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E A Schmalzer

Publications and source records attributed to E A Schmalzer.

14 recordsLinked to original sources
PubMed1989

Filtration of sickle cells: recruitment into a rigid fraction as a function of density and oxygen tension.

The rheologic behavior of sickle cells was evaluated with a constant flow filtration system at 37 degrees C by using filters with pores of 4.8 microns diameter. Analysis of the shape of the pressure-time curves suggested that sickle cells were subdivided into two discrete subpopulations: (1) relatively deformable cells and (2) cells so rigid that they plugged the pores. The analysis allowed calculation of the fraction of cells causing plugging (FP), even when FP represented less than 0.01% of the population. FP rose with falling Po2 level, apparently with the recruitment of progressively less dense cells into the plugging fraction. A density profile for each sample was constructed. When we made the assumption that the plugging cells represented the denser moiety, this profile allowed identification of the threshold Po2 level at which cells of a given density, deoxygenated under these conditions, became unable to traverse the 4.8 microns pore.

Anemia, Sickle Cell↗
PubMed1987

Rheology of leukocytes.

The rheological properties of human leukocytes (WBCs) have been studied by micropipette aspiration and filtration tests. A small aspiration pressure applied via a micropipette (diameter approximately equal to 3 micron) causes the WBC to undergo a rapid elastic deformation followed by a slow creep. The data can be analyzed with a viscoelastic model: an elastic element K1 in parallel with a Maxwell element (elastic element K2 in series with viscous element mu). Neutrophils and B lymphocytes are similar in K1, K2, and mu, but these values are higher for T lymphocytes. Treatment of neutrophils with colchicine decreases K2 and mu without changing K1, whereas cytochalasin B decreases all three coefficients; these results indicate the importance of cytoskeletal microtubules and microfilaments in WBC rheology. In the presence of Ca2+, WBCs form protopods which have increased viscoelastic coefficients. Inhibition of protopod formation with pentoxifylline is associated with an increase in WBC deformability. The ruffled surface of the apparently round WBC provides an area about twice that needed to enclose a smooth sphere of the same volume; this geometric feature plays an important role in whole WBC deformability tested through 4-5 micron filter pores or micropipettes. Because of its larger volume and higher cellular viscosity, each WBC is equivalent to approximately 700 erythrocytes in its tendency to block 5-micron channels. The rheology of WBCs has significant implications in their functional behavior, including flow through the microcirculation and interaction with endothelial cells.

Capillaries↗
PubMed1987

Rheology of sickle cells and its role in microcirculatory dynamics.

The alterations in the viscoelastic properties of the hemoglobin S solution following deoxygenation can be correlated, on the one hand, with the gelation of the HbS molecules and, on the other hand, with changes in the rheological behavior of the deoxygenated SS erythrocytes. The abnormal rheology of SS erythrocytes forms the basis of their altered flow behavior through filter pores in vitro and microcirculation in vivo. The results support the notion that the rheological behavior of sickle cells is an important link between the molecular events in hemoglobin S following deoxygenation and the behavior of the cell in the microcirculation. Although recent advances have shed considerable lights on the rheology of sickle cells in a variety of conditions, further studies are needed in order to elucidate the pathophysiological role of cell rheology in this disease, especially in terms of the influence of individual SS cells in the heterogeneous populations and the correlation between in vitro and in vivo behavior of SS cells.

Anemia, Sickle Cell↗
PubMed1984

Viscoelastic properties of leukocytes.

