Korean Circ J.  2012 Jun;42(6):397-405. 10.4070/kcj.2012.42.6.397.

Impact of Heterogeneous Overlapping Drug-Eluting Stents on the Arterial Responses of Rabbit Iliac Arteries: A Comparison With Overlapping Bare Metal Stents

• Rha SW
• Chen KY
• Oh DJ
• Li YJ
• Jin Z
• Poddar KL
• Ramasamy S
• Minami Y
• Elnagar A
• Choi BG
• Hong SP
• Cheon BW
• Moon SK
• Im SI
• Kim SW
• Na JO
• Choi CU
• Lim HE
• Kim JW
• Kim EJ
• Han SW
• Park CG
• Seo HS
• Kim JH
• Hong YJ
• Jeong MH

• KMID: 1433859
• DOI: http://doi.org/10.4070/kcj.2012.42.6.397

Abstract

BACKGROUND AND OBJECTIVES
Although the use of heterogeneous overlapping drug-eluting stents (DES) is not uncommon in clinical practice, whether the implantation sequences of heterogeneous DES will influence the endothelialization or arterial responses differently remains unclear.
MATERIALS AND METHODS
Twenty-one rabbits were randomized to receive overlapping stents in the iliac artery for 3 months {distal sirolimus-eluting stent (SES, Cypher(TM))+proximal paclitaxel-eluting stent (PES, Taxus(TM)) (C+T, n=7), distal Taxus+proximal Cypher (T+C, n=7) and bare metal stent (BMS)+BMS (B+B, n=7)}. Endothelial function was evaluated by the acetylcholine provocation test during follow-up angiography. Histopathological changes in proximal, overlapped, and distal stented segments were evaluated.
RESULTS
Although the overall angiographic outcomes were comparable, late loss (mm) in the distal stented segment was higher in the B+B (0.39+/-0.07) and C+T (0.40+/-0.20) than that in the T+C (0.06+/-0.02) group (p<0.001). The incidence of acetylcholine-induced spasm was higher in the DES groups compared with BMS, regardless of the implantation sequences (85.7% in C+T vs. 14.3% in B+B vs. 71.4% in T+C, p=0.017). Notably, only the distal Cypher implantation group (C+T) had three cases of stent fracture. A histopathological analysis showed that despite similar arterial injury scores, Taxus and Cypher stents had higher inflammatory reactions at the overlapped and distal segments compared with those of BMS.
CONCLUSION
Despite similar arterial injury, higher inflammatory reactions were observed in overlapping DES segments regardless of the implantation sequence compared with that of BMS. Moreover, DES was associated with impaired endothelial function on the adjacent non-stented segments.

Keyword

Drug-eluting stents; Endothelium; Vasoconstriction

MeSH Terms

Acetylcholine
Angiography
Drug-Eluting Stents
Endothelium
Follow-Up Studies
Iliac Artery
Incidence
Rabbits
Spasm
Stents
Taxus
Vasoconstriction
Acetylcholine

Figure

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  Fig. 1 A representative case of stent fracture, associated occlusion and ischemic necrosis. A: limb ischemia caused by stent fracture and subsequent arterial occlusion. Arrow indicates the fractured struts. B: gross appearance of limb necrosis.

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  Fig. 2 Overall endothelialization under a microscope. A: bare metal stent group. B: distal Cypher+proximal Taxus group. C: distal Taxus+proximal Cypher group. From left to right are proximal segment, overlapped segment, and distal segment, respectively.

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  Fig. 3 High power light microscopic findings (×200) of hematoxylin and eosin staining. A: bare metal stent group. B: distal Cypher+proximal Taxus group. C: distal Taxus+proximal Cypher group. From left to right are proximal segment, overlapped segment, and distal segment, respectively. More large round mononuclear cells (inflammatory white blood cells, black arrows) were observed in the drug eluting stent groups (B and C) compared with those in the bare metal stent group (A).

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  Fig. 4 Acetylcholine provocation test. A: significant iliac artery spasm (luminal narrowing >90%) induced by acetylcholine infusion (50 µg/min). B: vasodilation after nitroglycerine infusion.

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