Williams R E, Zweier J L, Flaherty J T
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Circulation. 1991 Mar;83(3):1006-14. doi: 10.1161/01.cir.83.3.1006.
Iron may play a central role in oxygen radical generation during myocardial ischemia and after reperfusion. Because conditions during ischemia may also liberate iron, we hypothesized that administration of the iron chelator deferoxamine during ischemia would result in improved functional and metabolic recovery after postischemic reperfusion.
Isolated, perfused rabbit hearts were studied by phosphorus-31 nuclear magnetic resonance spectroscopy. The hearts received one of three treatments: deferoxamine at the onset of 30 minutes of global ischemia (n = 9), deferoxamine as a bolus followed by a continuous 15-minute infusion begun at reflow (n = 9), or standard perfusate (n = 7). Hearts treated with deferoxamine during ischemia showed better recovery of developed pressure than did control hearts (63.2 +/- 7.5% versus 41.2 +/- 2.9% of baseline) (p = 0.02) and better recovery of myocardial phosphocreatine content (92.4 +/- 10.3% versus 68.2 +/- 4.5% of baseline, p less than 0.05). These functional and metabolic benefits were comparable to those obtained with deferoxamine treatment during early reperfusion. In 15 additional hearts, intraischemic treatment with deferoxamine resulted in no reduction in oxygen radical concentrations as measured on frozen tissue by electron paramagnetic resonance spectroscopy at end ischemia, but the treatment eliminated the reperfusion-induced increase of free radical generation observed in control hearts (2.9 +/- 0.01 versus 7.0 +/- 0.07 microM, p less than 0.001). The magnitude of reduction was similar to that when deferoxamine was given at the onset of reflow (2.4 +/- 0.02 microM, p less than 0.001 versus control).
These results demonstrate improved functional and metabolic recovery of myocardium treated with deferoxamine during ischemia, accompanied by a reduction in reperfusion-induced oxygen free-radical generation to the same degree as reflow treatment, confirming the importance of iron in the pathogenesis of myocardial reperfusion injury.
铁可能在心肌缺血及再灌注过程中氧自由基的产生中起核心作用。由于缺血时的状况也可能释放铁，我们推测在缺血期间给予铁螯合剂去铁胺会使缺血后再灌注时的功能和代谢恢复得到改善。
采用磷-31核磁共振波谱法对离体灌注兔心进行研究。心脏接受三种处理之一：在全心缺血30分钟开始时给予去铁胺（n = 9）；在再灌注开始时给予一次大剂量去铁胺，随后持续输注15分钟（n = 9）；或给予标准灌注液（n = 7）。缺血期间用去铁胺处理的心脏，其左室舒张末压的恢复情况优于对照心脏（分别为基线的63.2±7.5%和41.2±2.9%）（p = 0.02），心肌磷酸肌酸含量的恢复也更好（分别为基线的92.4±10.3%和68.2±4.5%，p < 0.05）。这些功能和代谢方面的益处与早期再灌注时用去铁胺处理所获得的益处相当。在另外15个心脏中，缺血期间用去铁胺处理，在缺血末期通过电子顺磁共振波谱法在冷冻组织上测量氧自由基浓度未降低，但该处理消除了对照心脏中观察到的再灌注诱导的自由基生成增加（分别为2.9±0.01和7.0±0.07微摩尔，p < 0.001）。降低幅度与再灌注开始时给予去铁胺时相似（2.4±0.02微摩尔，与对照相比p < 0.001）。
这些结果表明，缺血期间用去铁胺处理的心肌功能和代谢恢复得到改善，同时再灌注诱导的氧自由基生成减少程度与再灌注处理相同，证实了铁在心肌再灌注损伤发病机制中的重要性。
