Morgan R A, Manning P B, Coran A G, Drongowski R A, Till G O, Ward P D, Oldham K T
Shock Research Laboratory, Mott Children's Hospital, Ann Arbor, MI 48109.
Circ Shock. 1988 Aug;25(4):319-23.
Free radicals generated during purine catabolism or by activated granulocytes cause tissue injury by peroxidation of lipid membranes. In a canine model of sepsis initiated by intravenous live Escherichia coli, fluorescent products of lipid peroxidation (FP) were measured in serum. Four groups of five dogs infused with 10(9)E. coli/kg were analyzed--I: no further treatment; II: prior depletion of granulocytes with a cytotoxic antibody; III: pre-treatment with superoxide dismutase and catalase; and IV: resuscitation after bacterial infusion to maintain cardiac output greater than 80% of pre-bacteremic levels. In Groups I, II, and III, cardiac output fell to less than 50% of baseline within 1 hr and remained there throughout the study. FP in Groups I and II rose to greater than 200% of baseline (P less than .02 and less than .03). In Groups III and IV, FP did not rise significantly from baseline. The rise in serum FP and the prevention of this rise by-treatment with antioxidants indicate generation of oxygen radicals. Their presence had no effect on hemodynamic parameters. Granulocyte depletion did not alter appearance of FP; however, prevention of low cardiac output blocked FP formation. These data suggest that oxygen free radicals were generated by tissue ischemia, rather than by granulocytes, in this model of septic shock.
嘌呤分解代谢过程中产生的自由基或活化的粒细胞所产生的自由基，可通过脂质膜的过氧化作用导致组织损伤。在通过静脉注射活大肠杆菌引发的犬类败血症模型中，测定了血清中脂质过氧化的荧光产物（FP）。对四组每组五只静脉注射10⁹大肠杆菌/千克的犬进行了分析——第一组：不进行进一步治疗；第二组：先用细胞毒性抗体耗竭粒细胞；第三组：用超氧化物歧化酶和过氧化氢酶预处理；第四组：在细菌注入后进行复苏以维持心输出量大于菌血症前水平的80%。在第一组、第二组和第三组中，心输出量在1小时内降至基线的50%以下，并在整个研究过程中维持在该水平。第一组和第二组中的FP升至基线的200%以上（P<0.02和<0.03）。在第三组和第四组中，FP与基线相比没有显著升高。血清FP的升高以及抗氧化剂治疗对这种升高的预防表明有氧自由基的产生。它们的存在对血流动力学参数没有影响。粒细胞耗竭并未改变FP的出现；然而，预防低心输出量可阻止FP的形成。这些数据表明，在这个感染性休克模型中，氧自由基是由组织缺血产生的，而不是由粒细胞产生的。
