BIOCHEMICAL MECHANISMS OF REPERFUSION LUNG INJURY

脑缺血再灌流过程中氧化剂的损伤 组织已经在许多器官中被报道，但并不是很好 在肺里研究。再灌注损伤是一个潜在的重要因素。 肺部疾病的机制，并可能解释许多 再扩张性肺水肿的表现 肺移植后的浮肿、肺栓塞或 甚至成人呼吸窘迫综合征(ARDS)。在其他器官中， 缺血期间细胞内三磷酸腺苷的下降与 再灌流期间超氧阴离子(02-)的产生 再次变得可用。肺可能与其他肺不同 然而，器官中的细胞内ATP甚至可能在 如果微血管闭塞或血管闭塞，将面临持续供应 大栓子阻止将底物葡萄糖输送到血管细胞 肺泡毛细血管单位。在这种情况下，氧化剂可以 甚至在再灌流之前就会产生，因为02的可用性是 通过肺泡通风来维持。 这项提议的目标是研究生物化学和 机械通气性和再灌注性损伤的病理生理学研究 非通气性灌流兔肺。氧化剂的贡献 对再灌注损伤的评估将使用自由基清除剂， 氧化剂产生的抑制剂和超氧化物歧化的直接测定 (02-)由肺灌流产生。中国经济衰退的时间进程 高能磷酸盐及其再灌注后的恢复 肺组织中三磷酸腺苷及其代谢物的高效液相色谱分析监测 组织。炎性介质在血管内皮细胞损伤中的作用 花生四烯酸代谢对再灌注损伤的研究 使用抑制剂和测定肺灌流液中的介质。 循环血白细胞、红细胞和血浆的影响 白蛋白、铜蓝蛋白和转铁蛋白等蛋白质 再灌注损伤也将被调查。生物化学 在这个项目中定义的机制应该会导致改进 对几种重要肺部疾病的病理生理认识。

Injury from oxidants generated during reperfusion of ischemic tissue has been reported in a number of organs but is not well studied in the lung. Reperfusion injury is a potentially important mechanism of disease in the lung, and might explain many manifestations of re-expansion pulmonary edema, pulmonary edema following lung transplantation, pulmonary embolism or even adult respiratory distress syndrome (ARDS). In other organs, the decline in cellular ATP during ischemia has been linked to generation of superoxide anion (02-) during reperfusion when 02 again becomes available. The lung might differ from other organs, however, in that intracellular ATP could fall even in the face of continued supply if vascular occlusion from micro or macroemboli prevented delivery of subtrate glucose to cells of the alveolar capillary unit. Under these conditions, oxidants could be generated even before reperfusion, since 02 availability is maintained by alveolar ventilation. The goal of this proposal is to study the biochemistry and pathophysiology of reperfusion injury in both ventilated and nonventilated perfused rabbits lungs. The contribution of oxidants to reperfusion injury will be assessed with free radical scavengers, inhibitors of oxidant production, and direct assay of superoxide (02-) generation by perfused lung. The time course of decline in high energy phosphates and their recovery after reperfusion will be monitored by HPLC analysis of ATP and its metabolites in lung tissue. The contribution of inflammatory mediators of arachidonic acid metabolism to reperfusion injury will be studied with inhibitors and measurement of mediators in lung perfusate. The effect of circulating blood leukocytes, red cells, and plasma proteins such as albumin, ceruloplasmin and transferrin on reperfusion injury will also be investigated. The biochemical mechanisms defined in this project should lead to an improved pathophysiologic understanding of several important lung diseases.