Korean Circ J.  2017 Jan;47(1):115-122. 10.4070/kcj.2016.0278.

Effect of Stents Coated with Artemisinin or Dihydroartemisinin in a Porcine Coronary Restenosis Model

• Jang S
• Jeong MH
• Lim KS
• Bae IH
• Park JK
• Park DS
• Shim JW
• Kim JH
• Kim HK
• Sim DS
• Hong YJ
• Ahn Y
• Kang JC

• KMID: 2365290
• DOI: http://doi.org/10.4070/kcj.2016.0278

Abstract

BACKGROUND AND OBJECTIVES
Artemisinin and dihydroartemisinin are drugs used to treat malaria. These drugs suppress inflammatory reactions. The aim of this study was to examine the anti-intima hyperplasia effect of a novel drug-eluting stent with artemisinin or dihydroartemisinin in a porcine coronary restenosis model.
MATERIALS AND METHODS
Pigs were randomized into four groups; in the first, the coronary arteries (20 pigs, a total of 40 coronary arteries, with 10 coronary arteries in each group) was implanted with bare metal stents (BMS, n=10); the second group was given polymer-coated stents (PCS, n=10); the third group was treated with artemisinin-eluting stents (AES, n=10); and the fourth group was given dihydroartemisinin-eluting stents (DAES, n=10). Histopathologic analysis was performed 28 days after stenting.
RESULTS
The injury and fibrin scores among the four groups were not significantly different. However, the internal elastic lamina, lumen area, and neointima area were significantly different. Moreover, the percent area of stenosis (46.2±18.66% in BMS vs. 89.4±10.92% in PCS vs. 83.3±17.07% in AES vs. 36.7±11.20% in DAES, p<0.0001) and inflammation score (1.0 [range: 1.0-1.0] vs. 3.0 [range: 2.25-3.0] vs. 3.0 [range: 1.0-3.0] vs. 2.0 [range: 1.75-3.0] in BMS, PCS, AES, and DAES, respectively; p<0.001) were markedly decreased in the DAES group compared to the PCS group.
CONCLUSION
DES, which uses a natural substance, dihydroartemisinin, showed a neointima and inflammatory suppressive effect in a porcine coronary restenosis model.

Keyword

Stents; Coronary restenosis; Inflammation

MeSH Terms

Constriction, Pathologic
Coronary Restenosis*
Coronary Vessels
Drug-Eluting Stents
Fibrin
Hyperplasia
Inflammation
Malaria
Neointima
Stents*
Swine
Fibrin

Figure

• 

  Fig. 1 Optical microscopy was used to assess uniformity of stent surface. (A) Surface morphology of PCS, (B) AES, and (C) DAES by optical microscopy (×10). PCS: polymer-coated stent, AES: artemisinin-eluting stent, DAES: dihydroartemisinin-eluting stent.

• 

  Fig. 2 The SEM pictures indicate uniform coating on stent surface without webbing and bridge. SEM images (magnification, ×50 and ×100) of (A, B) PCS, (C, D) AES, and (E, F) DAES. SEM: scanning electron microscopy, PCS: polymer-coated stent, AES: artemisinin-eluting stent, DAES: dihydroartemisinin-eluting stent.

• 

  Fig. 3 In vitro release kinetics of artemisinin (dashed line) and dihydroartemisinin (filled line) from the stent over time. AES: artemisinineluting stent, DAES: dihydroartemisinin-eluting stent.

• 

  Fig. 4 Representative images of hematoxylin and eosin staining at 4 weeks after stenting. Specimens show implanted BMS (A, ×20), PCS (C, ×20), AES (E, ×20) and DAES (G, ×20). Carstairs' fibrin stain (magnification, ×20) for fibrin infiltration in implanted BMS (B, ×20), PCS (D, ×20), AES (F, ×20), and DAES (H, ×20). BMS: bare metal stent, PCS: polymer-coated stent, AES: Artemisinin-eluting stent, DAES: dihydroartemisinin-eluting stent.

• 

  Fig. 5 DAES showed superior neointima and inflammation suppressive effect compare to PCS in graph F and G. (A) Injury score, (B) fibrin score, (C) internal elastic lamina, (D) lumen area, (E) neointimal area, (F) percent area of stenosis, and (G) inflammation score of BMS, PCS, AES, and DAES. (A), (B), and (G) are expressed as median (interquartile range). NS: not statistically significant, BMS: bare metal stent, PCS: polymer-coated stent, AES: artemisinin-eluting stent, DAES: dihydroartemisinin-eluting stent.

• 

  Fig. 6 Micro-CT analysis of in-stent restenosis of BMS, PCS, AES, and DAES. CT: computed tomography, BMS: bare metal stent, PCS: polymer-coated stent, AES: artemisinin-eluting stent, DAES: dihydroartemisinin-eluting stent, OR: occiusion rate.

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