Study on Ca^<2+> sensitivity of reperfusion hypertrophied immature heart

肥大未成熟心脏再灌注Ca^<2>敏感性研究

• 批准号: 07457599
• 负责人: ITOI Toshiyuki
• 金额: $ 1.15万
• 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 (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457599/
• 关键词: immature heart; reperfusion injury; myocardial metabolism; isolated perfused heart; myocardial hypertrophy; 肥大心; 再灌流; カルシウムイオン

We developed chlonic pressure overloaded or volume overloaded heart on immature rabbits as a in situ model of congenital heart desease. The isolated hypertrophied heats subjected to overload were perfused and studied the mechanism of reperfusion injury in immature herat. was stuied Firstly, we studied effects of extracellular calcium concentrations on functional recovery after global ischemia. Secondly, the relation between intracardiac pH and Ca^<2+> sensitivity of contractile proteins in reperfused immature hearts.Results1)Increase of Ca^<2+> from 1.75mM to 2.5mM at the initiation of reperfusion after 40 min of global ischemia improved mechanical function of isolated one-week old rabbit hearts.2)Na^+/H^+ inhibiter (amirolide), reported to improve mechanical function of adult heart, showed no remarkable effect on immature reperfused hearts.3)No significant effect has also seen in addition of Cl^-/HCO3^- inhibiter (SITS) on reperfused one-week old rabbit hearts.4)Ca^<2+> sensitizer (pimobendan) improved dramatically contractile function of reperfused immature rabbit herats.5)We modified perfusion system to allow that high energy phosphates signal can be detected at each 4 min in ^<32>P-NMR mounted 25mm coil.

我们在未成熟的兔子上开发了慢性压力超负荷或容量超负荷的心脏作为先天性心脏病的原位模型。对超负荷条件下的孤立肥厚肝进行灌注，研究未成熟肝再灌注损伤的机制。首先，我们研究了细胞外钙浓度对整体缺血后功能恢复的影响。其次，再灌注未成熟心脏中心内pH与收缩蛋白Ca^<2+>敏感性之间的关系。结果1)全局缺血40分钟后再灌注开始时Ca^<2+>从1.75mM增加至2.5mM，改善了离体一周龄兔心脏的机械功能。2)Na^+/H^+抑制剂(阿米罗利)据报道可改善机械功能 3）添加Cl^-/HCO3^-抑制剂（SITS）对再灌注一周龄兔心脏没有显着影响。4）Ca^2+敏化剂（匹莫苯）显着改善再灌注未成熟兔心脏的收缩功能。5）我们修改了灌注系统以允许检测高能磷酸盐信号 在 32 P-NMR安装的25mm线圈中每4分钟一次。