1998 Fiscal Year Final Research Report Summary
Assessment of Ca2+ regulating function of cardiac sarcoplasmic reticulum in the development of heart failure
| Project/Area Number |
09670722
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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 |
Circulatory organs internal medicine
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| Research Institution | Yamaguchi University |
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Principal Investigator |
KOHNO Michihiro Yamaguchi University Hospital associate professor, 医学部附属病院, 講師 (70243649)
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| Co-Investigator(Kenkyū-buntansha) |
OHKUSA Tomoko Yamaguchi University School of Medicine assistant professor, 医学部, 助手 (00294629)
YANO Masafumi Yamaguchi University School of Medicine assistant professor, 医学部, 助手 (90294628)
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| Project Period (FY) |
1997 – 1998
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| Keywords | heart failure / sarcoplasmic reticulum / relaxation / ryanodine receptor / inotropic agent |
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| Research Abstract |
In tachycardia-induced heart failure (HF), LV function was assessed in parallel with the function of sarcoplasmic reticulum (SR) taken from LV muscle. Not only Ca uptake function but also the rapid Ca releasing function of SR is disturbed in association with the decrease in the number of ryanodine receptors, leading to the impairment of LV systolic and diastolic dysfunction. The effects of inotropic agents on LV function and SR function were also evaluated. In HF, positive inotropic effects of mihinone or dobutamine were decreased, whereas positive lusitropic effects were well preserved. The enhancement of the sensitivity of SR Ca ATP ase on cyclic AMP was observed in HF, which might be involved in this preservation of positive lusitropy. Particularly, low dose of milrinone (PDEIII inhibitor) substantially improved LV relaxation and SR Ca ATP ase activity compared with dobutamine, probably due to the direct inhibition of SR membrane-bound PDEIII and hence the local elevation of cyclic AMP near SR Ca ATP ase.
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