Rheological comparison of hemoglobin solutions and erythrocyte suspensions.

Hemoglobin solutions prepared from hemolyzed human erythrocyte packs have Newtonian flow properties. Diluted solutions are also Newtonian. All solutions have a viscosity lower than the apparent viscosity of erythrocyte suspensions of equal oxygen-carrying capacity. The presence of cell debris in hemoglobin solutions causes non-Newtonian (pseudoplastic or rheopectic) flow behavior.

Mechanical stimulation of nitric oxide synthesizing mechanisms in erythrocytes.

It has been previously demonstrated that red blood cells (RBC) possess functional nitric oxide (NO) synthesizing mechanisms. RBC are also equipped with variety of intracellular control mechanisms, and respond to mechanical forces and to various biological stimuli by increased release of ATP. Nitric oxide has also been demonstrated to be released from RBC under certain circumstances, and it has been hypothesized that NO synthase (NOS), which is located in both the RBC membrane and cytoplasm, might be activated by mechanical factors. The present study aimed at investigating NOS activation and NO export induced by mechanical stress applied to RBC in suspension. Heparinized venous blood samples were obtained from healthy, adult volunteers and their hematocrit adjusted to 0.4 l/l. The RBC suspensions were equilibrated at room temperature (22+/-2 degrees C) with either room air or made hypoxic (36 mmHg, approximately 70% saturation) using moisturized 100% nitrogen. The samples were then continuously pumped through a glass tube (diameter = 0.06 cm; length = 33 cm) for 30 min using a dual syringe pump to maintain a wall shear stress of 0.5-2 Pa with NO concentrations in the RBC suspensions measured electrochemically. NO concentration significantly increased under the influence of 2 Pa in hypoxic RBC suspensions: 105.0+/-14.2 nM to 127.1+/-12.0 nM as the peak value at 20 min of perfusion. No increase was observed at lower levels of shear stress. Plasma nitrite/nitrate concentrations were measured in samples obtained at five minute intervals. Application of fluid shear stress to hypoxic RBC suspensions resulted in a significant, time-dependent increase of plasma nitrite/nitrate levels, reaching to 14.7+/-1.5 microM from a control value of 11.2+/-1.3 microM. The presence of the non-specific NOS inhibitor L-NAME (10(-3) M) prevented this increment. Additionally, both eNOS and serine 1177 phosphorylated eNOS immuno-fluorescence staining in RBC cytoplasm were shown to increase in response to applied shear stress. Our results support the hypothesis that RBC NO synthase is activated and that export of NO from RBC is enhanced by mechanical stress.

Inter-species differences in hematocrit to blood viscosity ratio.

Hematocrit (Hct) is the major determinant of whole blood viscosity and of its oxygen binding capacity: with increasing Hct, viscosity increases exponentially and oxygen capacity increases linearly. Thus, the theoretical oxygen transport potential of blood, as indexed by the ratio of Hct to viscosity (Hct/viscosity), generally yields a curve concave to the Hct axis with a maximum at an "optimal hematocrit" value. This study analyzed relations between Hct, blood viscosity and shear rate for rats and dogs to explore whether different optima exist for Hct or Hct/viscosity. Our results reveal differences depending on both shear rate and species: at equal Hct, rats had higher blood viscosity and thus lower Hct/viscosity levels. Optimum values for Hct/viscosity were markedly different between the two species at shear rates of 90 and 200 s-1. Conversely, Hct/viscosity data at 10 s-1 did not exhibit an optimum but rather a linear decrease of the ratio with increasing hematocrit. Relations between Hct and blood viscosity thus differ among animal species. Inasmuch as animal studies are often utilized as an aid to understanding hemorheological aspects of clinical conditions and/or therapy, evaluating Hct/viscosity ratios may be a useful supplementary tool for research focused on various physiological and patho-physiological processes.

The effects of renal ischemia-reperfusion on hemorheological factors: preventive role of allopurinol.

