Clark S C, Sudarshan C, Khanna R, Roughan J, Flecknell P A, Dark J H
Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne, United Kingdom.
J Thorac Cardiovasc Surg. 1998 Jun;115(6):1335-41. doi: 10.1016/S0022-5223(98)70217-X.
Rodent models have suggested that initial low-pressure reperfusion of transplanted lungs reduces injury after ischemia. We investigated this phenomenon and the use of pentoxifylline in a porcine model of left single lung transplantation.
Donor lungs were preserved with Euro-Collins solution for a mean ischemic time of 18.4 hours. Neutrophil trapping in the graft, pulmonary artery pressure, and gas exchange were assessed over a 12-hour period. Partial occlusion of the contralateral pulmonary artery allowed manipulation of the pulmonary artery pressure in the transplanted lung. Group A (n = 5) was perfused at a mean pulmonary artery pressure of 20 mm Hg, group B was reperfused at a mean pulmonary artery pressure of 45 mm Hg for 10 minutes before reducing the pressure to the same as group A, and group C was reperfused at a mean pressure of 20 mm Hg for 10 minutes, then increased to a mean of 45 mm Hg for the remainder of the experiment. Group D was reperfused as in group A with the addition of intravenous pentoxifylline.
Leukocyte sequestration was observed in the first 10 minutes after reperfusion in groups A, B, and C, with maximal sequestration at 2 minutes. Significantly more sequestration was observed in the first 6 minutes in group B than in groups A and C, which were similar. Pentoxifylline significantly reduced leukocyte sequestration. Pulmonary venous oxygen tension in the allograft lung was worst in group B. Groups A and C were similar, but group D was superior to all other groups (p < 0.001).
Low-pressure reperfusion, even when limited to the first 10 minutes, modulates reperfusion injury possibly through a leukocyte-dependent mechanism. The addition of pentoxifylline in the recipient confers significant additional benefit.
啮齿动物模型表明,移植肺的初始低压再灌注可减少缺血后的损伤。我们在左单肺移植猪模型中研究了这一现象以及己酮可可碱的应用。
供体肺用欧洲柯林斯溶液保存,平均缺血时间为18.4小时。在12小时内评估移植物中的中性粒细胞滞留、肺动脉压和气体交换。对侧肺动脉部分闭塞可控制移植肺的肺动脉压。A组(n = 5)以平均20 mmHg的肺动脉压进行灌注,B组在将压力降至与A组相同之前,先以平均45 mmHg的肺动脉压再灌注10分钟,C组先以平均20 mmHg的压力再灌注10分钟,然后在实验剩余时间内将压力升至平均45 mmHg。D组在A组的基础上再灌注,并添加静脉注射己酮可可碱。
A、B、C组在再灌注后的前10分钟观察到白细胞滞留,在2分钟时滞留量最大。B组在前6分钟的滞留量明显多于A组和C组,A组和C组相似。己酮可可碱显著减少白细胞滞留。同种异体移植肺的肺静脉氧分压在B组最差。A组和C组相似,但D组优于所有其他组(p < 0.001)。
低压再灌注,即使仅限于前10分钟,也可能通过白细胞依赖性机制调节再灌注损伤。在受体中添加己酮可可碱可带来显著的额外益处。