UC San Diego

Vein graft maladaptation, leading to poor long-term patency, is a serious clinical problem in patients receiving coronary artery bypass grafts (CABGs). Mechanics is known to play a key role as a stimulus contributing towards vein graft failure. Mechanical stimuli are key to understanding disease progression and clinically observed differences in failure rates between arterial and venous grafts following coronary artery bypass graft surgery. But little has been done to quantify the mechanics in these grafts and its effects on long-term outcomes on grafts. Hence, one of the goals of this thesis was to quantify mechanical stimuli acting on the grafts and the other goal was to develop continuum mechanics based models of growth and remodeling (G&R) to simulate long-term adaptation.

We quantify biologically relevant mechanical stimuli, not available from standard imaging, in patient-specific simulations incorporating non-invasive clinical data. We couple computational fluid dynamics with closed-loop circulatory physiology models to quantify biologically relevant indices, including wall shear, oscillatory shear, and wall strain. We account for vessel-specific material properties in simulating vessel wall deformation. Wall shear was significantly lower and atheroprone area significantly

higher in venous compared to arterial grafts. Wall strain in venous grafts was significantly lower than in arterial grafts while no significant difference was observed in oscillatory shear index. Simulations demonstrate significant differences in mechanical stimuli acting on venous vs. arterial grafts, in line with clinically observed graft failure rates, offering a promising avenue for stratifying patients at risk for graft failure.

We also propose a computational model of venous adaptation to altered hemodynamics based on a constrained mixture theory of G&R. We identify constitutive parameters that optimally match biaxial data from a mouse vena cava, then numerically subject the vein to altered hemodynamic conditions and quantify the extent of adaptation. We identify constitutive relations and parameters that enable adap-

tations for a moderate perturbation in hemodynamics. We then fix these relations and parameters, and subject the vein to a range of combined loads (pressure and flow), from moderate to severe, and identify plausible mechanisms of adaptation versus maladaptation. We also explore the beneficial effects of a gradual increase in load on adaptation.