Device-associated thromboembolism is a major problem in blood-contacting prosthetic devices (e.g. oxygenators, total artificial hearts, ventricular assist devices, kidneys, lungs, etc.) and cause severe complications. ATtempts to control thromboembolism with drugs are not always successful, primarily because the process of thromboembolization is initiated and sustained by a number of factors, many of which are not well understood. The design of the device and resulting flow patterns, the nature and composition of the materials used, and the coagulation state of the recipient of the device, all contribute in the process of thrombogenesis. This proposal is a study of thrombogenesis in blood pumps (ventricular assist devices, extracorporeal circulations) with the help of an unique team of investigators and novel techniques. Researchers with biomedical and engineering background will investigate the sequence of events that lead to thromboembolization. An ex-vivo calf model with externalized transparent left ventricular assist device with a light scattering detector installed in the outflow conduit and a transposed kidney will be used. A light scattering detector will detect not only the microemboli passing through the detector cell, it will also measure their size and frequency. A filtration model will determine the potential of these microemboli to occlude smaller blood vessels, the transposed kidney will indicate the percentage of the microemboli lodged in the kidney. These three methods will complement each other in providing useful information concerning the onset of the thromboembolic phenomena and its progress over the time. The contribution of flow and its impact on thromboembolism will be analyzed. Similarly, the proposed quantitation methods may prove ideal in establishing the effectiveness of drug regimen in controlling the thromboembolism. The effect of 2 drugs, heparin and aspirin, will be carefully examined. During the course of this study, a number of hematologic parameters will be monitored to help identify early markers of thrombogenesis in circulating blood. These efforts should help us better understand the process of thrombogenesis, provide clues as to where thrombogenesis is initiated, the role of rheological factors, and the biomaterials, and may help pave the way for elimination of adverse effects by design modifications, improved material surfaces, or appropriate combination of therapeutic agents.
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