Menger M D, Pelikan S, Steiner D, Messmer K
Institute for Surgical Research, University of Munich, Federal Republic of Germany.
Am J Physiol. 1992 Dec;263(6 Pt 2):H1901-6. doi: 10.1152/ajpheart.1992.263.6.H1901.
Ischemia-reperfusion (I/R)-induced microvascular injury is characterized by capillary "no-reflow" and reflow-associated events, termed "reflow paradox," including leukocyte-endothelium interaction and increase in microvascular permeability. The major objectives of this study were 1) to elucidate the significance of reflow paradox after 4 h of tourniquet-induced ischemia in striated muscle and 2) to determine the role of reactive oxygen metabolites in the pathogenesis of reflow paradox-dependent microcirculatory alterations. By use of in vivo fluorescence microscopy in a striated muscle preparation of hamsters, leukocyte-endothelium interaction in postcapillary venules and macromolecular extravasation from capillaries and venules were quantified before ischemia and after 30 min, 2 h, and 24 h of reperfusion. I/R elicited marked enhancement (P < 0.01) of leukocyte rolling during initial reperfusion and a 20-fold increase of leukocyte adherence (P < 0.01) lasting for the entire postischemic reperfusion period (n = 7). These phenomena were accompanied by significant leakage (P < 0.01) of macromolecules from capillaries and in particular from postcapillary venules (n = 9). Both superoxide dismutase (SOD, 20 mg/kg body wt, n = 7) and allopurinol (50 mg/kg body wt, n = 7) were effective in attenuating I/R-induced leukocyte rolling and adherence. In addition, microvascular leakage was significantly reduced by allopurinol (n = 9) and completely abolished by SOD (n = 9) (P < 0.01). These results support the concept that reactive oxygen metabolites contribute to I/R-induced reflow paradox, resulting in leukocyte accumulation, adherence, and increase in microvascular permeability.
缺血再灌注（I/R）诱导的微血管损伤的特征是毛细血管“无复流”以及与复流相关的事件，即“复流悖论”，包括白细胞与内皮细胞相互作用以及微血管通透性增加。本研究的主要目的是：1）阐明在止血带诱导的横纹肌缺血4小时后复流悖论的意义；2）确定活性氧代谢产物在依赖复流悖论的微循环改变发病机制中的作用。通过在仓鼠横纹肌制备物中使用体内荧光显微镜，在缺血前以及再灌注30分钟、2小时和24小时后，对毛细血管后微静脉中的白细胞与内皮细胞相互作用以及毛细血管和微静脉中的大分子外渗进行定量分析。I/R在初始再灌注期间引起白细胞滚动显著增强（P<0.01），并且白细胞黏附增加20倍（P<0.01），在整个缺血后再灌注期间持续存在（n = 7）。这些现象伴随着大分子从毛细血管尤其是从毛细血管后微静脉的显著渗漏（P<0.01）（n = 9）。超氧化物歧化酶（SOD，20mg/kg体重，n = 7）和别嘌呤醇（50mg/kg体重，n = 7）均能有效减轻I/R诱导的白细胞滚动和黏附。此外，别嘌呤醇显著减少了微血管渗漏（n = 9），而SOD完全消除了微血管渗漏（n = 9）（P<0.01）。这些结果支持了活性氧代谢产物促成I/R诱导的复流悖论，导致白细胞积聚、黏附以及微血管通透性增加这一概念。
