2000 Fiscal Year Final Research Report Summary
Arrhythmogenic [Ca^<2+>]_i dynamics of the pefused heart revealed by confocal microscopy
| Project/Area Number |
11670702
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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 | Kyoto Prefectural University of Medicine |
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Principal Investigator |
TANAKA Hideo Kyoto Prefectural University of Medicine, Assistant, 医学部, 助手 (60236619)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAMATSU Tetsuro Kyoto Prefectural University of Medicine, Professor, 医学部, 教授 (40154900)
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| Project Period (FY) |
1999 – 2000
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| Keywords | calcium / calcium wave / myocardial injury / triggered activity / arrhythmia / confocal microscopy |
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| Research Abstract |
Abnormal intracellular Ca^<2+> ([Ca^<2+>]_i) handling, which deyelops under Ca^<2+> overloaded conditions of the heart by e.g., ischemia-reperfusion injury, has been considered to be an important substrate for tachyarrhythmias. However, it is unknown whether and how altered [Ca^<2+>]_i dynamics of the injured heart contributes to the development of tachyarrhythmias. To address this question, we studied spatiotemporal changes in [Ca^<2+>]_i at the epicardial regions of the fluo-3/AM-loaded rat heart with and without cryo-injury using real-time confocal microscopy. The following results were obtained.
1) Under quiescent conditions, the intact regions of the heart exhibited Ca^<2+> waves sporadically at 4 waves/min/cell, which were totally abolished by Ca^<2+> transients.
2) The Ca^<2+> waves occurred more frequently as the heart was more highly Ca^<2+>-overloaded. The waves at the Ca^<2+>-overloaded regions (Ca^<2+>-overloaded waves) often propagated to the surrounding myocytes, whereas th
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e waves at highly damaged regions showed extremely high-frequency with neither cell-to-cell propagation nor abolition by Ca^<2+> transients.
3) When cryo-injury was applied to the heart via liquid nitrogen, the border zones exhibited prevalent Ca^<2+> waves, in sharp contrast to the intact zones, where only homogeneous Ca^<2+> transients but no Ca^<2+> waves occurred. The border zones exhibited two different types of Ca^<2+> waves : the highly frequent Ca^<2+> waves (210/min/cell), which were unaffected by the surrounding Ca^<2+> transients, occurred at just adjacent to the cryo-necrosed regions, and the less frequent waves (79/min/cell), totally diminished by the transients, occurred at the vicinities.
4) The frequent Ca^<2+> waves at the adjacent regions occurred asynchronously to either the intrinsic heart rhythm or high-frequency (2-3 Hz) excitation, whereas the less-frequent waves at the vicinities occurred more frequently and prevalently as the heart was stimulated at higher frequencies.
These observations may represent abnormal [Ca^<2+>]_i handling during acute myocardial injury. The Ca^<2+> waves at the injured regions may become a substrate for triggered arrhythmias and contractile failure. Less
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Research Products
(5 results)
