Atrial high energy phosphate content and mitochondrial enzyme activity during chronic atrial fibrillation
Atrial high energy phosphate content and mitochondrial enzyme activity during chronic atrial fibrillation
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DOI：
10.1016/s0008-6363(00)00139-5
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发表时间：
2000-09-01
影响因子：
10.8
通讯作者：
Borgers, M
中科院分区：
文献类型：
--
作者：
Ausma, J;Coumans, WA;Borgers, M
目的：延长心房颤动（AF）导致心房心肌细胞的（超）结构重塑，类似于缺血引起的心室冬眠。这些变化背后的机制尚不完全清楚。在本研究中，我们探讨了慢性房颤期间能量状态的严重失衡作为结构重塑刺激的假设。方法和结果：测定了在窦性心律（SR）和以爆发性起搏维持AF 1、2、4、8和16周后山羊心房组织样本中高能磷酸盐和相关化合物的含量，以及已知在缺血条件下发生改变的选定数量的线粒体酶。通过计算心肌溶解率为10%的细胞百分比来量化心房重构。在房颤结构重构逐渐发展的过程中，8周后约40%的心房肌细胞受到影响。AF期间，腺嘌呤核苷酸及其降解产物的浓度无明显变化，线粒体细胞色素c氧化酶活性与AF和sr相似，线粒体nadh氧化酶和质子易位atp酶活性不受AF的影响，组织中磷酸肌酸含量在AF第1周下降60%，但在AF第8 ~ 16周完全恢复。房颤期间的腺嘌呤核苷酸分析没有提供严重心房缺血发展的指示。这一观点得到了酶细胞化学发现的支持。然而，房颤诱导的心房重构与磷酸肌酸含量的短暂降低有关，这表明房颤早期能量需求增加。随后磷酸肌酸池的恢复表明慢性纤颤心房能量需求和供应平衡的恢复。(C) 2000 Elsevier Science B.V.版权所有
Objective: Prolonged atrial fibrillation (AF) results in (ultra)structural remodelling of atrial cardiomyocytes resembling alterations seen in ischemia-induced ventricular hibernation. The mechanisms underlying these changes are incompletely understood. In the present study we explored the hypothesis that a profound imbalance in energy status during chronic AF acts as a stimulus for structural remodelling. Methods and Results: The content of high energy-phosphates and related compounds together with a selected number of mitochondrial enzymes, known to be altered under ischemic conditions, were determined in tissue samples taken from atria of goats in sinus rhythm (SR) and after 1, 2, 4, 8 and 16 weeks of AF maintained by burst pacing. Atrial remodelling was quantified by counting the percentage of cells with >10% myolysis. During AF structural remodelling developed progressively, after 8 weeks about 40% of the atrial myocytes were affected. The concentration of adenine nucleotides and their degradation products did not change significantly during AF. Also the activity of mitochondrial cytochrome c oxidase activity was similar during AF and SR. Mitochondrial NADH-oxidase and proton-translocating ATPase activities were not induced by AF. The tissue content of phosphocreatine decreased during the first week by 60%, but completely recovered between 8 and 16 weeks of AF. Conclusions: The analysis of adenine nucleotides during AF provided no indication for the development of severe atrial ischemia. This notion is supported by enzyme cytochemical findings. However, AF-induced atrial remodelling was associated with a transient lowering of phosphocreatine content, suggesting an increase in energy demand during the early phase of AF. The subsequent recovery of the phosphocreatine pool indicates restoration of the balance between energy demand and supply in chronically fibrillating atria. (C) 2000 Elsevier Science B.V. All rights reserved.