Changes in hemorheological parameters were studied in dogs following unilateral renal artery clamping (45-minute ischemia then reperfusion), with and without preoperative administration of allopurinol. Sham-operated animals were also evaluated. Blood samples were collected preoperatively, at beginning and at 30, 60 and 120 minutes of reperfusion, then on the 1st, 3rd, 5th and 7th days. Filtration properties of erythrocytes (relative cell transit time, RCTT), whole blood and plasma viscosity (WBV, PV), fibrinogen level and hematology parameter were determined. RCTT significantly increased for both ischemic groups at 30 minutes of reperfusion, and remained elevated on the 1st and 2nd postoperative days; these changes were abolished by allopurinol pretreatment. WBV and hematocrit increased on the 1st day, and PV and fibrinogen level showed elevation on 1st-5th postoperative days. We thus conclude that decreases of RBC deformability (i.e., higher RCTT) were characteristic and specific on early postoperative days after renal ischemia-reperfusion and that these alterations were prevented by pre-ischemia administration of allopurinol.

RBC aggregation: laboratory data and models.

The reversible aggregation of red blood cells (RBC) into linear and three-dimensional structures continues to be of basic science and clinical interest: RBC aggregation affects low shear blood viscosity and microvascular flow dynamics, and can be markedly enhanced in several clinical states. Until fairly recently, most research efforts were focused on relations between suspending medium composition (i.e., protein levels, polymer type and concentration) and aggregate formation. However, there is now an increasing amount of experimental evidence indicating that RBC cellular properties can markedly affect aggregation, with the term "RBC aggregability" coined to describe the cell's intrinsic tendency to aggregate. Variations of aggregability can be large, with some changes of aggregation substantially greater than those resulting from pathologic states. The present review provides a brief overview of this topic, and includes such areas as donor-to-donor variations, polymer-plasma correlations, effects of RBC age, effects of enzymatic treatment, and current developments related to the mechanisms involved in RBC aggregation.

Hemorheological parameters as determinants of myocardial tissue hematocrit values.

It is well known that the hematocrit in microvessels with diameters smaller than 1000 microm is lower than either venous or arterial hematocrit, thereby resulting in significantly lower mean hematocrit values for vessels perfusing a given tissue (i.e., lower tissue hematocrit). The mechanisms that underlie this reduction of microvascular hematocrit include axial migration, plasma skimming and the Fahraeus Effect. It has been previously demonstrated in rats that a linear hematocrit gradient normally exists through the thickness of the left ventricular myocardium, and that this gradient is sensitive to alterations of the rheological properties of the circulating blood. The gradient is abolished if the RBC in the perfusate are rigid; fibrinogen infusions, and thus increases of both plasma viscosity and RBC aggregation, also affect this gradient. In a new series of studies, it has been observed that enhanced RBC aggregation affects the myocardial hematocrit gradient regardless of alterations of plasma viscosity. Although the exact mechanisms responsible for the myocardial hematocrit gradient, as well as its physiological significance, are not yet clearly known, it is possible to speculate that alterations in local hematocrit could adversely affect myocardial perfusion and function.

Effects of preparative procedures on the volume and content of resealed red cell ghosts.

The effects of variations in preparative procedures on the volume and content of resealed red cell ghosts have been investigated. Following hypotonic lysis at 0 degrees C, and after a variable delay time (td), concentrated buffer was added to restore isotonicity; resealing was then induced by incubation at 37 degrees C for one hour. Using this procedure, both the resealed ghost volume and the residual hemoglobin (Hb) content decreased for increasing td. If ghosts were maintained at 0 degree C (i.e., no 37 degrees C incubation), they remained nearly spherical until isotonicity was restored. Their volume then fell abruptly, but subsequently increased toward an intermediate level. The fall in volume was greater and the final level achieved was smaller for longer delay times. At 0 degree C, return to isotonicity also halted the otherwise gradual loss of residual Hb from unsealed ghosts. In addition, ghosts with internal osmolality of 40 to 300 mosmol/kg were prepared by adding different amounts of concentrated buffer before resealing for one hour at 37 degrees C. Under these conditions, the final ghost volume was inversely related to the resealing osmolality (i.e., lower osmolality yielded a larger volume). Ghost volume also increased, along with Hb content, if the quantity or concentration of the red cell suspension added to the lysing medium was increased. We conclude that resealed ghost volume is influenced by the ratio of lysate to resealing medium osmolality and by the colloid osmotic pressure of the residual ghost Hb. These data indicate methods by which ghosts with desired characteristics can be prepared, and have potential application for studies of ghost mechanical and biophysical behavior.

t-Butyl hydroperoxide-induced changes in the physicochemical properties of human erythrocytes.

