Journal of the Korean Society of Radiology (대한영상의학회지)

The Korean Society of Radiology (대한영상의학회)
권호 표지
DOI QR코드

DOI QR Code

Development of a Rabbit Iliac Arterial Stenosis Model Using a Controlled Cholesterol Diet and Pullover Balloon Injury

콜레스테롤 식이 및 내막 손상을 통한 토끼 장골동맥 협착 전임상 모델 개발

  • Hooney D. Min (Department of Radiology, Seoul National University Bundang Hospital) ;
  • Chong-ho Lee (Department of Radiology, Seoul National University Bundang Hospital) ;
  • Jae Hwan Lee (Department of Radiology, Seoul National University Bundang Hospital) ;
  • Kun Yung Kim (Department of Radiology, Seoul National University Bundang Hospital) ;
  • Chang Jin Yoon (Department of Radiology, Seoul National University Bundang Hospital) ;
  • Minuk Kim (Department of Radiology, SMG-SNU Boramae Medical Center)
  • 민훈 (분당서울대학교병원 영상의학과) ;
  • 이종호 (분당서울대학교병원 영상의학과) ;
  • 이재환 (분당서울대학교병원 영상의학과) ;
  • 김건영 (분당서울대학교병원 영상의학과) ;
  • 윤창진 (분당서울대학교병원 영상의학과) ;
  • 김민욱 (서울특별시립 보라매병원 영상의학과)
  • Received : 2023.08.26
  • Accepted : 2023.10.25
  • Published : 2024.03.01
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose This study aimed to develop a rabbit iliac stenosis model and evaluate the effects of different mechanical injury techniques on the degree of arterial stenosis. Materials and Methods Eighteen rabbits were divided into three groups: cholesterol-fed with pullover balloon injury (group A; n = 6), cholesterol-fed with localized balloon dilatation (group B; n = 6), and chow-diet with pullover balloon injury (group C; n = 6). After baseline angiography, the left iliac arteries of all rabbits were injured with a 3 × 10 mm noncompliant balloon using either a wide pullover technique (groups A and C) or a localized balloon dilatation technique (group B). A nine-week follow-up angiography was performed, and the angiographic late lumen loss and percentage of stenosis were compared. Results Group A exhibited the most severe late lumen loss (A vs. B, 0.67 ± 0.13 vs. 0.04 ± 0.13 mm, p < 0.0001; A vs. C, 0.67 ± 0.13 vs. 0.26 ± 0.29 mm, p < 0.05; stenosis percentage 32.02% ± 6.54%). In contrast, group B showed a minimal percentage of stenosis (1.75% ± 6.55%). Conclusion Pullover-balloon injury can lead to significant iliac artery stenosis in rabbits with controlled hypercholesterolemia. This model may be useful for elucidating the pathogenesis of atherosclerosis and for evaluating the efficacy of novel therapeutic interventions.

목적 콜레스테롤 식이 및 기계적 혈관 내막 손상 유발을 통한 토끼 장골동맥 협착 모델을 개발하고 서로 다른 내막 손상 방법에 따른 협착 유발 정도를 평가하고자 한다. 대상과 방법 18마리의 토끼를 콜레스테롤 식이 후 풍선으로 당김 손상(pullover injury)을 가한 군(group A, 6마리), 콜레스테롤 식이 후 국소 확장 손상(localized balloon dilatation) 군(group B, 6마리), 일반 사료 식이 후 당김 손상을 가한 군(group C, 6마리)로 나누었다. 모든 군에서 혈관조영술을 시행하고 좌측 장골동맥에 직경 3 mm, 길이 10 mm의 비순응성(noncompliant) 풍선 카테터를 이용하여 당김 손상(group A, C) 또는 국소 확장 손상(group B)를 가하였다. 실험 시작 후 9주째 추적 혈관조영술을 시행하여 혈관조영술상 장골동맥의 협착 정도(후기 내강 손실, 협착 비율)을 정량적으로 비교 평가하였다. 결과 A군이 9주째 추적 혈관조영술에서 가장 심한 후기 내강 손실을 보였고 32.02% ± 6.54%의 협착이 확인되었다(A군 vs. B군: 0.67 ± 0.13 mm vs. 0.04 ± 0.13 mm, p < 0.0001; A군 vs. C군: 0.67 ± 0.13 mm vs. 0.26 ± 0.29 mm, p < 0.05). B군에서는 혈관조영술상 협착이 1.75% ± 6.55%로 매우 낮게 나타났다. 결론 콜레스테롤 식이 및 당김 손상 기법을 이용한 기계적 내막 손상이 토끼 장골 동맥에서 유의한 협착을 유발함을 확인하였다. 이 전임상 모델은 전임상 말초동맥 질환의 질병 모델로 사용될 수 있을 것으로 예상된다.

