| Project/Area Number |
03454250
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Toyama Medical and Pharmaceutical University |
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Principal Investigator |
ASANO Hidetsugu (1992-1993) Toyama Medical and Pharmaceutical University Hospital, Associated Professor, 附属病院, 講師 (00150128)
篠山 重威 (1991) 富山医科薬科大学, 医学部, 教授 (70109007)
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| Co-Investigator(Kenkyū-buntansha) |
MIWA Kunihisa Toyama Medical and Pharmaceutical University, School of Medicine, Lecturer, 医学部, 助手 (70166221)
KIHARA Yasuki Kyodo University Hospital, Lecturer, 附属病院, 助手 (40214853)
麻野井 英次 富山医科薬科大学, 附属病院, 助手 (00150128)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1991: ¥4,800,000 (Direct Cost: ¥4,800,000)
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| Keywords | tachycardia-induced heart failure / left ventricular contractility and relaxation / failing myocardium / force-frequency response / calcium transient / developed tension / 発性張力 / Ca^<2+>トランジェント / 頻脈誘発性心不全 / Ca2+トランジェント / 発生張力 / 心収縮性 / Ca^<2+>トランジエント / うっ血性心不全 / 左室弛緩特性 / 心筋細胞 / カルシウムイオン / エクオリン / 活動電位 / 雑種成犬 |
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| Research Abstract |
In the present study we produced chronic experimental heart failure by rapid cardiac pacing in conscious dogs instrumented with a micromanometer and conductance catheter to monitor instantaneous left ventricular pressure and volume. We also examined intracellular Ca2+ handling to elucidate whether abnormal calcium homeostasis could be a cause of abnormal contraction and relaxation in the failing myocardium of this model. There was profound diastolic dysfunction associated with abnormalities in systolic function. Responses of contractile function to cardiotonic agents were attenuated in the failing heart compared to the normal heart, but the lusitropic responses were relatively well preserved. Consequently, coupling between contraction and relaxations was not linear, suggesting enhanced load sensitivity of left ventricular relaxation in the failing heart. Force-frequency response was also attenuated in the failing heart. Peak isometric tension development at 1 mM Ca2+ tended to be reduced in the failing myocardium, but these changes did not reach statistical significance in our experments. Times to peak tension and aequorin light and for decline from peak tension and peak light were considerably prolonged in muscle from the dogs with heart failure. This delayd intracellular Ca2+ cycling resulted in reversed force-frequency response, where the resting tension became substantially elevated. In the normal myocardium, aequorin light signals consisted of a single component preceding tension development. In the failing myocardium, there was evidence of two temporally distinct components in the aequarin light signal. These findings suggest that diastolic dysfunction in this heart failure model could be largely related to increased left ventricular systolic load and that abnormal Ca2+ handling plays an important role in systolic and diastolic dysfunction with increasing heart rate.
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