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H J Meiselman

Publications and source records attributed to H J Meiselman.

At least 55 records · Page 3Linked to original sources

Red blood cell aggregation in experimental sepsis.

Red blood cell (RBC) aggregation was investigated in a rat model of sepsis with special emphasis on RBC-related factors. Sepsis was produced by cecal ligation/puncture, whereas another group had only laparotomy (sham operation); blood samples also were obtained from control, unoperated-on animals. RBC aggregation was measured in autologous plasma and in 3% dextran 70, 18 hours after the operations, by using a Myrenne Aggregometer system and the zeta sedimentation ratio (ZSR) method. RBC aggregation in autologous plasma was found to be enhanced in both sham-operated and septic animals and was consistent with their increased plasma fibrinogen levels. However, RBC aggregation in dextran was significantly higher than control only in the sepsis group. RBCs from septic animals also aggregated more in septic plasma compared with RBCs from control animals. In the sepsis group, RBC deformability was significantly decreased, whereas RBC lipid peroxidation was significantly increased. Our results thus confirm the known increase of RBC aggregation in septicemia and, in addition, demonstrate marked alterations of intrinsic RBC properties that further enhance red cell aggregation.

Animals↗

The anti-neoplastic drug 5-fluorouracil produces echinocytosis and affects blood rheology.

The anti-neoplastic agent 5-fluorouracil (5-FU) in high therapeutic doses can induce angina pectoris and myocardial infarction. The pathophysiological mechanism of this side-effect has not yet been elucidated. We analysed the influence of 5-FU on blood rheology in vitro. Whole blood, blood cell suspensions and plasma were incubated with increasing concentrations of 5-FU (final concentrations 0, 0.08, 0.4, 2, 10 and 25 mg/ml 5-FU) at 37 degrees C. Erythrocyte morphology was analysed after fixation with glutaraldehyde. Viscosity was measured at high and low shear rates (94 and 0.1 s[-1]). Erythrocyte aggregation and the cell transit times of erythrocytes through 5 microm pores and polymorphonuclear leucocytes through 8 microm pores were determined. 5-FU induced a dose-dependent formation of echinocytes within minutes and was reversible upon removal of 5-FU, which reflected a preferential intercalation of the drug in the outer hemileaflet of the cell membrane. High shear blood viscosity was increased at the highest 5-FU concentration (148 +/- 12%), and at low shear rate a dose-dependent decrease was found (0 mg/ml: 100%, 0.08 mg/ml: 87 +/- 10%, 0.4 mg/ml: 80 +/- 19%, 2 mg/ml: 70 +/- 15%, 10 mg/ml: 40 +/- 19%, 25 mg/ml: 33 +/- 5%). Erythrocyte aggregation was decreased by the 5-FU-induced echinocytosis. The transit time of erythrocytes through narrow pores was increased in a dose-dependent manner by 5-FU, whereas the transit time of polymorphonuclear leucocytes was initially decreased at 10 mg/ml and returned to control after 60 min incubation. We conclude that 5-FU interacts with the cell membrane, induces echinocytosis and vesiculation and affects blood rheology in several ways which may contribute to cardiovascular complications.

Antimetabolites, Antineoplastic↗

Flow resistance of individual neutrophils in coronary artery disease: decreased pore transit times in acute myocardial infarction.

