The long-term goal of this research is to extend the base of knowledge regarding the development of mural thrombi on natural and artificial surfaces, as well as their subsequent embolization. Mural thrombosis and embolization is involved in the cessation of blood loss after injury, thrombotic complications of atherosclerosis and coronary heart disease, and thrombotic complications in the use of blood-contacting artificial internal organs.
The specific aims of this project are to i develop an experimental technique to visualize and measure thrombosis on a variety of surfaces in vitro; ii develop a technique to measure and quantify embolus generation; iii utilize existing biochemical techniques to assess the state of platelet activation; iv utilize the above to perform fundamental studies of thrombosis and embolization on natural surfaces; and v utilize the above to investigate the mechanisms involved in thrombosis and embolization on artificial surfaces. Epifluorescence video microscopy will be employed to visualize the thrombotic surface while in contact with blood flowing in a parallel plate flow chamber. The video signal will be analyzed by digital image processing techniques to measure thrombus morphology as a function of time at one local region, and to measure thrombus morphology and platelet accumulation along the length of the flow chamber at one particular time. Emboli will be examined microscopically in post-contact blood to determine, using image processing, the embolus size distribution and number. Biochemical assays will be performed to measure the release of dense- and alpha-granules and lysozomes, and the generation of thromboxane A2 and fibrin. These techniques will be used to investigate mural thrombosis on glass coated with materials to provide experimental models of subendothelium, e.g., collagen of various types, fibronectin, fibrinogen, and von Willebrand Factor, and atherosclerotic lesions, e.g., various glycosaminoglycans, cholesterol, and lipoproteins. Artificial polymers will be investigated to understand the effect of surface free energy and surface chemical groups on thrombosis and embolization. Polymers currently in clinical use will be investigated, as well as model polymer systems with systematically modifiable surface properties. Additionally, glass surface will modified in order to understand the bioadhesive function of various chemical moieties. The rheological control of embolus size will be addressed.
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