Takashima Seiki, Koukoulis Giovanna, Inokawa Hidetoshi, Sevala Mayura, Egan Thomas M
Department of Cancer and Thoracic Surgery (Surgery II), Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
J Thorac Cardiovasc Surg. 2006 Jul;132(1):132-9. doi: 10.1016/j.jtcvs.2006.02.032.
If 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.
An 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.
Nitric 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.
Administration 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.
如果能够从非心脏跳动供体获取肺脏，那么肺移植供体严重短缺的状况有望得到缓解。然而，经历热缺血的肺脏在再灌注时会出现水肿。我们推测，仅在热缺血期间、再灌注期间或在这两个阶段都用一氧化氮对非心脏跳动供体的大鼠肺脏进行通气，可能会减轻缺血再灌注损伤。
采用离体灌注大鼠肺模型，通过湿/干重比来测量滤过系数和肺水积聚情况。将供体大鼠实施安乐死，然后在死亡后即刻、死后2小时或3小时获取肺脏。对死后获取的肺脏，要么不通气，要么仅用100%氧气通气，要么用含40 ppm一氧化氮的氧气通气。在灌注回路中，肺脏用含或不含40 ppm一氧化氮的肺泡气进行通气。
对非心脏跳动供体或在灌注回路中给予一氧化氮可降低滤过系数和湿/干重比。死后2小时获取的肺脏，用一氧化氮通气或在再灌注时用一氧化氮处理，其滤过系数和湿/干重比与死亡后即刻获取的肺脏相似。对于死后3小时获取的肺脏，在热缺血期间和再灌注时都给予一氧化氮最为有益。通过酶联免疫吸附测定法测定发现，在灌注回路中给予一氧化氮会使肺组织中环磷酸鸟苷水平升高。
在热缺血期间和再灌注时对非心脏跳动供体给予一氧化氮，可能通过减轻缺血再灌注损伤和毛细血管渗漏，促进非心脏跳动供体肺脏的移植。
