Balloon Injury With Low Shear Stress Augments Neointimal Thickening in Carotid Arteries

Amito Chandiwal, MD, James Vosicky, Ralph Weichselbaum, MD, Lewis Schwartz, MD and Christopher Skelly, MD
Vascular Surgery, University of Chicago, Chicago, IL

Objectives: Arteries remodel in response to low shear stress (τ) or balloon injury through the process of neointimal thickening (NIT). The purpose of this study was to determine whether extremely low τ, balloon injury or a combination of the two would result in the development of NIT approximating that seen in clinical arterial restenosis.

Methods: Using standard aseptic techniques, the common carotid artery (CCA) of 24 NZ White Rabbits was exposed. For the “low τ” group (n=7), the CCA was ligated distal to cranial thyroid branch. For the “balloon injury” group (n=7), injury was created using 3 passes of a 3F balloon catheter inflated with 0.1ml fluid (balloon:artery ratio of 1.1:1) and the arteriotomy was repaired. For the “low τ with balloon injury” group (n=7) the artery was balloon injured as described and restricted by ligating over a 0.014 guide wire distal to the cranial thyroid branch.
For the sham (n=3), the left CCA was exposed as for the other groups and subcutaneous tissue and skin sutured again.Flow and pressure were measured at the initial surgery and harvest. At 3 days (n=8) and 14 days (n=4), CCA was removed and processed for protein analysis. Proliferating cell nuclear antigen (PCNA) expression was determined using both immunohistochemistry and Western Blot analysis. After 4 weeks, the remaining arteries were perfusion-fixed and NIT measured and compared using One Way ANOVA and significance assigned at p<0.05.

Results: All arteries were patent at sacrifice. Western blot analysis of the carotid arteries from the combined “low τ” and balloon injury group revealed greater expression of the PCNA at day 3 as compared to either the “low τ” or the balloon injury model. At day 14, the PCNA expression was only seen in the combined “low τ” and balloon injury model (Figure 1)

Although NIT observed in the “low τ” (63+ 27 μm, τ = 0.40 + 0.17 dyne/cm²) and “balloon injury” groups was not significantly different (51 + 17 μm, τ = 4.32 + 1.92 dyne/cm²), a considerably greater NIT was observed with the combination of “low τ and balloon injury” (176 + 17 μm, τ = 1.83 + 0.48 dyne/cm²) p=0.001. (Fig.2)

Conclusions: Although extremely low τ and balloon injury alone result in NIT, the magnitude of thickening is negligible. However, the combination of the two, synergistically increase NIT approximating that seen in clinical restenosis. There is also a corresponding increase in PCNA expression at both 3 and 14 days. This model can serve as an excellent platform to assess the response of therapeutic strategies to pure arterial restenosis.