DOI QR코드

DOI QR Code

The Protective Effects of Statins towards Vessel Wall Injury Caused by a Stent Retrieving Mechanical Thrombectomy Device : A Histological Analysis of the Rabbit Carotid Artery Model

  • Lee, Seung Hwan (Department of Neurosurgery, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University) ;
  • Shin, Hee Sup (Department of Neurosurgery, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University) ;
  • Oh, Inho (Department of Neurosurgery, Veterans Health Service Medical Center)
  • 투고 : 2020.10.23
  • 심사 : 2021.03.03
  • 발행 : 2021.09.01

초록

Objective : Endovascular mechanical thrombectomy (MT) has been regarded as one of the standard treatments for acute ischemic stroke caused by large vessel occlusion. Despite the wide use of stent retrievers for MT, arterial intimal damage caused when deployed stent is pulled has been a certain disadvantage. We hypothesized that statin could protect and stabilize vessel damage after endovascular MT using a stent retriever. In this animal study, we observed the protective effects of the statins towards MT-induced vessel wall injury. Methods : Twenty-eight carotid arteries of fourteen rabbits were used in the experiments with MT using stent retriever. We divided the rabbits into four groups as follows : group 1, negative control; group 2, positive control; group 3, statin before MT; and group 4, statin after MT. After MT procedures, we harvested the carotid arteries and performed histomorphological and immunohistochemical analyses. Results : In histomorphological analysis with hematoxylin and eosin and Masson's trichrome stain, significant intimal thickening (p<0.05) was observed in the positive control (group 2), compared to in the negative control (group 1). Intimal thickening was improved in the statin-administered groups (groups 3 and 4 vs. group 2, p<0.05). We also observed that statin administration after MT (group 4) resulted in a more effective decrease in intimal thickness than statin administration before MT (group 3) (p<0.05). We performed immunohistochemical analysis with the antibodies for tumor necrosis factor-alpha (TNF-α), cluster of differentiation (CD)11b, and CD163. In contrast to the negative control (group 1), the stained percentage areas of all immunological markers were markedly increased in the positive control (group 2) (p<0.05). Based on statin administration, the percentage area of TNF-α staining was significantly reduced (p<0.05) in group 3, compared to the positive control group (group 2). However, significant differences were not observed for CD11b and CD163 staining. In group 4, no significant differences were observed for TNF-α, CD11b, and CD163 staining (p≥0.05). The differences in the percentage areas of the different markers between the statin-administered groups (groups 3 and 4) were also not revealed. Conclusion : We presented that statin administration before and after MT exerted protective effects towards vessel wall injury. The efficacy of statins was greater post-administration than pre-administration. Thus, statin administration in routine prescriptions in the peri-procedural period is strongly advised.

키워드

과제정보

This work was supported by a grant from Kyung Hee University in 2018 (KHU-20180940). We would like to thank Jong Un Moon for the technical support in animal experiments.

