Korean Circulation Journal

The Korean Society of Cardiology (대한심장학회)
권호 표지

The Effect of Oral Administration of Alpha Lipoic Acid and Alpha Lipoic Acid Coated Stent in Porcine In-Stent Restenosis Model

돼지 관상동맥 스텐트 재협착 모형에서 경구 Alpha Lipoic Acid 투여 및 Alpha Lipoic Acid 부착 스텐트의 효과

Lim, Sang-Yup;Bae, Eun-Hui;Jeong, Myung-Ho;Kim, Ju-Han;Ahn, Young-Keun;Cho, Jeong-Gwan;Park, Jong-Chun;Kang, Jung-Chaee;Cho, Dong-Lyun;Kim, Ki-Seok;Joo, Seung-Jae
임상엽;배은희;정명호;김주한;안영근;조정관;박종춘;강정채;조동련;김기석;주승재

  • Published : 20060000
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Abstract

Background and Objectives：Alpha lipoic acid (ALA) is beneficial for improving endothelial dysfunction and preventing 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 coronary arteries in 12 pigs. Four weeks after the balloon overdilation injury, 24 bare metal stents were placed for 24 injured coronary arteries. We randomized into two groups (12 stents per group; control group: aspirin and clopidogrel only, ALA group: aspirin and clopidogrel plus 100 mg/kg ALA during 4 weeks). The Second experiment: Stents were randomly implanted in 2 coronary arteries in 8 pigs. Group I was the control stent group (n=8), and group II was the ALA coated stent group (n=8). Follow-up coronary angiogram and histopathologic assessment were performed at 4 weeks after stenting in both experiments. Results：The First experiment On histopathologic analysis, the injury score and internal elastic lamina area did not differ significantly between the two groups. The neointimal area was 7.3${\pm}$0.9 mm2 in the control group and 2.2${\pm}$1.1 mm2 in the ALA group (p<0.001), and the histopathologic area of stenosis was 75.9${\pm}$8.5% in the control group and 23.5${\pm}$10.5% in the ALA group (p<0.001). The Second experiment: The injury score and internal elastic lamina area were not significantly different between the two groups. The neointimal area was 7.4${\pm}$1.1 mm2 in the control group and 1.4${\pm}$0.8 mm2 in the ALA group (p<0.001), and the histopathologic area of stenosis was 77.6${\pm}$10.9% in the control group and 15.6${\pm}$7.6% in the ALA group (p<0.001). Conclusion：Both a high dose of oral ALA and ALA coated stents inhibited neointimal hyperplasia in this porcine coronary artery stent restenosis model. (Korean Circulation J 2006;36:495-502)

