Inhaled nitric oxide reduces ischemia-reperfusion injury in rat lungs from non-heart-beating donors.
Inhaled nitric oxide reduces ischemia-reperfusion injury in rat lungs from non-heart-beating donors.
复制标题
吸入一氧化氮可减少无心跳供体大鼠肺部的缺血再灌注损伤。
DOI：
10.1016/j.jtcvs.2006.02.032
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Egan,ThomasM
中科院分区：
文献类型：
--
作者：
Takashima,Seiki;Koukoulis,Giovanna;Inokawa,Hidetoshi;Sevala,Mayura;Egan,ThomasM
目的若能从非心脏供体中提取肺，可缓解肺移植严重短缺的问题。然而，当再灌注时，遭受热缺血的肺会出现水肿。我们假设，仅在热缺血、再灌注或两者同时进行时，用一氧化氮对非心脏供体大鼠肺进行通气可能会减少缺血-再灌注损伤。方法采用离体灌注大鼠肺模型，采用干湿比法测定肺水过滤系数和肺水蓄积量。对供体大鼠实施安乐死，死后立即或死后2 ~ 3小时取肺。死后取出的肺要么不通气，要么单独用100%的氧气或含40 ppm一氧化氮的氧气通气。在回路中，用含有或不含40 ppm一氧化氮的肺泡气体进行肺部通气。结果一氧化氮在非心脏供体或灌注回路中可降低滤过系数和干湿比。死后2小时用一氧化氮通气或再灌注时用一氧化氮处理的肺的过滤系数和湿/干重量比与死后立即取出的肺相似。在热缺血和死后3小时肺再灌注时给予一氧化氮是最有益的。通过酶联免疫吸附法测定，回路中一氧化氮给药与肺环鸟苷单磷酸水平升高有关。结论在热缺血和再灌注时给药一氧化氮可能通过减少缺血再灌注损伤和毛细血管渗漏促进非心脏供体肺移植。
OBJECTIVEIf lungs could be retrieved from non–heart-beating donors, the critical shortage of lungs for transplantation could be alleviated. However, lungs subjected to warm ischemia develop edema when reperfused. We hypothesized that ventilation of rat lungs from non–heart-beating donors with nitric oxide during the period of warm ischemia alone, with reperfusion, or both might reduce ischemia-reperfusion injury.METHODSAn isolated perfused rat lung model measured the filtration coefficient and accumulation of lung water by the wet/dry weight ratio. Donor rats were euthanized, and then lungs were retrieved immediately after death or 2 or 3 hours postmortem. Lungs retrieved postmortem were either not ventilated or ventilated with 100% oxygen alone or 40 ppm nitric oxide in oxygen. In the circuit, lungs were ventilated with alveolar gas with or without 40 ppm nitric oxide.RESULTSNitric oxide administration to the non–heart-beating donor or in the perfusion circuit reduced filtration coefficient and wet/dry weight ratio. Lungs retrieved 2 hours postmortem ventilated with nitric oxide or treated with nitric oxide on reperfusion had filtration coefficients and wet/dry weight ratios similar to those of lungs retrieved immediately after death. Nitric oxide was most beneficial when administered both during warm ischemia and at reperfusion in lungs retrieved 3 hours postmortem. Nitric oxide administration in the circuit was associated with increased lung levels of lung cyclic guanosine monophosphate, determined by enzyme-linked immunosorbent assay.CONCLUSIONSAdministration of nitric oxide to non–heart-beating donors during warm ischemia and with reperfusion might facilitate transplantation of lungs from non–heart-beating donors by reducing ischemia-reperfusion injury and capillary leak.
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