OBJECTIVE: To investigate single neutrophil flow resistance in coronary artery disease, including myocardial infarction before initiation of reperfusion therapy. DESIGN: Neutrophil flow resistance was measured in 93 subjects in five groups: (group 1) 28 patients within 12 hours after the onset of myocardial infarction, before reperfusion therapy; (group 2) 18 with unstable angina; (group 3) 13 with stable angina; (group 4) 13 age matched patients without coronary disease, and (group 5) 21 healthy volunteers. MAIN PARAMETERS: Single neutrophil transit times through 8 microns oligopore filters determined with a modified cell transit analyser. RESULTS: Leucocyte count (10(9)/l) was increased in coronary disease, especially in myocardial infarction and unstable angina (mean and 95% confidence intervals for groups 1 to 5: 12.6 (11.0 to 14.2), 11.3 (8.5 to 14.1), 8.5 (7.4 to 9.6), 8.0 (6.0 to 10.0), 7.0 (6.1 to 7.9)). Polymorphonuclear granulocyte (PMN) flow resistance correlated negatively with white blood cell (WBC) count and was significantly decreased in coronary artery disease (CAD), especially in myocardial infarction; mean transit times (ms) for groups 1 to 5 were: 13.6 (11.8 to 15.4), 16.9 (13.9 to 19.0), 16.9 (12.8 to 21.0), 22.0 (19.6 to 24.4), and 18.6 (15.7 to 21.5). CONCLUSION: Neutrophil flow resistance was decreased in CAD, especially in myocardial infarction before reperfusion therapy. In contrast to previous findings in reperfused myocardial infarction, the present study showed that stiffened PMNs were not yet present in the circulating blood pool. Thus a pharmacological approach aimed at suppressing leucocyte activation before or during reperfusion therapy may be feasible.

Acute Disease↗

Contribution of red blood cell aggregation to venous vascular resistance in skeletal muscle.

The effects of red blood cell aggregation on venous vascular resistance and conductance were examined in the cat lateral gastrocnemius muscle. During perfusion with blood of normal hematocrit, venous conductance fell linearly by 41% when blood flow was reduced from 5 to 1 ml x min(-1) x 100 g tissue(-1) and increased linearly by 155% when flow was increased from 5 to 20 ml x min(-1) x 100 g tissue(-1). This effect was not seen when the muscle was perfused with an acellular solution of 12% Dextran 40 in Ringer solution and was greatly reduced or absent with a nonaggregating suspension of red blood cells in Ringer solution + Dextran 40. Also, the venous vascular conductance at a control flow of 5 ml x min(-1) x 100 g tissue(-1) during perfusion with the nonaggregating red blood cell suspension was twice that with normal blood of the same hematocrit. The effect of flow on venous conductance was significantly reduced when red blood cell aggregation was increased by addition of Dextran 250 to the blood (200 mg/kg body wt) and was also reduced in animals with systemic hematocrit >50%. These findings suggest that red blood cell aggregation contributes importantly to venous vascular resistance in resting muscle.

Animals↗

Erythrocyte aggregation tendency and cellular properties in horse, human, and rat: a comparative study.

Horse blood has a higher tendency to form red blood cell (RBC) aggregates compared with human blood, with this enhanced aggregation previously attributed to differences in plasma factors. Our results confirm this observation and further indicate that washed horse RBC also have a significantly higher aggregation tendency in dextran 70 solutions (i.e., horse RBC have a higher "aggregability"). In contrast, the aggregation tendency of rat RBC, both in autologous plasma and in dextran 70, is significantly less compared with human and horse RBC. Other rheological findings for horse and rat RBC include smaller changes in RBC deformation indexes over the same shear stress range and a lower RBC shape recovery time constant. Rat RBC also had higher two-phase aqueous polymer partition coefficients, suggesting a higher surface charge. Membrane protein analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed marked differences: 1) band 4.2 protein was lacking in horse RBC membranes, and 2) carbohydrate groups have different distributions in human, rat, and horse RBC, as indicated by different patterns in periodic acid-Schiff-stained protein bands. Our results clearly indicate significant differences in RBC aggregability among the three species and indicate that cellular factors contribute importantly to these differences. Furthermore, they suggest that systematic studies of blood and RBC from different species should provide insight into the mechanism(s) of RBC aggregation.

Animals↗

Surface properties of irreversibly sickled cells differ from those of the bulk of sickle cells. Studies by partitioning in aqueous phase systems.

