Cardiac surgery: myocardial energy balance, antioxidant status, and endothelial function after ischemia-reperfusion

Cardiac surgery: myocardial energy balance, antioxidant status, and endothelial function after ischemia-reperfusion
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DOI:
10.1016/s0753-3322(02)00286-x
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发表时间:
2002-12-01
影响因子:
7.5
通讯作者:
Marinello, E
Marinello, E
中科院分区:
医学2区
文献类型:
--
作者:
Carlucci, F;Tabucchi, A;Marinello, E

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在心脏手术的缺血再灌注过程中,心肌和内皮损伤仍然是一个广泛争论的问题。我们评估了 14 名接受冠状动脉搭桥术 (CABG) 的患者的心肌嘌呤代谢、抗氧化防御机制、氧化状态和内皮功能障碍标志物。在主动脉交叉钳夹之前(t1)、钳夹移除之前(t2)和再灌注后 30 分钟(t3)进行心脏活检;通过毛细管电泳 (CE) 分析组织的高氯提取物的谷胱甘肽、NAD、核苷酸核苷和碱基含量。在来自冠状窦的血浆样本中,我们评估了:通过 CE 评估硝酸盐和亚硝酸盐浓度,通过 ELISA 评估血浆谷胱甘肽过氧化物酶 (plGPx),通过 RIA 评估内皮素-1 (ET-1),通过比色测定评估活性氧代谢物 (ROM)。在缺血期 (t2),我们观察到细胞 NAD 和 GSH 水平以及硝酸盐、亚硝酸盐和 plGPx 水平降低。 ATP和GTP水平下降,其分解代谢产物AMP、GMP、IMP、腺苷、肌苷和次黄嘌呤积累。能量电荷、ATP/ADP 比率和核苷酸/(核苷+碱基)比率下降。在 0 时,血浆 ET-1 水平增加,单磷酸核苷酸趋于恢复至基础值。能量电荷没有增加,但核苷酸/(核苷+核碱基)比率有所恢复。硝酸盐和亚硝酸盐的水平继续下降。未观察到 ROM 水平的显着变化。我们的数据表明,氧化应激和内皮损伤是 CABG 期间的主要事件,压倒了肌细胞的清除能力,并在再灌注后 30 分钟内阻碍正常能量平衡的恢复。导致 IMP 产生的 AMP 脱氨酶途径在缺血期间很活跃,并且腺苷不是人心脏中 ATP 分解产生的主要化合物。还讨论了体外循环的可能作用。 (C) 2002 年科学与医学版 Elsevier SAS。版权所有。
Myocardial and endothelial damage is still a widely debated problem during the ischemia-reperfusion sequence in heart surgery. We evaluated myocardial purine metabolites, antioxidant defense mechanisms, oxidative status and endothelial dysfunction markers in 14 patients undergoing coronary artery by-pass graft (CABG). Heart biopsies were taken before aortic cross-clamping (t1), before clamp removal (t2) and 30 min after reperfusion (t3); perchloric extracts of the tissue were analyzed for glutathione, NAD, nucleotide nucleoside and base content by capillary electrophoresis (CE). In plasma samples from the coronary sinus we evaluated: nitrate and nitrite concentrations by CE, plasma glutathione peroxidase (plGPx) by ELISA, endothelin-1 (ET-1) by RIA and reactive oxygen metabolites (ROM) by colorimetric assay. During the ischemic period (t2)-we observed a reduction in cellular NAD and GSH levels, as well as nitrate, nitrite and plGPx. ATP and GTP levels decreased and their catabolic products AMP, GMP, IMP, adenosine, inosine and hypoxanthine accumulated. The energy charge, ATP/ADP ratio, and nucleotide/(nucleoside + base) ratios decreased. At 0, levels of plasma ET-1 increased and monophosphate nucleotides tended to return to basal values. The energy charge did not increase but the nucleotide/(nucleoside + nucleobase) ratio recovered to some extent. Levels of nitrates plus nitrites continued to decrease. No significant variation in ROM levels was observed. Our data indicate that oxidative stress and endothelial damage are major events during CABG, overwhelming the scavenging capacity of the myocyte and preventing restoration of the normal energy balance for 30 min after reperfusion. The AMP deaminase pathway leading to IMP production is active during ischemia and adenosine is not the main compound derived from ATP break-down in the human heart. The possible role of extracorporeal circulation is also discussed. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.