Keywords

References

  1. Holmes DR Jr, Leon MB, Moses JW, et al. Analysis of 1-year clinical outcomes in the SIRIUS trial: a randomized trial of a sirolimus -eluting stent versus a standard stent in patients at high risk for coronary restenosis. Circulation 2004;109:634-40 https://doi.org/10.1161/01.CIR.0000112572.57794.22
  2. Salam AM, al Suwaidi J, Holmes DR Jr. Drug-eluting coronary stents. Curr Probl Cardiol 2006;31:8-119 https://doi.org/10.1016/j.cpcardiol.2005.09.002
  3. Leon MB, Bakhai A. Drug-eluting stents and glycoprotein IIb/ IIIa inhibitors: combination therapy for the future. Am Heart J 2003;146(4 Suppl):S13-7 https://doi.org/10.1016/j.ahj.2003.09.004
  4. Mintz GS, Tinana A, Hong MK, et al. Impact of preinterventional arterial remodeling on neointimal hyperplasia after implantation of (non-polymer-encapsulated) paclitaxel-coated stents: a serial volumetric intravascular ultrasound analysis from the ASian Paclitaxel-Eluting Stent Clinical Trial (ASPECT). Circulation 2003;108:1295-8 https://doi.org/10.1161/01.CIR.0000091254.73351.D6
  5. Nebeker JR, Virmani R, Bennett CL, et al. Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the Research on Adverse Drug Events and Reports (RADAR) project. J Am Coll Cardiol 2006;47:175-81 https://doi.org/10.1016/j.jacc.2005.07.071
  6. Packer L, Witt EH, Tritschler HJ. Alpha-lipoic acid as a biological antioxidant. Free Radic Biol Med 1995;19:227-50 https://doi.org/10.1016/0891-5849(95)00017-R
  7. Ahn YK, Jeong MH, Kim JW, et al. Preventive effects of heparin coated stent on restenosis in the porcine model. Catheter Cardiovasc Interv 1999;48:324-30 https://doi.org/10.1002/(SICI)1522-726X(199911)48:3<324::AID-CCD20>3.0.CO;2-K
  8. Schwartz RS, Huber KC, Murphy JG, et al. Restenosis and the proportional neointimal response to coronary artery injury: results in a porcine model. J Am Coll Cardiol 1992;19:267-74 https://doi.org/10.1016/0735-1097(92)90476-4
  9. Welt FG, Rogers C. Inflammation and restenosis in the stent era. Arterioscler Thromb Vasc Biol 2002;22:1769-76 https://doi.org/10.1161/01.ATV.0000037100.44766.5B
  10. Tanaka H, Sukhova G, Schwartz D, Libby P. Proliferating arterial smooth muscle cells after balloon injury express TNF alpha but not interleukin-1 or basic fibroblastic growth factor. Arterioscler Thromb Vasc Biol 1996;16:12-8 https://doi.org/10.1161/01.ATV.16.1.12
  11. Clausell N, de Lima VC, Molossi S, et al. Expression of tumor necrosis factor alpha and accumulation of fibronectin in coronary artery restenotic lesions retrieved by artherectomy. Br Heart J 1995;73:534-9 https://doi.org/10.1136/hrt.73.6.534
  12. Lindner V, Reidy MA. Expression of basic fibroblast growth factor and its receptor by smooth muscle cells and endothelium in injured rat arteries. Circ Res 1993;73:589-95 https://doi.org/10.1161/01.RES.73.3.589
  13. Morice MC, Serruy PW, Sousa JE, et al. A randomized comparison of a sirolimus-eluting stent with standard stent for coronary revascularization. N Engl J Med 2002;346:1773-80 https://doi.org/10.1056/NEJMoa012843
  14. Abizaid A, Costa MA, Blanchard D, et al. Sirolimus-eluting stents inhibit neointimal hyperplasia in diabetic patients: insights from the RAVEL Trial. Eur Heart J 2004;25:107-12 https://doi.org/10.1016/j.ehj.2003.11.002
  15. Kang WC, Han SH, Ahn TH, Son MS, Son JW, Shin EK. The long-term clinical outcomes of primary PTCA with heparincoated stent in acute myocardial infarction. Korean Circ J 2004;34:540-7 https://doi.org/10.4070/kcj.2004.34.6.540
  16. Park HW, Jeong MH, Park OY, et al. The Long-term clinical effects of heparin-coated coronary stent. Korean Circ J 2002; 32:773-80 https://doi.org/10.4070/kcj.2002.32.9.773
  17. Kim W, Jeong MH, Lim SY, et al. The first clinical trial of antioxidant, carvedilol-eluting stent in coronary artery diseases. Korean Circ J 2006;36:115-20 https://doi.org/10.4070/kcj.2006.36.2.115
  18. Hong YJ, Jeong MH, Kim W, et al. Effect of abciximab-coated stent on in-stent intimal hyperplasia in human coronary arteries. Am J Cardiol 2004;94:1050-4 https://doi.org/10.1016/j.amjcard.2004.06.066
  19. Hong YJ, Jeong MH, Kim W, et al. The effects of abciximab ($ReoPro^{\circled R}$)-coated stents on extracellular matrix synthesis and apoptosis. Korean Circ J 2005;35:290-301 https://doi.org/10.4070/kcj.2005.35.4.290
  20. Kim W, Jeong MH, Kim KH, et al. The clinical results of a platelet glycoprotein IIb/IIIa receptor blocker (Abciximab: $ReoPro^{\circled R}$) -coated stent in acute myocardial infarction. J Am Coll Cardiol 2006;47:933-8 https://doi.org/10.1016/j.jacc.2005.10.054
  21. Midaoui AE, Elimadi A, Wu L, Haddad PS, de Champlain J. Lipoic acid prevents hypertension, hyperglycemia, and the increase in heart mitochondrial superoxide production. Am J Hypertens 2003;16:173-9 https://doi.org/10.1016/S0895-7061(02)03253-3
  22. Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid: a 3-week multicentre randomized controlled trial(ALADIN Study). Diabetologia 1995;38:1425-33 https://doi.org/10.1007/BF00400603
  23. Suzuki YJ, Tsuchiya M, Packer L. Thioctic acid and dihydrolipoic acid are novel antioxidants which interact with reactive oxygen species. Free Radic Res Commun 1991;15:255-63 https://doi.org/10.3109/10715769109105221
  24. Scott BC, Arouma OI, Evans PJ, et al. Lipoic and dihydrolipoic acid as antioxidants: a critical evaluation. Free Radic Res 1994;20:119-33 https://doi.org/10.3109/10715769409147509
  25. el Midaoui A, de Champlain J. Prevention of hypertension, insulin resistance, and oxidative stress by alpha-lipoic acid. Hypertension 2002;39:303-7 https://doi.org/10.1161/hy0202.104345
  26. Kaminski KA, Bonda TA, Korecki J, Musial WJ. Oxidative stress and neutrophil activation-the two keystones of ischemia/ reperfusion injury. Int J Cardiol 2002;86:41-59 https://doi.org/10.1016/S0167-5273(02)00189-4
  27. ordberg J, Arner ES. Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic Biol Med 2001;31:1287-312 https://doi.org/10.1016/S0891-5849(01)00724-9
  28. Sung MJ, Kim W, Ahn SY, et al. Protective effect of alphalipoic acid in lipopolysaccharide-induced endothelial fractalkine expression. Circ Res 2005;97:880-90 https://doi.org/10.1161/01.RES.0000186522.89544.4D
  29. Lee KM, Park KG, Kim D, et al. Alpha-lipoic acid inhibits fractalkine expression and prevents neointimal hyperplasia after balloon injury in rat carotid artery. Atherosclerosis 2006 Jan 10;[Epub ahead of print]
  30. Suzuki T, Kopia G, Hayashi S, et al. Stent-based delivery of sirolimus reduces neointimal formation in a porcine coronary model. Circulation 2001;104:1188-93 https://doi.org/10.1161/hc3601.093987