The objective of this project is to study the contribution of hemorrheology to arterial and venous thrombosis using the arterio-venous (A-V) fistula hemodialysis access loop graft as a model. Intraoperative measurement of geometry and flowrates will be made after completion of the brachial artery to cephalic vein A-V loop graft in patients with chronic renal failure. Follow-up measurements will be made when patient returns to the hospital for routine hemodialysis treatment (approximately 3 times a week). These measurements will include: 1) velocity profiles in the host artery using a transcutaneous range-gated ultrasonic Doppler velocimeter probe, 2) phonoangiographic recording of the "thrill" at the venous anastomosis using a precalibrated microphone. The signal recorded will be analyzed for the power spectral density function (PSDF) using a high-speed computer. 3) Thrombogenicity in the graft and host vein will be measured using 111 Indium labeled autologous platelets in patients with significantly altered PSDF from that of the control. 4) Platelet half-life will also be measured in these patients, using the same 111 Indium labeled autologous platelets. Based on the result of our preliminary animal study, we determined that an animal model using the common femoral artery to common femoral vein loop graft in dogs closely resembles the anatomy of the hemodialysis access loop graft in patients. Seventy-two femoral-to-femoral loop gragts will be constructed in 36 healthy, preconditioned male dogs. Six groups of six dogs each will be reoperated at intervals of 24 hrs, 5, 10, 25, 40, and 60 wks postoperatively to obtain 1) phonoangiographic recordings for PSDF, 2) velocity profiles at several sections in the host artery near the anastomosis, 3) physical properties of the host vessels and the graft, 4) detailed lumen geometry by RTV silicone rubber injection, 5) histopathologic examination of the graft and the host vessels include both anastomoses. Based on the animal data, a series of six to ten in vitro flow models will be fabricated using clear Silastic to represent the venous anastomosis at the various stages of occlusion development. The model will be installed in the pulsatile flow loop using a blood analog non-Newtonian fluid. Detailed study of flow patterns, structure of turbulence will be made using laser Doppler anemometer. The distributions of wall shear stress and Reynolds stress in the flow field will be correlated to the platelet deposition-thrombus formation and histopathological data obtained from patients and animal model.
NIH ExPorter
NIH ExPorter