| Project/Area Number |
12670640
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KOHYA Tetsuro Hokkaido Univ., Grad. School of Med., Asso. Prof., 大学院・医学研究科, 助教授 (70205350)
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| Co-Investigator(Kenkyū-buntansha) |
SAWA Hirofumi Hokkaido Univ., Grad. School of Med., Asso. Prof., 大学院・医学研究科, 助教授 (30292006)
TAMAKI Nagara Hokkaido Univ., Grad. School of Med., Prof., 大学院・医学研究科, 教授 (30171888)
富田 文 北海道大学, 大学院・医学研究科, 助手 (40271655)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | cardiac sudden death / heart failure / angiotensin II receptor blocker / lethal ventricular arrhythmias |
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| Research Abstract |
Several large prospeptive randomized studies demonstrated that treatment with angiotensin converting enzyme inhibitors (ACE-I) improved the prognosis of patients suffering from chronic heart failure (CHF). Although ACE-I exerts many pathophysiological actions, it is generally thought that inhibition of angiotensin-II (Ang-II) formation could account for the beneficial effects. However, it is still to be determined whether Ang-II receptor blocker (ARB) has the similar or superior effects on CHF patients compared to those of ACE-I. By using radionucleotide imaging and electrophyiological methods, we tried to compare the effects of ACE-I and ARB on experimental failing animal hearts, especially preventive effects on lethal ventricular arrhythmias, a leading cause of sudden cardiac death. We established a method of making myocardial infarction in rats that manifest congestive heart failure. Our first goal was to evaluate the changes in myocardial fatty acid metabolism (by BMIPP) as well as sympathetic nerve activity (by MIBG) at the different stages of heart failure, and to clarify the relation between these metabolic and autonomic alterations and arrhythmogenesis. Then, we will examine how ACE-I and ARB affect these pathophysiological processes. With the use of BMIPP, we observed, so called, "ischemic memory" in rats with myocardial infarction and investigated its mechanisms. In addition, there was an interesting relationship between "ischemic memory" and genesis of lethal ventricular arrhythmias. Although our project is still under way, these preliminary results have prompted us to further clarify the mechanisms of sudden death in patients with CHF. In the theoretical viewpoints, it is likely that ARB with high selectivity to Ang-II type 1-receptor (AT1-R) is more effective than ACE-I. We would like to continue our study in order to obtain the definitive answers.
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