Neointimal vascularization and intimal thickening in response to self-expanding stents: a swine model.

Abstract

Background: Neovascularization has been suggested as a biological response to vessel injury and associated with restenosis. Self-expanding (SE) stents generate a lasting force on the arterial wall and may lead to an increased arterial response with time.

Objectives: To characterize the process of neovascularization with SE stents, and to correlate it with vascular injury, inflammation and intimal proliferation.

Methods: Sixty-nine SE stents were im-planted in 37 non-atherosclerotic pigs.Detailed, multisection histological examination was performed at 15 days, 1, 3 and 6 months post-deployment. Neo-vascularization in addition to other histologic parameters where determined and scored.

Results: Intravascular-ultrasound-based average vessel diameter was 3.3 +/- 0.04 mm; stent size was 3.75 +/- 0.35 mm leading to an oversizing ratio of 1.14 +/- 0.15. Intimal thickness (IT), inflammatory score (IFS) and vascularization score(VAS) reached peak values at three months (IT = 344 +/- 202 1m, IFS = 0.91 +/- 0.5, and VAS = 1.56 +/- 0.8). In contrast,the injury score (INS) continued to increase at all time-points, with maximum value at six months (INS = 1.6 +/- 0.7). Both vascularization and inflammation indices increased with an increase in the injury score (p < 0.01). When vessels were divided according to vascularization score (VAS <1.5 and >1.5) there was a significant difference in IT.

Conclusion: Neovascularization in response to SE stents is a time-dependent phenomenon and interacts with injury and inflammation. The remodeling of the vessel wall caused by the sustained force of the SE stent on the arterial wall enhances the formation of neovascularization. Neointimal formation is related to the degree of neovascularization.