The aim of this research is to apply high quality rheological techniques and transport phenomena models to the study of specific problems in coagulation and thrombosis. Four major areas of investigation are proposed. The first is the utilization of dynamic materials testing to follow the change in elasticity, viscosity and contractile force as a clot is formed. Models from polymer science are employed to obtain information on the kinetics of clot structure formation and an estimate of final """"""""crosslink"""""""" density from these material property measurements. Human PRP and PFP as well as samples prepared from purified proteins will be studied. The biochemical control of platelet-fibrin interaction will be studied using drugs and monoclonal antibodies to specific platelet membrane glycoproteins. The second area involves the use of dynamic materials testing to investigate the biochemical control mechanisms of internal platelet actin filament and microtubule assembly - using a platelet extract system and a reconstituted platelet cytoplasm, starting with purified platelet actin and tubulin. The third area is the study of the possible influence of controlled pulsatile flow on stimulation of production of metabolites of arachidonic acid from endothelial cells and platelets (mainly PGI2 and thromboxane A2 respectively). This is an area of potentially great physiological importance, as there is very recent evidence from our group and others, that a change in wall shear stress can greatly stimulate cultured endothelial cell PGI2 production - while the absolute level of shear stress is of less importance. We have shown that pulsatile shear produces a time average rate of production of PGI2 per cell that if four times that at the same steady flow (time average) and over ten times that of quiescent tissue culture controls. The final area of investigation is the use of convective mass transfer equations to numerically simulate the coagulation reactions occurring in model vessels. Recently quantitative measurements of rates of reaction for some of the individual steps in the cascade have been made. Since flow is laminar in most of the circulation and most of the proteins involved in these reactions are fairly large (and therefore have low molecular diffusivities), many of the coagulation reactions may be mass transfer limited in vivo. The interaction between fluid convection and molecular diffusion may be very important in controlling or amplyfying the effects of some of the biologically active compounds formed.
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