Counter-current distribution (CCD) of red blood cells (RBC) from individuals with homozygous sickle cell (HbSS) disease in a charge-sensitive aqueous dextran-poly(ethylene glycol) phase system, which fractionates cells on the basis of surface properties, indicates that the percentage of irreversibly sickled cells (ISC) increases and the percentage of reticulocytes decreases with increasing cell partition ratios. The high partition ratios of ISC correspond to those of older RBC when RBC from normal individuals are subjected to CCD. Our results thus indicate that ISC differ in surface properties from those of the bulk of sickle RBC (including reticulocytes) in the population and that the difference is, most likely, charge-related. While the question as to whether ISC are indeed old cells has not yet been unequivocally answered, this view finds support in the fact that the independent parameters of ISC surface properties, as reflected by partition ratios, and densities correlate as they do in older RBC from normal individuals.

Cell Separation↗

Sickle erythrocytes adhere to polymorphonuclear neutrophils and activate the neutrophil respiratory burst.

The vasoocclusive process in patients with sickle cell disease (SCD) is complex and involves interactions among sickle erythrocytes (SS-RBC), vascular endothelium, and plasma and cellular components. The role of neutrophils (PMN) in vasoocclusion has not been examined. Patients with SCD appear to have chronically activated PMN. Because the first step in PMN activation is particle recognition, we explored whether normal PMN recognize SS-RBC and whether this recognition results in PMN monolayers, significantly more SS-RBC adhered to the PMN than did normal erythrocytes (AA-RBC; P < .001). Preincubation of erythrocytes with autologous plasma significantly increased the adherence of SS-RBC to PMN but had no effect on AA-RBC (P < .001). When adhesion of density fractionated SS-RBC was performed, dense SS-RBC showed greater adherence to the PMN monolayers than did light SS-RBC (P < .001). To determine mechanisms of this adhesion, IgG and Arg-Gly-Asp-Ser (RGDS) receptor sites on PMN were saturated. IgG inhibited adherence of dense SS-RBC, whereas RGDS inhibited adherence in both fractions, although to a greater extent in the light fraction. We measured SS-RBC activation of PMN by incubating SS-RBC with 2', 7'-Dichloro-fluroescin Diacetate (DCF)-labeled PMN. Incubation of PMN with SS-RBC resulted in a significant increase in fluorescence compared to AA-RBC. We show here that PMN recognize SS-RBC through multiple mechanisms and that this recognition results in activation of PMN. These findings contribute to the understanding of vasoocclusive crisis in patients with SCD and may have therapeutic implications.

Amino Acid Sequence↗

Mean red cell volume as a correlate of blood pressure.

BACKGROUND: Clinical studies suggest that hypertensives have lower mean corpuscular volume (MCVs) than do normotensives. Epidemiological studies show no relation or higher MCVs. In the present study of elderly men (71 to 93 years of age) of the Honolulu Heart Program, elements of both findings are confirmed. METHODS AND RESULTS: Three groups are identified: (1) those receiving no hypertension treatment, (2) those receiving treatment with any diuretic, and (3) those receiving treatment with nondiuretics only. MCV is lower in group 3 than in group 1 (-0.85 fL, P<.001) but the same in groups 1 and 2. Within groups 1 and 3, inverse relations of -0.22 and -0.09 mm Hg/fL (P<.05) are noted for systolic (SBP) and diastolic (DBP) blood pressures. No relations are observed in group 2. MCV and red blood cell count (RBC) are inversely correlated (r=-.45). In group 2, adjustment for RBC unmasks a direct relation between MCV and SBP (0.5 mm Hg/fL, P=.02) and DBP (0.3 mm Hg/fL, P=.02). In groups 1 and 3, relations between SBP and MCV are lost after adjustment for RBC (0.005 mm Hg/fL). For DBP, adding RBC plus an MCV x RBC interaction is significant (P<.001). DBP is 5 mm Hg greater in the highest RBC quartile than in the lowest. A +3 mm Hg difference between extreme MCV quartiles is noted only at high RBC levels. CONCLUSIONS: The relation between blood pressure and red cell measures is probably mediated by whole blood viscosity. Hematocrit is a determinant of whole blood viscosity. Viscosity affects peripheral resistance to blood flow, and peripheral resistance affects DBP. At high RBC levels, MCV may be "downregulated." This may lower whole blood viscosity and partially reduce DBP without compromising flow.

