1993 Fiscal Year Final Research Report Summary
Mechanisms for Abnormal Excitation-Contraction Coupling in the Reversible Heart Failure Induced by Rapid Ventricular Pacing
| 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 Toyama Medical and Pharmaceutical University Hospital, Associated Professor, 附属病院, 講師 (00150128)
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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)
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| Project Period (FY) |
1991 – 1993
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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 |
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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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