肥大心における機械的収縮、電気的興奮のフィードバック機構の不整脈発生に対する関与-Stretch activated channel の関与と自律神経が与える影響について-

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It has been reported that the mechanical stress affects on the process of electrical excitation in the heart. This phenomenon is called to be "contraction-excitation feedback". Although it has been considered that the stretch activated ion channel is involved in its mechanisms, the precise mechanism is unclear.We measured QT-interval as an indicator of electrical excitation in various conditions such as pressure-overload to the left ventricle, volume-overload to the left ventricle, valsalva stimulation, dvsopyramide application. Furthermore, we also studied myocardial endothelin-1 and contraction-excitation feedback.Cardiac myocytes as well as vascular endothelium produce endothelin (ET)-1. In the heart, ET-1 induces myocardial hypertrophy and causes cellular injury of cardiac myocytes. In this study, we investigated roles of ET-1 in heart diseases such as chronic heart failure (CHF) and cardiac hypertrophy. We used coronary artery-ligated rat model as a CHF model animal (CHF rats). It … More was revealed that production of ET-1 (both peptide and mRNA levels) is increased in the failing heart of the CHF rats. We also obtained the data that the upregulated myocardial ET-1 system may play an aggravating role in the progression of CHF,because long-term (12 weeks) treatment with the ET receptor antagonist BQ-123 greatly improved survival rate of CHF rats. Twelve weeks after BQ-123 application, survival rate of the CHF rats treated with BQ-123 (CHF-BQ rats) was markedly higher than that of the CHF rats treated with saline alone (CHF-saline rats) (85% vs 43%, P<0.01). Hemodynamic parameters of surviving rats were ameliorated by chronic BQ-123 treatment. BQ-123 treatment effectively prevented unfavorable ventricular remodeling of the CHF rats. In the hypertrophied left ventricle of the aorta-banded rats, the expression of ET-1 mRNA was significantly increased. Treatment with BQ-123 for 7 days significantly reduced cardiac hypertrophy of the aortabanded rats.Above various studies, we conclude that contraction-excitation feedback mechanism is involved in arrhythmias in many cases. Less