Treatment of human erythrocytes with micromolar concentrations of t-butyl hydroperoxide causes a variety of changes in the physical properties of the cells. Red cells exposed to concentrations of t-butyl hydroperoxide of less than 750 microM for 15 min exhibited significant decreases in cellular and membrane deformability, increases in membrane-associated protein cross-linking, osmotic fragility and the viscosity of the intracellular hemoglobin solution. No changes in the volume or density of the cells were observed. Changes in cellular deformability are probably attributable solely to changes in the mechanical properties of the cell membrane. Conversely, when red cells are exposed to t-butyl hydroperoxide concentrations in excess of 750 microM for 15 min they exhibited decreases in cellular deformability which may be related to increases in cell volume as well as membrane rigidity.

Influence of preparative procedures on the membrane viscoelasticity of human red cell ghosts.

The effects of systematic variations in the preparative procedures on the membrane viscoelastic properties of resealed human red blood cell ghosts have been investigated. Ghosts, prepared by hypotonic lysis at 0 degrees C and resealing at 37 degrees C, were subjected to: measurement of the time constant for extensional recovery (tc); measurement of the membrane shear elastic modulus (mu) via three separate techniques; determination of the membrane viscosity (eta m) via a cone-plate Rheoscope. Membrane viscosity was also determined as eta m = mu X tc. Compared to intact cells, ghosts had shorter tc, regardless of their residual hemoglobin concentration (up to 21.6 g/dl). However, prolonged exposure to hypotonic media did increase their recovery time toward the intact cell value. The shear elastic modulus, as judged by micropipette aspiration of membrane tongues (mu p), was similar for all ghosts and intact cells. This result, taken with the tc data, indicates that ghosts have reduced membrane viscosity. Rheoscopic analysis also showed that eta m was reduced for ghosts, with the degree of reduction (approx. 50%) agreeing well with that estimated by the product mu p X tc. However, flow channel and pipette elongation estimates indicated that the ghost membrane elastic modulus was somewhat elevated compared to intact cells. We conclude that: ghosts have reduced membrane viscosity; ghosts have membrane rigidities close to intact cells, except possibly when the membrane is subjected to very large strains; the reduction in eta m is not directly related to the loss of hemoglobin; prolonged exposure of ghosts to low-ionic strength media increases the membrane viscosity toward its initial cellular level. These data indicate that the mechanical characteristics of ghost membranes can be varied by changing the methods of preparation and thus have potential application to further studies of the structural determinants of red cell membrane viscoelasticity.

Activated polymorphonuclear leukocytes affect red blood cell aggregability.

Activated leukocytes can affect adjacent cells by generating oxygen free radicals and secreting proteolytic enzymes, and red blood cells (RBC) exposed to such agents should be susceptible to their effects. This study was thus designed to investigate the effects of activated polymorphonuclear leukocytes (PMN) on RBC aggregability (i.e., on intrinsic RBC aggregation characteristics). PMN were isolated from human blood by density separation and suspended in glucose-enriched buffer with RBC isolated from the same blood sample (RBC/PMN ratio of 150:1). PMN were then activated in this suspension by adding 1 ng/mL tumor necrosis factor alpha (TNF-alpha) and 10(-7) M N-formyl-methionyl-leucyl-phenylalanine (fMLP) or fMLP alone. After incubation for 2 h at 37 degrees C, RBC aggregation behavior in autologous plasma was assessed; RBC deformability and partition coefficients were also measured. RBC aggregation was significantly increased after incubation and deformability and partitioning were decreased; these effects were prevented by phenylmethylsulfonyl fluoride (1 mM) or superoxide dismutase (20 microg/mL) plus catalase (40 microg/mL). TNF-alpha and fMLP alone had no effect on RBC aggregation if PMN were not present. Activated PMN can thus markedly affect RBC aggregability, apparently via both proteolytic enzymes and oxygen free radicals; enhanced aggregation seen in clinical states associated with PMN activation or observed during in vivo RBC aging may also involve such PMN-RBC interactions.

An automated tube-type blood viscometer: validation studies.