The viscoelastic properties of leukocytes (WBCs) during small deformation were determined by micropipette aspiration. The passive deformation behavior of neutrophils suspended in a Ca2+-free medium in response to a step aspiration pressure consists of an initial rapid, elastic response followed by a creep displacement. These time-dependent responses can be modeled by a viscoelastic solid in which an elastic element (K1) is in parallel with a Maxwell element composed of another elastic element (K2) in series with a viscous element (mu). Variations in temperature (9-40 degrees C) cause an inverse change in mu, but have no effects on K1 and K2. All three coefficients are not affected by decreases in pH down to 5.4; with pH greater than or equal to 7.8, however, K1 and mu increase. Increases in osmolality cause a rise in all three coefficients, especially mu. Colchicine treatment results in selective decreases in mu and K2 without affecting K1. B lymphocytes have viscoelastic coefficients similar to those of neutrophils, but T lymphocytes have higher values for these coefficients. In the presence of 2 mM Ca2+, the neutrophils have higher viscoelastic coefficients than in Ca2+-free medium, and they form protopods which have greater resistance than the main cell body to deformation by micropipette aspiration. Morphometric analysis shows that WBCs have large excess membrane area due to the presence of membrane foldings, which facilitate WBC deformation at constant area. During filtration through 5-micrometers sieves, WBCs are much more prone to pore plugging than erythrocytes because of their higher cellular viscosity and the presence of nucleus. The rheological properties of WBCs have significant implications in their functions and flow dynamics in the microcirculation.

Colchicine↗
PubMed1984

Evaluation of red blood cell filterability test: influences of pore size, hematocrit level, and flow rate.

To improve understanding of the basic principles of the red blood cell filtration test, we studied the influence of pore size, flow rate, and hematocrit level. Suspensions of washed red blood cells in Ringer's solution with hematocrit values of 5%, 10%, and 15% were pumped at flow rates of 0.42 and 0.82 ml/min through polycarbonate filters with pore sizes of 2.6 +/- 0.2, 4.5 +/- 0.6, and 6.9 +/- 0.8 micron (mean +/- SD). The initial pressure generated at the filter was normalized for pressure reading obtained with cell-free Ringer's solution at the same flow rate and used for the calculation of the relative resistance of one red blood cell in a pore. This measurement was independent of the flow rate and the hematocrit level, but it varied inversely with the pore size: 175.1 +/- 62.5, 5.2 +/- 1.2, and 2.4 +/- 0.8 for the 2.6, 4.5, and 6.9 micron pores, respectively. Plugging of filter pores as evidenced by progressive pressure rise at constant flow was a prominent feature for 2.6 micron filters, but was not significant for 6.9 micron filters. At the flow rates studied, less than 1% of the filtered red blood cells showed morphologic changes or underwent hemolysis. We found that 2.6 micron filters are most sensitive in detecting altered red blood cell filterability induced in vitro and occurring in vivo. These results may help to define an optimum filtration test for clinical investigations.

Adult↗
PubMed1984

Filterability of subpopulations of leukocytes: effect of pentoxifylline.

Human leukocytes were separated by density into two fractions, one containing predominantly granulocytes (FI) and the other, lymphocytes and monocytes (FII). The filterability of these fractions and their mixture was determined from the pressure measured during constant flow through 5-microns Nuclepore filters. The pressure-time curve of FI indicates the behavior of a relatively homogeneous cell population. The FII pressure-time curve can be analyzed to distinguish the effect of the more numerous and more filterable lymphocytes from that of the sparser but less filterable monocytes. Pressure generated by mixed leukocytes, which had been treated with 1 and 10 mmol/L of pentoxifylline (PTX) or its metabolite I, was substantially less than untreated control; at 10 mmol/L, the pressure was reduced to about 50% of control. PTX appears to affect the filterability of monocytes and polymorphonuclear leukocytes but not lymphocytes. Scanning electron microscopy showed an inhibition of protopod formation in the treated granulocytes. The degree of cell adhesion to the filter, as measured by the number of cells remaining on the outflow side of the filter, was similar in all groups (FI and FII, treated and untreated). The results indicate that the variations in filterability between the leukocyte subpopulations and the improvement by PTX treatment reflect differences in the cells' ability to deform under the test conditions.

Cell Separation↗
PubMed1983

Role of white blood cells in filtration of blood cell suspensions.

