Pickford M A, Green C J, Sarathchandra P, Fryer P R
Section of Surgical Research, MRC Clinical Research Centre, Northwick Park Hospital, Harrow, UK.
Int J Exp Pathol. 1990 Aug;71(4):513-28.
Using a left lung orthotopic isograft model in AS strain rats, we have investigated ultrastructural changes in lungs preserved for 48 h at 0 degrees C after a simple flush technique. Lungs were examined after storage alone and after storage followed by up to 1 h reperfusion with blood in vivo. Grafts were flushed with either isotonic saline (NaCl) or hypertonic citrate solution (HCA) alone, or with HCA containing either verapamil (a Ca2+ channel blocker), desferrioxamine (a Fe2+ antagonist), prostacyclin PGI2, nifedipine (a Ca2+ channel blocker) or allopurinol (a xanthine oxidase inhibitor). These agents were also given intravenously to both donor and recipient. Storage in NaCl produced gross cytoplasmic swelling and disruption with widespread nuclear injury. Reperfusion for 1 h resolved cell swelling but some endothelial loss and alveolar capillary wall rupture were seen. HCA with or without additional agents protected against cell swelling but endothelial blebbing and widening of the basement membrane occurred. Reperfusion for 1 h led to recovery of the basement membrane thickness but widespread endothelial loss was observed which was reduced by the addition of verapamil, desferrioxamine, nifedipine or allopurinol to the flush, but not by prostacyclin. Examination of lungs reperfused for shorter periods (5 and 15 min) identified three main types of damage to the vascular endothelium: (1) gross cell swelling, (2) detachment of intact endothelial cells from the underlying basal lamina, and (3) attenuation of cytoplasm due to blebbing. The results suggest that endothelial injury occurring on reperfusion is partly Fe2+ and Ca2(+)-mediated and that reactions catalysed by xanthine oxidase (which include oxygen free radical production) may also be important.
在AS品系大鼠中使用左肺原位同种移植模型，我们研究了采用简单冲洗技术后，在0℃保存48小时的肺的超微结构变化。分别在单独保存后以及保存后再进行长达1小时的体内血液再灌注后对肺进行检查。移植物分别用等渗盐水（NaCl）或单纯高渗枸橼酸盐溶液（HCA）冲洗，或者用含有维拉帕米（一种Ca2+通道阻滞剂）、去铁胺（一种Fe2+拮抗剂）、前列环素PGI2、硝苯地平（一种Ca2+通道阻滞剂）或别嘌呤醇（一种黄嘌呤氧化酶抑制剂）的HCA冲洗。这些药物也分别静脉给予供体和受体。保存在NaCl中会导致细胞质广泛肿胀和破坏，并伴有广泛的核损伤。再灌注1小时可缓解细胞肿胀，但会出现一些内皮细胞丢失和肺泡毛细血管壁破裂。添加或未添加其他药物的HCA均可防止细胞肿胀，但会出现内皮细胞气泡形成和基底膜增宽。再灌注1小时可使基底膜厚度恢复，但会观察到广泛的内皮细胞丢失，向冲洗液中添加维拉帕米、去铁胺、硝苯地平或别嘌呤醇可减少这种情况，但添加前列环素则无此效果。对再灌注较短时间（5分钟和15分钟）的肺进行检查，确定了血管内皮损伤的三种主要类型：（1）细胞广泛肿胀，（2）完整的内皮细胞从下方的基膜脱离，（3）由于气泡形成导致细胞质变薄。结果表明，再灌注时发生的内皮损伤部分由Fe2+和Ca2+介导，黄嘌呤氧化酶催化的反应（包括氧自由基的产生）可能也很重要。
