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首页> 外文学位 >Intra- & Extra-Cardiac Neural Remodeling In Mammalian Ventricle: Implications For Arrhythmogenesis.
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Intra- & Extra-Cardiac Neural Remodeling In Mammalian Ventricle: Implications For Arrhythmogenesis.

机译：哺乳动物心室内和心脏外的神经重塑：对心律失常的影响。

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摘要

The cardiac sympathetic nervous system (SNS) exerts profound influence on ventricular myocardial excitability. Disturbances in excitability result in ventricular arrhythmias (VAs). Remodeling of cardiac SNS is associated with risk of VAs, however the mechanistic underpinnings of this relationship remain poorly understood.;To characterize structural intra-cardiac (ventricular) SNS remodeling (ICNR), ventricular myocardium from humans and porcine with ischemic or non-ischemic cardiomyopathy (ICM and NICM respectively), and normal controls (CON) of both species were subjected to detailed histologic and immuno-histochemical (IHC) analyses. Similarly, structural characterization of extra-cardiac neural remodeling (ECNR) within left and right stellate ganglia (LSG and RSG respectively) were performed using histologic and IHC methods to determine neuronal characteristics in normal vs. ICM and NICM. Lastly, the functional consequences of ICNR and ECNR were studied in porcine with myocardial infarcts (MI), and compared to CON.;In myocardium, structural sympathetic nerve remodeling consists of increased sympathetic nerve density at border-zones of scar and normal myocardium. In stellate ganglia of humans with ICM and NICM (and porcine with MI), neuronal size was significantly increased. LSG and RSG from porcine with MI, also showed a decrease in the percentage of non-adrenergic neurons, compared to CON, indicating that ECNR also consisted of a shift from non-adrenergic to adrenergic phenotypes. Functional mapping of myocardial activation recovery intervals (ARIs), an accepted surrogate for action potential duration (APD) in normal porcine hearts showed that RSG innervation predominated on the anterior wall, while LSG innervation predominated on the posterior wall. After MI, ICNR and ECNR resulted in loss of innervation patterns seen in normal. Further, dispersion of repolarization (DOR) was increased in the infarct and border zone regions of infarcted porcine compared to other cardiac regions, but this was not the case in CON. In addition, global DOR (including or excluding the infarct zones) was greater in the hearts of infarcted animals compared to normal controls.;In conclusion, following MI significant remodeling of stellate ganglion neurons, and nerve terminals within the heart occurs. This results in significant functional alteration of innervation patterns, and worsening of repolarization heterogeneity. These mechanisms partly explain the association between SNS remodeling and arrhythmogenesis.
机译：心脏交感神经系统（SNS）对心室心肌兴奋性产生深远影响。兴奋性障碍会导致室性心律失常（VA）。心脏SNS的重塑与VA的风险相关，但是这种关系的机制基础仍然知之甚少;为表征结构性心脏内（心室）SNS重塑（ICNR），人的心室心肌以及具有缺血性或非缺血性的猪对这两种物种的心肌病（分别为ICM和NICM）和正常对照（CON）进行了详细的组织学和免疫组化（IHC）分析。类似地，使用组织学和IHC方法对左和右星状神经节（分别为LSG和RSG）内的心脏外神经重塑（ECNR）进行结构表征，以确定正常与ICM和NICM的神经元特征。最后，在猪心肌梗死（MI）中研究了ICNR和ECNR的功能后果，并与CON进行了比较；在心肌中，结构性交感神经重塑包括瘢痕和正常心肌边界区域的交感神经密度增加。在患有ICM和NICM（以及患有MI的猪）的人的星状神经节中，神经元大小明显增加。与CON相比，带有MI的猪的LSG和RSG也显示出非肾上腺能神经元的百分比降低，这表明ECNR也包括从非肾上腺素向肾上腺素表型的转变。正常猪心脏中心肌激活恢复间隔（ARIs）（动作电位持续时间（APD）的公认替代物）的功能图显示，RSG神经支配在前壁占主导地位，而LSG神经支配在后壁占主导地位。 MI后，ICNR和ECNR导致正常的神经支配方式丧失。此外，与其他心脏区域相比，梗死猪的梗死区和边界区的复极分散度（DOR）有所增加，但CON情况并非如此。此外，与正常对照组相比，梗死动物心脏的整体DOR（包括或不包括梗死区域）更大；总之，MI后星状神经节神经元发生了重大的重塑，并在心脏内发生了神经末梢。这导致神经支配模式的重大功能改变，并使复极化异质性恶化。这些机制部分解释了SNS重塑与心律失常的关系。

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  • 作者

    Ajijola, Olujimi Adeoluwa, II.;

  • 作者单位

    University of California, Los Angeles.;

  • 授予单位 University of California, Los Angeles.;
  • 学科 Physiology.;Neurosciences.
  • 学位 Ph.D.
  • 年度 2013
  • 页码 153 p.
  • 总页数 153
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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