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

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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.