| Project/Area Number |
09470009
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Okayama University |
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Principal Investigator |
SUGA Hiroyuki Okayama Univ. Medical School, Professor, 医学部, 教授 (90014117)
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| Co-Investigator(Kenkyū-buntansha) |
IRIBE Gentaro Okayama Univ. Medical School, Assistant, 医学部, 助手 (90284885)
MOHRI Satoshi Okayama Univ. Medical School, Assistant, 医学部, 助手 (00294413)
ARAKI Junichi Okayama Univ. Medical School, Assistant Professor, 医学部, 助教授 (80271055)
實金 健 岡山大学, 医学部, 助手 (10294406)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1998: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | heart failure / ryanodine / stunning / calcium paradox / Emax / postextrasystolic potentiation / sarcoplasmic reticulum / excitation-contraction coupling / 不全心 / 収縮期末圧容積関係 / 収縮期末圧容積面積 / 酸素消費量 / エネルギー変換効率 / 生体位心 / 心機能の評価 / メカノエナジェティクス / カルシウム動態 / 統合生理学 |
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| Research Abstract |
We have developed an organ-level systems approach to quantify total CaィイD12+ィエD1 handling in normal hearts. However, its direct application to failing hearts, where futile CaィイD12+ィエD1 cycling via the CaィイD12+ィエD1-leaky sarcoplasmic reticulum (SR) required an increased CaィイD12+ィエD1 handling VoィイD22ィエD2, was not legitimate. To quantify total CaィイD12+ィエD1 handling even in such failing hearts, we calculated internal CaィイD12+ィエD1 recirculation fraction (RF) from the exponential decay component of postextrasystolic potentiation (PESP) and combined the RF with the halved left ventricular (LV) contractility (Emax) and its OィイD22ィエD2 cost.
We applied this new integrative method to three kinds of failing hearts.
1. Failing hearts after intracoronary ryanodine at nanomolar concentrations halved Emax without significantly decreasing CaィイD12+ィエD1 handling VoィイD22ィエD2. We found that ryanodine significantly decreased RF from 0.6 to 0.5 on the average. We also found that futile CaィイD12+ィエD1 cycling via
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the SR increased to >1 cycle/beat after ryanodine from presumably zero before ryanodine.
2. We analyzed total CaィイD12+ィエD1 handling of the LV in the mildly failing heart preparation induced by a temporary intracoronary CaィイD12+ィエD1 overloading intervention. This intervention decreased Emax by 40% and CaィイD12+ィエD1 handling VoィイD22ィエD2 by 30% without increasing the OィイD22ィエD2 cost of Emax. We found that these failing hearts had a slightly but significantly increased RF accompanied by either a slightly increased futile CaィイD12+ィエD1 cycling or a slightly decreased CaィイD12+ィエD1 reactivity of Emax, or both. Any of these three possible changes can account for the unchanged OィイD22ィエD2 cost of Emax.
3. Postischemic myocardial stunning halved Emax and doubled OィイD22ィエD2 cost of Emax. Stunning decreased RF from 0.63 to 0.43 on the average. We found a decreased total CaィイD12+ィエD1 transport and a considerable shift of the relation between futile CaィイD12+ィエD1 cycling and CaィイD12+ィエD1 reactivity in an energy-wasteful direction in the stunned heart. Less
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