A study on the dynamics of intracellular calcium ion in myocardium of isolated, perfused hearts during ischemia and after reperfusion.

缺血和再灌注后离体灌注心脏心肌细胞内钙离子动态的研究。

• 批准号: 63570393
• 负责人: KUSUOKA Hideo
• 金额: $ 1.34万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570393/
• 关键词: Ischemia; Reperfusion; Isolated, perfused heart; Intracellular free Ca^<2+>; Fluorine Nuclear Magnetic Resonance; 5F-BAPTA; Calcium Overload; 5FーBAPTA; 摘出灌流心標本; カルシウム・オーバーロード

This project aimed on the study of excitation-contraction coupling, especially dynamics of Intracellular free ion Ca^<2+>, in myocardium of ischemlc or reperfused hearts. The intracellular concentration of activator Ca^<2+> ([Ca^<2+>]_i) was measured in Isolated, perfused whole heart using fluorine nuclear magnetic resonance spectroscopy (^<19>F-NMR) coupled with Ca^<2+> chelator, 5F-BAPTA. The amounts of Ca^<2+> bounded and Ca^<2+> free 5F-BAPTA in myocardium were obtained from the signals of them in F-NMR spectrum, and [Ca^<2+>]_i was determined by the ratio of them. The following results were obtained in this project.1. The changes in [Ca^<2+>]_i during ischemia and after reperfusion were investigated. The intracellular Ca^<2+> concentration significantly increased after 10 minutes of global ischemia at 37ﾟC compared with control, but rapidly came back to the control level during early phase of reperfusion after 15 minutes of ischemia.2. We also focused on the pathophysiology of "stunned myocardium", i.e., myocardium reperfused after a brief period of ischemia. Such a brief ischemia is not enough to make necrosis but produces prolonged contractile failure. Developed pressure in the hearts reperfused after 15 minute of global ischemia at 37ﾟC showed only 70% of control (stunned myocardium) even the hearts were loaded with 5F-BAPTA. The amplitude of calcium translent, i.e., cyclical changes in [Ca^<2+>]_i, was significantly increased in stunned myocardium compared with that before ischemia. Coupled with our previous study, theses results revealed that this contractile dysfunction is due to the decrease in maximal Ca^<2+>-activated force in myofildment and the shift of myofilament Ca^<2+>-sensitivity to higher Ca with paradoxical increase in amplitude of calcium transients.

本项目旨在研究缺血或再灌注心脏心肌中的兴奋-收缩耦合，特别是细胞内游离离子Ca^2+的动态。使用与Ca 2+ 螯合剂5F-BAPTA联用的氟核磁共振波谱( 19 F-NMR)在分离的、灌注的全心脏中测量激活剂Ca 2+ ([Ca 2+ ]_i)的细胞内浓度。从F-NMR谱中的信号获得心肌中结合的Ca ^ 2+ 和游离的Ca ^ 2+ 5F-BAPTA的量，并根据它们的比率确定[Ca ^ 2+ ]_i。本课题取得了以下成果： 1．研究了缺血期间和再灌注后[Ca^2+]_i的变化。 37℃全缺血10分钟后细胞内Ca^2+浓度较对照显着升高，但缺血15分钟后再灌注早期迅速恢复至对照水平。2．我们还关注“心肌顿抑”的病理生理学，即心肌在短暂缺血后重新灌注。如此短暂的缺血不足以造成坏死，但会导致长期的收缩衰竭。即使心脏负载有 5F-BAPTA，在 37°C 15 分钟的整体缺血后再灌注的心脏中产生的压力也仅显示出 70% 的控制（心肌顿抑）。与缺血前相比，顿顿心肌中钙转运的幅度，即[Ca^2+]_i的周期性变化，显着增加。结合我们之前的研究，这些结果表明，这种收缩功能障碍是由于肌丝中最大Ca ^ 2+ 激活力的降低以及肌丝Ca ^ 2+ 敏感性向更高Ca 的转变以及钙瞬变幅度的反常增加所致。

项目成果

Kusuoka,H.: "Cardiac mechanics and function in the normal and diseased heart." SpringerーVerlag, (1989)

Kusuoka, H.：“正常和患病心脏的心脏力学和功能”，Springer-Verlag，(1989)

Porterfield JK: "Reperfusion and revascularization in acute myocardial infarction." Springer-Verlag, (1988)

Porterfield JK：“急性心肌梗死的再灌注和血运重建。”

Kusuoka H: Cardiac mechanics and function in the normal and diseased heart.Springer-Verlag, (1989)

Kusuoka H：正常和患病心脏的心脏力学和功能。Springer-Verlag，（1989）

楠岡英雄: Coronavy.

楠冈秀夫：冠状病毒。

楠岡英雄: "Stunned Myocardiumにおける収縮機能低下の機作に関する基礎的検討" Coronary. 6(Supp1.2). 45-50 (1989)

Hideo Kusuoka：“心肌顿挫的收缩功能障碍机制的基础研究”6（Supp1.2）（1989）。