| Project/Area Number |
10558136
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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 | 展開研究 |
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| Research Field |
Biomedical engineering/Biological material science
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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) |
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)
ITOH Haruo SI Medico-Tech, President (Research Position), 代表取締役(研究職)
IRIBE Gentaro Okayama Univ. Medical School, Assistant, 医学部, 助手 (90284885)
實金 健 岡山大学, 医学部, 助手 (10294406)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥12,200,000 (Direct Cost: ¥12,200,000)
Fiscal Year 1999: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1998: ¥8,400,000 (Direct Cost: ¥8,400,000)
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| Keywords | myocardial CaィイD12+ィエD1 handling / postextrasystolic potentiation / transient alternans / excitation-contraction coupling / tailing heart / ryanodine / stunning / Emax / 期外収縮後収縮性増強 / 筋小胞体 / カルシウム / 不全心 |
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| Research Abstract |
We have found that postextrasystolic potentiation decays in transient alternans in the canine left ventricle (LV). We used for the curve fitting the following equation : y = a・exp[-(x-1)/κィイD2eィエD2] + b・exp[-(x-1)/κィイD2eィエD2]cos[(x-1)] +1, where x = beat number and y = normalized contractility (Emax) of the postextrasystolic beats. Internal CaィイD12+ィエD1 recirculation (RF) was obtained from τe, according to the definition : RF = exp(-1/κィイD2eィエD2). We combined RF the mechanoenergetic data and the two-fold difference of the stoichiometry between the SR CaィイD12+ィエD1 pump and the transsarcolemmal extrusion route.
Using this framework, we investigated the effects of intracoronary CaィイD12+ィエD1 and epinephrine (EP) and found that CaィイD12+ィエD1 increased RF but EP did not. We obtained 40-110 micromol/kg as the total amount of CaィイD12+ィエD1 handled per beat in control and enhanced contractile state.
To evaluate myocardial CaィイD12+ィエD1 handling hearts, we hypothesized that OィイD22ィエD2 wasting of Caィイ
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D12+ィエD1 handling in the E-C coupling could be reflected by a decreased RF in ryanodine-treated hearts. intracoronary ryanodine halved LV Emax without decreasing myocardial OィイD22ィエD2 consumption for the E-C coupling. We speculated this mehcanoenergetics to manifest energy wasting of CaィイD12+ィエD1 handling due to ryanodine-induced CaィイD12+ィエD1 leakage from the SR (futile cycle). Ryanorine decreased RF from 0.6 to 0.5 on average and the futile cycle was 1.4 times the effective cycle of CaィイD12+ィエD1 handled via the SR.
Stunning also halved LV Emax and doubled OィイD22ィエD2 cost of Emax. We found stunning decreased RF from 0.63 to 0.43 on average and caused a considerable shift of the relation between futile cycle and CaィイD12+ィエD1 reactivity in an energy-wasteful direction. These results reasonably accounted for the doubled OィイD22ィエD2 cost of Emax in stunning. Thus, we have validated the usefulness of our integrative analysis method to evaluate myocardial CaィイD12+ィエD1 handling in beating whole hearts. (297 words) Less
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