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Arrhythmogenic [Ca^<2+>]_i dynamics of the pefused heart revealed by confocal microscopy

共聚焦显微镜揭示灌注心脏的致心律失常 [Ca^<2 >]_i 动力学

基本信息

批准号：
11670702
负责人：
TANAKA Hideo
金额：
$ 1.28万
依托单位：
Kyoto Prefectural University of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670702/
关键词：
calcium calcium wave myocardial injury triggered activity arrhythmia confocal microscopy ランゲンドルフ潅流心

项目摘要

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 … More 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

异常的细胞内Ca^2+（[Ca^2+]_i）处理，在心脏Ca^2+超载条件下发生，例如，缺血-再灌注损伤被认为是快速性心律失常的重要基质。然而，目前尚不清楚受伤心脏的[Ca^<2+>]_i动态变化是否以及如何导致快速性心律失常的发生。为了解决这一问题，我们研究了时空变化的[Ca^<2+>]_i在fluo-3/AM负载大鼠心脏的心外膜区域与无冷冻损伤使用实时共聚焦显微镜。结果表明：（1）在静息状态下，心脏完整区域以4波/min/细胞的速度出现钙波，但钙波可被钙瞬变完全消除;（2）心脏钙超载程度越高，钙波出现的频率越高。Ca^<2+>超载区的波（Ca^<2+>超载波）通常传播到周围的肌细胞，而在Ca^<2+>超载区的波（Ca^<2+>超载波）通常传播到周围的肌细胞。 ...更多信息严重损伤区的e波频率极高，既没有细胞间的传播，也没有Ca^2+瞬变的消除。3）当通过液氮对心脏施加冷冻损伤时，边缘区表现出普遍的Ca^2+波，与完整区形成鲜明对比，完整区只有均匀的Ca^2+瞬变，而没有Ca^2+波发生。边界区表现出两种不同类型的Ca^<2+>波：高频Ca^<2+>波（210/min/细胞），不受周围Ca^2+瞬变的影响，发生在紧邻冷冻坏死区的位置，（79/min/cell），完全被瞬变减少，4）邻近区域的频繁Ca^<2+>波与固有心律或高频（2-3 Hz）不同步发生结果表明，在急性心肌损伤时，[Ca^<2+>]_i的异常变化可能与心肌细胞内[Ca^<2+>]_i的异常变化有关。损伤区的Ca^2+波可能成为触发性心律失常和收缩衰竭的基质。少