Aged↗

Effects of pressure on red blood cell geometry during micropipette aspiration.

Micropipette aspiration is a potentially useful and accurate technique to measure red blood cell (RBC) geometry. Individual RBCs are partially aspirated and from the resulting sphere diameter, total cell length, and pipette diameter, membrane area and cell volume can be calculated. In this study we have focused on possible shape artifacts associated with the aspirated portion of RBC. We observed that the apparent RBC geometry (calculated area and volume) changed markedly (P < 0.001) with the applied aspiration pressure; for normal human RBC the area increased by 5.6 +/- 0.6% and volume decreased by 4.7 +/- 0.6% when the aspiration pressure was increased from 20 to 100 mm water. The calculated membrane area dilation modulus was 7.4 dyn/ cm, which is far below the expected value, and microscopic observations revealed a membrane folding artifact as a possible artifact. These assumptions were strengthened by using a short-duration (3 s) pressure peak of 20-100-20 mm water. The folding then disappeared permanently, but a small (0.31 +/- 0.09%; P < 0.001) area decrease was detected which yields a realistic dilation modulus of 215 dyn/cm. We conclude that membrane folding can critically affect RBC micropipette measurements and that a transient pressure peak can unfold the RBC membrane, thus allowing accurate measurements of RBC geometry.

Adult↗

Decreased deformability of polymorphonuclear leukocytes in diabetic cats.

OBJECTIVE: Polymorphonuclear leukocytes (PMN) have been found to be less deformable in humans with non-insulin-dependent diabetes. It has therefore been hypothesized that white blood cells (WBC) may affect the development of diabetic microangiopathy. This study was designed to determine whether PMN or small and large lymphocytes were less deformable in a large animal model of diabetes-chronically hyperglycemic pancreatectomized cats. METHODS: Venous blood was withdrawn from 13 normal and 14 diabetic cats. The diabetic cats had been kept in poor metabolic control since their pancreatectomy (7-113 months before this study). Blood cell counts, hemoglobin concentration, hematocrit, erythrocyte volume, and WBC differential counts were obtained from the blood samples. Purified mononuclear WBC and PMN fractions were obtained by separating the blood on a discontinuous Percoll gradient. The deformability of each cell fraction was determined using a Cell Transit Analyzer (ABX, Montpellier, France) that measures the transit time of cells through 7.5-microns pores. By varying the sampling rate of the CTA and the pressure difference across the filter, the subpopulations of the mononuclear fractions (small and large lymphocytes) could be identified and each subpopulation analyzed separately. RESULTS: Median transit times for the PMN and small lymphocytes were significantly greater for the diabetic cats, but no difference was found in the large lymphocyte fractions. CONCLUSIONS: These results are in accordance with the finding that PMN are less deformable in humans with diabetes. We also showed that the small lymphocytes from diabetic cats have prolonged transit times. The results suggest that PMN may contribute to the development of microangiopathies like diabetic retinopathy. Diabetic cats may prove useful for testing potential therapies to improve WBC deformability.

Animals↗

Inhibition of red blood cell-induced platelet aggregation in whole blood by a nonionic surfactant, poloxamer 188 (RheothRx injection).

