Acute hibernation decreases myocardial pyruvate carboxylation and citrate release
Acute hibernation decreases myocardial pyruvate carboxylation and citrate release
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DOI：
10.1152/ajpheart.2001.281.4.h1613
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发表时间：
2001-10-01
影响因子：
4.8
通讯作者：
Stanley, WC
中科院分区：
文献类型：
--
作者：
Panchal, AR;Comte, B;Stanley, WC
在灌注良好的心脏中，丙酮酸羧化占柠檬酸循环（CAC）通量的3-6%，并且CAC碳通过柠檬酸盐释放而损失。我们研究了冠状动脉流量急性减少对这些过程和CAC中间体的组织含量的影响。在开胸麻醉猪模型上进行测量，通过体外灌注回路控制冠状动脉左前降支血流，并将流量减少40%持续80 min以诱导心肌冬眠（n = 8）。冠状动脉内输注[U-C-13（3）]乳酸盐和[U-C-13（3）]丙酮酸盐，以测量丙酮酸盐通过CAC中间体的C-13标记同位素异构体的丙酮酸羧化进入CAC。与正常冠状动脉流量相比，心肌冬眠导致平行减少65%和79%的丙酮酸羧化和净柠檬酸释放的心肌，分别和维护的CAC中间含量。动脉丙酮酸浓度升高1 mM没有影响。因此，冠状动脉血流量减少40%导致丙酮酸羧化和柠檬酸盐释放的同时减少以及CAC中间体的维持。
In the well-perfused heart, pyruvate carboxylation accounts for 3-6% of the citric acid cycle (CAC) flux, and CAC carbon is lost via citrate release. We investigated the effects of an acute reduction in coronary flow on these processes and on the tissue content of CAC intermediates. Measurements were made in an open-chest anesthetized swine model, Left anterior descending coronary artery blood flow was controlled by a extracorporeal perfusion circuit, and flow was decreased by 40% for 80 min to induce myocardial hibernation (n = 8). An intracoronary infusion of [U-C-13(3)]lactate and [U-C-13(3)]pyruvate was given to measure the entry of pyruvate into the CAC through pyruvate carboxylation from the C-13-labeled isotopomers of CAC intermediates. Compared with normal coronary flow, myocardial hibernation resulted in parallel decreases of 65% and 79% in pyruvate carboxylation and net citrate release by the myocardium, respectively, and maintenance of the CAC intermediate content. Elevation of the arterial pyruvate concentration by 1 mM had no effect. Thus a 40% decrease in coronary blood flow resulted in a concomitant decrease in pyruvate carboxylation and citrate release as well as maintenance of the CAC intermediates.