The objectives are to help to ascertain the locations, mechanisms and kinetics of vasocclusion of the microcirculation by sickle disease erythrocytes, so as to permit a better understanding of the events leading to crises in patients with sickle cell disease, and to put selection of potential therapeutic measures on a more rational basis. Bloods and other suspensions of erythrocytes and mixtures of normal cells and hardened, deformed erythrocytes will be pumped through real-scale model microvasculatures, with or without simultaneous oxygen transfer from or to the blood. Microscopic observation of the flow and measurement of important parameters (such as local oxygen saturation levels in the flowing blood) will permit characterization of conditions when vasocclusion occurs. By varying compositional and characteristic properties of the erythrocytes and cell suspensions, as well as flow conditions and oxygen saturation levels, the roles of erythrocyte deformability characteristics, cell-vessel wall adherence and hemoglobin gelation kinetics in microvascular vasocclusion will be ascertained. Mathematical models of the oxygen transport processes in the experimental flow system will be used to define boundary conditions for pertinent experiments and to analyze the experimental results. The mathematical modelling will include studies of the oxygen transport, oxygen-hemoglobin reaction, and deoxyhemoglobin gelation processes within stationary and flowing erythrocytes; models will be tested with experimental data.
| Makhijani, V B; Cokelet, G R (1994) In vivo polymerization of sickle-cell hemoglobin: a theoretical study. Blood Cells 20:169-83;discussion 184-90 |
| Makhijani, V B; Cokelet, G R; Clark Jr, A (1990) Dynamics of oxygen unloading from sickle erythrocytes. Biophys J 58:1025-52 |