RheothRx Injection, an aqueous solution of a nonionic block copolymer (poloxamer 188) formulated for intravenous administration, was investigated as an inhibitor of red blood cell (RBC)-induced platelet aggregation at plasma concentrations of 0.05-5mgmL-1. Platelet aggregation was determined by measuring the fall in single platelet counts after mechanical agitation of 2mL aliquots of citrated whole blood in a 37 degrees C shaking waterbath. Inhibition of RBC-induced platelet aggregation of > 95% was observed for poloxamer 188 at a concentration of 1mgmL-1, and 41% inhibition was observed at 0.05mgmL-1. Poloxamer 188 was observed to be a more effective inhibitor of RBC-induced platelet aggregation than 2-chloradenosine (2-ClAd) or phosphoenolpyruvate/pyruvate kinase (PEP/PK). Studies using platelet rich plasma (PRP) showed that platelet aggregation could not be induced by shaking in the absence of RBC, though aggregation was induced by the addition of exogenous adenosine diphosphate (ADP). Poloxamer 188 did not inhibit ADP-induced platelet aggregation. We propose that poloxamer 188 protects RBC from mechanical trauma by non-specific adsorption of copolymer to the RBC surface (via the hydrophobic polyoxypropylene moiety), and that this effect prevents mechanical damage and hence leakage of ADP from RBC. RheothRx Injection has been shown to have value in the treatment of acute ischemic disorders such as myocardial infarction. The observation of significant inhibition of RBC-induced platelet aggregation at clinically relevant concentrations suggests that RheothRx Injection may have antithrombotic properties in vivo, and may therefore have potential not only in acute ischemia but also to prevent thrombosis within vascular prostheses or to prevent rethrombosis after angioplasty or endarterectomy.

Adult↗

Optical and mathematical corrections of micropipette measurements of red blood cell geometry during anisotonic perifusion.

Accurate knowledge of red blood cell (RBC) membrane surface area and cellular volume is critical to understanding the geometric factors that affect RBC deformability. A useful method to determine RBC geometry is via micropipette aspiration in which the cell partially enters the tip of a glass pipette with a diameter of about 2 microns. Measurement of the cell while in the pipette allows calculation of cell geometry, but such measurements are subject to several artifacts. Herein, we analyze the effects of three artifacts on calculated RBC geometry during experimental osmotic manipulation. 1) The pipette internal diameter, as measured optically, requires correction for refractive index and focusing errors; 2) the pipette barrel is tapered rather than cylindrical; 3) the observed RBC outline is affected by a diffraction phenomenon. These optical and mathematical errors were all found to influence the calculated RBC geometry; both absolute values and relative changes during osmotic manipulation were affected. For RBC in isotonic medium, use of the above corrections significantly (p < 0.001) reduced the calculated area by 3.7%, the volume by 7.0%, and the minimum cylindrical diameter by 3.9%. The calculated membrane area dilation for cells exposed to hypotonic media was also significantly reduced; at 200 mOsm, the dilation was 2.8% +/- 0.2% without correction vs. 1.5% +/- 0.2% when all corrections were employed (p < 0.01). We therefore suggest that micropipette aspiration of RBC requires use of these correction techniques to obtain accurate values for RBC geometry and that such correction methods are of particular importance when RBC of different sizes are compared.

Adult↗

Decreased polymorphonuclear leukocyte deformability in NIDDM.

OBJECTIVE: To determine the rheological properties of polymorphonuclear leukocytes (PMN) from non-insulin-dependent diabetes mellitus (NIDDM) patients. RESEARCH DESIGN AND METHODS: The deformability of PMN from 33 NIDDM subjects, 13 with impaired glucose tolerance (IGT), and 22 with normal glucose tolerance (NGT) was studied. A Cell Transit Analyzer that measures the transit time of PMN through 8-microns pores was used. Studies were performed under three different conditions: 1) basal state; 2) after incubation with cytochalasin B (20 microM) to dissociate f-actin from the cytoskeleton; and 3) following activation with N-formyl-methionyl-leucyl-phenylalanine (fMLP, 1 nM). RESULTS: PMN from diabetic patients were more rigid (i.e., had longer transit time) than those from subjects with NGT or IGT under basal conditions and after cytochalasin B, but not after stimulation with fMLP. The deformability of PMN from subjects with IGT was similar to those of the NGT group. In the pooled data, basal transit time correlated with age; systolic and diastolic blood pressure; HbA1c; and serum creatinine, cholesterol, and triglyceride concentrations (r = 0.29, 0.34, 0.37, 0.48, 0.25, 0.36, 0.29, respectively, P < 0.05 for each). Hypertensive diabetic patients had less deformable PMN than normotensive ones. No relation was found between PMN deformability and the duration of diabetes, type of treatment, or the presence of retinopathy. CONCLUSIONS: These data indicate increased rigidity of PMN in NIDDM that may contribute to development of microcirculatory disturbances and microangiopathy.

