Dutkowski P, Schönfeld S, Heinrich T, Watzka M, Winkelbach V, Krysiak M, Odermatt B, Junginger T
Department of Surgery, University of Mainz, Germany.
Transplantation. 1999 Jul 15;68(1):44-50. doi: 10.1097/00007890-199907150-00009.
ATP resynthesis during reperfusion after liver preservation has been shown to be well correlated with the function of transplanted grafts. Nevertheless, the advantages of a cellular energy charge loading during the preservation period are yet not fully understood. This study evaluates the effects of different nucleotide levels at the end of preservation on metabolic changes and oxidative stress during reperfusion.
Two experimental groups were chosen reflecting different energy charge states after preservation: static cold storage for 10 hr and hypothermic oxygenated oscillating perfusion for 10 hr. In both experimental groups, normothermic ex vivo acellular reperfusion over 40 min was performed. A third group consisted of nonpreserved livers similarly reperfused for 40 min. Superoxide formation was detected by the superoxide dismutase inhibitable reduction of ferricytochrome c added to the normothermic perfusate.
Superoxide formation and lipid peroxidation malondialdehyde were significantly lower during reperfusion after the energy charge loading before reperfusion by the hypothermic oscillating perfusion technique. However, oxygen radical formation, liver cell injury (lactate dehydrogenase [LDH] release), and TNFalpha release were significantly higher in energy charge-depleted groups (nonpreserved and cold stored livers).
Hypothermic oscillating oxygenated perfusion led to the elevated energy charge during preservation and led to reduced oxygen radical formation as well as less lipid peroxidation during reperfusion, in contrast to cold stored livers and nonpreserved livers. This suggests a correlation between the energy charge before reperfusion and oxygen radical formation as well as liver injury at reperfusion.
肝保存后再灌注期间的ATP再合成已被证明与移植肝脏的功能密切相关。然而,保存期细胞能量负荷加载的优势尚未完全了解。本研究评估保存结束时不同核苷酸水平对再灌注期间代谢变化和氧化应激的影响。
选择两个实验组,反映保存后不同的能量负荷状态:静态冷藏10小时和低温氧合振荡灌注10小时。在两个实验组中,进行了40分钟的常温离体无细胞再灌注。第三组由同样再灌注40分钟的未保存肝脏组成。通过添加到常温灌注液中的超氧化物歧化酶可抑制的高铁细胞色素c还原来检测超氧化物的形成。
低温振荡灌注技术在再灌注前进行能量负荷加载后,再灌注期间超氧化物的形成和脂质过氧化丙二醛显著降低。然而,能量负荷耗尽组(未保存和冷藏的肝脏)中的氧自由基形成、肝细胞损伤(乳酸脱氢酶[LDH]释放)和TNFα释放显著更高。
与冷藏肝脏和未保存肝脏相比,低温振荡氧合灌注导致保存期间能量负荷升高,并导致再灌注期间氧自由基形成减少以及脂质过氧化减少。这表明再灌注前的能量负荷与再灌注时的氧自由基形成以及肝损伤之间存在相关性。