Menasché P, Pasquier C, Bellucci S, Lorente P, Jaillon P, Piwnica A
Service de Chirurgie Cardio-Vasculaire, Hôpital Lariboisière, Paris, France.
J Thorac Cardiovasc Surg. 1988 Oct;96(4):582-9.
We assessed the effects of the iron chelator deferoxamine in 24 adult patients (12 controls, 12 treated) undergoing cardiopulmonary bypass for various cardiac operations. Deferoxamine was given both intravenously (30 mg/kg of body weight, starting 30 minutes before and ending 30 minutes after bypass) and as an additive to the cardioplegic solution (250 mg/L). Right atrial blood samples were taken before, during, and after bypass, and isolated polymorphonuclear neutrophils were evaluated for their capacity to generate superoxide radicals after stimulation with N-formyl-methionyl-leucyl-phenylalanine (FLMP, 10(-7) mol) and phorbol myristate acetate (100 ng/ml). At the same sampling times, measurement of the plasma levels of 6-keto-prostaglandin F1 alpha, the stable derivative of prostacyclin, was used as an index of membrane phospholipid breakdown. The two groups were not significantly different with regard to age, duration of bypass, and quantitative changes in polymorphonuclear neutrophil counts during the operation. Before bypass, the superoxide production of FMLP-stimulated polymorphonuclear neutrophils was comparable in the two groups. Conversely, after bypass, polymorphonuclear neutrophils harvested from deferoxamine-treated patients produced significantly fewer superoxide radicals than those of control patients (1.9 +/- 0.3 versus 3.7 +/- 0.2 nmol/10(6) polymorphonuclear neutrophils per minute, p less than 0.05). Stimulation of polymorphonuclear neutrophils by phorbol myristate acetate yielded similar changes, as the postbypass superoxide production was 12.6 +/- 2.5 nmol/10(6)/min in control patients and 7.1 +/- 0.9 nmol/10(6)/min in those receiving deferoxamine (p less than 0.05). In contrast, plasma levels of 6-keto-prostaglandin F1 alpha were not significantly different between the two groups. We conclude that deferoxamine-exposed polymorphonuclear neutrophils have a decreased oxidative responsiveness, compatible with the fact that they may have been less "primed" by secretagogues released during bypass, as compared with cells of untreated patients. Our results are consistent with the hypothesis that deferoxamine, by inhibiting iron-catalyzed free radical production, may limit the free radical-mediated amplification of the inflammatory response to bypass and as such could be effective in reducing the harmful effects of extracorporeal circulation.
我们评估了铁螯合剂去铁胺对24例接受各种心脏手术体外循环的成年患者（12例对照，12例治疗）的影响。去铁胺通过静脉给药（30mg/kg体重，在体外循环开始前30分钟开始，结束后30分钟结束），并作为心脏停搏液的添加剂（250mg/L）。在体外循环前、期间和之后采集右心房血样，分离多形核中性粒细胞，评估其在用N-甲酰甲硫氨酰亮氨酰苯丙氨酸（FLMP，10⁻⁷mol）和佛波酯肉豆蔻酸酯（100ng/ml）刺激后产生超氧阴离子自由基的能力。在相同的采样时间，测量血浆中前列环素稳定衍生物6-酮-前列腺素F1α的水平，作为膜磷脂分解的指标。两组在年龄、体外循环持续时间和手术期间多形核中性粒细胞数量的定量变化方面无显著差异。体外循环前，两组中FMLP刺激的多形核中性粒细胞的超氧阴离子产生相当。相反，体外循环后，从接受去铁胺治疗的患者中采集的多形核中性粒细胞产生的超氧阴离子自由基明显少于对照组患者（1.9±0.3对3.7±0.2nmol/10⁶多形核中性粒细胞每分钟，p<0.05）。佛波酯肉豆蔻酸酯刺激多形核中性粒细胞也产生了类似的变化，因为体外循环后对照组患者的超氧阴离子产生为12.6±2.5nmol/10⁶/分钟，接受去铁胺治疗的患者为7.1±0.9nmol/10⁶/分钟（p<0.05）。相比之下，两组间血浆6-酮-前列腺素F1α水平无显著差异。我们得出结论，暴露于去铁胺的多形核中性粒细胞氧化反应性降低，这与它们可能比未治疗患者的细胞更少受到体外循环期间释放的促分泌素“启动”这一事实相符。我们的结果与以下假设一致，即去铁胺通过抑制铁催化的自由基产生，可能限制自由基介导的对体外循环炎症反应的放大，因此可能有效减少体外循环的有害影响。
