Arrhythmogenic Effect of Sympathetic Histamine in Mouse Hearts Subjected to Acute Ischemia
Arrhythmogenic Effect of Sympathetic Histamine in Mouse Hearts Subjected to Acute Ischemia
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DOI：
10.2119/molmed.2011.00225
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发表时间：
2012-01-01
影响因子：
5.7
通讯作者：
Luo, Xiaoxing
中科院分区：
文献类型：
--
作者：
He, Gonghao;Hu, Jing;Luo, Xiaoxing
组胺作为一种新发现的交感神经递质，其突触后效应在很大程度上依赖于交感神经的活动。心脏交感神经在急性心肌缺血条件下变得过度激活，并释放大量神经递质，诱导室性心律失常。因此，有人提出，心脏交感组胺，除了去甲肾上腺素，可能有显着的致心律失常作用。为了验证这一假设，我们观察了心脏交感神经组胺的释放和相关的心室肥大，这是由急性缺血诱导的小鼠离体心脏。肥大细胞缺陷小鼠（MCDM）和组氨酸脱羧酶敲除（HDC-/-）小鼠用于排除肥大细胞的潜在参与。电场刺激和急性缺血-再灌注诱发MCDM和野生型（WT）小鼠心脏释放化学交感神经敏感性组胺，但HDC-/-小鼠没有。MCDM和WT小鼠心脏组胺的释放与急性缺血诱导的室性心动过速和室颤的发生有关。在选择性组胺H-2受体拮抗剂法莫替丁的存在下，发现诱导的室性心律失常的发生率和持续时间减少。此外，释放的组胺促进了同时释放的去甲肾上腺素的致炎作用。我们认为，在急性缺血条件下，过度活跃的交感神经末梢释放的心脏交感组胺通过H-2受体发挥了一定的促心律失常作用。这些发现提供了新的见解交感组胺的病理生理作用，这可能是一个新的治疗急性缺血性心律失常的目标。
The role of histamine as a newly recognized sympathetic neurotransmitter has been presented previously, and its postsynaptic effects greatly depended on the activities of sympathetic nerves. Cardiac sympathetic nerves become overactivated under acute myocardial ischemic conditions and release neurotransmitters in large amounts, inducing ventricular arrhythmia. Therefore, it is proposed that cardiac sympathetic histamine, in addition to norepinephrine, may have a significant arrhythmogenic effect. To test this hypothesis, we observed the release of cardiac sympathetic histamine and associated ventricular arrhythmogenesis that was induced by acute ischemia in isolated mouse hearts. Mast cell-deficient mice (MCDM) and histidine decarboxylase knockout (HDC-/-) mice were used to exclude the potential involvement of mast cells. Electrical field stimulation and acute ischemia-reperfusion evoked chemical sympathectomy-sensitive histamine release from the hearts of both MCDM and wild-type (WT) mice but not from HDC-/- mice. The release of histamine from the hearts of MCDM and WT mice was associated with the development of acute ischemia-induced ventricular tachycardia and ventricular fibrillation. The incidence and duration of induced ventricular arrhythmias were found to decrease in the presence of the selective histamine H-2 receptor antagonist famotidine. Additionally, the released histamine facilitated the arrhythmogenic effect of simultaneously released norepinephrine. We conclude that, under acute ischemic conditions, cardiac sympathetic histamine released by overactive sympathetic nerve terminals plays a certain arrhythmogenic role via H-2 receptors. These findings provided novel insight into the pathophysiological roles of sympathetic histamine, which may be a new therapeutic target for acute ischemia-induced arrhythmias.