Pentoxifylline in flush solution improves early lung allograft function.

Pentoxifylline in flush solution improves early lung allograft function.
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冲洗液中的己酮可可碱可改善早期同种异体肺移植功能。

DOI:
10.1016/0003-4975(96)00015-x
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发表时间:
1996
期刊:
The Annals of thoracic surgery
影响因子:
--
通讯作者:
Patterson,GA
Patterson,GA
中科院分区:
--
文献类型:
--
作者:
Yamashita,M;Schmid,RA;Okabayashi,K;Ando,K;Kobayashi,J;Cooper,JD;Patterson,GA

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缺血后再灌注损伤是临床肺移植中常见的、难以预测的问题。戊茶碱(PTX)具有许多可以减轻再灌注损伤的作用:减少中性粒细胞与内皮的粘附,减少肿瘤坏死因子的产生,减少血小板聚集和增加血管内皮的血管舒张素的产生。我们以前已经证明,在储存前和再灌注期间给予PTX可减少肺再灌注损伤。本研究的目的是确定这些观察是否是存储或reperfusioneffects.Methodsfourteen犬左肺同种异体移植。用改良的Euro-Collins溶液冲洗供体肺,并在1 ℃下储存24小时。移植后立即结扎对侧右主肺动脉和支气管,以评估孤立的同种异体移植物功能。处死前6小时评估血流动力学指标和动脉血气分析(吸入氧分数1.0)。评估同种异体移植物髓过氧化物酶活性。从同种异体肺中叶获得支气管肺泡灌洗液用于中性粒细胞计数。根据PTX给药时间将动物分为三组。第1组(n = 5)动物未接受PTX。第2组(n = 4)动物在再灌注前接受PTX(20 mg/kg),并在评估期间持续输注(0.1 mg · kg-1· min-1)。第3组(n = 5),供体肺仅接受PTX(200 mg/L)冲洗液,观察到仅接受PTX冲洗液的肺(第3组)中存在良好的气体交换。第3组移植物髓过氧化物酶活性明显降低。此外,蛋白质水平和中性粒细胞计数在支气管肺泡灌洗液中显着减少组3 allografts. CONCLUSIONSPenophylline改善肺移植物再灌注损伤时,在冲洗液中。我们的数据表明,PTX将防止移植物内皮功能障碍,在24小时冷缺血储存,因此将防止中性粒细胞活化和迁移到肺组织。
BACKGROUNDPostischemic ischemia reperfusion injury is a frequent and unpredictable problem in clinical lung transplantation. Pentoxifylline (PTX) has a number of effects that could decrease reperfusion injury: reduced neutrophil adhesion to endothelium, decreased production of tumor necrosis factor, decreased platelet aggregation and increased production of vasodilatory prostaglandins by vascular endothelium. We have demonstrated previously that PTX administered before storage and again during reperfusion reduced lung reperfusion injury. The purpose of the present study was to determine whether these observations were storage or reperfusion effects.METHODSFourteen canine left lung allotransplantations were performed. Donor lungs were flushed with modified Euro-Collins solution and stored for 24 hours at 1°C. Immediately after transplantation, the contralateral right main pulmonary artery and bronchus were ligated to assess isolated allograft function. Hemodynamic indicers and arterial blood gas analysis (inspired oxygen fraction 1.0) were assessed for 6 hours before sacrifice. Allograft myeloperoxidase activity was assessed. Bronchoalveolar lavage fluid was obtained from the allograft middle lobe for neutrophil counts. The animals were divided into three groups based on the timing of PTX administration. Group 1 (n = 5) animals received no PTX. Group 2 (n = 4) animals received PTX (20 mg/kg) just before reperfusion as well as continuous infusion (0.1 mg · kg−1· min−1) during the assessment period. In group 3 (n = 5), donor lungs received PTX (200 mg/L) in the flush solution only.RESULTSSuperior gas exchange was noted in the lungs receiving PTX only in the flush solution (group 3). Myeloperoxidase activity in group-3 allograft was significantly reduced. In addition, protein levels and neutrophil counts in the bronchoalveolar lavage fluid were significantly reduced in group-3 allografts.CONCLUSIONSPentoxifylline ameliorates lung allograft reperfusion injury when administered in the flush solution. Our data suggest that PTX will prevent graft endothelial dysfunction during 24-hour cold ischemic storage and consequently will prevent neutrophil activation and migration into lung tissue.