This research seeks to extend current knowledge of the deformability of the human erythrocyte, in both health and disease, and the physiological impact of deformability loss in these cells.
Specific aims of this application are: 1. To elucidate the nature of the physical/chemical changes in erythrocytes which cause their sequestration in the spleen and other organs in vivo. 2. To study the deformability of erythrocytes parasitized by different strains of malaria (plasmodium berghei and cynomolgi) at different stages of maturation. 3. To assess in vitro the deformability of erythrocytes in post-splenectomy subjects and in individuals with hereditary spherocytosis and various hemolytic anemias. 4. To determine whether the age of circulating erythrocytes in normal subjects is reflected in their sequestration in vivo. 5. To determine whether erythrocytes from diabetics with proliferative retinopathy and/or in poor metabolic control differ from those of normal subjects in their rheological behavior in vitro and in vivo. Longer term objectives are: 6. To investigate the influence of specific environmental factors on erythrocyte deformability, e.g., platelet-activation products, vasoactive hormones, hyperphysiologic shear stress and pharmacologic agents. 7. To develop and refine mathematical models of the motion and deformation of individual erythrocytes freely suspended in simple shear and pure extensional flows. The methodology is primarily experimental, consisting of (i) microrheologic measurements of erythrocyte deformation in simple shear and pure extensional flows, (ii) physical/chemical characterizations of erythrocytes and erythrocyte membranes, (iii) in vivo perfusions designed to quantify sequestration of erythorocytes in different organs. Mathematical modeling will be pursued with the aim of deducing intrinsic rheological properties of erythrocyte membrane from measurements of cellular elongation, membrane rotation (tank-treading) and transient shape recovery.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL012839-16
Application #
3334527
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1978-12-01
Project End
1987-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
16
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Washington University
Department
Type
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Desai, S A; McCleskey, E W; Schlesinger, P H et al. (1996) A novel pathway for Ca++ entry into Plasmodium falciparum-infected blood cells. Am J Trop Med Hyg 54:464-70
Williamson, J R; Arrigoni-Martelli, E (1992) The roles of glucose-induced metabolic hypoxia and imbalances in carnitine metabolism in mediating diabetes-induced vascular dysfunction. Int J Clin Pharmacol Res 12:247-52
Sutera, S P; Chang, K; Marvel, J et al. (1992) Concurrent increases in regional hematocrit and blood flow in diabetic rats: prevention by sorbinil. Am J Physiol 263:H945-50
Desai, S A; Schlesinger, P H; Krogstad, D J (1991) Physiologic rate of carrier-mediated Ca2+ entry matches active extrusion in human erythrocytes. J Gen Physiol 98:349-64
Krogstad, D J; Sutera, S P; Boylan, C W et al. (1991) Intraerythrocytic parasites and red cell deformability: Plasmodium berghei and Babesia microti. Blood Cells 17:209-21;discussion 222-7
Sutera, S P; Krogstad, D J (1991) Reduction of the surface-volume ratio: a physical mechanism contributing to the loss of red cell deformability in malaria. Biorheology 28:221-9
Marvel, J S; Sutera, S P; Krogstad, D J et al. (1991) Accurate determination of mean cell volume by isotope dilution in erythrocyte populations with variable deformability. Blood Cells 17:497-512;discussion 513-5
Krogstad, D J; Sutera, S P; Marvel, J S et al. (1991) Calcium and the malaria parasite: parasite maturation and the loss of red cell deformability. Blood Cells 17:229-41;discussion 242-8
Sutera, S P; Mueller, E R; Zahalak, G I (1990) Extensional recovery of an intact erythrocyte from a tank-treading motion. J Biomech Eng 112:250-6
Sutera, S P; Pierre, P R; Zahalak, G I (1989) Deduction of intrinsic mechanical properties of the erythrocyte membrane from observations of tank-treading in the rheoscope. Biorheology 26:177-97

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