Gasparri R I, Jannis N C, Flameng W J, Lerut T E, Van Raemdonck D E
Center for Experimental Surgery and Anesthesiology, Katholieke Universiteit Leuven, Belgium.
Eur J Cardiothorac Surg. 1999 Dec;16(6):639-46. doi: 10.1016/s1010-7940(99)00335-8.
Ischemic preconditioning achieved by brief periods of ischemia followed by reperfusion before a prolonged period of ischemia, is well known to reduce myocardial damage. We investigated whether ischemic preconditioning of the lung could also attenuate ischemia-reperfusion injury following pulmonary preservation.
Transient ischemia of the right lung was achieved in rabbits (n = 4 in each group) by occluding the main bronchus and pulmonary artery, followed by reperfusion according to a protocol that differed between study groups: group 1 (control), 45 min ventilation; group 2, 30 min ventilation, 5 min ischemia and 10 min reperfusion; group 3, three periods of 5 min ischemia and 10 min reperfusion; group 4, five periods of 3 min ischemia and 6 min reperfusion. Donor lungs were then flushed with a crystalloid solution followed by inflated storage at 37 degrees C for 2 h. The function of the right lung was assessed during reperfusion for 2 h with homologous, diluted and deoxygenated blood in an isolated, pressure-limited, and room-air ventilated model.
Significant differences (P < 0.0001) were observed between groups 1 and 2 vs. groups 3 and 4 in veno-arterial oxygen pressure gradient (29 +/- 6 and 24 +/- 6 mmHg vs. 124 +/- 24 and 132 +/- 14 mmHg, respectively), and in weight gain (88 +/- 13 and 98 +/- 13% vs. 44 +/- 9 and 29 +/- 3%, respectively) after 1 h of reperfusion, and in wet-to-dry weight ratio (15.5 +/- 1.5 and 14.3 +/- 0.4 vs. 10.1 +/- 1.6 and 9.0 +/- 0.8, respectively) at the end of reperfusion. No significant differences in any of these parameters were observed between group 1 vs. group 2 neither between group 3 vs. group 4.
These data suggest: (1) That 15 min, but not 5 min of transient ischemia prior to pulmonary preservation can significantly reduce edema in the lung graft upon reperfusion, thus improving oxygenation capacity and (2) although not significant, this beneficial effect seems to be slightly better with more repetitive periods of transient ischemia. Further research is warranted to investigate whether ischemic preconditioning in the human organ donor may become a new strategy to protect lung tissue during a planned ischemic event as in pulmonary transplantation.
短暂缺血后再灌注，继而进行长时间缺血，由此实现的缺血预处理可减轻心肌损伤，这是广为人知的。我们研究了肺的缺血预处理是否也能减轻肺保存后的缺血再灌注损伤。
通过阻断主支气管和肺动脉实现兔右肺的短暂缺血（每组n = 4），然后根据研究组不同的方案进行再灌注：第1组（对照组），通气45分钟；第2组，通气30分钟，缺血5分钟，再灌注10分钟；第3组，三个周期的5分钟缺血和10分钟再灌注；第4组，五个周期的3分钟缺血和6分钟再灌注。然后用晶体溶液冲洗供体肺，接着在37℃充气保存2小时。在一个孤立的、压力限制且空气通气的模型中，用同源、稀释且脱氧的血液在再灌注2小时期间评估右肺功能。
在再灌注1小时后，第1组和第2组与第3组和第4组之间在动静脉氧分压梯度上观察到显著差异（P < 0.0001）（分别为29±6和24±6 mmHg 对比 124±24和132±14 mmHg），以及在体重增加方面（分别为88±13和98±13%对比44±9和29±3%），并且在再灌注结束时的湿干重比方面（分别为15.5±1.5和14.3±0.4对比10.1±1.6和9.0±0.8）也有显著差异。在第1组和第2组之间以及第3组和第4组之间，这些参数均未观察到显著差异。
这些数据表明：（1）肺保存前15分钟的短暂缺血而非5分钟，可显著减轻再灌注时肺移植中的水肿，从而改善氧合能力；（2）尽管不显著，但这种有益效果似乎在更频繁的短暂缺血周期时略好。有必要进一步研究人体器官供体中的缺血预处理是否可能成为在肺移植等计划性缺血事件期间保护肺组织的一种新策略。
