Hoerter J A, Lauer C, Vassort G, Guéron M
Institut National de la Santé et de la Recherche Médicale U. 241, Université Paris-Sud, Orsay, France.
Am J Physiol. 1988 Aug;255(2 Pt 1):C192-201. doi: 10.1152/ajpcell.1988.255.2.C192.
A model of high-energy phosphate depletion was developed in the normoxic isovolumic rat heart perfused with acetate, 2-deoxy-D-glucose (2DG), and insulin. Intracellular phosphorylation of 2DG abstracts phosphorus from its normal pathways. This results in a decrease of high-energy phosphates without any increase in Pi. During the first 15 min of 2DG phosphorylation, the changes in ATP, Pi, and intracellular pH (pHi) were slight, and work was unaltered, although phosphocreatine (PCr) concentration dropped by 50%. After 45 min, the heart reached a new steady state characterized by a drastic reduction in both PCr and ATP: PCr was 15% of control, and in most hearts ATP became invisible on the nuclear magnetic resonance (NMR) spectra. Nevertheless, the heart still developed 65% of its original systolic pressure, whereas diastolic pressure was unchanged. Oxygen consumption per unit work remained constant during 2DG perfusion. This is, to our knowledge, the first experimental model of sustained cardiac contractility at such low contents of both ATP and PCr. However, our results are compatible with present knowledge of the cytosolic energy transfer by PCr and of the control of force in myofilaments.
在灌注有乙酸盐、2-脱氧-D-葡萄糖（2DG）和胰岛素的常氧等容大鼠心脏中建立了高能磷酸耗竭模型。2DG的细胞内磷酸化从其正常途径中提取磷。这导致高能磷酸盐减少，而无机磷酸盐（Pi）没有增加。在2DG磷酸化的前15分钟内，三磷酸腺苷（ATP）、Pi和细胞内pH值（pHi）的变化轻微，并且功未改变，尽管磷酸肌酸（PCr）浓度下降了50%。45分钟后，心脏达到一个新的稳定状态，其特征是PCr和ATP都急剧减少：PCr为对照的15%，并且在大多数心脏中，ATP在核磁共振（NMR）光谱上变得不可见。然而，心脏仍能产生其原始收缩压的65%，而舒张压未改变。在2DG灌注期间，单位功的耗氧量保持恒定。据我们所知，这是第一个在ATP和PCr含量如此低的情况下维持心脏收缩力的实验模型。然而，我们的结果与目前关于PCr的胞质能量转移以及肌丝中力的控制的知识是相符的。
