首页> 外文期刊>Lung. >Mannitol dose-dependently attenuates lung reperfusion injury following liver ischemia reperfusion: a dose-response study in an isolated perfused double-organ model.
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Mannitol dose-dependently attenuates lung reperfusion injury following liver ischemia reperfusion: a dose-response study in an isolated perfused double-organ model.

机译:甘露醇剂量依赖性地减轻肝脏缺血再灌注后的肺再灌注损伤:在孤立的灌注双器官模型中的剂量反应研究。

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摘要

We had previously studied different modes of prevention of liver ischemia-reperfusion (IR)-induced remote organ reperfusion injury, a challenge that remains partly unmet. We have now studied the capability of mannitol at different doses in abrogating liver IR-induced lung reperfusion injury in an isolated double-organ model. Rat livers ( n = 8/group) were perfused with Krebs-Henseleit solution (control) or made globally ischemic (IR) for 2 h, after which they were paired with normal lungs and "reperfused" together for 15 min. The lungs were then perfused alone with the accumulated Krebs for an additional 45 min. Another 4 control and 4 IR pairs were reperfused with Krebs containing mannitol at.22 mmol,.55 mmol,.77 mmol, or 1.1 mmol. Mannitol.22 mmol and 1.1 mmol failed to attenuate IR-lung injury as indicated by 50-95% increases in inspiratory and perfusion pressures and compliance reduction, a 70% increase in weight gain, and a 2-50-fold increase in bronchoalveolar lavage volume and content. Mannitol.55 mmol prevented all these abnormalities, and.77 mmol attenuated only changes in ventilatory parameters. The latter two treatments were also associated with a 50% reduction in xanthine oxidase activity and a 35-45% increase in the reduced glutathione tissue content compared with the nontreated IR-paired lungs. It is concluded that mannitol in a narrow therapeutic dose range can reduce oxidalive stress-induced lung damage that is related to liver IR.
机译:我们之前已经研究了预防肝脏缺血再灌注(IR)引起的远端器官再灌注损伤的不同模式,这一挑战目前尚待部分解决。现在,我们已经在分离的双器官模型中研究了不同剂量甘露醇消除肝IR引起的肺再灌注损伤的能力。用Krebs-Henseleit溶液(对照组)灌注大鼠肝脏(n = 8 /组)或使其整体缺血(IR)2小时,然后将它们与正常肺配对并一起“再灌注” 15分钟。然后将肺与累积的克雷布斯单独灌注另外45分钟。再用含甘露醇浓度为.22 mmol,.55 mmol,.77 mmol或1.1 mmol的Krebs再灌注另外4对对照和4对IR。甘露糖醇。22毫摩尔和1.1毫摩尔无法减轻IR肺损伤,如吸气和灌注压力增加50-95%和顺应性降低,体重增加70%和支气管肺泡灌洗增加2-50倍所表明数量和内容。甘露醇55 mmol预防了所有这些异常,77 mmol仅减弱了通气参数的变化。与未经治疗的IR配对肺相比,后两种治疗还与黄嘌呤氧化酶活性降低50%和减少的谷胱甘肽组织含量增加35-45%有关。结论是,在较窄的治疗剂量范围内,甘露醇可减少与肝脏IR相关的氧化应激诱导的肺损伤。

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