The technical complexity of previous rheometers has tended to limit the availability of blood viscosity data obtained over a wide range of shear rates. However, an automated tube-type viscometer, the Rheolog, has been developed; it employs a disposable flow assembly and less than five minutes are required to obtain blood viscosity results over a shear rate range of 1-1500 s(-1). We have carried out validation studies of the Rheolog using normal human blood and have compared these results with those obtained by cone-plate and Couette viscometers; storage time and temperature effects were also evaluated. Replicate measurements indicated mean CV levels less than 5%, and were independent of hematocrit and shear rate. Rheolog blood viscosity data agreed closely with those from other viscometers: average Rheolog differences from mean cone-plate and Couette values were -0.3% at 28% hematocrit, -1.4% at 41% hematocrit (i.e., native), and 1.0% at 56% hematocrit. Storage at room temperature up to 8 hours and at 4 degrees C up to 4 days had minimal effects whereas notable changes were observed when stored for 3 hours at 37 degrees C. Our results indicate that, within the hematocrit and shear rate limits employed herein, the Rheolog provides rapid, accurate and reproducible blood viscosity data, and suggest its usefulness for both basic science and clinical studies.

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.

Ineffective erythropoiesis in beta-thalassemia major is due to apoptosis at the polychromatophilic normoblast stage.

Beta-thalassemia major is characterized by ineffective erythropoiesis, although it is difficult to define the dynamics of this process from the static information revealed by analysis of bone marrow (BM) aspirates. We aimed to study the kinetics of sequential erythroid differentiation in beta-thalassemia major. We isolated the progenitor cells (CD34(+) and CD34(+)CD38(-) cells) from BM of thalassemia major patients and studied in vitro erythropoiesis. This is the first report of an in vitro study in human beta-thalassemia major from purified BM CD34(+) progenitor cells, using erythroid culture conditions, which allow unilineage differentiation to mature enucleated red blood cells. In contrast to normal donors, a high proportion of BM CD34(+) and CD34(+)CD38(-) progenitors from beta-thalassemia major coexpressed the late erythroid lineage-specific protein glycophorin A and generated a higher proportion of erythroid colonies. However, despite the marked increase in erythroid clonogenicity of the progenitor population, erythroid cultures initiated from beta-thalassemia major BM CD34(+) cells expanded 10- to 20-fold less than from normal BM. There were less viable cells during differentiation, specifically after the polychromatophilic normoblast stage. There was a progressive increase in the apoptotic erythroid progeny with differentiation, and apoptosis occurred predominantly at the polychromatophilic normoblast stage. In thalassemia major, BM progenitor cells show increased erythroid clonogenicity, increased expression of late erythroid lineage-specific proteins, and accelerated erythroid differentiation. However, despite the apparent increased erythroid commitment, ineffective erythropoiesis occurs due to apoptosis at the polychromatophil stage. Identification of the differentiation stage at which apoptosis occurs will permit further studies of the underlying mechanisms and target therapeutic strategies to improve red cell production.

Effect of superoxide anions on red blood cell rheologic properties.

The human red blood cell (RBC) is known to be susceptible to oxidant damage, with both structural and functional properties altered consequent to oxidant attack. Such oxidant-related alterations may lead to changes of RBC rheologic behavior (i.e., deformability, aggregability). Two different models of oxidant stress were used in this study to generate superoxide anions either internal or external to the RBC. Our results indicate that generation of superoxide within the RBC by phenazine methosulfate decreases RBC deformability without effects on cell aggregation. Conversely, superoxide generated externally by the xanthine oxidase-hypoxanthine system primarily affects RBC aggregability: the shear rate necessary to disaggregate RBC was markedly increased while the extent of aggregation decreased slightly. Increased disaggregation shear rate (i.e., greater aggregate strength) as a result of superoxide radical damage may adversely affect the dynamics of blood flow in low-shear portions of the circulation, and may also play a role in the no-reflow phenomena encountered after ischemia-reperfusion.

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.

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.

Hemorheologic abnormalities in patients with human immunodeficiency virus infection and ophthalmic microvasculopathy.

