Paterson I S, Smith F C, Tsang G M, Hamer J D, Shearman C P
Department of Vascular Surgery, Queen Elizabeth Hospital, Edgbaston, Birmingham, U.K.
Ann Vasc Surg. 1993 Jan;7(1):68-75. doi: 10.1007/BF02042662.
Aortic aneurysm repair produces inflammatory mediators, neutrophil activation, and remote organ injury. Reperfusion plasma from these patients produces microvascular injury in an ex vivo chemotactic model. This study investigates the mechanism of this injury. Vena caval blood was obtained before and 15 minutes after aortic clamp removal (n = 16) or at laparotomy (n = 10). Plasma or saline solution was introduced into unit dose chambers fixed atop dermabrasions on the back of depilated anesthetized rabbits. Animals were treated with intravenous saline solution (n = 4); made neutropenic with nitrogen mustard (n = 4); pretreated with the xanthine oxidase inhibitor allopurinol (n = 4); or cotreated intravenously with the free radical scavengers superoxide dismutase (SOD) and catalase (n = 4). Three hours later neutrophil counts (polymorphonuclear cells [PMN]/mm3) and activity (free radical production by flow cytometry), protein leakage, and inflammatory mediators (thromboxane [TX] and leukotriene B4 [LTB4]) were measured. In contrast to control plasma in untreated rabbits, reperfusion plasma produced TX and LTB4 generation (1090 +/- 105 and 794 +/- 91 pg/ml, respectively, p < 0.01), PMN accumulation (1636 +/- 210/mm3, p < 0.01) and activation (276 +/- 31 mean fluorescent units), and microvascular permeability (554 +/- 90 micrograms/ml, p < 0.01). Neutropenia (3 +/- 1 PMN/mm3) and cotreatment with SOD and catalase abolished these responses, whereas pretreatment with allopurinol did not. Human reperfusion plasma contains a soluble factor that stimulates free radical generation by rabbit neutrophils to produce a microvascular injury characterized by de novo TX production, neutrophil accumulation and activation, and increased microvascular permeability to protein.
主动脉瘤修复会产生炎症介质、中性粒细胞活化及远隔器官损伤。这些患者的再灌注血浆在体外趋化模型中会导致微血管损伤。本研究旨在探究这种损伤的机制。在移除主动脉夹之前及之后15分钟获取腔静脉血（n = 16），或在剖腹手术时获取（n = 10）。将血浆或盐溶液注入固定在脱毛麻醉兔背部磨皮处上方的单位剂量腔室。动物接受静脉注射盐溶液治疗（n = 4）；用氮芥使其中性粒细胞减少（n = 4）；用黄嘌呤氧化酶抑制剂别嘌呤醇预处理（n = 4）；或静脉联合使用自由基清除剂超氧化物歧化酶（SOD）和过氧化氢酶（n = 4）。3小时后，测量中性粒细胞计数（多形核细胞[PMN]/mm³）和活性（通过流式细胞术检测自由基产生）、蛋白渗漏以及炎症介质（血栓素[TX]和白三烯B4[LTB4]）。与未治疗兔的对照血浆相比，再灌注血浆产生TX和LTB4（分别为1090±105和794±91 pg/ml，p<0.01）、PMN聚集（1636±210/mm³，p<0.01）和活化（平均荧光单位为276±31）以及微血管通透性（554±90 μg/ml，p<0.01）。中性粒细胞减少（3±1 PMN/mm³）以及与SOD和过氧化氢酶联合治疗可消除这些反应，而用别嘌呤醇预处理则无效。人再灌注血浆含有一种可溶性因子，该因子可刺激兔中性粒细胞产生自由基，从而导致微血管损伤，其特征为新产生TX、中性粒细胞聚集和活化以及微血管对蛋白的通透性增加。
