Although venous thrombosis is a well described disease entity, the exact pathophysiologic mechanisms of this process have not been elucidated. Progress to date has yielded an ex vivo swine model of venous thrombosis that does not require the use of anticoagulated blood and provides a means for controlling hemodynamic factors such as perfusion pressure and blood flow as they relate to clot formation. The ability to study intravascular clot formation under precisely controlled conditions makes this model an appropriate experimental tool for the study of the mechanisms involved in venous thrombosis.
The aims of this proposal are to clarify the mechanisms involved in the production of venous thrombi. Specifically, the goals of the study are: 1) to histologically characterize venous thrombosis as it occurs over time in a de-endothelialized venous segment; 2) to investigate the influence of blood flow rate and perfusion pressure on the development of intravascular thrombus formation; 3) to investigate differences in the character of thrombus formation within various vascular tissues; 4) to determine the relative role of platelets and the coagulation factors in the development of venous thrombosis and 5) to ascertain differences in clot formation in the postoperative and unoperated states, and to investigate the relative role of the blood components and the vessel wall in postoperative venous thrombosis. These experiments will yield information on the importance of various factors involved in venous thrombosis. In addition, the proposed experiments will explore the use of antiplatelet and anticoagulant agents in the modification of the thrombotic prccess. In this way an objective scientific basis may be developed for planning subsequent clinical trials aimed at the prohylaxis of deep venous thrombosis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HL040889-04
Application #
3472172
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1989-04-01
Project End
1994-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Ouriel, K; Welch, E L; Shortell, C K et al. (1995) Comparison of streptokinase, urokinase, and recombinant tissue plasminogen activator in an in vitro model of venous thrombolysis. J Vasc Surg 22:593-7
Cho, J S; Ouriel, K; DeWeese, J A et al. (1995) Thrombus formation on polytetrafluoroethylene surfaces: the importance of von Willebrand factor. Cardiovasc Surg 3:645-51
Ouriel, K; Shortell, C K; Green, R M et al. (1995) Differential mechanisms of failure of autogenous and non-autogenous bypass conduits: an assessment following successful graft thrombolysis. Cardiovasc Surg 3:469-73
Cho, J S; Ouriel, K (1995) Differential thrombogenicity of artery and vein: the role of von Willebrand factor. Ann Vasc Surg 9:60-70
Ouriel, K; Shortell, C K; DeWeese, J A et al. (1994) A comparison of thrombolytic therapy with operative revascularization in the initial treatment of acute peripheral arterial ischemia. J Vasc Surg 19:1021-30
Stroughton, J; Ouriel, K; Shortell, C K et al. (1994) Plasminogen acceleration of urokinase thrombolysis. J Vasc Surg 19:298-303;discussion 303-5
Ouriel, K; Shortell, C K; Azodo, M V et al. (1994) Acute peripheral arterial occlusion: predictors of success in catheter-directed thrombolytic therapy. Radiology 193:561-6
Donayre, C E; Ouriel, K; Rhee, R Y et al. (1992) Future alternatives to heparin: low-molecular-weight heparin and hirudin. J Vasc Surg 15:675-82
Rhee, R Y; Donayre, C E; Ouriel, K et al. (1991) Low dose heparin therapy: in vitro verification of antithrombotic effect. J Vasc Surg 14:628-34
Ouriel, K; Donayre, C; Shortell, C K et al. (1991) The hemodynamics of thrombus formation in arteries. J Vasc Surg 14:757-62;discussion 762-3