The long range objective of the proposed research is to advance the science of hemorheology in the realm of the microcirculation.
The specific aims fall into five major areas: (i) to study the effect of particular chemical/physical perturbations on red cell deformability; (ii) to define the mechanisms underlying the loss of red cell deformability observed with intraerythrocytic parasites; (iii) to test the hypotheses that impaired red cell deformability in vivo (a) can induce increased capillary permeability and (b) leads to red cell sequestration in the spleen and other organs; (iv) to define the sensitivity of the rheoscopic methodology to clinically significant degrees of deformability impairment and to develop unambiguous links between indices of deformability observable in the rheoscope and the intrinsic material properties which govern red cell deformability; to study mechanisms of shear-induced platelet alterations, particularly under conditions of pulsatile flow. In the longer term the applicability of the rheoscope to the study of white cell rheology will be tested. The methodology of the planned interdisciplinary effort is predominantly experimental: In vitro studies of red cell deformability will rely on the rheoscope technique and filtrometry. These will be complemented by physical and chemical assays of membrane ultrastructure and by mathematical modeling of red cell tank-treading under shear. Platelets will be subjected to pulsatile shear in a cone-plate viscometer and their response determined by chemical assays post shear; their interactions with a collagen-coated glass surface under shear will be studied in the rheoscope. This research is expected to improve understanding of the impact of impaired red cell deformability on vascular pathophysiology. The proposed studies of shear-induced platelet alterations are pertinent to thrombotic and thromboembolic events in the natural circulation and in the presence of blood-processing artificial organs and vascular prostheses.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Surgery and Bioengineering Study Section (SB)
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Washington University
Biomed Engr/Col Engr/Engr Sta
Saint Louis
United States
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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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