Electrocardiographic findings in mdx mice:: A cardiac phenotype of Duchenne muscular dystrophy
Electrocardiographic findings in mdx mice:: A cardiac phenotype of Duchenne muscular dystrophy
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DOI：
10.1002/mus.10223
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发表时间：
2002-10-01
期刊：
影响因子：
3.4
通讯作者：
Hampton, TG
中科院分区：
文献类型：
--
作者：
Chu, V;Otero, JM;Hampton, TG
MDX小鼠是Duchenne肌营养不良症(DMD)的模型。由于许多DMD患者死于心力衰竭，我们调查了MDX小鼠是否表现出临床相关的心脏表型。我们应用最近开发的一种无创记录心电图的方法来研究雄性MDX小鼠(n=15)和对照小鼠(n=15)。MDX小鼠有明显的心动过速和心率变异性降低，这与在DMID患者中观察到的一致。MDX组小鼠的心率比对照组快近15%(P<；0.05)。MDX组校正QT间期和PR间期较对照组缩短(P<；0.05)。M受体拮抗剂阿托品能显著增加C57小鼠的心率，缩短PR间期。相比之下，阿托品显著降低所有mdx小鼠的心率，延长PR间期。药理自主神经阻断和压力感受性反射敏感性测试显示，自主神经系统对心率的调节失衡，mdx小鼠的副交感神经活动减少，交感神经活动增加。神经元型一氧化氮合酶(NNOS)缺陷小鼠的基线心电图和阿托品阻断毒扁豆碱的相反反应提示，mdx小鼠的自主神经功能障碍可能不依赖于心肌nNOS的降低。这些Dstrophin缺陷小鼠的心电图结果可能为诊断、了解和治疗DMD患者提供新的基础。(C)2002年威利期刊公司。
The mdx mouse is a model of Duchenne muscular dystrophy (DMD). As many DMD patients die of cardiac failure, we investigated whether mdx mice exhibited clinically relevant cardiac phenotypes. We applied a recently developed method for noninvasively recording electrocardiograms (ECGs) to study male mdx mice (n = 15) and control mice (n = 15). The mdx mice had significant tachycardia and decreased heart rate variability, consistent with observations in DMID patients. Heart rate was nearly 15% faster in mdx mice than control mice (P < 0.05). The rate-corrected QT interval duration and PR interval were shorter in mdx compared to control mice (P < 0.05). The muscarinic antagonist atropine significantly increased heart rate and decreased PR interval in C57 mice. In contrast, atropine significantly decreased heart rate and increased PR interval in all mdx mice. Pharmacological autonomic blockade and baroreflex sensitivity testing demonstrated an imbalance in autonomic nervous system modulation of heart rate, with decreased parasympathetic activity and increased sympathetic activity in mdx mice. Baseline ECGs and contrary responses to muscarinic blockade by atropine in mice deficient in neuronal nitric oxide synthase (nNOS) suggest that the autonomic dysfunction in mdx mice may be independent of decreased myocardial nNOS. These electrocardiographic findings in dystrophin-deficient mice may provide new bases for diagnosing, understanding, and treating DMD patients. (C) 2002 Wiley Periodicals, Inc.