Keywords

Acknowledgement

This study was supported by grant no.02-2022-0008 from the SNUBH Research Fund.

References

  1. Alvelo JL, Papademetris X, Mena-Hurtado C, Jeon S, Sumpio BE, Sinusas AJ, et al. Radiotracer imaging allows for noninvasive detection and quantification of abnormalities in angiosome foot perfusion in diabetic patients with critical limb ischemia and nonhealing wounds. Circ Cardiovasc Imaging 2018;11:e006932
  2. Fowkes FG, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet 2013;382:1329-1340
  3. Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). J Vasc Surg 2000;31(1 Pt 2):S1-S296
  4. Ferrer MD, Esteban E, Liste F, Carrillo JM, Ramos JJ, Balastegui MT, et al. [The rabbit as an experimental model: technique for the induction of vascular lesions and incidents]. Radiologia 2010;52:45-50. Spanish
  5. Waters RE, Terjung RL, Peters KG, Annex BH. Preclinical models of human peripheral arterial occlusive disease: implications for investigation of therapeutic agents. J Appl Physiol (1985) 2004;97:773-780
  6. Schwartz RS, Chronos NA, Virmani R. Preclinical restenosis models and drug-eluting stents: still important, still much to learn. J Am Coll Cardiol 2004;44:1373-1385
  7. Schwartz RS, Edelman ER, Carter A, Chronos NA, Rogers C, Robinson KA, et al. Preclinical evaluation of drug-eluting stents for peripheral applications: recommendations from an expert consensus group. Circulation 2004;110:2498-2505
  8. Nakazawa G, Nakano M, Otsuka F, Wilcox JN, Melder R, Pruitt S, et al. Evaluation of polymer-based comparator drug-eluting stents using a rabbit model of iliac artery atherosclerosis. Circ Cardiovasc Interv 2011;4:38-46
  9. Metz J, Wolf O, Schmelz A, Pill J, Stegmeier KH, Hartig F. Atherosclerosis in the aorta of hypercholesterolemic rabbits and the influence of daltroban. Exp Pathol 1991;41:57-69
  10. Kolodgie FD, Katocs AS Jr, Largis EE, Wrenn SM, Cornhill JF, Herderick EE, et al. Hypercholesterolemia in the rabbit induced by feeding graded amounts of low-level cholesterol. Methodological considerations regarding individual variability in response to dietary cholesterol and development of lesion type. Arterioscler Thromb Vasc Biol 1996;16:1454-1464
  11. Dornas WC, Oliveira TT, Augusto LE, Nagem TJ. Experimental atherosclerosis in rabbits. Arq Bras Cardiol 2010;95:272-278
  12. Yanni AE. Laboratory rabbit and high-cholesterol diet: what is taken for granted may not be so simple. Lab Anim 2014;48:349-350
  13. Fan J, Kitajima S, Watanabe T, Xu J, Zhang J, Liu E, et al. Rabbit models for the study of human atherosclerosis: from pathophysiological mechanisms to translational medicine. Pharmacol Ther 2015;146:104-119
  14. Phinikaridou A, Hallock KJ, Qiao Y, Hamilton JA. A robust rabbit model of human atherosclerosis and atherothrombosis. J Lipid Res 2009;50:787-797
  15. Yanni AE. The laboratory rabbit: an animal model of atherosclerosis research. Lab Anim 2004;38:246-256
  16. Zhou X, Mou Y, Shen X, Yang T, Liu J, Liu F, et al. The role of atorvastatin on the restenosis process post-PTA in a diabetic rabbit model. BMC Cardiovasc Disord 2016;16:153
  17. Jain M, Frobert A, Valentin J, Cook S, Giraud MN. The rabbit model of accelerated atherosclerosis: a methodological perspective of the iliac artery balloon injury. J Vis Exp 2017;128:55295
  18. Libby P. Inflammation in atherosclerosis. Nature 2002;420:868-874
  19. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002;105:1135-1143
  20. Ip JH, Fuster V, Badimon L, Badimon J, Taubman MB, Chesebro JH. Syndromes of accelerated atherosclerosis: role of vascular injury and smooth muscle cell proliferation. J Am Coll Cardiol 1990;15:1667-1687
  21. Verrier ED, Boyle EM Jr. Endothelial cell injury in cardiovascular surgery. Ann Thorac Surg 1996;62:915-922
  22. Gould RG. Lipid metabolism and atherosclerosis. Am J Med 1951;11:209-227