Ischemic Conditioning Is Safe and Effective for Octo- and Nonagenarians in Stroke Prevention and Treatment

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• 作者：Ran Meng ; Yuchuan Ding ; Karam Asmaro ; David Brogan ; Lu Meng ; Meng Sui…
• 关键词：Remote ischemic preconditioning ; octogenarian ; nonagenarians ; intracranial arterial stenosis ; stroke ; recurrence
• 刊名：Neurotherapeutics
• 出版年：2015
• 出版时间：July 2015
• 年：2015
• 卷：12
• 期：3
• 页码：667-677
• 全文大小：1,004 KB
• 参考文献：1.Wong KS, Li H. Long-term mortality and recurrent stroke risk among chinese stroke patients with predominant intracranial atherosclerosis. Stroke 2003;34:2361-2366.PubMed View Article
  2.Prabhakaran S, Romano JG. Current diagnosis and management of symptomatic intracranial atherosclerotic disease. Curr Opin Neurol 2011;25:18-26.View Article
  3.Kasner SE, Chimowitz MI, Lynn MJ, et al. Predictors of ischemic stroke in the territory of a symptomatic intracranial arterial stenosis. Circulation 2006;113:555-563.PubMed View Article
  4.Turan TN, Derdeyn CP, Fiorella D, et al. Treatment of atherosclerotic intracranial arterial stenosis. Stroke 2009;40:2257-2261.PubMed Central PubMed View Article
  5.Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med 2011;365:993-1003.PubMed Central PubMed View Article
  6.Kasner SE, Lynn MJ, Chimowitz MI, et al. Warfarin vs aspirin for symptomatic intracranial stenosis: Subgroup analyses from WASID. Neurology 2006;67:1275-1278.PubMed View Article
  7.Suri MF, Tariq N, Siddiq F, et al. Intracranial angioplasty and/or stent placement in octogenarians is associated with a threefold greater risk of periprocedural stroke or death. J Endovasc Ther 2010;17:314-319.PubMed View Article
  8.Przyklenk K, Bauer B, Ovize M, et al. Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation 1993;87:893-899.PubMed View Article
  9.Hausenloy DJ, Yellon DM. The therapeutic potential of ischemic conditioning: An update. Nat Rev Cardiol 2011;8:619-629.PubMed View Article
  10.Hoole SP, Heck PM, Sharples L, et al. Cardiac remote ischemic preconditioning in coronary stenting (crisp stent) study: A prospective, randomized control trial. Circulation 2009;119:820-827.PubMed View Article
  11.Botker HE, Kharbanda R, Schmidt MR, et al. Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: A randomised trial. Lancet 2010;375:727-734.PubMed View Article
  12.Hu S, Dong H, Zhang H, et al. Noninvasive limb remote ischemic preconditioning contributes neuroprotective effects via activation of adenosine a1 receptor and redox status after transient focal cerebral ischemia in rats. Brain Res 2012;1459:81-90.PubMed View Article
  13.Zare Mehrjerdi F, Aboutaleb N, Habibey R, et al. Increased phosphorylation of mTOR is involved in remote ischemic preconditioning of hippocampus in mice. Brain Res 2013;1526:94-101.PubMed View Article
  14.Geng X, Ren C, Wang T, et al. Effect of remote ischemic postconditioning on an intracerebral hemorrhage stroke model in rats. Neurol Res 2012;34:143-148.PubMed
  15.Hoda MN, Siddiqui S, Herberg S, et al. Remote ischemic perconditioning is effective alone and in combination with intravenous tissue-type plasminogen activator in murine model of embolic stroke. Stroke 2012;43:2794-2799.PubMed Central PubMed View Article
  16.Jensen HA, Loukogeorgakis S, Yannopoulos F, et al. Remote ischemic preconditioning protects the brain against injury after hypothermic circulatory arrest. Circulation 2012;123:714-721.View Article
  17.Hougaard KD, Hjort N, Zeidler D, et al. Remote ischemic preconditioning in thrombolysed stroke patients: Randomized study of activating endogenous neuroprotection—design and MRI measurements. Int J Stroke 2013; 8:141-146.PubMed View Article
  18.Meng R, Asmaro K, Meng L, et al. Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis. Neurology 2012;79:1853-1861.PubMed View Article
  19.Leone MA, Gaviani P, Ciccone G. Inter-coder agreement for ICD-9-CM coding of stroke. Neurol Sci 2006;27:445-448.PubMed View Article
  20.Sheehan OC, Merwick A, Kelly LA, et al. Diagnostic usefulness of the ABCD2 score to distinguish transient ischemic attack and minor ischemic stroke from noncerebrovascular events: The north Dublin TIA study. Stroke 2009;40:3449-3454.PubMed View Article
  21.Brott TG, Hobson RW 2nd, Howard G, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 2010;363:11-23.PubMed Central PubMed View Article
  22.Coutts SB, Eliasziw M, Hill MD, et al. An improved scoring system for identifying patients at high early risk of stroke and functional impairment after an acute transient ischemic attack or minor stroke. Int J Stroke 2008;3:3-10.PubMed View Article
  23.North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991;325:445-453.View Article
  24.Goldstein LB, Jones MR, Matchar DB, et al. Improving the reliability of stroke subgroup classification using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Stroke 2001;32:1091-1098.PubMed V
• 作者单位：Ran Meng (1)
  Yuchuan Ding (2)
  Karam Asmaro (2)
  David Brogan (2)
  Lu Meng (3)
  Meng Sui (4)
  Jingfei Shi (1)
  Yunxia Duan (1)
  Zhishan Sun (1)
  Yang Yu (1) (5)
  Jianping Jia (1)
  Xunming Ji (1)
  
