Potential players in the hood.
Potential players in the hood.
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引擎盖里的潜在玩家。
DOI：
10.1007/s10840-012-9697-y
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Robinson,RichardB
中科院分区：
文献类型：
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作者：
Boyden,PenelopeA;Robinson,RichardB
心律失常的药理学治疗主要局限于改变心脏肌细胞电功能的药物。事实上，这个市场的主要参与者是肾上腺素能阻滞剂。由于自主神经张力的调节，这类药物是有帮助的。然而，对于房颤（Af），目前大多数药物都没有多大帮助，房颤的病程也几乎没有改变。相邻单元中的其他参与者可能会获得重要性。在Mao et al.[1]的论文中，自主神经调节具有额外的含义，因为在本研究中，这些作者认为是心房神经网络（即脂肪垫的心房神经网络）的调节促进了房颤。这与他们认为自主神经刺激或自主神经去神经支配调节自主神经活动的生理和/或病理生理功能是一致的。值得注意的是，Mao等人的实验是用naïve对照动物完成的，而不是对持续性房颤敏感的动物。事实上，在乙酰胆碱（Ach）存在的情况下，记录到的最长房颤持续时间为33分钟，乙酰胆碱被用来模拟刺激左右神经节丛（GPs）时释放的神经递质。目前尚不清楚在心房高度重塑甚至老化的动物身上是否会出现同样的结果，以及是否使用了重塑的全科医生。本研究未探讨心房神经网络对房颤底物的重塑机制，因此尚不清楚。我们知道，与疾病相关的肾上腺素能/胆碱能信号的中断可能是功能性去神经支配的一种形式，如果这些途径有助于维持成人心脏表型（如果功能性和解剖性去神经支配具有相同的效果），那么这可能导致额外的心肌细胞重塑。文献中有明确的例子表明心房快速起搏产生心房颤动，室性心动过速、室性心动过速和猝死与异质心房神经支配以神经萌芽[2]的形式相关。心房细胞电[3-6]或自主神经重塑[7]可能只是心房副交感神经和交感神经控制之间拮抗作用改变的反映。已知迷走神经输入可通过交感神经末梢的（Ach）受体抑制交感神经传递。交感神经刺激可以产生长期的迷走神经抑制。后一种效应被认为是由神经肽y （NPY）引起的，它与交感神经末梢的去甲肾上腺素共定位。NPY对心脏细胞的作用是多种多样的，表现为急性和慢性作用。利用心肌神经元共培养，实验室现在已经确定了神经元如何首先影响心脏表型的一些方面[8-10]。我们中的一位深入研究了持续交感神经支配如何调节离子通道表达和自主神经反应，以及这些影响如何归因于NPY作为营养因子的作用[11,12]。Mao等人认为另一种肽VIP可能起作用。VIP效应就没有那么明确了。它与乙酰胆碱一起释放，但导致HR显著增加。它是否也有营养作用尚不清楚。显然，这里还需要用心脏组织做更多的工作。
Pharmacologic treatment of cardiac arrhythmias has been mostly confined to drugs that alter the electrical function of the myocytes of the heart. In fact, big players in this market have been the adrenergic blocking agents. By virtue of modulation of autonomic tone, this class of drugs can be helpful. However in the case of atrial fibrillation (Af), most current agents are not that helpful and the course of Af is little changed. It is possible that other players in the neighbor “hood” of cells may gain importance. In the paper of Mao et al.[1], autonomic modulation takes on an additional meaning in that in this study, it is the modulation of atrial neural networks, namely those of the fat pads, that these authors believe promote Af. This is consistent with their ideas that autonomic nerve stimulation or autonomic denervation modulates autonomic activity in physiologic and/or pathophysiologic functions. Notably, the experiments of Mao et al. were completed using naïve control animals and not animals susceptible to persistent Af. In fact, the longest Af duration noted was 33 min in the presence of acetylcholine (Ach), which was used to mimic the neurotransmitter released with stimulation of the left and right ganglionated plexi (GPs). It is not known whether the same outcomes would occur in animals with highly remodeled or even aged atria as well as if remodeled GPs had been used.The mechanism of remodeling of the Af substrate by atrial neural networks was not explored in this study and thus remains unknown. We know that disease-associated disruptions of adrenergic/cholinergic signaling would be a form of functional denervation and if these paths serve to maintain the adult cardiac phenotype (and if functional and anatomic denervation have equivalent effects) then that could lead to additional myocyte remodeling. There are clear examples in the literature that Af produced by rapid atrial pacing, and VT, Vf and sudden death are associated with heterogeneous atrial innervation in the form of nerve sprouting [2]. Atrial cell electrical [3–6] or autonomic remodeling [7] may be just a reflection of an altered antagonism between the parasympathetic and sympathetic controls of the atria. It is known that vagal input can inhibit sympathetic neurotransmission via (Ach) receptors on the sympathetic nerve terminals. Sympathetic stimulation can produce long-lived vagal inhibition. This latter effect is thought to be caused by neuropeptideY (NPY) which colocalizes with Norepinephrine in sympathetic nerve terminals. NPY effects are varied showing both acute and chronic effects on cardiac cells. Using myocardial neuronal cocultures, labs have now defined some aspects of how neurons first impact the cardiac phenoptype [8–10]. One of us has studied intensely how sustained sympathetic innervation regulates ion channel expression and autonomic responsiveness and how some of these effects can be ascribed to NPY acting as a trophic factor [11, 12]. Mao et al. suggest that another peptide, VIP, may play a role. VIP effects are less well defined. It is released with Ach but causes a marked increase in HR. Whether it too has trophic effects is not known. Obviously more needs to be done here using cardiac tissues.