Yassin Magdi M I, Harkin Denis W, Barros D'Sa Aires A B, Halliday M Isla, Rowlands Brian J
Department of Surgery, The Queen's University of Belfast, Institute of Clinical Sciences, Grosvenor Road, Belfast BT12 6BJ, Northern Ireland, UK.
World J Surg. 2002 Jan;26(1):115-21. doi: 10.1007/s00268-001-0169-2. Epub 2001 Oct 25.
Restoration of blood flow to an acutely ischemic lower limb may, paradoxically, result in systemic complications and unexpected mortality. We investigated the effect of acute ischemia-perfusion of the lower limb on cytokine production and end organ function. Plasma concentrations of tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6) were determined in five groups of male Wistar rats: control, 3 hours of bilateral hind limb ischemia alone, and 3 hours of bilateral hind limb ischemia followed by 1 hour, 2 hours, or 3 hours of reperfusion, respectively. In a second experiment, the effect of lower limb ischemia-reperfusion on remote organs (lung, liver, and kidney) was assessed biochemically and histologically. There was a significant increase in plasma concentrations of TNF-a in plasma of animals subjected to 3 hours of bilateral hind limb ischemia followed by 1 hour of reperfusion, 40.1 +/- 4.4 pg/ml, when compared with controls, 22.6 +/- 4.4 pg/ml, or animals in the ischemia-alone group, 16.3 +/- 5.2 (p <0.05). Plasma concentration of IL-6 increased progressively and significantly in animals subjected to bilateral hind limb ischemia followed by 1 hour of reperfusion, 720 +/- 107 pg/ml; 2 hours of reperfusion, 1987 +/- 489 pg/ml; or 3 hours of reperfusion, 6284 +/- 1244 (p <0.0001), compared with controls, 104 +/- 43 pg/ml; or animals in the ischemia-alone group, 140 +/- 55 pg/ml. In the study comparing portal and systemic concentrations of IL-6, systemic concentrations of IL-6, 967 +/- 184 pg/ml were significantly higher than those in the portal circulation 577 +/- 127 pg/ml (p <0.05). There was a significant increase in plasma concentrations of urea, creatinine, aspartate transaminase, alanine transaminase, and lactic dehydrogenase in reperfused animals compared with controls (p <0.001). Morbidity and mortality following reperfusion of the acutely ischemic limb may be a manifestation of multiple organ dysfunction caused by a systemic inflammatory response triggered by reperfusion of the ischemic extremities.
矛盾的是，急性缺血性下肢恢复血流可能会导致全身并发症和意外死亡。我们研究了下肢急性缺血-灌注对细胞因子产生和终末器官功能的影响。在五组雄性Wistar大鼠中测定了血浆肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的浓度：对照组、仅双侧后肢缺血3小时组，以及双侧后肢缺血3小时后分别再灌注1小时、2小时或3小时组。在第二个实验中，通过生化和组织学方法评估了下肢缺血-再灌注对远处器官（肺、肝和肾）的影响。与对照组（22.6±4.4 pg/ml）或仅缺血组动物（16.3±5.2 pg/ml）相比，双侧后肢缺血3小时后再灌注1小时的动物血浆中TNF-α浓度显著升高，为40.1±4.4 pg/ml（p<0.05）。与对照组（104±43 pg/ml）或仅缺血组动物（140±55 pg/ml）相比，双侧后肢缺血后再灌注1小时（720±107 pg/ml）、2小时（1987±489 pg/ml）或3小时（6284±1244 pg/ml）的动物血浆IL-6浓度逐渐显著升高（p<0.0001）。在比较IL-6门静脉和全身浓度的研究中，全身IL-6浓度（967±184 pg/ml）显著高于门静脉循环中的浓度（577±127 pg/ml，p<0.05）。与对照组相比，再灌注动物血浆中尿素、肌酐、天冬氨酸转氨酶、丙氨酸转氨酶和乳酸脱氢酶的浓度显著升高（p<0.001）。急性缺血肢体再灌注后的发病率和死亡率可能是缺血肢体再灌注引发的全身炎症反应导致多器官功能障碍的一种表现。