The time-dependent filtration pressure curves of cell suspensions pumped through 5 microns polycarbonate filters at a constant flow rate were analyzed with the aid of a theoretical model developed in an accompanying paper. The cell suspensions contained mixtures of erythrocytes and leukocytes, the concentrations of which were systematically varied. The pressure-time (P-t) curves generally showed multiphasic components. Following the attainment of a quasi-steady state level, the pressure rose first rapidly and then more slowly. The rates of pressure rise in the fast and slow phases were normalized by using the steady state pressure reading (PO) obtained with Ringer solution at the same flow rate, and are designated k1 and k2, respectively. Both k1 and k2 increased with rising concentrations of leukocytes, [WBC], or erythrocytes, [RBC]. [WBC] is 700-1000 times more effective than [RBC] in affecting k1 and k2. k1 is related to the dynamic plugging and unplugging of filter pores, primarily by leukocytes. k2 is attributable to the "permanent" plugging of filter pores, again predominantly by leukocytes. The experimental P-t curves can be fitted with the theoretical model by using appropriate constants for leukocyte plugging. The results indicate that nearly 2/3 of the entering leukocytes cause transient plugging of pores, with an unplugging rate of 4.1 percent/sec/unit pressure rise, and that approximately 2.2 percent of the entering leukocytes are "permanently" lodged. These results underscore the important role of leukocytes in determining the later phase of the P-t curve and support the concept that leukocyte plugging may have pathophysiological significance in causing microvascular occlusion in disease states.

Erythrocytes↗
PubMed1983

Influence of red cell concentration on filtration of blood cell suspensions.

Pressure-time curves obtained by passing suspensions of blood cells in Ringer solution through a 5 microns polycarbonate filter at constant flow (1.6 ml/min) were evaluated for their ability to reflect the deformability of the erythrocytes. The initial pressure reading (Pi) obtained in a quasi-steady state during the first 1-2 sec of pumping was found to be reproducible for hematocrit values between 10 and 30 percent. This Pi value was normalized by the pressure generated by the cell-free suspending medium (PO) at the same flow rate. The ratio Pi/PO was found to be linearly proportional to hematocrit up to 30 percent but independent of leukocyte concentration up to 12,000/mm3. Later portions of the curve did vary with leukocyte count. By using the equations developed from theoretical modeling of cells passing through a filter, the experimentally determined relation of Pi/PO to hematocrit, and the known geometry of the filter pores, we were able to calculate parameters reflecting the deformability of red cells. These include beta, the ratio of resistance in a pore containing a red cell to that in a pore containing only the suspending medium, and alpha, the proportion of pores filled by erythrocytes in transit. The application of theoretical analysis to experimental data has provided quantitative insights into the behavior of red cells during filtration tests in normal and disease states.

Erythrocytes↗
PubMed1983

Theoretical modeling of filtration of blood cell suspensions.

A theoretical model of filtration of suspensions containing red blood cells (RBCs) and white blood cells (WBCs) has been developed. Equations are written for the pressure drop, the filtration flow and the fractions of filter pores containing RBCs (alpha) and WBCs (alpha*). Because the relative resistances (ratios of resistance of cell to resistance of suspending fluid) of RBCs (beta) and WBCs (beta*) through the filter pore are greater than one, the transit of these cells (especially WBCs) through the filter is slower than that of suspending fluid; this leads to values of alpha and alpha* higher than those simply expected from the hematocrit and leukocrit, respectively, in the entering and exiting suspensions. In the absence of pore plugging by the cells (steady flow), the pressure drop can be computed from alpha, alpha*, beta and beta*. In order to model unsteady flow, differential equations are written to include pore plugging and the subsequent unplugging by the rising filtration pressure at a constant flow. By specifying the fractions of entering RBCs (epsilon) and WBCs (epsilon*) which would plug the pores and the rate at which the plugged pores would unplug in response to pressure rise (epsilon u), as well as the fractions of entering RBCs (epsilon p) and WBCs (epsilon p*) that would plug the pores permanently, theoretical pressure-time curves can be generated by numerical integration, and the results fit the experimental data well. From such fitting of theoretical curve to experimental data, information can be deduced for epsilon, epsilon*, epsilon u, epsilon p and epsilon* p.

