Cardiac efficiency is improved after ischemia by altering both the source and fate of protons
Cardiac efficiency is improved after ischemia by altering both the source and fate of protons
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DOI：
10.1161/01.res.79.5.940
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发表时间：
1996-11-01
影响因子：
20.1
通讯作者：
Lopaschuk, GD
中科院分区：
文献类型：
--
作者：
Liu, B;Clanachan, AS;Lopaschuk, GD
严重缺血后心脏效率降低。我们确定是否减少产生的H+从葡萄糖代谢或抑制清除H-通过Na-H+交换可以增加心脏再灌注期间的效率。这是通过使用二氯乙酸（DCA）刺激葡萄糖氧化和5-（N，N-二甲基）-阿米洛利（DMA）抑制Na+-H+交换来实现的。分别离体工作大鼠心脏进行30分钟的全脑缺血和60分钟的再灌注。测量了葡萄糖、乳酸盐和棕榈酸盐的糖酵解和氧化速率。测定再灌注期间心脏功恢复、O-2消耗（MVO（2））、乙酰辅酶A和ATP产生率。缺血后，对照心脏（n = 23）的心脏作功恢复到缺血前值的35 ± 5%，尽管MVO（2）。三羧酸（TCA）循环活性和糖酵解和氧化代谢产生的ATP迅速恢复到缺血前水平。心脏效率的降低伴随着葡萄糖代谢产生大量的H-。DCA导致葡萄糖氧化增加2.2倍，H-产生减少46 +/- 17%，心脏效率增加10倍，再灌注期间心脏做功增加2.0倍（n = 17）。用DMA抑制Na+-H+交换并不改变TCA循环活性和ATP产生速率，但确实导致心脏效率增加1.8倍，心脏作功增加1.7倍（n = 12）。这些数据表明，心脏效率和缺血后的收缩功能可以通过降低再灌注期间葡萄糖代谢产生的H+的速率或通过Na+-H+交换抑制H+的清除来改善。我们的数据表明，增加ATP的需求，以恢复缺血-再灌注引起的离子稳态的改变，有助于缺血后心脏效率和收缩功能的下降。
Cardiac efficiency is decreased in hearts after severe ischemia. We determined whether reducing the production of H+ from glucose metabolism or inhibiting the clearance of H- via Na--H+ exchange could increase cardiac efficiency during reperfusion. This was achieved using dichloroacetate (DCA) to stimulate glucose oxidation and 5-(N,N-dimethyl)-amiloride (DMA) to inhibit Na+-H+ exchange. respectively. Isolated working rat hearts were subjected to 30 minutes of global ischemia and 60 minutes of reperfusion. Glycolysis and oxidation rates of glucose, lactate, and palmitate were measured. Recovery of cardiac work, O-2 consumption (MVO(2)), and rates of acetyl-coenzyme A and ATP production during reperfusion were determined. After ischemia, cardiac work recovered to 35 +/- 5% of preischemic values in control hearts (n = 23), although MVO(2). tricarboxylic acid (TCA) cycle activity, and ATP production from glycolysis and oxidative metabolism rapidly recovered to preischemic levels. This decrease in cardiac efficiency was accompanied by a substantial production of H- from glucose metabolism. DCA caused a 2.2-fold increase in glucose oxidation, a 46 +/- 17% decrease in H- production, a 10-fold increase in cardiac efficiency, and a 2.0-fold increase in cardiac work during reperfusion (n = 17). Inhibition of Na+-H+ exchange with DMA did not alter TCA cycle activity and ATP production rates but did result in a 1.8-fold increase in cardiac efficiency and a 1.7-fold increase in cardiac work (n = 12). These data show that cardiac efficiency and the contractile function after ischemia can be improved by either reducing the rate of H+ production from glucose metabolism during reperfusion or inhibiting the clearance of H+ via Na+-H+ exchange. Our data suggest that an increased requirement for ATP to restore ischemia-reperfusion-induced alterations in ion homeostasis contributes to the decrease in cardiac efficiency and contractile function after ischemia.