참고문헌

  1. Alexandrov AV, Molina CA, Grotta JC, Garami Z, Ford SR, Alvarez-Sabin J, et al. : Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med 351 : 2170-2178, 2004 https://doi.org/10.1056/NEJMoa041175
  2. Arai D, Ishii A, Chihara H, Ikeda H, Miyamoto S : Histological examination of vascular damage caused by stent retriever thrombectomy devices. J Neurointerv Surg 8 : 992-995, 2016 https://doi.org/10.1136/neurintsurg-2015-011968
  3. Auerbach BJ, Krause BR, Bisgaier CL, Newton RS : Comparative effects of HMG-CoA reductase inhibitors on apo B production in the casein-fed rabbit: atorvastatin versus lovastatin. Atherosclerosis 115 : 173-180, 1995 https://doi.org/10.1016/0021-9150(94)05508-G
  4. Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, et al. : A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 372 : 11-20, 2015 https://doi.org/10.1056/NEJMoa1411587
  5. Bhatia R, Hill MD, Shobha N, Menon B, Bal S, Kochar P, et al. : Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke: real-world experience and a call for action. Stroke 41 : 2254-2258, 2010 https://doi.org/10.1161/STROKEAHA.110.592535
  6. Bradley JR : TNF-mediated inflammatory disease. J Pathol 214 : 149-160, 2008 https://doi.org/10.1002/path.2287
  7. Brekenfeld C, Schroth G, El-Koussy M, Nedeltchev K, Reinert M, Slotboom J, et al. : Mechanical thromboembolectomy for acute ischemic stroke: comparison of the catch thrombectomy device and the Merci Retriever in vivo. Stroke 39 : 1213-1219, 2008 https://doi.org/10.1161/STROKEAHA.107.495614
  8. Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, et al. : Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 372 : 1009-1018, 2015 https://doi.org/10.1056/NEJMoa1414792
  9. Chen Z, Fukutomi T, Zago AC, Ehlers R, Detmers PA, Wright SD, et al. : Simvastatin reduces neointimal thickening in low-density lipoprotein receptor-deficient mice after experimental angioplasty without changing plasma lipids. Circulation 106 : 20-23, 2002 https://doi.org/10.1161/01.CIR.0000022843.76104.01
  10. del Zoppo GJ, Poeck K, Pessin MS, Wolpert SM, Furlan AJ, Ferbert A, et al. : Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann Neurol 32 : 78-86, 1992 https://doi.org/10.1002/ana.410320113
  11. Faul F, Erdfelder E, Buchner A, Lang AG : Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods 41 : 1149-1160, 2009 https://doi.org/10.3758/BRM.41.4.1149
  12. Faul F, Erdfelder E, Lang AG, Buchner A : G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 39 : 175-191, 2007 https://doi.org/10.3758/BF03193146
  13. Gascou G, Lobotesis K, Machi P, Maldonado I, Vendrell JF, Riquelme C, et al. : Stent retrievers in acute ischemic stroke: complications and failures during the perioperative period. AJNR Am J Neuroradiol 35 : 734-740, 2014 https://doi.org/10.3174/ajnr.A3746
  14. Gauthier TW, Scalia R, Murohara T, Guo JP, Lefer AM : Nitric oxide protects against leukocyte-endothelium interactions in the early stages of hypercholesterolemia. Arterioscler Thromb Vasc Biol 15 : 1652-1659, 1995 https://doi.org/10.1161/01.ATV.15.10.1652
  15. Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, et al. : Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 372 : 1019-1030, 2015 https://doi.org/10.1056/NEJMoa1414905
  16. Haussen DC, Rebello LC, Nogueira RG : Optimizating clot retrieval in acute stroke: the push and fluff technique for closed-cell stentrievers. Stroke 46 : 2838-2842, 2015 https://doi.org/10.1161/STROKEAHA.115.010044
  17. Istvan ES, Deisenhofer J : Structural mechanism for statin inhibition of HMG-CoA reductase. Science 292 : 1160-1164, 2001 https://doi.org/10.1126/science.1059344
  18. Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, et al. : Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 372 : 2296-2306, 2015 https://doi.org/10.1056/NEJMoa1503780
  19. Kato M, Sada T, Mizuno M, Kitayama K, Inaba T, Koike H : Effect of combined treatment with an angiotensin II receptor antagonist and an HMG-CoA reductase inhibitor on atherosclerosis in genetically hyperlipidemic rabbits. J Cardiovasc Pharmacol 46 : 556-562, 2005 https://doi.org/10.1097/01.fjc.0000179434.18750.28
