Intracellular sodium increase and susceptibility to ischaemia in hearts from type 2 diabetic db/db mice
Intracellular sodium increase and susceptibility to ischaemia in hearts from type 2 diabetic db/db mice
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DOI：
10.1007/s00125-005-0091-5
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发表时间：
2006-03-01
期刊：
影响因子：
8.2
通讯作者：
Feuvray, D
中科院分区：
文献类型：
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作者：
Anzawa, R;Bernard, M;Feuvray, D
目的/假设：对缺血敏感性的一个重要决定因素是离子稳态的改变，特别是细胞内Na+ (Na-i(+))处理的干扰。由于到目前为止还没有研究在2型糖尿病中研究这一点，我们检查了糖尿病db/db和对照db/+小鼠离体心脏对缺血-再灌注的易感性，并确定短暂缺血期间Na-i（+）的量增加是否以及在多大程度上有助于再灌注时的功能改变。方法：等容心脏局部缺血30min后再灌注。采用Na-23核磁共振（NMR）谱监测Na-i(+)， P-31核磁共振（NMR）谱监测细胞内pH（pH(i)）。结果：db/db心脏再灌注后室性心动过速持续时间延长，室性心动过速退化为心室颤动。左室发达压恢复降低。缺血引起的Na-i（+）升高在db/db心脏中高于对照心脏，再灌注时pHi恢复速率增加。cariporide对Na+/H+交换的抑制显著降低了缺血结束时Na-i（+）的增益。这与两组心脏中室性心动过速发生率较低有关，并且在db/db心脏中抑制室性心动过速变性为心室颤动。结论/解释：这些发现有力地支持了在db/db糖尿病心脏中观察到的Na-i（+）增加对缺血敏感性增强起致病作用的假设。
Aims/hypothesis: An important determinant of sensitivity to ischaemia is altered ion homeostasis, especially disturbances in intracellular Na+ (Na-i(+)) handling. As no study has so far investigated this in type 2 diabetes, we examined susceptibility to ischaemia-reperfusion in isolated hearts from diabetic db/db and control db/+ mice and determined whether and to what extent the amount of Na-i(+) increase during a transient period of ischaemia could contribute to functional alterations upon reperfusion. Methods: Isovolumic hearts were exposed to 30-min global ischaemia and then reperfused. Na-23 nuclear magnetic resonance (NMR) spectroscopy was used to monitor Na-i(+) and P-31 NMR spectroscopy to monitor intracellular pH (pH(i)). Results: A higher duration of ventricular tachycardia and the degeneration of ventricular tachycardia into ventricular fibrillation were observed upon reperfusion in db/db hearts. The recovery of left ventricular developed pressure was reduced. The increase in Na-i(+) induced by ischaemia was higher in db/db hearts than in control hearts, and the rate of pHi recovery was increased during reperfusion. The inhibition of Na+/H+ exchange by cariporide significantly reduced Na-i(+) gain at the end of ischaemia. This was associated with a lower incidence of ventricular tachycardia in both heart groups, and with an inhibition of the degeneration of ventricular tachycardia into ventricular fibrillation in db/db hearts. Conclusions/interpretation: These findings strongly support the hypothesis that increased Na-i(+) plays a causative role in the enhanced sensitivity to ischaemia observed in db/db diabetic hearts.