Adult↗

Beta-S gene cluster haplotypes modulate hematologic and hemorheologic expression in sickle cell anemia. Use in predicting clinical severity.

PURPOSE: The rate of progression of major organ failure in sickle cell anemia is genetically controlled. It is the direct consequence of the sickle cell-evoked vasculopathy. PATIENTS AND METHODS: Presence of the beta S gene cluster haplotypes and alpha gene deletions as genetic markers indicate the expected frequency of illness and the risk of end-stage major organ failure. The risk of irreversible soft tissue organ failure is greatest in patients with a Central African Republic (CAR) chromosome, whereas morbidity is consistently lowest in patients with a Senegalese chromosome. Presence of alpha-thalassemia-2 decreases the risk of soft tissue organ failure in all haplotype combinations. RESULTS: Other laboratory abnormalities, when combined with haplotype and alpha gene status, also predict the risk of clinical morbidity. The mean hemoglobin level (or red blood cell count) is lowest in patients with the most severe clinical manifestations. On the other hand, the platelet count and leukocyte count as well as the plasma fibrinogen level are elevated in the sickest patients. A threshold level of hemoglobin F at 1.2 g/dl (approximately 20% hemoglobin F) decreases the risk of major organ failure and is attained most frequently in those with a Senegalese chromosome. Hemorheologic findings observed during the most stable state of patients with sickle cell anemia indicate two trends: (a) the mean percentage of dense red cells is nearly twice as high in the maximal severity patients as compared with the minimal severity patients; and (b) mean red cell rigidity is greatest in the maximal severity group and least in the minimal severity group. These findings suggest that a greater percentage of dense, poorly deformable red cells are present in sickle cell patients in the genotypic category of maximal severity. CONCLUSIONS: The combination of the beta S gene cluster haplotype and alpha-gene status correlates with both phenotypic laboratory findings (hematologic profile) and morbidity. These associations increase our ability to predict clinical severity and the future risk of major organ failure.

Anemia, Sickle Cell↗

Arterial oxygen content and age are determinants of middle cerebral artery blood flow velocity.

BACKGROUND AND PURPOSE: Transcranial Doppler blood flow velocities are inversely related to age and hematocrit, but the relative importance of age, oxygenation, and hemorheological factors has not previously been examined. We evaluated the relative contributions of these factors to middle cerebral artery blood flow velocity in adults with chronic renal failure, a population subject to significant fluctuations in hematologic profile. METHODS: Twenty-six subjects were studied, with arterial shunt blood sampled at the time of transcranial Doppler before dialysis. Twenty subjects from the original cohort were studied twice to examine the effects of intraindividual changes in blood oxygenation and rheology on Doppler velocities. RESULTS: Age (r = -.61, P < .001), high-shear viscosity (r = -.46, P < .02), and arterial oxygen content (r = -.44, P < .05) were all inversely related to middle cerebral artery blood flow velocity. Age was the strongest velocity predictor, accounting for 37% of variance by simple regression analysis. Intraindividual change in arterial oxygen content explained most (54%) of the middle cerebral artery blood flow velocity variation between studies (r = -.74, P < .001). Multiple regression analysis showed that inclusion of additional variables could not account for more velocity variation than change in arterial oxygen content alone. CONCLUSIONS: In this population, age and arterial oxygen content were the most important determinants of interindividual middle cerebral artery blood flow velocity variance and intraindividual middle cerebral artery blood flow velocity variation, respectively.

Adult↗

Fåhraeus and Fåhreaus-Lindqvist effects for neonatal and adult red blood cell suspensions.

