The objective of the investigators is to understand better the role of the biomaterial in thromboembolic complications of vascular prostheses, catheters, and stents. Platelet activation is hypothesized to be due to direct material contact or indirect effects of complement, platelet release or activation of the coagulation cascade. A unique canine AV shunt will be used to assess the effect of material surface chemistry on ex vivo platelet consumption. Flow cytometry (FAFC) will be used to study the activation of platelets and leukocytes in vitro and in the chronic shunt. In vitro and ex vivo shunt studies will be employed to show 1) which surfaces are platelet and leukocyte reactive, 2) what alterations they induce in platelets and leukocytes, and 3) what the extent of platelet destruction/removal is via microparticle formation and activated platelet associations with leukocytes. They are especially interested in the reactive roles of thrombin and activated complement in these processes and how pharmacologic agents (thrombin or complement inhibitors) may define these contributions. Hydrogel coated surfaces and hydrophobic surfaces appear to act differently in this context, with hydrogels resulting in low platelet adhesion but high consumption, including microparticle generation. Understanding the mechanism(s) behind this phenomenon is important to the design of biomaterials with truly low thrombogenicity.
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