This is a revised application. Studies performed in phase I SBIR grants #1R43DK55385-01A1 and #1R43DK 59062-01A1 have proven in vitro the concepts advanced in phase I: (a) contrary to common belief, the single jet of the current venous needle (CVN) causes high turbulence inside the vascular access, (b) a new hemodialysis venous needle (NVN) with three jets decreases the velocity and turbulence of the flow past the needle by 66%. In addition, (c) the NVN does not cause more hemolysis than the CVN, and it can be manufactured using existing technology. These data justify performance of the phase II study in animals and patients to prove safety and effectiveness. Mock dialysis will be performed in dogs using the NVN and the CVN. The degree of lysis of red blood cells, white blood cells (WBC), platelets and platelet activation will be demonstrated by measuring free plasma hemoglobin, WBC, platelet count, haptoglobin and platelet activation by flow cytometry. Also, difference in time to stop bleeding from venipuncture sites and the size of thrombus inside the needles will be compared. After three dialyses using the same type of needle inserted in the same lilac vein, the vein will be resected, cut in 12 sections, stained and the degree of endothelial erosion caused by the needle jets will be measured by morphometry. If the NVN is safe in dogs: shown by equal or less lysis of cells, activation of platelets, thrombus formation and endothelial damage compared to the CVN, one hundred dialysis patients with PTFE dialysis grafts will be studied; fifty will use the CVN and fifty will use the NVN. The severity of lysis of cells and thrombus formation caused by the needles will be compared. If the NVN is safe: equal or less lysis of cells and thrombus formation than the CVN, for the following 18 months the graft blood flow rate, recirculation of dialysis blood, venous needle pressure and the incidence of graft thrombosis and graft loss will be compared. The NVN will be considered to be effective if it decreases the incidence of access thrombosis and access loss. The NVN will be more useful in PTFE grafts; short grafts and dialysis with high blood flow rate (>300-600 ml/min) and will decrease morbidity and cost of care. If so, the NVN could be used by 350,000 patients with grafts and by many of the 385,000 patients with arterio-venous fistulas worldwide. This will be the first study to determine whether less turbulence decreases intimal hyperplasia and stenosis in grafts.
