1999 Fiscal Year Final Research Report Summary
Macro-micro correspondence in mechanoenagetics of failing hearts
| 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)
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| Project Period (FY) |
1997 – 1999
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| Keywords | heart failure / ryanodine / stunning / calcium paradox / Emax / postextrasystolic potentiation / sarcoplasmic reticulum / excitation-contraction coupling |
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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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Research Products
(26 results)
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[Publications] Hosogi, S., Araki, J., Syuu, Y., Suzuki, S., Mohri, S., Mikane, T., Matsubara, H., Ohe, T., Hirakawa, M., Suga, H.: "Calcium equally increased internal calcium recirculation faction before and after β-blockade in canine left ventricles"Heart Vessels. 12. 280-286 (1997)
Description
「研究成果報告書概要(和文)」より
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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)
Description
「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)
Description
「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)
Description
「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)
Description
「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)
Description
「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)
Description
「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)
Description
「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)
Description
「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).
Description
「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).
Description
「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).
Description
「研究成果報告書概要(和文)」より
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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).
Description
「研究成果報告書概要(和文)」より
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