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-

已有报道称，机械应力影响心脏的电兴奋过程。这种现象被称为“收缩-激励反馈”。虽然认为牵张激活的离子通道参与了其机制，但其确切的机制尚不清楚。我们测量了不同条件下的QT间期作为电兴奋的指标，如左心室压力超负荷、左心室容量超负荷、Valsalva刺激、Dvsopyraamine应用。此外，我们还研究了心肌内皮素-1和收缩-兴奋反馈。心肌细胞和血管内皮细胞产生内皮素-1。在心脏中，ET-1诱导心肌肥大，引起心肌细胞损伤。在这项研究中，我们研究了ET-1在慢性心力衰竭(CHF)和心肌肥厚等心脏病中的作用。采用冠脉结扎大鼠模型作为CHF模型动物(CHF大鼠)。IT…更多的研究表明，在CHF大鼠衰竭的心脏中，ET-1的产生(肽和mRNA水平)都增加了。长期(12周)应用ET受体拮抗剂BQ-123可显著提高CHF大鼠的存活率，提示心肌ET-1系统的上调可能在CHF的发展过程中起着加重作用。应用BQ-123 12周后，BQ-123治疗的CHF大鼠(CHF-BQ大鼠)的存活率显著高于单纯生理盐水组(CHF-生理盐水大鼠)(85%比43%，P&lt；0.01)。慢性BQ-123治疗可改善存活大鼠的血流动力学参数。BQ-123治疗可有效预防CHF大鼠不良的心室重构。在主动脉结扎大鼠肥厚的左心室中，ET-1mRNA的表达显著增加。经BQ-123治疗7天后，大鼠心脏肥厚明显减轻。多项研究表明，收缩-兴奋反馈机制在许多情况下参与了心律失常。较少

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