  20. Kurre W, Perez MA, Horvath D, Schmid E, Bazner H, Henkes H : Does mechanical thrombectomy in acute embolic stroke have long-term side effects on intracranial vessels? An angiographic follow-up study. Cardiovasc Intervent Radiol 36 : 629-636, 2013 https://doi.org/10.1007/s00270-012-0496-8
  21. Laufs U, La Fata V, Plutzky J, Liao JK : Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 97 : 1129-1135, 1998 https://doi.org/10.1161/01.CIR.97.12.1129
  22. Laufs U, Liao JK : Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. J Biol Chem 273 : 24266-24271, 1998 https://doi.org/10.1074/jbc.273.37.24266
  23. Laufs U, Marra D, Node K, Liao JK : 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors attenuate vascular smooth muscle proliferation by preventing rho GTPase-induced down-regulation of p27(Kip1). J Biol Chem 274 : 21926-21931, 1999 https://doi.org/10.1074/jbc.274.31.21926
  24. Lee SG, Lee SJ, Thuy NVP, Kim JS, Lee JJ, Lee OH, et al. : Synergistic protective effects of a statin and an angiotensin receptor blocker for initiation and progression of atherosclerosis. PLoS One 14 : e0215604, 2019 https://doi.org/10.1371/journal.pone.0215604
  25. Liao JK, Laufs U : Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 45 : 89-118, 2005 https://doi.org/10.1146/annurev.pharmtox.45.120403.095748
  26. McTaggart F : Comparative pharmacology of rosuvastatin. Atheroscler Suppl 4 : 9-14, 2003 https://doi.org/10.1016/S1567-5688(03)00004-7
  27. Mordasini P, Hiller M, Brekenfeld C, Schroth G, Fischer U, Slotboom J, et al. : In vivo evaluation of the Phenox CRC mechanical thrombectomy device in a swine model of acute vessel occlusion. AJNR Am J Neuroradiol 31 : 972-978, 2010 https://doi.org/10.3174/ajnr.A1928
  28. Mordasini P, Frabetti N, Gralla J, Schroth G, Fischer U, Arnold M, et al. : In vivo evaluation of the first dedicated combined flow-restoration and mechanical thrombectomy device in a swine model of acute vessel occlusion. AJNR Am J Neuroradiol 32 : 294-300, 2011 https://doi.org/10.3174/ajnr.A2270
  29. Neville RF, Sidawy AN : Myointimal hyperplasia: basic science and clinical considerations. Semin Vasc Surg 11 : 142-148, 1998
  30. Pecoraro V, Moja L, Dall'Olmo L, Cappellini G, Garattini S : Most appropriate animal models to study the efficacy of statins: a systematic review. Eur J Clin Invest 44 : 848-871, 2014 https://doi.org/10.1111/eci.12304
  31. Perren F, Kargiotis O, Pignat JM, Pereira VM : Hemodynamic changes may indicate vessel wall injury after stent retrieval thrombectomy for acute stroke. J Neuroimaging 28 : 412-415, 2018 https://doi.org/10.1111/jon.12513
  32. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. : Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 50 : e344-e418, 2019
  33. Ribo M, Alvarez-Sabin J, Montaner J, Romero F, Delgado P, Rubiera M, et al. : Temporal profile of recanalization after intravenous tissue plasminogen activator: selecting patients for rescue reperfusion techniques. Stroke 37 : 1000-1004, 2006 https://doi.org/10.1161/01.STR.0000206443.96112.d9
  34. Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, et al. : Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 372 : 2285-2295, 2015 https://doi.org/10.1056/NEJMoa1415061
  35. Sirtori CR : The pharmacology of statins. Pharmacol Res 88 : 3-11, 2014 https://doi.org/10.1016/j.phrs.2014.03.002
  36. Smith WS : Safety of mechanical thrombectomy and intravenous tissue plasminogen activator in acute ischemic stroke. Results of the multi Mechanical Embolus Removal in Cerebral Ischemia (MERCI) trial, part I. AJNR Am J Neuroradiol 27 : 1177-1182, 2006
  37. Sterpetti AV, Cucina A, Lepidi S, Randone B, Stipa F, Aromatario C, et al. : Progression and regression of myointimal hyperplasia in experimental vein grafts depends on platelet-derived growth factor and basic fibroblastic growth factor production. J Vasc Surg 23 : 568-575, 1996 https://doi.org/10.1016/S0741-5214(96)80034-6
  38. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al. : 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation 129 : S1-S45, 2014 https://doi.org/10.1161/01.cir.0000437738.63853.7a
  39. Yin NS, Benavides S, Starkman S, Liebeskind DS, Saver JA, Salamon N, et al. : Autopsy findings after intracranial thrombectomy for acute ischemic stroke: a clinicopathologic study of 5 patients. Stroke 41 : 938-947, 2010 https://doi.org/10.1161/STROKEAHA.109.576793