Ionic movement and tolerance to ischemia in congenital heart disease : Sodium movement via the Na^+/H^+ exchange during reoxygenation is a determinant of post-ischemic functional recovery in the rat myocardium

先天性心脏病中的离子运动和缺血耐受性：再氧合过程中通过 Na^ /H^ 交换进行的钠运动是大鼠心肌缺血后功能恢复的决定因素

• 批准号: 16591383
• 负责人: YAMAMOTO Hiroshi
• 金额: $ 2.24万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591383/
• 关键词: myocardium; ischemia; reperfusion injury; sodium ion; proton; Na^+; H^+ exchange; dimethyl amiloride; HCO_3^- cotransporter; Na; H交換機構; 先天性心疾患; 細胞成熟度; イオンチャネル; 細胞内Ca濃度

Objectives : To determine whether or not sodium ion movement during reoxygenation is a determinant of post-ischemic recovery of cardiac function, we examined i) the effect of Na^+/H^+ exchange inhibition during reperfusion or reoxygenation on post-ischemic recovery of cardiac function and ii) the involvement of Na+/HCO_3^-cotransporter in the sodium ion movement.Methods : Isolated rat hearts were Langendorff-perfused with Krebs-Henseleit bicarbonate buffer and subjected to 20 minutes of normothermic (37C) global ischemia followed by normothermic (37℃) reperfusion. i) 100 μM dimethyl amiloride (DMA) was given during the first 10 min of reperfusion (protocol I) or for 10 minutes after 5-minute hypoxic reperfusion (protocol II). ii) a bicarbonate-free HEPES buffer was used during the first 10 minutes of reperfusion (protocol III). All the protocols were then followed by 25 minutes of noromoxic reperfusion.Results : i) In protocols I and II, the post-ischemic recovery of left ventricular developed pressure (%LVDP) was significantly greater in the DMA group than in the control group (68.6±5.9 vs. 52.0±6.1%, respectively in protocol Land 66.6±2.8 vs. 52.0±5.5%, respectively in protocol II). In protocol III, there was no difference between the bicarbonate-free group and the control group (35.9±4.9 vs. 24.7±6.7%, respectively).Conclusions : Sodium ion movement via the Na^+/H^+ exchange during reoxygenation is a determinant of post-ischemic recovery of cardiac function. The Na^+/HCO_3^- cotransporter may not be involved in the sodium ion movement during reperfusion.

目的：为了确定复氧过程中钠离子运动是否是缺血后心功能恢复的决定因素，我们检查了 i）再灌注或复氧过程中 Na^+/H^+ 交换抑制对缺血后心功能恢复的影响，以及 ii）Na+/HCO_3^-协同转运蛋白参与钠离子运动。方法：离体大鼠 心脏用Krebs-Henseleit碳酸氢盐缓冲液进行Langendorff灌注，并进行20分钟的常温（37℃）全局缺血，然后进行常温（37℃）再灌注。 i) 再灌注前 10 分钟内给予 100 μM 二甲基阿米洛利 (DMA)（方案 I）或 5 分钟缺氧再灌注后 10 分钟（方案 II）。 ii) 在再灌注的前 10 分钟内使用不含碳酸氢盐的 HEPES 缓冲液（方案 III）。所有方案均随后进行 25 分钟的常氧再灌注。 结果：i) 在方案 I 和 II 中，DMA 组左心室发展压 (%LVDP) 的缺血后恢复显着高于对照组（方案中分别为 68.6±5.9 与 52.0±6.1%，方案中分别为 66.6±2.8 与 52.0±5.5%） 二）。在方案 III 中，无碳酸氢盐组和对照组之间没有差异（分别为 35.9±4.9 与 24.7±6.7%）。结论：复氧过程中通过 Na^+/H^+ 交换的钠离子运动是缺血后心功能恢复的决定因素。 Na^+/HCO_3^- 协同转运蛋白可能不参与再灌注过程中的钠离子运动。