Cardiac preconditioning with 4-h, 17°C ischemia reduces [Ca2+]i load and damage in part via KATP channel opening
Cardiac preconditioning with 4-h, 17°C ischemia reduces [Ca2+]i load and damage in part via KATP channel opening
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DOI：
10.1152/ajpheart.01032.2001
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发表时间：
2002-06-01
影响因子：
4.8
通讯作者：
Stowe, DF
中科院分区：
文献类型：
--
作者：
Chen, Q;Camara, AKS;Stowe, DF
常温缺血前的短暂缺血可保护心脏免受再灌注损伤（缺血预处理，IPC），但尚不清楚其是否可保护长期中度低温缺血。我们在离体豚鼠心脏中探索了1）4小时前两次2分钟的常温缺血，17 ℃低温缺血对心脏细胞内[Ca 2 +]，机械和代谢功能以及梗死面积的影响，和2）K-ATP通道在引发心脏保护中的潜在作用。我们发现，IPC前4小时亚低温改善心肌灌注，收缩力和舒张在常温再灌注。保护作用与整个低温储存和再灌注期间舒张期[Ca 2 +]负荷显著降低有关。整体梗死面积从36 +/- 2（SE）%显著降低至15 +/- 1%。用200 μ M 5-羟基癸酸或10 μ M格列本脲包围缺血性脉冲分别使梗死面积增加到28 +/- 3%和26 +/-4%。这些结果表明，短期缺血前长期低温储存增加了低温的心脏保护作用，这是与降低胞浆[Ca 2 +]负荷和增强ATP敏感性K通道开放。
Brief ischemia before normothermic ischemia protects hearts against reperfusion injury (ischemic preconditioning, IPC), but it is unclear whether it protects against long-term moderate hypothermic ischemia. We explored in isolated guinea pig hearts 1) the influence of two 2-min periods of normothermic ischemia before 4 h, 17degreesC hypothermic ischemia on cardiac cytosolic [Ca2+], mechanical and metabolic function, and infarct size, and 2) the potential role of K-ATP channels in eliciting cardioprotection. We found that IPC before 4 h moderate hypothermia improved myocardial perfusion, contractility, and relaxation during normothermic reperfusion. Protection was associated with markedly reduced diastolic [Ca2+] loading throughout both hypothermic storage and reperfusion. Global infarct size was markedly reduced from 36 +/- 2 (SE)% to 15 +/- 1% with IPC. Bracketing ischemic pulses with 200 muM 5-hydroxydecanoic acid or 10 muM glibenclamide increased infarct size to 28 +/- 3% and 26 +/- 4%, respectively. These results suggest that brief ischemia before long-term hypothermic storage adds to the cardioprotective effects of hypothermia and that this is associated with decreased cytosolic [Ca2+] loading and enhanced ATP-sensitive K channel opening.