An Experiment-Based Model of Vein Graft Remodeling Induced by Shear Stress

Abstract

Vein graft intimal hyperplasia induced by shear stress is considered to be one of the major causes of vein graft failure. We have developed a mathematical model of vein graft intimal hyperplasia induced by shear stress based on experimental data. Intimal thickness and the rate of intimal thickness change are expressed as functions of shear stress and time. The model coefficients are derived from animal experiments where bilateral rabbit carotid vein grafts are exposed to different shear stress levels. Morphology data of the vein grafts are obtained over multiple time points. The model describes the well-known behavior of intimal thickening, which is inversely related to shear stress. It also depicts the time-dependent behavior of vein graft intimal hyperplasia. Finally, the model is used to simulate the intimal growth around a focal stenosis, which was created by ligating the middle of a vein graft using a suture. Simulation results and experimental data agree qualitatively, and demonstrate that the intima thickens more distal to the stenosed area. These experiments establish the potential of the general experiment-based approach for predicting human vein graft remodeling. Other mechanical and biological factors can be included following a similar approach in order to obtain a more accurate vein graft remodeling model.

Computational Simulation of the Adaptive Capacity of Vein Grafts in Response to Increased Pressure

“…The few available studies concentrate on short term responses [16,17,40,45]. Nonetheless, parallels can be drawn between the current results and observed trends in arterial G&R in hypertension (which is a modest pressure perturbation relative to that considered here).…”

“…Some previous attempts at modeling vein graft adaptations have prescribed changes in geometry as functions of time and stress [17,43]. In contrast, the current model makes changes in geometry, structure, and composition of the vessel a consequence of the cell mediated G&R that tries to restore homeostatic stresses; that is, the results of the present model are "emergent."…”

“…This approach is motivated by prior studies that show medial thickening to associate best with increased intramural circumferential stress or strain [16]. There is also evidence that circumferential stress plays a primary role and wall shear stress plays a secondary role in determining overall vein graft dimensions [10], though shear stress likely controls neointimal formation [17]. Toward this end, we first identify constitutive parameters for a normal mouse vena cava based on published experimental data from pressure-diameter and axial force-length tests [18].…”

Constitutive modeling of human saphenous veins at overloading pressures

“…As an undesirable effect of the changed conditions, the patency of the graft may be substantially compromised by an intimal hyperplasia or thrombosis (Fitzgibbon et al, 1996;Hwang et al, 2012). Much work is now being done to deepen our knowledge of the mechanobiology of graft remodeling, but this process is still not completely understood (Tran-Son-Tay et al, 2008;Hwang et al, 2012;2013;Sassani et al, 2013). The adaptation to the changed conditions leads not only to a change in the diameter and thickness of the graft wall, but also to a changed internal structure and thus a change in the constitutive equation (Hwang et al, 2012).…”

Correlates of Saphenous Vein Graft Hyperplasia and Occlusion 1 Year After Coronary Artery Bypass Grafting

“…Tran-Son-Tay et al 18 previously showed that SVG walls are particularly susceptible to remodeling early after CABG and that hyperplasia growth becomes slower over time. Based on the above and the findings of the current study, the use of β-blockers early after CABG may be particularly important in keeping with current clinical guidelines, supporting their use to prevent adverse events in the postoperative period.…”