1999 Fiscal Year Final Research Report Summary
Assessment of the total amount of CAィイD12+ィエD1 handled in the E-C coupling by analyzing postextrasystolic potentiation and OィイD22ィエD2 consumption : Systems approach
| 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)
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| Project Period (FY) |
1998 – 1999
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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 |
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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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[Publications] Suzuki, S., Araki, J., Morita, T., Mohri, S., Mikane, T., Yamaguchi, H., Sano, S., Ohe, T., Hirakawa, M., Suga, H.: "Ventricular contractility in atrial fibrillation is predictable by mechanical restitution and potentiation"Am. J. Physiol.. 275. H1513-H1519 (1998)
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「研究成果報告書概要(和文)」より
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[Publications] Shimizu, J., Araki, J., Mizuno, J., Lee, S., Syuu, Y., Hosogi, S., Mohri, S., Mikane, T., Takaki, M., Taylor T.W., Suga, H.: "A new integrative method to quantify total Ca^<2+> handling and futile Ca^<2+> cycling in failing hearts"Am. J. Physiol.. 275. H2325-H2333 (1998)
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「研究成果報告書概要(和文)」より
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[Publications] Syuu, Y., Araki, J., Lee, S., Suzuki, S., Mizuno, J., Mohri, S., Mikane, T., Shimizu, J., Takaki, M., and Suga, H.: "Effects of Ca^<2+> and epinephrine on Ca^<2+> recirculation fraction and total Ca^<2+> handling in canine left ventricles"Jpn. J. Physiol.. 48. 123-132 (1998)
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「研究成果報告書概要(和文)」より
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[Publications] Lee, S., Ohga, Y., Tachibana, H., Syuu, Y., Ito, H., Harada, M., Suga, H., Takaki, M.: "Effects of myosin isozyme shift on curvilinearity of the left ventricular end-systolic pressure-volume relation of in situ rat hearts"Jpn. J. Physiol.. 48. 445-455 (1998)
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「研究成果報告書概要(和文)」より
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[Publications] Mizuno, J., Mikane, T., Araki, J., Hatashima, M., Moritani, T, Ishikawa, T., Komukai, K., Kurihara, S., Hirakawa, M., Suga, H.: "Hybrid logistic characterization of isometric twitch force curve of isolated ferret right ventricular papillary muscle"Jpn. J. Physiol.. 49. 145-158 (1999)
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「研究成果報告書概要(和文)」より
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[Publications] Mizuno, J., Araki, J., Iribe, G., Maesako, M., Morita, T., Miyaji, K., Imaoka, T., Mohri, S., Sano, S., Ohe, T., Hirakawa, M., Suga, H.: "Total Ca handling in canine mild Ca overload failing heart"Heart Vessels. 14. 38-51 (1999)
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「研究成果報告書概要(和文)」より
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[Publications] Mohri, S., Araki, J., Imaoka, T., Iribe, G., Maesako, M., Shimizu, J., Matsubara, H., Ohe, T., Hirakawa, M., Suga, H.: "Myocardial mechanical restitution and potentiation partly underlie alternans decay of postextrasystolic potentiation : simulation"Heart Vessels. 14. 82-89 (1999)
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「研究成果報告書概要(和文)」より
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[Publications] Mikane, T., Araki, J., Suzuki, S., Mizuno, J., Shimizu, J., Mohri, S., Matsubara, H., Hirakawa, M., Ohe, T., Suga, H.: "O_2 cost of contractility but not of mechanical energy increases with temperature in canine oft ventricle"Am. J. Physiol.. 277. H65-H73 (1999)
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「研究成果報告書概要(和文)」より
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[Publications] Araki, J., Matsubara, H., Shimizu, J., Mikane, T., Mohri, S., Mizuno, J., Takaki, M., Ohe, T., Hirakawa, M., Suga, H.: "Weibull distribution function for cardiac contraction : Integrative analysis"Am. J. Physiol.. 277. H1940-H1945 (1999)
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「研究成果報告書概要(和文)」より
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[Publications] Lee, S., Araki, J., Imaoka, T., Maesako, M., Iribe, G., Miyaji, K., Mohri, S., Shimizu, J., Harada, M., Ohe, T., Hirakawa M., Suga, M.: "Energy-wasteful total calcium handling underlies increased O_2 cost of contractility in canine stunned heart"Am. J. Physiol.. (in press).
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「研究成果報告書概要(和文)」より
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[Publications] Shimizu, J., Araki, J., Iribe, G., Imaoka, T., Mohri, S., Hohno, K., Matsubara, H., Ohe, T., Takaki, M., Suga. H.: "Postextrasystolic contractile decay independent of extrasystolic interval and compensatory pause in canine heart"Am. J. Physiol.. (in press).
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「研究成果報告書概要(和文)」より
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[Publications] Mitani, H., Yamaguchi, H., Morita, T., T. Oshima, Y., Shimizu, J., Ito, H., Araki, J., Takai, M., Sano, S., Suga, H.: "Effective arterial elastance (Ea) of irregular beats during atrial fibrillation in canine let vnerticle"Jpn. J. Physiol.. (in press).
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[Publications] Takasago, T., Goto, Y., Hata, K., Saeki, A., Nishioka, T., Taylor, T.W., Iribe, G., Mohri, S., Shimizu, J., Araki, J, Suga, H.: "Mechanoenergetics characterizing oxygen wasting effect of caffeine in canine left ventricle"Jpn. J. Physiol.. (in press).
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