돼지 관상동맥 스텐트 재협착 모형에서 경구 Alpha Lipoic Acid투여 및 Alpha Lipoic Acid 부착 스텐트의 효과 = The Effect of Oral Administration of Alpha Lipoic Acid and Alpha Lipoic Acid Coated Stent in Porcine In-Stent Restenosis Model

다국어 초록 (Multilingual Abstract)

Background and Objectives：Alpha lipoic acid (ALA) is beneficial for improving endothelial dysfunction andpreventing atherosclerosis-related diseases. We evaluated the affect of ALA on stent restenosis in a porcine model.Materials and Methods：The First experiment: Balloon overdilation injuries were performed in two coronaryarteries in 12 pigs. Four weeks after the balloon overdilation injury, 24 bare metal stents were placed for 24 injuredcoronary arteries. We randomized into two groups (12 stents per group; control group: aspirin and clopidogrelonly, ALA group: aspirin and clopidogrel plus 100 mg/kg ALA during 4 weeks). The Second experiment: Stentswere randomly implanted in 2 coronary arteries in 8 pigs. Group I was the control stent group (n=8), and group IIwas the ALA coated stent group (n=8). Follow-up coronary angiogram and histopathologic assessment wereperformed at 4 weeks after stenting in both experiments. Results：The First experiment On histopathologicanalysis, the injury score and internal elastic lamina area did not differ significantly between the two groups. Theneointimal area was 7.3±0.9 mm2 in the control group and 2.2±1.1 mm2 in the ALA group (p<0.001), andthe histopathologic area of stenosis was 75.9±8.5% in the control group and 23.5±10.5% in the ALA group(p<0.001). The Second experiment: The injury score and internal elastic lamina area were not significantlydifferent between the two groups. The neointimal area was 7.4±1.1 mm2 in the control group and 1.4±0.8 mm2in the ALA group (p<0.001), and the histopathologic area of stenosis was 77.6±10.9% in the control group and15.6±7.6% in the ALA group (p<0.001). Conclusion：Both a high dose of oral ALA and ALA coated stentsinhibited neointimal hyperplasia in this porcine coronary artery stent restenosis model. (Korean Circulation J2006;36:495-502)

국문 초록 (Abstract)

배경 및 목적：Alpha lipoic acid(ALA)는 동맥경화성 질환의 예방 및 혈관 내피세포 기능의 개선효과를 가지고 있다. 이에 돼지의관상동맥 재협착 모형에서 고농도의 ALA 경구투여 및 ALA가 코팅된 스텐트의 재협착 억제효과를 알아보고자 하였다.방 법：1차 실험: 총 12마리의 암퇘지를 무작위로 2개의 관상동맥을 선택하여 풍선손상을 가하였다. 풍선손상 4주 후 24개의 3.0×18 mm의 일반 금속 스텐트를 풍선손상을 가하였던 관상동맥에 삽입하였다. I군은 대조군(n=6), II군은 스텐트시술 후 경구로 ALA 100 mg/kg를 다시 4주간 투여한군(n=6)으로 분류하였다.2차 실험: 총 8마리의 암퇘지를 2개의 관상동맥을 선택하Sang Yup Lim, et al：Alpha Lipoic Acid in Porcine Model·501여 각각의 동맥에 무작위로 3.0×18 mm 일반 금속 스텐트(n=8)와 ALA를 코팅한 3.0×18 mm 스텐트(n=8)를 삽입하였다. 스텐트 삽입 4주 후 추적 관상동맥 조영술을 시행한후 돼지를 희생시켜, 스텐트를 함유하고 있는 관상동맥을 분리, 관류고정한 후 조직병리 관찰 및 측정을 시행하였다.
결 과：
1차 실험: 조직형태학적 검사에서 손상지수, 내탄력층 면
적 등은 두 군 간에 유의한 차이를 보이지 않았다. 신생내막
면적은 I군 7.3±0.9 mm2, II군 2.2±1.1 mm2로서 II군에서
유의하게 작았고(p<0.001), 면적 협착은 I군 75.9±8.5%, II
군 23.5±10.5%으로 II군에서 유의하게 적었다(p<0.001).
신생내막의 염증세포의 비율은 I군 51.8±16.5%, II군 21.5±
9.6%로서 I군에서 유의하게 많았다(p<0.001).
2차 실험: 조직형태학적 검사에서 손상지수, 내탄력층 면
적 등은 두 군 간에 유의한 차이를 보이지 않았다. 신생내막
면적은 I군 7.3±1.1 mm2, II군 1.4±0.8 mm2로서 II군에서
유의하게 작았고(p<0.001), 면적 협착은 I군 77.6±10.9%,
II군 15.6±7.6%으로 II군에서 유의하게 적었다(p<0.001). 신
생내막의 염증세포의 비율은 I군 63.2±23.7%, II군 17.6±
11.6%로서 I군에서 유의하게 많았다(p<0.001).
결 론：
고용량의 경구 ALA투여 및 ALA를 코팅한 스텐트는 신생
내막 증식 및 염증반응을 효과적으로 억제할 수 있었다.

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