Korean Circ J.  2011 Sep;41(9):535-541. 10.4070/kcj.2011.41.9.535.

Effects of Ramiprilat-Coated Stents on Neointimal Hyperplasia, Inflammation, and Arterial Healing in a Porcine Coronary Restenosis Model

• Hong YJ
• Jeong MH
• Song SJ
• Sim DS
• Kim JH
• Lim KS
• Hachinohe
• Ahmed K
• Hwang SH
• Lee MG
• Ko JS
• Park KH
• Yoon HJ
• Yoon NS
• Kim KH
• Park HW
• Kim JH
• Ahn Y
• Cho JG
• Cho DL
• Park JC
• Kang JC

• KMID: 2094106
• DOI: http://doi.org/10.4070/kcj.2011.41.9.535

Abstract

BACKGROUND AND OBJECTIVES
The renin-angiotensin-aldosterone system has been implicated in the pathogenesis of neointimal hyperplasia, and a role for angiotensin II in the migration and proliferation of vascular smooth muscle cells in restenotic lesions has been proposed. The aim of this study was to determine the anti-proliferative and anti-inflammatory effects of ramiprilat-coated stents in a porcine coronary overstretch restenosis model.
SUBJECTS AND METHODS
Pigs were randomized into two groups in which the coronary arteries {16 pigs (16 coronaries in each group)} had a 3.0x17 mm ramiprilat-coated MAC stent or a 3.0x17 mm control MAC stent (AMG, Munich, Germany) implanted with oversizing (stent-to-artery ratio, 1.3 : 1) in porcine coronary arteries, and histopathologic analysis was assessed 28 days after stenting.
RESULTS
There were no significant differences in the injury and inflammation scores between the two groups (1.20+/-0.43 vs. 1.23+/-0.57, p=0.8; and 1.21+/-0.39 vs. 1.25+/-0.49, p=0.6, respectively). Within the neointima, most inflammatory cells were lymphohistiocytes. Significant positive correlations existed between inflammatory cell counts and the neointima areas (r=0.567, p<0.001), and between inflammatory cell counts and the percent area stenosis (r=0.478, p<0.001). There was no significant difference in the inflammatory cell counts normalized to the injury (110+/-89 vs. 123+/-83, p=0.4) and fibrin scores (0.15+/-0.06 vs. 0.17+/-0.07, p=0.8) between the 2 groups. There were trends toward a smaller neointima area (1.06+/-0.51 mm2 vs. 1.28+/-0.35 mm2, p=0.083) and a smaller percent area stenosis (18.9+/-8.7% vs. 21.8+/-7.2%, p=0.088) in the ramiprilat-coated stent group.
CONCLUSION
Although the ramiprilat-coated stent did not show significant inhibitory effects on neointimal hyperplasia, the ramiprilat-coated stent showed good effects on the inflammatory reaction and arterial healing similar to the control stent in a porcine coronary restenosis model.

Keyword

Angiotensin-converting enzyme inhibitors; Stents; Inflammation; Coronary restenosis

MeSH Terms

Angiotensin II
Angiotensin-Converting Enzyme Inhibitors
Cell Count
Constriction, Pathologic
Coronary Restenosis
Coronary Vessels
Fibrin
Hyperplasia
Inflammation
Muscle, Smooth, Vascular
Neointima
Renin-Angiotensin System
Stents
Swine
Angiotensin II
Angiotensin-Converting Enzyme Inhibitors
Fibrin

Figure

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  Fig. 1 In vitro screening of ramiprilat release from stent surfaces. The amount of ramiprilat released to buffer solution was measured using an absorbance test for ultraviolet at 278 nm.

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  Fig. 2 Scanning electron microscopic findings after ramiprilat coating on the surface of the stent (magnification left top: ×30, right top: ×150, left bottom: ×250, right bottom: ×500).

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  Fig. 3 The hematoxylin-eosin stain (magnitude ×20) in ramiprilat-coated (A) and control bare-metal stent (B) groups. Note that neointimal overage of stent struts tended to be smaller in the ramiprilat-coated stent group compared with the control bare-metal stent group.

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  Fig. 4 The Carstair's fibrin stain (left: magnitude ×20, right: magnitude ×200) in ramiprilat-coated (A) and control bare-metal stent (B) groups. Fibrin deposition (reddish-orange stain) is noted around the stent struts.

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  Fig. 5 Correlations between the inflammatory counts and neointimal area (A) and between the inflammatory counts and percent area stenosis (B). Significant positive correlations existed between the inflammatory counts and the neointima area, and between the inflammatory counts and the percent area stenosis.

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  Fig. 6 The neointimal inflammatory cell counts normalized to injury by ramiprilat-coated and control bare-metal stents. Inflammatory cell counts normalized to injury scorse are not significantly different between the ramiprilat-coated and control bare-metal stent groups.

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  Fig. 7 The fibrin score for ramiprilat-coated and control bare-metal stents. The fibrin score was not significantly different between the ramiprilat-coated and control bare-metal stent groups.

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