The severity of conjunctival microvascular changes and the presence of cotton-wool spots were compared to factors that may affect blood flow (hematocrit level, red cell aggregation, fibrinogen level, plasma viscosity, circulating immune complexes, and quantitative immunoglobulin levels) in 22 human immunodeficiency virus-infected individuals. The severity of conjunctival disease was associated with increased zeta sedimentation ratios (a measure of red cell aggregation) and fibrinogen levels. The presence of cotton-wool spots was also associated with higher fibrinogen levels. Plasma viscosity and quantitative IgG levels were above normal levels in most patients, although a relationship to disease severity was not established. Altered blood flow may contribute to vascular damage and ocular ischemic lesions in patients with human immunodeficiency virus infection.

A new, pluronic-based, bone hemostatic agent that does not impair osteogenesis.

OBJECTIVE: Intraoperative bone hemostasis can be accomplished using surgical beeswax (bone wax). However, bone wax locally interferes with osteogenesis, and its use is avoided when bone fusion is critical. We describe the use of a Pluronic copolymer blend as a biocompatible, absorbable, hemostatic agent. METHODS: A rat femur defect model and a femur gap nonunion model were used. For each surgical model, 24 rats were divided into three treatment groups, i.e., those receiving bone wax implants, Pluronic (90% Pluronic P85/10% Pluronic F88) implants, or no implants (control group). After 10, 21, or 42 days, animals were killed and femora were removed for radiographic analysis and hematoxylin and eosin staining. RESULTS: In the femur defect model, no differences were observed between the Pluronic-treated and control groups; hematoxylin and eosin staining demonstrated bone formation and osteocytes within the defect. In the femur gap nonunion model, no fusions occurred in any group. Development of an osseous callus at the gap site was observed for the control and Pluronic-treated groups. In both models, rats that received bone wax implants exhibited no osseous growth. CONCLUSION: The Pluronic blend exhibits handling properties similar to those of bone wax, readily achieves hemostasis, and does not inhibit bone regrowth. Pluronic compounds may serve as effective absorbable hemostatic agents for the treatment of bone bleeding in sites where fusion is critical. In addition, this copolymer blend may find use as a vehicle for the short-term release of pharmacological agents, which may further reduce the incidence of infections, reduce inflammation, and improve fusion rates.

Increased polymorphonuclear leucocyte rigidity in HIV infected individuals.

AIM: Individuals with human immunodeficiency virus (HIV) infection were evaluated for evidence of abnormal polymorphonuclear leucocyte (PMN) rigidity, which can alter capillary blood flow. METHODS: The transit time of individual PMN through 8 microm pores in a cell transit analyser was used as a measure of cell rigidity. PMN transit time was compared between HIV infected individuals (n=45) with and without CMV retinitis and HIV negative controls (n=17). RESULTS: Transit times were longer for PMN from HIV infected individuals than for PMN from controls (p<0.001). PMN from HIV infected individuals with CMV retinitis (n=13) had longer transit times than PMN from those without CMV retinitis (n=32, p<0.001). Transit times were longer in HIV infected individuals with lower CD4+ T lymphocyte counts (p<0.001). Regression analysis indicated that the relation between transit times and the presence of CMV retinitis could not be explained solely on the basis of low CD4+ T lymphocytes. In HIV infected individuals, mean transit time was not correlated with age, blood pressure, or serum creatinine, cholesterol, or triglycerides. CONCLUSIONS: HIV infected individuals appear to have increased PMN rigidity, a cellular change that might be involved in the pathogenesis of HIV related retinal microvasculopathy. PMN rigidity appears to be related to severity of immune dysfunction. PMN rigidity may remain high in patients with CMV retinitis after elevations of CD4+ T lymphocyte counts that result from potent antiretroviral therapy.

The Effect of Hemorheologic Factors on Middle Cerebral Artery Blood Flow Velocity in Young Individuals.

Analysis of the effect of hemorheologic factors on middle cerebral artery (MCA) blood flow velocity in 55 healthy individuals aged 18 to 30 years demonstrated an inverse association between mean MCA blood flow velocity and hematocrit (r = -0.27, p < 0.05). This association was largely explained by the effect of whole-blood viscosity. Neither fibrinogen concentration nor plasma viscosity were significantly associated with MCA blood flow velocity in this group; this lack of a fibrinogen association is in contrast to results previously obtained in elderly individuals where an inverse association was observed. These findings thus demonstrate age-dependent differences in the relationship between fibrinogen and MCA blood flow velocity.