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Analysis of Left Ventricular Remodeling and Hemodynamics in Dilated Cardiomyopathy and Myocarditis and Application for Regeneration Therapy

扩张型心肌病和心肌炎的左心室重构和血流动力学分析及再生治疗的应用

基本信息

批准号：
16590678
负责人：
NISHIO Ryosuke
金额：
$ 1.98万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

Recent reports have emphasized the important role of immune systems in the pathophysiology of dilated cardiomyopathy and viral myocarditis. However, the role of immune responses in left ventricular remodeling and hemodynamics of these heart diseases remain unclear. In this research, we examined the role of immune factors including cytokines in left ventricular remodeling and hemodynamics using experimental viral myocarditis. in addition, we developed new devices for regeneration therapy of this disease.Four-week-old DBA/2 mice were inoculated with encephalomyocarditis virus. In this model, myocardial lesions appear several days after viral inoculation, resulting in severe congestive heart failure. In the chronic phase, left ventricle is dilated like hearts in patients with DCM. We examined the relationship between cytokine or chemokine production and hemodynamic parameters in this animal model of viral myocarditis. We used the real-time PCR method and tissue ELISA assay. In addition, we used the Millar 1.4 Fr catheter composed of 4 conductance electrodes and a micromanometer. This catheter was advanced via the right carotid artery into left ventricle. Pressure-Volume Relationship were measured by transiently compressing the inferior vena cava. Parallel volume of each mouse was calibrated by hypertonic saline. We also measured right atrial pressure. These hemodynamic data provide new insights into the nathophysiology of viral myocarditis, and were useful in the development of therapeutic interventions.In the next series of experiments, we develop new devices, including micro-catheters and micro-balloons, for regeneration therapy.We are going to expand these new devices to clinical intervention for regeneration therapy of dilated cardiomyopathy.

最近的报道强调了免疫系统在扩张型心肌病和病毒性心肌炎的病理生理中的重要作用。然而，免疫反应在这些心脏病的左室重构和血流动力学中的作用仍不清楚。在本研究中，我们利用实验性病毒性心肌炎研究了包括细胞因子在内的免疫因子在左心室重构和血流动力学中的作用。此外，我们还开发了一种新的再生治疗装置，用于这种疾病的再生治疗。在该模型中，心肌病变在病毒接种后几天出现，导致严重的充血性心力衰竭。在慢性期，左心室像DCM患者的心脏一样扩张。我们研究了病毒性心肌炎动物模型中细胞因子或趋化因子产生与血流动力学参数之间的关系。采用实时荧光定量PCR方法和组织ELISA方法。此外，我们使用了由4个电导电极和一个微压计组成的Millar 1.4 Fr导管。该导管通过右颈动脉推进到左心室。通过瞬时压迫下腔静脉测量压力-容积关系。用高渗盐水校准每只小鼠的平行体积。我们还测量了右心房压力。这些血流动力学数据为病毒性心肌炎的神经生理学提供了新的见解，并有助于开发治疗干预措施。在接下来的一系列实验中，我们开发了用于再生治疗的新设备，包括微导管和微球囊。我们将把这些新设备扩展到临床干预，用于扩张型心肌病的再生治疗。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Suppression of cytokines and nitric oxide production, and protection against lethal endotoxemia and viral myocarditis by a new NF-kappaB inhibitor.

新型 NF-kappaB 抑制剂可抑制细胞因子和一氧化氮的产生，并预防致命的内毒素血症和病毒性心肌炎。

DOI：
发表时间：
2004
期刊：
Eur J Heart Fail. 6
影响因子：
0
作者：
Matsumori A;Nunokawa Y;Yamaki A;Yamamoto K;Hwang MW;Miyamoto T;Hara M;Nishio R;Kitaura-Inenaga K;Ono K.
通讯作者：
Ono K.

Histone acetyltransferase activity of p300 is required for the promotion of left ventricular remodeling after myocardial infarction in adult mice in vivo