1996 Fiscal Year Final Research Report Summary
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-
| Project/Area Number |
07670751
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | Institute of Clinical Medicine, University of Tsukuba |
|---|
Principal Investigator |
YAMAGUCHI Iwao University of Tsukuba, Institute of Uinical Medicin Associate Professor, 臨床医学系, 助教授 (30111389)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KUGA Keisuke University of Tsukuba, Institute of Uinical Medicin, Lecturer, 臨床医学系, 講師 (60241816)
MIYAUCHI Takashi University of Tsukuba, Institute of Uinical Medicin, Lecturer, 臨床医学系, 講師 (60222329)
|
|---|
| Project Period (FY) |
1995 – 1996
|
| Keywords | Cardiac hypertrophy / arrhythmia / stretch acfivated ion channel / antonomic nerves / mechanical contraction / excitation |
|---|
| Research Abstract |
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
|
-
-
-
-
-
-
-
-
-
-
[Publications] Ishikawa, S., Miyauchi, T., Sakai, S., Yamaguchi, I., Sugishita, Y.and Goto, K.: "Elevated plasma endothelin-1 in young patients with pulmonary hypertension due to congenital heart diseases is decreased after successful surgical repair." The Journal of Thoracic and Cardiovascular Surgery. 110. 271-273 (1995)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Ishikawa S,Miyauchi T,Ueno H,Ushinohama H,Sagawa K,Fusazaki N,Snagawa H,Honda S,Sakai S,Yamaguchi I,Goto K,Sugishita Y.: "Influence of pulmonary blood pressure and flow on endothelin-1 production in humans." Journal of Cardiovascular Pharmacology. 26. S429-S433 (1995)
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
