Platelet-mediated thrombogenesis and platelet release products are thought to be major factors in the pathogenesis of acute thrombosis, myointimal hyperplasia, and distal vasospastic abnormalities during healing of a carotid endarterectomy. If this hypothesis is valid, selective blockage of the platelet cyclo- oxygenase, whose major product, thromboxane A2 modulates platelet function, should interrupt this sequence by decreasing platelet aggregation and release phenomena. If local prostacyclin production by the arterial wall maintained its """"""""normal"""""""" physiological balance with thromboxane A2, an additional endogenous protection against the pathological platelet-vessel wall inter- action might be postulated. These mechanisms for altering thrombotic and proliferative sequellae using a selective aspirin dose have not been probed. Using a sub-human primate model, a low dose of aspirin which selectively blocks platelet production of thromboxane A2 while preserving arterial production of prostacyclin will be administered to test the above hypothesis. This theoretically more ideal dose of aspirin will be compared to animals receiving no aspirin therapy and those receiving a non-selective, high dose of aspirin which blocks cyclo-oxygenase activity in both platelet and the arterial wall. In addition, the effect of chronic fish oil supplements will be tested. The patency and the response of the endarterectomized arterial wall to both fish oil and selective versus non-selective aspirin therapy will be correlated 1) biochemical characterization of platelet and arterial production of eicosanoids, 2) smooth muscle cell activation in media following endarterectomy, 3) degree and timing of platelet interaction with the flow surface, and 4) direct morphology and morphometric studies of the neointima and media. We will probe one hypothesized mechanism for proliferative and thrombotic sequelae to this specific model of arterial injury. We hope to define an optimal balance of antiplatelet therapy, eicosanoid balance of the arterial wall, and diet which would re- duce the incidence of thrombosis and proliferative arterial wall lesions associated with carotid endarterectomy. In addition, we will establish a unique data base on the biochemical and morphological facets of this sub-human primate model in order that standardized testing of dietary manipulations and/or adjunctive drug therapies can be rapidly completed prior to clinical trials in patients undergoing carotid endarterectomy.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL040795-01
Application #
3358025
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1988-04-01
Project End
1991-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Type
Schools of Medicine
DUNS #
201373169
City
New York
State
NY
Country
United States
Zip Code
10065