| Project/Area Number |
09670053
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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 |
General physiology
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| Research Institution | Nara Medical University |
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Principal Investigator |
TAKAKI Miyako Nara Medical University-Medicine professor, 医学部, 教授 (00033358)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | mechanoenergetic / slices / 2, 3-butanedione monoxime / thapsigargin / cyclopiazonic acid / Ca^<2+>handling / basal metabolism / sarcoplasmic reticulum (SR) Ca^<2+>pump / カルシウムイオン / 酸素消費 / メカノエナジェティクス / 2,3ブタンジオンモノオキシム / シクロピアゾン酸 / タプシガルギン / 機械的無負荷 / 心筋スライス / サプシガルギン |
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| Research Abstract |
Increasing the population of elders, increasing acute and chronic cardiovascular diseases. Thus, physiological and pathophysiological aspects of failing hearts are important issue on Scientific Research on Priority Area. However, it is little known about the energetic efficiency of Ca^<2+> handling in normal and failing hearts on the beat to beat basis. Mechanoenergetics in whole hearts revealed an 0_2 wasting effect or Ca^<2+> futile cycling during the development of failing hearts. To this end, we have recently established a new measurement system of myocardial 0_2 consumption (V0_2) per min of mechanically unloaded rat left ventricular (LV)slices. Using this system, we have revealed that an increment in V0_2(delta V0_2) by electrical stiumulation represents energy expenditure for 0a2+ handling in the excitaiton-contraction (E-C) coupling. We consider that delta V0_2 does not contain V0_2 for residual cross-bridge cycling from the results showing no effect of 2,3-butanedione monoxime (BDM) on delta V0_2. We also established a measurement system slice mechanically unloaded contraction. This contraction is expressed by the motility index. BDM largely decreased this motility index. This result also supported no V0_2 for residual crossbridge cycling was included in delta V0_2. We also revealed that V0_2 without stimulation represents basal metabolism which is much higher than in other mammalian hearts and corresponds to that in the KCI-arrested rat whole heart prepartion. We finally obtained the results showing that sarcoplasmic reticulum (SR) Ga^<2+> pump blockers, thapsigargin and cyclopiazonic acid, did not reduce basal metabolic V0_2 but both of them reduced delta V0_2by 33 and 68% and reduced the motility index by 63 and 81%. We conclude that unloaded myocardial V0_2 is composed of V0_2 for E-C coupling and basal metabolism and does not contain V0_2 for residual crossbridge cycling.
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