Lipopolysaccharide preconditioning induces robust protection against brain injury resulting from deep hypothermic circulatory arrest
Lipopolysaccharide preconditioning induces robust protection against brain injury resulting from deep hypothermic circulatory arrest
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DOI：
10.1016/j.jtcvs.2006.12.056
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发表时间：
2007-06-01
影响因子：
6
通讯作者：
Ungerleider, Ross M.
中科院分区：
文献类型：
--
作者：
Hickey, Edward J.;You, Xiaomang;Ungerleider, Ross M.
目的：延迟预适应可使缺血性损伤的反应发生基因重编程。亚临床细菌脂多糖通过预处理起作用，有力地防止实验性中风。我们研究了脂多糖对心肺转流相关脑损伤的保护作用。方法：新生仔猪随机分为脂多糖组（n = 6）和生理盐水组（n = 6）。三天后，他们经历了2小时的深低温停循环，然后断奶，并在重症监护室中支持麻醉20小时。对照组包括无深低温停循环的体外循环（n =3）和无体外循环（n = 3）。通过光学和荧光显微镜（Fluoro-Jade; Histo-Chem，Inc，Jefferson，方舟）定量脑损伤。实验组之间的围手术期和术后参数相似。对照组动物均未出现假阳性。在脂多糖处理的动物中，皮质、基底神经节和海马的组织学评分分别为0.33 +/- 0.21、0.66 +/- 0.42和0.5 +/- 0.24，但在所有盐水对照动物中显著更差（1.33 +/- 0.21，P <0.01; 1.66 +/- 0.33，P = 0.09;和6.0 +/- 1.5，P <0.01）。一个脂多糖治疗的大脑是从controls.Conclusions组织学上无法区分：这是第一个证据表明，脂多糖可以预处理心肺转流相关的损伤。由于脂多糖预处理是一种全身性现象，可提供针对心肌、肝脏和肺损伤的保护，因此该技术为保护与心肺转流相关的全身性新生儿损伤提供了巨大的潜力。
Objective: Delayed preconditioning genetically reprograms the response to ischemic injury. Subclinical bacterial lipopolysaccharide acts through preconditioning, powerfully protecting against experimental stroke. We investigated the potential for lipopolysaccharide to protect against brain injury related to cardiopulmonary bypass.Methods: Neonatal piglets were blindly polysaccharide (n = 6) or saline (n = 6). Three days later, they experienced 2 hours of deep hypothermic circulatory arrest before being weaned and supported anesthetized for 20 hours in an intensive care setting. Controls included cardiopulmonary bypass without deep hypothermic circulatory arrest (n =3) and no cardiopulmonary (n = 3). Brain injury was quantified by light and flourescent microscopy (Fluoro-Jade; Histo-Chem, Inc, Jefferson, Ark).Results: All animals were clinically indistinguishable before surgery. Perioperative and postoperative parameters between experimental groups were similar. No control animal scored falsely positive. Histologic scores were 0.33 +/- 0.21, 0.66 +/- 0.42, and 0.5 +/- 0.24 in the cortex, basal ganglia, and hippocampus, respectively, in the lipopolysaccharide-treated animals but significantly worse in all saline control animals (1.33 +/- 0.21, P < .01; 1.66 +/- 0.33, P = .09; and 6.0 +/- 1.5, P < .01). One lipopolysaccharide-treated brain was histologically indistinguishable from controls.Conclusions: This is the first evidence that lipopolysaccharide can precondition against cardiopulmonary bypass-related injury. Because lipopolysaccharide preconditioning is a systemic phenomenon offering proven protection against myocardiasl, hepatic, and pulmonary injury, this technique offers enormous potential for protecting against systemic neonatal injury related to cardiopulmonary bypass.