Mitrev Z, Ihnken K, Poloczek Y, Hallmann R, Herold H, Unkelbach U, Zimmer G, Freisleben H J, Beyersdorf S, Beyersdorf F
Klinik für Thorax-, Herz- und Gefsschirurgie, Johann Wolfgang Goethe-Universität Frankfurt/M.
Zentralbl Chir. 1996;121(9):774-87.
Our previous studies in isolated rat hindlimbs using crystalloid perfusion solutions have shown that control of the initial reperfusion reduces postischemic complications. However, no experimental study has been undertaken to evaluate the concept of controlled limb reperfusion experimentally in an in-vivo blood-perfused model and to assess the local as well as systemic effects of normal blood reperfusion and controlled limb reperfusion. Of twenty pigs undergoing preparation of the infrarenal aorta and iliac arteries, six were observed for 7.5 hours and served as controls. Fourteen other pigs underwent 6 hours of complete infrarenal occlusion. Thereafter, embolectomy was stimulated in 8 pigs by removing the aortic clamp and establishing normal blood reperfusion at systemic pressure. In 6 other pigs, control of the composition of the reperfusate and control of the conditions of reperfusion was done during the first 30 min, followed by normal blood reperfusion. Six hours of infrarenal aortic occlusion lead to a severe decrease in high energy phosphates and muscle temperature and a slight increase in creating kinase (CK) and potassium in the systemic circulation. Normal blood reperfusion resulted in severe reperfusion injury: massive edema developed (80.6% vs. 76.6%, p < 0.0009), the tissue showed a marked decrease in oxygen consumption (7.3 +/- 1.1 vs. 14.3 +/- 2.5 mL )2/100 g/min, p < 0.02), glucose consumption (0.19 +/- 0.06 vs. 0.51 +/- 0.03 mg/100 g/min, p < 0.06), tissue ATP (18.3 +/- 1.9 vs. 36.1 +/- 0.9 mumol/g protein, p < 0.000001), total adenine nucleotides (26.3 +/- 2.6 vs. 45.8 +/- 1.5 mumol/g protein, p < 0.00001), muscle pH (5.9 +/- 0.1 vs. 7.3 +/- 0.1, p < 0.000006) and total calcium in the femoral vein (2. +/- 0.1 vs. 2.7 +/- 0.1 mmol/L, p < 0.002). Furthermore, a massive increase was seen in CK concentration (12,743 +/- 2,562 vs. 513 +/- 80 U/L, p < 0.0003), potassium (7.9 +/- 0.3 vs. 4.4 +/- 0.2 mmol/L, p < 0.000001) and muscle rigidity (60 +/- 11 vs. 122 +/- 1 degree, p < 0.00008). In sharp contrast, initial treatment of the ischemic skeletal muscle by controlled limb reperfusion resulted in normal water content (77.6 +/- 0.4 vs. 76.8 +/- 0.3%), oxygen consumption (13.2 +/- 1.6 vs. 14.9 +/- 3.2 mL O2/100 g/min), glucose consumption (0.58 +/- 0.18 vs. 0.46 +/- 0.11 mg/100 g/min), flow (5.4 +/- 1.1 vs. 4.6 +/- 4.6 +/- 0.5 mL/100 g/min) and muscle rigidity (106 +/- 4 vs. 122 +/- 1 degree). Furthermore, controlled limb reperfusion resulted in higher total adenine nucleotides content (78% vs. 57% of control), less tissue acidosis (6.6 +/- 0.2 vs. 5.9 +/- 0.1, p < 0.002), severely reduced CK release (2,618 +/- 702 vs. 12,743 +/- 2.562, p < 0.02) and potassium release (5.1 +/- 0.3 vs. 7.9 +/- 0.3 mmol/L, p < 0.0002) as compared to normal blood reperfusion. In conclusion this study shows that 6 hours of acute infrarenal aortic occlusion will result in a severe reperfusion injury (postischemic syndrome) if normal blood at systemic pressure is given in the initial reperfusion phase. In contrast, initial treatment of the ischemic skeletal muscle by controlled limb reperfusion reduces the metabolic, functional and biochemical alterations.
我们之前使用晶体灌注溶液对大鼠离体后肢进行的研究表明,控制初始再灌注可减少缺血后并发症。然而,尚未有实验研究在体内血液灌注模型中对控制性肢体再灌注的概念进行实验评估,也未评估正常血液再灌注和控制性肢体再灌注的局部及全身效应。在20头接受肾下腹主动脉和髂动脉制备的猪中,6头观察7.5小时作为对照。另外14头猪进行6小时的完全肾下动脉闭塞。此后,8头猪通过移除主动脉夹并在体循环压力下建立正常血液再灌注来刺激取栓。另外6头猪在最初30分钟内对再灌注液成分和再灌注条件进行控制,随后进行正常血液再灌注。6小时的肾下主动脉闭塞导致高能磷酸盐和肌肉温度严重降低,全身循环中肌酸激酶(CK)和钾略有升高。正常血液再灌注导致严重的再灌注损伤:出现大量水肿(80.6%对76.6%,p<0.0009),组织氧耗显著降低(7.3±1.1对14.3±2.5mL O₂/100g/min,p<0.02),葡萄糖消耗降低(0.19±0.06对0.51±0.03mg/100g/min,p<0.06),组织ATP降低(18.3±1.9对36.1±0.9μmol/g蛋白,p<0.000001),总腺嘌呤核苷酸降低(26.3±2.6对45.8±1.5μmol/g蛋白,p<0.00001),肌肉pH降低(5.9±0.1对7.3±0.1,p<0.000006),股静脉总钙降低(2.±0.1对2.7±0.1mmol/L,p<0.002)。此外,CK浓度大幅升高(12743±2562对513±80U/L,p<0.0003),钾升高(7.9±(此处原文似乎有误,推测应为7.9±0.3)对4.4±0.2mmol/L,p<0.000001),肌肉僵硬程度升高(60±11对12(此处原文似乎有误,推测应为122)±1度,p<0.00008)。形成鲜明对比的是,通过控制性肢体再灌注对缺血骨骼肌进行初始治疗,导致水含量正常(77.6±0.4对76.8±0.3%),氧耗(13.2±1.6对14.9±3.2mL O₂/100g/min),葡萄糖消耗(0.58±0.18对0.46±0.11mg/100g/min),血流量(5.4±1.1对4.6±(此处原文似乎有误,推测应为4.6±0.5)mL/100g/min)和肌肉僵硬程度(106±4对12(此处原文似乎有误,推测应为122)±1度)。此外,与正常血液再灌注相比,控制性肢体再灌注导致总腺嘌呤核苷酸含量更高(为对照的78%对57%),组织酸中毒减轻(6.6±此处原文似乎有误,推测应为6.6±0.2)对5.9±0.1,p<0.002),CK释放严重减少(2618±702对12743±2562,p<0.02),钾释放减少(5.1±0.3对7.9±0.3mmol/L,p<0.0002)。总之,本研究表明,如果在初始再灌注阶段给予体循环压力下的正常血液,6小时的急性肾下主动脉闭塞将导致严重的再灌注损伤(缺血后综合征)。相比之下,通过控制性肢体再灌注对缺血骨骼肌进行初始治疗可减少代谢、功能和生化改变。