Addition of a mast cell stabilizing compound to organ preservation solutions degreases lung reperfusion injury
Addition of a mast cell stabilizing compound to organ preservation solutions degreases lung reperfusion injury
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DOI：
10.1016/s0022-5223(98)70328-9
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发表时间：
1998-03-01
影响因子：
6
通讯作者：
Starnes, VA
中科院分区：
文献类型：
--
作者：
Barr, ML;Carey, JN;Starnes, VA
目的：肺移植保存的研究通常集中在中性粒细胞、实质细胞、巨噬细胞和内皮细胞的自由基和酶释放。肺中有大量肥大细胞，当它们被激活时，会释放出强有力的炎症介质。我们假设，在Euro-Collins和威斯康星州大学的保存液中加入肥大细胞脱颗粒抑制剂洛度沙胺氨丁三醇（10 μ mol/L），可以减少肺保存损伤。方法：分离大鼠肺，用相应的溶液冲洗，并在4 ℃下储存6或12小时。用新鲜血液再灌注肺，并用100%氧气通气。测定肺泡-动脉氧分压差、氧分压、毛细血管滤过系数和顺应性。结果如下：缺血储存6小时后：洛度沙胺氨丁三醇增强的Euro-Collins溶液将肺泡-动脉氧差从539降至457（p = 0.004），氧分压从119 mmHg增加至205 mmHg（p = 0.006），毛细血管滤过系数从3.9降至2.0（p < 0.001）;洛度沙胺氨丁三醇增强的威斯康星州大学溶液将肺泡-动脉氧差从546降至317（p < 0.001），氧分压从166增加到335 mm Hg（p < 0.001），毛细血管滤过系数从3.0降低到1.7（p < 0.001）。缺血性储存12小时后，洛度沙胺氨丁三醇增强的Euro-Collins溶液将肺泡-动脉氧差从588降至485（p < 0.001），氧分压从100 mmHg增加到161 mmHg（p = 0.012），毛细血管滤过系数从6.2降至2.6（p < 0.001），依从性从0.12增加到0.21（p < 0.001）;洛度沙胺氨丁三醇增强的威斯康星州大学溶液将肺泡-动脉氧差从478降至322（p < 0.001），氧分压从214 mmHg增加到335 mmHg（p < 0.001），毛细血管滤过常数从4.2降低到2.0（p < 0.001），顺应性从0.20增加到0.25（p < 0.001）。结论：在Euro-Collins或威斯康星州大学的溶液中加入洛度沙胺氨丁三醇可显著降低肺再灌注损伤，如氧合增加、微血管通透性降低和顺应性增加所示。这些结果具有相关性，因为Euro-Collins和威斯康星州大学的溶液是临床上最常用的肺保存溶液。这项研究还强调了驻留肥大细胞在保存损伤中的有害作用。
Objective: Research in lung transplant preservation has generally focused on free radicals and enzyme release from neutrophils, parenchymal cells, macrophages, and endothelium. The lung has a large resident population of mast cells that, when activated, release potent inflammatory mediators. We hypothesized that adding an inhibitor of mast cell degranulation, lodoxamide tromethamine (10 mu mol/L), to Euro-Collins and University of Wisconsin preservation solutions, would decrease lung preservation injury. Methods: Rat lungs were isolated, flushed with the respective solution, and stored at 4 degrees C for 6 or 12 hours. The lungs were reperfused with fresh blood and ventilated with 100% oxygen. Alveolar-arterial oxygen difference, oxygen tension, capillary filtration coefficient, and compliance were determined. Results: After 6 hours of ischemic storage: lodoxamide tromethamine-enhanced Euro-Collins solution decreased alveolar-arterial oxygen difference from 539 to 457 (p = 0.004), increased oxygen tension from 119 to 205 mm Hg (p = 0.006), and decreased capillary filtration coefficient from 3.9 to 2.0 (p < 0.001); lodoxamide tromethamine-enhanced University of Wisconsin solution decreased alveolar-arterial oxygen difference from 546 to 317 (p < 0.001), increased oxygen tension from 166 to 335 mm Hg (p < 0.001), and decreased capillary filtration coefficient from 3.0 to 1.7 (p < 0.001). After 12 hours of ischemic storage, lodoxamide tromethamine-enhanced Euro-Collins solution decreased alveolar-arterial oxygen difference from 588 to 485 (p < 0.001), increased oxygen tension from 100 to 161 mm Hg (p = 0.012), decreased capillary filtration coefficient from 6.2 to 2.6 (p < 0.001), and increased compliance from 0.12 to 0.21 (p < 0.001); lodoxamide tromethamine-enhanced University of Wisconsin solution decreased alveolar-arterial oxygen difference from 478 to 322 (p < 0.001), increased oxygen tension from 214 to 335 mm Hg (p < 0.001), decreased capillary filtration constant from 4.2 to 2.0 (p < 0.001), and increased compliance from 0.20 to 0.25 (p < 0.001). Conclusions: Addition of lodoxamide tromethamine to Euro-Collins or University of Wisconsin solution results in a marked decrease in lung reperfusion injury as demonstrated by increased oxygenation, decreased microvascular permeability, and increased compliance. These results are relevant as Euro-Collins and University of Wisconsin solutions are the most common clinically used lung preservation solutions. This study also highlights the deleterious role of resident mast cells in preservation injury.