Haniuda M, Dresler C M, Mizuta T, Cooper J D, Patterson G A
Department of Surgery, Washington University School of Medicine, St Louis, Missouri, USA.
Ann Thorac Surg. 1995 Nov;60(5):1376-81. doi: 10.1016/0003-4975(95)00620-Z.
Early allograft dysfunction remains a frequently encountered problem in clinical lung transplantation. Lung ischemia-reperfusion injury is associated with increased vascular permeability, which may be due in part to oxygen (O2) free radicals. However, it is not clear whether O2 free radicals are produced during ischemia under storage conditions in clinical lung transplantation.
Using an isolated ex vivo rabbit lung model, we studied the effects of preservation temperature on pulmonary capillary filtration coefficient (Kf) and lipid peroxidation in rabbit lungs inflated with 100% O2 after preservation with or without the O2 free radical scavenger dimethylthiourea. New Zealand white rabbits weighing 2.7 to 3.1 kg were intubated and ventilated with room air or 100% O2 (tidal volume = 25 mL). After heparinization and sternotomy, the pulmonary artery was flushed with low-potassium-dextran-1% glucose solution (200 mL). The heart-lung block was excised, submerged, and stored for 24 hours at 1 degree or 10 degrees C. After 24-hour preservation, the heart-lung block was suspended from a strain-gauge force transducer and ventilated with room air. The pulmonary artery cannula was connected to a reservoir of hetastarch solution. The lungs were flushed briefly with the hetastarch solution, and the reservoir was raised sequentially at 8-minute intervals to achieve 1.0 to 1.5 mm Hg increments in pulmonary artery pressure. Lung weight gain, airway pressure, pulmonary artery pressure, and left atrial pressure were measured continuously. The slope of steady-state lung weight gain was used to determine Kf (g.min-1.cm H2O-1 x 100 g-1 wet weight).
Twenty-four-hour lung preservation at both 1 degree and 10 degrees C increased Kf. A similar increase in Kf was observed in lungs stored at 1 degree C while inflated with 100% O2. However, a significant increase in Kf was observed when lungs inflated with 100% O2 were stored at 10 degrees C. This increase in Kf was ameliorated by dimethylthiourea. Thiobarbituric acid-reactive substance levels were increased in lungs stored at 10 degrees C while inflated with 100% O2. This finding was eliminated by dimethylthiourea.
These results indicate that free radical injury occurs during the ischemic phase when lungs are stored at moderate hypothermia while inflated with 100% O2.
早期移植肺功能障碍仍是临床肺移植中经常遇到的问题。肺缺血-再灌注损伤与血管通透性增加有关，这可能部分归因于氧（O2）自由基。然而，在临床肺移植的保存条件下，缺血期间是否产生O2自由基尚不清楚。
使用离体兔肺模型，我们研究了保存温度对在用或不用O2自由基清除剂二甲基硫脲保存后用100%O2充气的兔肺中肺毛细血管滤过系数（Kf）和脂质过氧化的影响。体重2.7至3.1 kg的新西兰白兔插管并用室内空气或100%O2通气（潮气量 = 25 mL）。肝素化和开胸术后，用低钾右旋糖酐-1%葡萄糖溶液（200 mL）冲洗肺动脉。切除心肺块，浸没，并在1℃或10℃下保存24小时。24小时保存后，将心肺块悬挂在应变片力传感器上并用室内空气通气。肺动脉插管连接到羟乙基淀粉溶液储液器。用羟乙基淀粉溶液短暂冲洗肺，然后储液器每隔8分钟依次升高，以使肺动脉压以1.0至1.5 mmHg的增量升高。连续测量肺重量增加、气道压力、肺动脉压力和左心房压力。用稳态肺重量增加的斜率来确定Kf（g·min-1·cm H2O-1×100 g-1湿重）。
在1℃和10℃下保存24小时均增加了Kf。在用100%O2充气的情况下，在1℃保存的肺中观察到Kf有类似的增加。然而，在用100%O2充气的肺在10℃保存时，观察到Kf显著增加。二甲基硫脲改善了这种Kf的增加。在用100%O2充气的情况下，在10℃保存的肺中硫代巴比妥酸反应性物质水平增加。二甲基硫脲消除了这一发现。
这些结果表明，当肺在中度低温下用100%O2充气保存时，在缺血期会发生自由基损伤。
