Increased susceptibility of aged hearts to ventricular fibrillation during oxidative stress
Increased susceptibility of aged hearts to ventricular fibrillation during oxidative stress
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DOI：
10.1152/ajpheart.00579.2009
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发表时间：
2009-11-01
影响因子：
4.8
通讯作者：
Karagueuzian, Hrayr S.
中科院分区：
文献类型：
--
作者：
Morita, Norishige;Sovari, Ali A.;Karagueuzian, Hrayr S.
Morita N，Sovari AA，Xie Y，Fishbein MC，Mandel WJ，Garfinkel A，Lin SF，Chen PS，Xie LH，Chen F，Qu Z，韦斯JN，Karagueuzian HS.氧化应激时老年心脏对室颤的易感性增加。Am J Physiol Heart Circ Physiol 297：H1594-H1605，2009.首次发表于2009年9月18日; doi：10.1152/ajpheart.00579.2009。过氧化氢（H2 O2）氧化应激容易促进早期后除极（埃兹）和触发活动（TA）在离体大鼠和兔心室肌细胞。在这里，我们研究了过氧化氢对心律失常的影响，在完整的Langendorff大鼠和家兔心脏，使用双膜电压和细胞内钙光学地图和玻璃微电极记录。年轻成年大鼠（3-5月龄，N = 25）和家兔（3-5月龄，N = 6）心脏在用H2 O2（0.1-2 mM）灌注长达3 h时未出现心律失常。然而，在33/35（94%）的老年（24-26个月）大鼠心脏，0.1 mM H2 O2引起EAD介导的TA，导致室性心动过速（VT）和纤维性颤动（VF）。老年兔（寿命，8-12岁）不可用，但10只中年兔（3-5岁）中有4只发生埃兹、TA、VT和VF。这些心律失常被还原剂N-乙酰半胱氨酸（2 mM）和CaMKII抑制剂KN-93（1 μ M）抑制，但不被其非活性形式（KN-92，1 μ M）抑制。H_2O_2处理前后，老年和青年大鼠心脏动作电位时程（APD）和APD恢复斜率无明显差异。然而，在组织学切片中，三色染色显示老年大鼠心脏表现出广泛的纤维化，范围为10-90%;中年兔心脏纤维化较少（5-35%），而年轻成年大鼠和兔心脏纤维化程度较低（10 - 30%）。
Morita N, Sovari AA, Xie Y, Fishbein MC, Mandel WJ, Garfinkel A, Lin SF, Chen PS, Xie LH, Chen F, Qu Z, Weiss JN, Karagueuzian HS. Increased susceptibility of aged hearts to ventricular fibrillation during oxidative stress. Am J Physiol Heart Circ Physiol 297: H1594-H1605, 2009. First published September 18, 2009; doi:10.1152/ajpheart.00579.2009.-Oxidative stress with hydrogen peroxide (H2O2) readily promotes early afterdepolarizations (EADs) and triggered activity (TA) in isolated rat and rabbit ventricular myocytes. Here we examined the effects of H2O2 on arrhythmias in intact Langendorff rat and rabbit hearts using dual-membrane voltage and intracellular calcium optical mapping and glass microelectrode recordings. Young adult rat (3-5 mo, N = 25) and rabbit (3-5 mo, N = 6) hearts exhibited no arrhythmias when perfused with H2O2 (0.1-2 mM) for up to 3 h. However, in 33 out of 35 (94%) aged (24-26 mo) rat hearts, 0.1 mM H2O2 caused EAD-mediated TA, leading to ventricular tachycardia (VT) and fibrillation (VF). Aged rabbits (life span, 8-12 yr) were not available, but 4 of 10 middle-aged rabbits (3-5 yr) developed EADs, TA, VT, and VF. These arrhythmias were suppressed by the reducing agent N-acetylcysteine (2 mM) and CaMKII inhibitor KN-93 (1 mu M) but not by its inactive form (KN-92, 1 mu M). There were no significant differences between action potential duration (APD) or APD restitution slope before or after H2O2 in aged or young adult rat hearts. In histological sections, however, trichrome staining revealed that aged rat hearts exhibited extensive fibrosis, ranging from 10-90%; middle-aged rabbit hearts had less fibrosis (5-35%), whereas young adult rat and rabbit hearts had