Carbon monoxide-saturated preservation solution protects lung grafts from ischemia-reperfusion injury.

Carbon monoxide-saturated preservation solution protects lung grafts from ischemia-reperfusion injury.
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DOI:
10.1016/j.jtcvs.2008.06.026
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发表时间:
2008-10
影响因子:
6
通讯作者:
McCurry, Kenneth R.
McCurry, Kenneth R.
中科院分区:
医学1区
文献类型:
--
作者:
Kohmoto, Junichi;Nakao, Atsunori;Sugimoto, Ryujiro;Wang, Yinna;Zhan, JiangHua;Ueda, Hideo;McCurry, Kenneth R.

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在以前的工作中,我们已经证明,通过吸入给供体和/或受体输送低浓度(250 ppm)的一氧化碳(CO)可以保护移植肺免受缺血再灌注损伤(IRI)(改善气体交换,减少移植物内和全身炎症,保留移植血管内皮细胞超微结构)。在这项研究中,我们研究了在保存液中将CO输送到肺移植物是否可以保护肺IRI。在同系刘易斯至刘易斯大鼠中进行原位左肺移植。将移植物在具有(CO-UW)或不具有(对照UW)CO的UW溶液中在4°C下保存6小时。在使用前,在4°C下将CO气体(5%或100%)鼓泡到UW溶液中5分钟。在对照组中,IR损伤导致移植物功能显著恶化,并与再灌注后2小时大量细胞浸润相关。然而,储存在CO-UW中的移植物(5%)表现出明显更好的气体交换和明显减少的移植物内炎症(减少的炎症介质和细胞浸润)。实验表明,100% CO-UW的保护效果不如5% CO-UW。这项研究表明,5%的CO作为冷冲洗/保存溶液的添加剂,可以在冷保存和移植肺移植后产生有效的抗炎和细胞保护作用。用CO对肺移植物的这种离体治疗可以使与CO吸入相关的问题最小化,并且可以提供显著推进CO在临床环境中的应用的机会。
In previous work, we have demonstrated that delivery of low concentrations (250 ppm) of carbon monoxide (CO) via inhalation to donor and/or recipients protects transplanted lungs from ischemia-reperfusion injury (IRI) (improved gas exchange, diminished intragraft and systemic inflammation and retention of graft vascular endothelial cell ultrastructure). In this study we examined whether delivery of CO to lung grafts in the preservation solution could protect against lung IRI. Orthotopic left lung transplantation was performed in syngeneic Lewis to Lewis rats. Grafts were preserved in UW solution with (CO-UW) or without (control UW) CO at 4°C for 6 hours. CO gas (5% or 100%) was bubbled into UW solution at 4°C for 5 minutes before use. In controls, IR injury resulted in significant deterioration of graft function and was associated with a massive cellular infiltrate 2 hours after reperfusion. Grafts stored in CO-UW (5%), however, demonstrated significantly better gas exchange and significantly reduced intragraft inflammation (reduced inflammatory mediators and cellular infiltrate). Experiments demonstrated that the protective effects afforded by 100% CO-UW were not as potent as those of 5% CO-UW. This study demonstrates that 5% CO as an additive to the cold flush/preservation solution can impart potent anti-inflammatory and cytoprotective effects following cold preservation and transplantation of lung grafts. Such ex vivo treatment of lung grafts with CO can minimize concerns associated with CO inhalation and may offer opportunity to significantly advance the application of CO in the clinical setting.
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