KATP 通道阻滞剂不能消除 Na+/H+ 交换 1 抑制对老年心肌缺血/再灌注的保护作用。

KATP channel blocker does not abolish the protective effect of Na+/H+ exchange 1 inhibition against ischaemia/reperfusion in aged myocardium.

机构信息

Department of Anesthesiology and Pain Medicine, University of California Davis, Sacramento, California 95817, USA.

出版信息

Eur J Anaesthesiol. 2010 Aug;27(8):740-6. doi: 10.1097/EJA.0b013e328337bb56.

DOI:10.1097/EJA.0b013e328337bb56

PMID:20216068

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2900462/

Abstract

BACKGROUND AND OBJECTIVE

Ageing is associated with an increase in myocardial susceptibility to ischaemia/reperfusion (I/R) injury. Na+/H+ exchange (NHE) inhibition and anaesthetic preconditioning (APC) are shown to protect myocardium from I/R injury. We set out to investigate whether NHE inhibition can induce protection against I/R injury and whether KATP channel inhibition can enhance this effect in aged rat myocardium.

METHODS

Hearts from 24-month-old rats were assigned to four groups: control group; APC group perfused with 2.5% sevoflurane before ischaemia; HOE group perfused with (3-methylsulfonyl-4-piperidinobenzoyl) guanidine methanesulfonate (HOE-694) prior to ischaemia; and HOE+5HD group perfused with both HOE and 5-hydroxydecanoic acid before ischaemia. We measured intracellular Na+ and Ca++ to quantitate the severity of myocardial injury.

RESULTS

Both intracellular Na+ and Ca++ were significantly increased at the end of ischaemia and both were attenuated by NHE inhibition. Intracellular Na+ was 134 +/- 12 mEq kg(-1) dry weight in control group and 55 +/- 7 in HOE group (P < 0.05). Intracellular Ca++ was 1764 +/- 142 nmol l(-1) in control group and 694 +/- 213 in HOE group (P < 0.05). Infarct size was measured at 28 +/- 4% in control group vs. 17 +/- 2% in HOE group (P < 0.05). High-energy phosphates and myocardial function were better preserved in HOE group compared with control (P < 0.05). The beneficial effect of HOE on myocardial preservation was not blocked by 5HD nor were there any differences between APC and control groups.

CONCLUSION

NHE inhibition was effective in protecting myocardium from I/R injury in aged rats, whereas APC was not. 5HD failed to block the protective effect of NHE inhibition.

摘要

背景与目的

年龄增长会导致心肌对缺血/再灌注（I/R）损伤的敏感性增加。已经证明，钠/氢交换（NHE）抑制和麻醉预处理（APC）可以保护心肌免受 I/R 损伤。我们旨在研究 NHE 抑制是否可以诱导对 I/R 损伤的保护作用，以及 KATP 通道抑制是否可以增强老年大鼠心肌中的这种作用。

方法

将 24 个月大的大鼠的心脏分为四组：对照组；在缺血前用 2.5%七氟醚灌注的 APC 组；在缺血前用（3-甲基磺酰基-4-哌啶基苯甲酰）胍甲烷磺酸盐（HOE-694）灌注的 HOE 组；以及在缺血前用 HOE 和 5-羟基癸酸同时灌注的 HOE+5HD 组。我们测量了细胞内的 Na+和 Ca++以定量评估心肌损伤的严重程度。

结果

在缺血结束时，细胞内的 Na+和 Ca++均显著增加，并且 NHE 抑制可减轻这两种物质的增加。对照组细胞内的 Na+为 134 +/- 12 mEq kg(-1) 干重，而 HOE 组为 55 +/- 7（P < 0.05）。对照组细胞内的 Ca++为 1764 +/- 142 nmol l(-1)，而 HOE 组为 694 +/- 213（P < 0.05）。对照组的梗死面积为 28 +/- 4%，而 HOE 组为 17 +/- 2%（P < 0.05）。与对照组相比，HOE 组的高能磷酸化合物和心肌功能保存更好（P < 0.05）。HOE 对心肌保护的有益作用不受 5HD 阻断，APC 组与对照组之间也没有差异。