Ventricular arrhythmias following exposure of failing hearts to oxidative stress in vitro
Ventricular arrhythmias following exposure of failing hearts to oxidative stress in vitro
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DOI：
10.1046/j.1540-8167.2005.40584.x
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发表时间：
2005-06-01
影响因子：
2.7
通讯作者：
Lacroix, D
中科院分区：
文献类型：
--
作者：
Brigadeau, F;Gelé, P;Lacroix, D
心力衰竭中的氧化应激与心律失常。导读：有实验证据表明心力衰竭（HF）是一种氧化应激，HF肌细胞可能被氧源性自由基损伤。然而，这些自由基在心衰中的致心律失常性尚未得到研究。方法与结果：分别从假手术（SHAM, n = 6）和快速起搏（250 ms， 2周）心力衰竭猪（HF, n = 8）中获得离体灌注心脏。灌注100、300、1000 mu mol/L H2O2后，心外膜纵、横向传导图绘制，密切监测室性心律失常。在相同条件下取左心室心外膜作动作电位记录。还评估了心肌硫代巴比妥酸活性物质水平和抗氧化酶能力。两组心外膜传导速度均未受H2O2影响。尽管抗氧化能力增加，包括Cu/Zn和Mn超氧化物歧化酶、过氧化氢酶、谷胱甘肽还原酶和谷胱甘肽过氧化物酶，但与SHAM相比，HF患者更常发生孤立性室性早搏和缓慢的心室节律。未观察到持续的心律失常。较高的硫代巴比妥酸反应物质水平在HF中被发现，证实了内源性氧化应激。在1000 μ mol/L的H2O2作用下，SHAM中动作电位持续时间增加，但在HF心外膜纤维中没有。结论：心衰模型出现氧化应激，同时抗氧化能力增加。心衰患者更容易发生氧化应激介导的心律失常。这些心律失常主要是室性心动过速或心室节律缓慢，不依赖于异常的心肌传导。
Oxidative Stress and Arrhythmias in Heart Failure. Introduction: There is experimental evidence that heart failure (HF) is an oxidative stress and that HF myocytes may be damaged by oxygen-derived free radicals. However, the arrhythmogenicity of these radicals has not been studied in HF.Methods and Results: Isolated perfused hearts were obtained from sham-operated (SHAM, n = 6), and fast pacing (250 ms, 2 weeks)-induced heart failure porcines (HF, n = 8). Epicardial conduction was mapped in the longitudinal and transverse directions and ventricular arrhythmias were closely monitored after perfusion of 100, 300, and 1000 mu mol/L H2O2. Left ventricular epicardium was sampled for action potentials recordings in the same conditions. Myocardial levels of thiobarbituric acid reactive substances and antioxidant enzymatic capacity were also assessed. Epicardial conduction velocities were unaffected by H2O2 in both groups. Isolated ventricular premature beats and runs of slow ventricular rhythm with H2O2 more frequently occurred in HF compared to SHAM despite an increased antioxidant capacity including Cu/Zn and Mn superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase. Sustained arrhythmias were not observed. Higher thiobarbituric acid reactive substances levels were found in HF confirming endogenous oxidative stress. Action potential duration at plateau level was increased following H2O2 in SHAM but not in HF epicardial fibers where a toxic effect developed at 1000 mu mol/L.Conclusion: Oxidative stress with concomitant increase in antioxidant capacity develops in this HF model. There is a greater proclivity to oxidative stress-mediated arrhythmias in HF. These arrhythmias are mainly extrasystoles or slow ventricular rhythms and not dependent on abnormal myocardial conduction.