In blood vessels with diameters less than 500 microns, both the hematocrit and viscosity decrease with decreasing tube diameter [Fåhraeus effect (FE) and Fåhraeus-Lindqvist effect (FLE)]. Because both effects may be influenced by red blood cell (RBC) volume and osmolality, the effects of RBC type and suspending medium osmolality (216, 294, and 473 mosmol/kg) on tube hematocrit (HT) and relative viscosity (eta r) in narrow tubes (32 to 145 microns diameter) were studied for 0.40 L/L (40%) hematocrit suspensions of human neonatal and adult RBC in buffer. Osmolality of 473 mosmol/kg caused shrinkage of RBC by 20% so that neonatal RBC assume the volume of adult RBC in isotonic buffer. The FLE and FE were present for both neonatal and adult RBC suspensions regardless of osmolality. The viscosity reduction when going from a 145- to a 32-microns tube was greatest for the hypertonic neonatal and adult RBC: changes were -44% (473 mosmol/kg) and -31% (294 mosmol/kg) for neonatal RBC, and -39% (473 mosmol/kg), -34% (294 mosmol/kg), and -21% (216 mosmol/kg) for adult RBC. The eta r were significantly lower (7% on average) for isotonic neonatal RBC compared with adult cells in 32-microns (p < 0.025), 46-microns, and 146-microns tubes (p < 0.001). In contrast, HT and thus the FE were less affected by RBC type or osmolality (only 13% change over entire range of osmolality and diameter): relative HT values were systematically lower (p < 0.02), and the FE greater, for isotonic neonatal versus adult RBC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Mechanical and geometrical properties of density-separated neonatal and adult erythrocytes.

Neonatal red blood cells (RBC) show large variations in size, density, and deformability, with a relatively high percentage of neonatal RBC being extremely dense, almost spherical, and poorly deformable. Previous reports suggest that loss of membrane and oxidation of fetal Hb might account for the generation of the dense, rigid RBC in neonates and the shortened life-span of neonatal RBC. To test whether the dense RBC population is particularly fragile and which mechanical properties are responsible for the rigidity of these cells, the following measurements were made for the top (least dense) and bottom (most dense) 3% fractions of density-separated neonatal and adult RBC: cellular deformability (rheoscope); RBC geometry (micropipette system); elasticity, fragility, and viscosity of RBC membrane (micropipette system); Hb solution viscosity (cone-plate viscometer); and selected biochemical parameters. Fetal Hb of neonatal RBC decreased with increasing cell density. When the bottom fractions were compared with the top fractions, neonatal RBC showed a greater reduction in glutamic oxalacetic transaminase activity (72% versus 53%), potassium (39% versus 19%), volume (32% versus 19%), and surface area (42% versus 21%), and a greater rise in density (3.5% versus 1.9%) and mean corpuscular Hb concentration (42% versus 23%) than adult RBC. Cellular deformability in the rheoscope (shear stress 5 Pa) decreased by 24% in adults and by 41% in neonates. Membrane extensional and bending elastic moduli (i.e. membrane deformability) and membrane fragility of neonatal and adult RBC did not significantly change with increasing cell density.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Disorders of blood viscosity.

In clinical situations associated with disturbed blood flow, the primary focus is usually on improving cardiovascular performance. However, during recent decades, both basic science and clinical literature reports have presented evidence that the flow properties of blood must also be considered in these situations. Thus, the relatively new fields of haemorheology and clinical haemorheology have evolved; the former deals with the flow and deformation behaviour of blood, plasma and the formed elements of blood, whereas the latter relates to alterations of their behaviour in various pathophysiologic states. This review therefore summarizes some of the salient aspects of clinical haemorheology and of the determinants of blood flow properties (flow rate, haematocrit, plasma viscosity, red cell aggregation, red cell deformability). In addition, it briefly describes several clinical disorders associated with abnormal blood, plasma or cell rheology ('hyperviscosity syndromes' occurring in polycythaemia, leukaemia, sickle cell disease, paraproteinaemias).

Blood Viscosity↗