  1. Neurology Department and Cerebral Vascular Diseases Research Institute (China-America Institute of Neuroscience), Xuanwu Hospital, Capital Medical University and the Center of Stroke, Beijing Institute for Brain Disorders, Beijing, 100053, China
  2. Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, 48201, USA
  3. Department of Biochemistry and Molecular Biology, Complex Carbohydrate Research Center, University of Georgia, Athens, GA, 30602, USA
  4. USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA, 90089, USA
  5. The 9th Medical College of Peking University, 100038, Beijing, China
  
• 刊物主题：Neurosciences; Neurology; Neurosurgery; Neurobiology;
• 出版者：Springer US
• ISSN：1878-7479

文摘

Symptomatic intracranial arterial stenosis (SIAS) is very common in octo- and nonagenarians, especially in the Chinese population, and is likely the most common cause of stroke recurrence worldwide. Clinical trials demonstrate that endovascular treatment, such as stenting, may not be suitable for octogenarians with systemic diseases. Hence, less invasive methods for the octogenarian patients are urgently needed. Our previous study (unique identifier: NCT01321749) showed that repetitive bilateral arm ischemic preconditioning (BAIPC) reduced the incidence of stroke recurrence by improving cerebral perfusion (confirmed by single photon emission computed tomography and transcranial Doppler sonography) in patients younger than 80?years of age; however, the safety and effectiveness of BAIPC on stroke prevention in octo- and nonagenarians with SIAS are still unclear. The objective of this study was to evaluate the safety and effectiveness of BAIPC in reducing stroke recurrence in octo- and nonagenarian patients with SIAS. Fifty-eight patients with SIAS were enrolled in this randomized controlled prospective study for 180 consecutive days. All patients enrolled in the study received standard medical management. Patients in the BAIPC group (n--0) underwent 5?cycles consisting of bilateral arm ischemia followed by reperfusion for 5?min each twice daily. Those in the control group (n--8) underwent sham-BAIPC twice daily. Blood pressure, heart rate, local skin status, plasma myoglobin, and plasma levels of thrombotic and inflammatory markers were documented in both groups before beginning the study and for the first 30?days. Finally, the incidences of stroke recurrence and magnetic resonance imaging during the 180?days of treatment were compared. Compared with the control, BAIPC had no adverse effects on blood pressure, heart rate, local skin integrity, or plasma myoglobin, and did not induce cerebral hemorrhage in the studied cohort. BAIPC reduced plasma high sensitive C-reactive protein, interleukin-6, plasminogen activator inhibitor-1, leukocyte count, and platelet aggregation rate and elevated plasma tissue plasminogen activator (all p-lt;-.01). In 180?days, 2 infarctions and 7 transient ischemic attacks were observed in the BAIPC group compared with 8 infarctions and 11 transient ischemic attacks in the sham BAIPC group (p-lt;-.05). BAIPC may safely inhibit stroke recurrence, protect against brain ischemia, and ameliorate plasma biomarkers of inflammation and coagulation in octo- and nonagenarians with SIAS. A multicenter trial is ongoing. Clinical Trial Registration: www.?clinicaltrials.?gov, unique identifier: NCT01570231.