Remote Ischemic Preconditioning Protects the Brain Against Injury After Hypothermic Circulatory Arrest

Remote Ischemic Preconditioning Protects the Brain Against Injury After Hypothermic Circulatory Arrest
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DOI:
10.1161/circulationaha.110.986497
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发表时间:
2011-02-22
期刊:
影响因子:
37.8
通讯作者:
Juvonen, Tatu
Juvonen, Tatu
中科院分区:
医学1区
文献类型:
--
作者:
Jensen, Hanna A.;Loukogeorgakis, Stavros;Juvonen, Tatu

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背景-缺血预处理(IPC)是一种在缺血和再灌注过程中保护组织免受损伤的机制。远程IPC(RIPC)可以通过对具有缺血耐受性的组织施加短暂的缺血来引起,从而保护更容易受到缺血损伤的重要器官。使用猪模型,我们确定是否RIPC的肢体是保护脑损伤引起的低温循环停(HCA.Methods和Results-Twelve小猪被随机分为对照组和RIPC组。在心肺转流之前,通过4个循环的5分钟后肢缺血诱导RIPC。所有动物均接受心肺转流术,然后在18 ℃下进行60分钟的HCA。HCA后8小时监测脑代谢和脑电图活动。术后一周进行神经功能状态评估。最后,收集脑组织进行组织病理学分析。研究组的基线和术中参数平衡。RIPC组脑乳酸浓度显著降低(P <0.0001,ANOVA),脑电图活动恢复更快(P <0.05,ANOVA)。在7天随访期间,RIPC对神经功能有有益的影响(行为评分;与对照组相比P <0.0001,ANOVA)。组织学分析表明,RIPC动物脑损伤显著减少(损伤评分;平均值[四分位数间距]:对照组5.8 [3.8 - 7.5] vs RIPC组1.5 [0.5 - 2.5],P <0.001,t检验)。RIPC可能对接受HCA手术的患者具有神经保护作用,并改善长期预后。临床试验来测试这一假设是必要的。(循环。2011; 123:714 - 721)。
Background-Ischemic preconditioning (IPC) is a mechanism protecting tissues from injury during ischemia and reperfusion. Remote IPC (RIPC) can be elicited by applying brief periods of ischemia to tissues with ischemic tolerance, thus protecting vital organs more susceptible to ischemic damage. Using a porcine model, we determined whether RIPC of the limb is protective against brain injury caused by hypothermic circulatory arrest (HCA).Methods and Results-Twelve piglets were randomized to control and RIPC groups. RIPC was induced in advance of cardiopulmonary bypass by 4 cycles of 5 minutes of ischemia of the hind limb. All animals underwent cardiopulmonary bypass followed by 60 minutes of HCA at 18 degrees C. Brain metabolism and electroencephalographic activity were monitored for 8 hours after HCA. Assessment of neurological status was performed for a week postoperatively. Finally, brain tissue was harvested for histopathological analysis.Study groups were balanced for baseline and intraoperative parameters. Brain lactate concentration was significantly lower (P < 0.0001, ANOVA) and recovery of electroencephalographic activity faster (P < 0.05, ANOVA) in the RIPC group. RIPC had a beneficial effect on neurological function during the 7-day follow-up (behavioral score; P < 0.0001 versus control, ANOVA). Histopathological analysis demonstrated a significant reduction in cerebral injury in RIPC animals (injury score; mean [interquartile range]: control 5.8 [3.8 to 7.5] versus RIPC 1.5 [0.5 to 2.5], P < 0.001, t test).Conclusions-These data demonstrate that RIPC protects the brain against HCA-induced injury, resulting in accelerated recovery of neurological function. RIPC might be neuroprotective in patients undergoing surgery with HCA and improve long-term outcomes. Clinical trials to test this hypothesis are warranted. (Circulation. 2011; 123: 714-721.)