Korean Circ J.  2013 Nov;43(11):744-751. 10.4070/kcj.2013.43.11.744.

Histopathological Comparison among Biolimus, Zotarolimus and Everolimus-Eluting Stents in Porcine Coronary Restenosis Model

Affiliations
  • 1Korea Cardiovascular Stent Institute, Jangseong, Korea. myungho@chollian.net
  • 2Heart Research Center Nominated by Korea Ministry of Health and Welfare, Gwangju, Korea.
  • 3Cardiovascular Research Center, Chonnam National University Hospital, Gwangju, Korea.
  • 4Regeneromics Research Center, Chonnam National University, Gwangju, Korea.

Abstract

BACKGROUND AND OBJECTIVES
The aim of this study was to examine the histolopathogical effects among the biolimus, zotarolimus, and everolimus eluting stent (EES) in the porcine coronary restenosis model.
SUBJECTS AND METHODS
Pigs were randomized into three groups in which the coronary arteries (15 pigs, 10 coronaries in each group) had either a biolimus A9 eluting stent (BES, n=10), zotarolimus eluting stent (ZES, n=10) or an EES (n=10). Histopathologic analysis was performed at 28 days after stenting.
RESULTS
There were no significant differences in the injury score among the three groups. There was a significant difference in the internal elastic lamina, lumen area, neointima area, percent area stenosis, and the fibrin and inflammation score among the three groups (4.3+/-0.53 mm2, 2.5+/-0.93 mm2, 1.8+/-1.03 mm2, 40.7+/-20.80%, 1.7+/-0.41, 1.4+/-0.72 in the BES group vs. 5.1+/-0.55 mm2, 2.3+/-1.14 mm2, 2.8+/-1.00 mm2, 55.4+/-21.23%, 2.0+/-0.39, 1.6+/-0.76 in the ZES group vs. 4.4+/-0.53 mm2, 1.7+/-1.22 mm2, 2.8+/-1.23 mm2, 64.0+/-26.00%, 1.8+/-0.76, 2.1+/-0.90 in the EES group, respectively). BES is more effective in inhibiting neointimal hyperplasia compared to ZES and EES (p<0.0001). According to the fibrin and inflammation score, BES and EES are more effective in decreasing the fibrin deposition compared to ZES (p<0.001). Moreover, BES and ZES are more effective in reducing the inflammatory reaction compared to EES (p<0.001).
CONCLUSION
The result demonstrates that BES shows better histopathological characteristics than ZES and EES at one month after stenting in the porcine coronary restenosis model.

Keyword

Drug-eluting stents; Percutaneous coronary intervention; Coronary restenosis; Inflammation

MeSH Terms

Alkanesulfonic Acids
Constriction, Pathologic
Coronary Restenosis*
Coronary Vessels
Drug-Eluting Stents
Fibrin
Hyperplasia
Inflammation
Neointima
Percutaneous Coronary Intervention
Sirolimus
Stents*
Swine
Everolimus
Alkanesulfonic Acids
Fibrin
Sirolimus

Figure

  • Fig. 1 Representative images of H&E staining after 4 weeks of stenting. Specimen BES implanted (A: ×20, A-1: ×200), ZES implanted (B: ×20, B-1: ×200), and EES implanted (C: ×20, C-1: ×200). Inflammatory reaction was more severe in the EES stented artery compared to BES and ZES. BES: biolimus A9-eluting stents, ZES: zotarolimus-eluting stents, EES: everolimus-eluting stents.

  • Fig. 2 The Carstair fibrin stain of the low-power fields (magnitude, ×20, ×200) of fibrin infiltration in BES implanted (A and A-1), ZES implanted (B and B-1), and EES implanted (C and C-1). Fibrin deposition surrounding the stent struts was higher in ZES than in BES and EES cases. BES: biolimus A9-eluting stents, ZES: zotarolimus-eluting stents, EES: everolimus-eluting stents.

  • Fig. 3 Representative images of immunohistochemistry using anti-smooth muscle actin monoclonal antibody in the neointima tissue. Immunofluorescence staining showing an expression of α-smooth muscle actin (bright red positive cells, ×200, A: BES, B: ZES, C: EES). BES: biolimus A9-eluting stents, ZES: zotarolimus-eluting stents, EES: everolimus-eluting stents.

  • Fig. 4 Injury score (A), internal elastic lamina (B), lumen area (C), neointima area (D), % area stenosis (E) fibrin score (F) and inflammation score (G), in the BES, ZES, and EES groups. BES: biolimus A9-eluting stents, ZES: zotarolimus-eluting stents, EES: everolimus-eluting stents.


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