Five-hundred thousand coronary artery bypass surgeries are performed every year, and the human saphenous vein (HSV) is the most often used conduit in this procedure. Unfortunately, a significant number of coronary artery vein grafts (CAVG) fail within the first post-operative month due to thrombotic occlusion. There is significant evidence which implicates in this prothrombotic response the new biomechanical environment to which the vein is abruptly exposed when transposed to the coronary arterial circulation. This includes an increase in flow (and shear stress), an increase in intraluminal pressure (and radial and circumferential wall stresses), and dynamic wall motion. The latter consists of cyclic radial wall excursion due to the pulsatile arterial pressure, and cyclic longitudinal stretching, bending and twisting due to the attachment of CAVG to the beating heart. We believe that the adverse prothrombotic response by HSV to the coronary arterial circulation may be reduced or eliminated by preconditioning them to this new environment. The particular hypothesis that we will address in this proposal is that, compared to an acute, abrupt exposure of HSV to the coronary arterial biomechanical environment, a gradual, incremental imposition results in a reduced thrombotic response. The applicant has performed clinical measurements and developed a unique biomechanical model to simulate realistic CAVG biomechanics. When interfaced with a physiologic perfusion system that enables metabolic support of freshly excised HSV specimens, novel investigations such as those proposed here are possible. Therefore, to address our hypothesis, we will utilize our unique experimental capabilities and freshly excised HSV specimens. Specifically, our aims are:
AIM 1 : Quantitatively measure the thrombotic response of freshly excised HSV +_____ segments abruptly exposed to simulated CAVG biomechanical conditions.
AIM 2 : Determine the mitigating effects of a biomechanical preconditioning +_____ regimen on the thrombotic response of freshly excised HSV segments to simulated CAVG biomechanical conditions. As markers of acute thrombogenesis, we will measure platelet deposition and tissue factor generation by HSV. Preliminary data is presented which indicate that these are appropriate end-points in the proposed study.
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