critically ill patients given total parenteral nutrition, the mortality being half as great. The return of increased EFT 1/2 to normal values occurred after 3-12 days of total parenteral nutrition in 6 patients investigated. A death rate twice as great was seen in patients with high EFT 1/2 as compared to the 27.7% mortality in patients with normal EFT 1/2, its correlation with increased filtration time being significant, r = 0.81 greater than 3 Sr, y = 1.291x + 27.44, n = 47.

Decrease of red blood cell filterability seen in intensive care. II. Red blood cell crenelation "in vivo" as morphological evidence of increased red blood cell viscosity in low flow states.

We have reported the finding of numerous spiculed erythrocytes in blood stored for 15-21 days with acid citrate dextrose, drawing attention to the possible decrease of stored red cell deformability because of the decrease of the surface to volume ratio. The presence of anisotropy with crenated spheres, equivalent to the internal crystallization of hemoglobin, is closely related to these altered red cell parameters. The increase of erythrocyte filtration time in blood stored with acid citrate dextrose correlated well with the duration of storage up to the 21st day, r = 0.74 greater than 3 Sr, y = 1.104x + 1.853, n = 47, as well as with the increase of the proportion of crenated red cells. Using higher magnification (X700-1000) of the microcirculation in the great omentum of shocked dogs, crenated spheres could be seen within the arterioles, venules and capillaries; during refractory shock, nearly all the red cells became crenated spheres. The observation of echinocytes "in vivo" is a morphological proof of the damage to deformability of normal red blood cells in low flow states.

Some haemorheological and haematological effects of alcohol.

This study, assesses effects of alcohol when ingested in moderate quantities typical of a social setting. In the 4 subjects studied highly significant changes were observed in platelet aggregation, whole blood viscosity and red cell filterability.

Impaired red cell filterability with elimination of old red blood cells during a 100-km race.

Impaired red cell filterability with elimination of old red blood cells during a 100-km race.

尿酸と血液粘度

Hyperuricemia is known to be frequently accompanied by hypertension, hyperlipidemia, diabetes mellitus, obesity and arteriosclerosis. But there is no reprot on the relationship between serum uric acid (SUA) and blood viscosity which is known to be an important factor of thrombosis. We measured blood viscosity, SUA, hematocrit and other general blood chemistry in 84 healthy volunteers. There was a significant correlation between SUA and blood viscosity. This apparent correlation was found to be mediated by higher hematocrit values in persons with higher SUA values, Actually, it is known that hyperuricemics have higher concentration of hemoglobin than normals.Treatment with 200mg allopurinol/day of hyperuricemic patients for 2 weeks decreased blood and plasma viscosities in 6 out of 7 patients, but not signifcantly. The incubation of red blood cells with UA (12mg/dl) containing buffer did not change the red cell filtrability to a filter with 5μ pores.Hyperuricemics are said to have high incidence of thrombotic diseases. This could partly be explained by our findings on the relationship between SUA and blood viscosity.

Properties of vitamin E-deficient erythrocytes following peroxidant injury.

Several membrane properties of vitamin E-deficient and normal erythrocytes were studied after incubation of these cells with hydrogen peroxide. Measurements of mean corpuscular volume, cation permeability, membrane Na+, K+ ATPase activity, red cell filterability through 5 mu millipore filters, and membrane protein pattern on sodium dodecyle sulfate-gel electrophoresis revealed marked alterations before lysis. Vitamin E sufficient cells were unaffected by a similar incubation with hydrogen peroxide. We speculate that the changes in membrane function, which follow peroxidant injury, contribute to the shortened red cell survival in the vitamin E deficient state.

Reduced red cell filtrability due to red cell plasma protein interactions.

The adsorption of protein on red cell surface was studied by the measurement of protein in plasma and incubation of blood with 131I-albumin. The protein concentration of the moderately hypertonic plasma clearly decreased by the addition of red cells. The decay counts of 131I-albumin increased in the centrifuged red cell segment as the ionic strength in the plasma increased. For the interpretation of these results it was assumed that the human red cells suspended in plasma are covered with albumin under the normal ionic strength and adsorb more albumin molecules when the ionic strength in the plasma is elevated by the addition of NaCl. A multilayer adsorption of albumin is suggested at the ionic strength of 450 mOsmol. The excess adsorption of albumin on red cells reduces the filtrability of red cells through the nuclepore filter.

Erythrocyte Filterability, Fragility, and Membrane Proteins in Folic Acid Deficient Guinea Pigs

The purpose of this study was to determine if erythrocytes from folic acid-deficient guinea pigs could be used as a model for the study of defects which have been reported in megaloblastic anemic patients. Reported defects include decreased deformability and abnormal membrane proteins. Red cell filterability was studied with polycarbonate sieves and cellulose filters. Membrane proteins were analyzed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. Severe folate deficiency in guinea pigs caused no change in erythrocyte filterability or membrane proteins. Thus, the defects which have been reported in human folic acid or vitamin B-12 deficiency are not present in all animals with the same nutrient deficiency. Folate deficiency, however, did cause guinea pig erythrocytes to be markedly less susceptible to hypotonic lysis than cells from control animals, a feature which is not characteristic of human megaloblastic anemia.Folic acid deficiency erythrocyte deformability erythrocyte fragility erythrocyte membrane