Impact of Shear Stress on Early Vein Graft Remodeling: A Biomechanical Analysis |
| Arterial occlusive disease, causing myocardial infarctions and strokes, affects millions of people and is one of the leading causes of death in the United States. In many cases, invasive surgical techniques, such as bypass vein grafting and angioplasties, have been used to alleviate vascular occlusions. Bypass vein grafting uses a vein taken from another part of the body to replace the obstructed blood vessel and inserts it into the arterial system to provide better blood flow. However, restenosis or occlusion can still occur in the time frame of months to years. Because of these reasons, many researchers have been attempting to improve these long-term patency results. An understanding of early vein graft adaptation and progression must be established in order to improve the long-term results. Currently, it is known that many factors, including physical forces, morphologic changes, and biochemical events, are involved in this adaptation process. Playing a key role in the remodeling process are the biomechanical forces. The changes in these biomechanical forces regulate the balance between intimal thickening and expansive remodeling, which govern the morphologic changes in the vein graft. The objective of this study is to characterize early vein graft remodeling by finding the correlation between the physical forces and morphologic changes by characterizing the dynamic shear and wall tensile forces with the intimal thickening and expansive remodeling that occurs in vein graft arterialization. |
| Previously ex vivo models were used to determine the hemodynamic forces in the steady state only. Our mathematical model uses an in vivo bilateral carotid vein graft with distal branch ligation model to collect the experimental flow rate data in a pulsatile hemodynamic environment. The experimental animal model created two flow environments with reduced flow/shear through the ligated vein graft and elevated flow/ shear in the contralateral vein graft (Figure 1). |
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Figure 1. The effects of low and high wall tension on a vein graft. |
| Using New Zealand white male rabbits, vein grafts were implanted and then harvested at 1, 3, 7, 14, and 28 days after initial surgical procedure. Hemodynamic and video measurements were collected before and after ligation for calculation of the shear and wall tensile forces. A computational program was developed to determine the velocity and shear stress profiles based on the collected hemodynamic data. Due to the size and length of the rabbit vein graft model (Figure 2), the pressure gradient is difficult to ascertain; therefore the flow measurement is used for the basis of our calculations. This approach is slightly different from previous models that relied upon the derived pressure gradient. |
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Figure 2. (A) Measurement of in vivo flow rate and pressure in rabbit vein graft. |
| Vein grafts were exposed to distinct flow environments characterized with a 6-fold difference in mean flow rate. Accelerated intimal hyperplasia and reduced outward remodeling were observed in the low flow grafts. At day 7, there was a peak in maximum and minimum shear stress with a delayed increase in lumen diameter leading to normalization of wall shear by day 28. At day 3, the intramural wall tension was at its maximum and there was an increase in wall thickness leading to a significant reduction of these stresses by day 14. There was no difference in incremental modulus of elasticity despite the significant difference in remodeling between the high and low flow grafts. |
| Our mathematical model provides a simple way to determine dynamic wall shear and tension in a pulsatile hemodynamic environment, using readily available technology. Our mathematical model reveals a correlation among shear stress, flow, and intimal thickening, which coincides with ex vivo studies modeling steady flow. Current research is working towards a more realistic development of computational modeling of pulsatile blood flow in this model as well as other more complicated configurations such as bifurcated blood vessels, which in the past have dealt with steady flow in ex vivo models. |
| 3-D movies of the velocity and wall shear stress in a vein graft under a pulsatile high flow environment: |
| The following movies illustrate the velocity and wall shear stress profiles in a rabbit vein graft under high flow conditions over one cardiac cycle. The wall shear stress movie shows the wall shear stress profile vs. the diameter of the vein graft over one cardiac cycle. The velocity profile shows the velocity vs. the diameter of the vein graft over one cardiac cycle. |
| 3-D movie of shear stress profile under high flow conditions |
| 3-D movie of velocity profile under high flow conditions |
| For more information on the experimental rabbit vein graft
model:
Jiang Z., Wu L, Miller BL, Goldman DR, Fernandez CM, Abouhamze ZS, Ozaki CK, Berceli SA. A novel vein graft model: adaptation to differential flow environments. Am J Physiol. Circ. Physiol. 286: H240-H245.
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