Erythrocytes↗
PubMed1980

Erythroid colony studies on sickle cell anemia in hypoproliferative crisis.

Bone marrow cells, peripheral blood lymphocytes, and sera from patients with sickle-cell anemia in hypoproliferative crisis were studied in the plasma clot culture system in the presence or absence of erythropoietin (Epo). Bone marrow cells from five patients demonstrated a marked ability to form erythroid colonies in the presence of Epo. These studies also suggested that bone marrow cells from some patients may have an increased sensitivity to Epo. The most outstanding observation in the present study was the marked erythroid colony inhibition by serum taken from one patient during crisis. Serum taken from the same patient two months after hypoproliferative crisis had no suppressive effect on erythroid colony formation. Lymphocytes taken from three patients in crisis had a stimulatory effect on erythroid colony formation when included in culture. The conclusion is that the defect of erythropoiesis in sickle-cell anemia during hypoproliferative crisis is not due to the absence of erythroid precursor cells or to the presence of suppressor lymphocytes, but may in some cases be associated with a circulating inhibitor of erythroid maturation.

Anemia, Sickle Cell↗
PubMed1976

Platelet dysfunction in vincristine treated patients.

Recent revival of interest in the use of vincristine (VCR) for the treatment of idiopathic thrombocytopenic purpura prompted us to evaluate the platelet function of our patients on VCR. Eighteen patients with acute lymphoblastic leukaemia (ALL) in remission, and nine children with solid tumours were studied on 80 occasions at different time intervals after their last VCR dose. A mildly elevated threshold for epinephrine-induced second phase aggregation and a delay in the onset of collagen-induced aggregation was found in patients with ALL not on VCR. Vincristine induced unobtainable second phase aggregation to epinephrine in 67%, 38%, 30% and to ADP in 53%, 13%, 33% of the patients 1 week, 2-3 weeks and 4 weeks respectively after administration. The thrombocytopathy was relative, not absolute, since collagen induced aggregation at all times. Platelet counts, uptake and release of serotonin, bleeding times, clot retractions and release of platelet factor 3 were normal. Platelet adhesion was abnormal in five of 12 patients tested. In vitro platelets are a hundred-fold less sensitive to VCR than in vivo. Cyclic adenosine monophosphate, cyclic guanosine monophosphate and dimethylsulfoxide do not protect platelets from VCR. The exact mechanism by which VCR abolishes second phase aggregation in patients is uncertain. Because of VCR's narrow therapeutic index between thrombocytopenia and thrombocythaemia, the use of VCR should be reserved for life-threatening haematologic disorders when treating non-malignant conditions.

Adenosine Diphosphate↗
PubMedDate not supplied

Viscosity of mixtures of sickle and normal red cells at varying hematocrit levels. Implications for transfusion.

Viscosity (eta) in a blood suspension is affected by the total hematocrit (HT) as well as by the deformability of the cells. The impact of these combined factors on the rheologic behavior of sickle cell suspensions and on guidelines for transfusion has not been explored fully. Therefore, the eta of mixtures of washed normal (AA) and sickle (SS) red cells was determined in a rotational viscosimeter as a function of the hematocrit level of SS cells (HS), HT, oxygen tension (PO2), and shear rate. The ratio HT:eta can be taken as an index of potential oxygen delivery. The optimal HT (for maximum HT:eta) became progressively higher as the HS or the HS:HT ratio was lowered: at a given HT, HT:eta rose with a decrease in HS, especially at low HS values. These data support the concept that simple transfusion alone is not as beneficial to the patient as exchange transfusion and that substantial benefit can be obtained by bringing the patient to very low HS levels. The finding that eta rose with HT more steeply when the HS:HT ratio rather than HS was held constant suggested that the absolute level of HS may be more useful than the HS:HT ratio as a guide for a transfusion regimen.

Anemia, Sickle Cell↗