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

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疾病的左心室重构和血流动力学中的作用尚不清楚。在这项研究中，我们研究了免疫因子包括细胞因子在实验性病毒性心肌炎左心室重构和血流动力学中的作用。此外，我们还开发了用于这种疾病再生治疗的新设备。用脑心肌炎病毒接种4周龄DBA/2小鼠。在这个模型中，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，DCM患者的左心室像心脏一样扩张。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的产生与血流动力学参数的关系。采用实时荧光定量PCR法和组织ELISA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。导管经右颈动脉进入左心室。通过短暂压迫下腔静脉测量压力-容积关系。用高渗盐水标定每只小鼠的平行体积。我们还测量了右心房压。这些血流动力学数据为病毒性心肌炎的病理生理学提供了新的见解，并有助于治疗干预措施的发展。在接下来的一系列实验中，我们将开发用于再生治疗的新设备，包括微导管和微气球。我们将把这些新设备扩展到扩张型心肌病再生治疗的临床干预。

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.