Askenasy N
Institute for Cellular Therapeutics, University of Louisville, USA. askenasy+@andrew.cmu.edu
J Mol Cell Cardiol. 2000 May;32(5):791-803. doi: 10.1006/jmcc.2000.1121.
Experimental evidence indicates a metabolic basis of contraction-perfusion coupling during an increase in cardiac work load. This study aims to characterize adjustment of myocardial energy metabolism in response to acute low flow ischemia (LFI), and to determine its involvement in perfusion-contraction coupling. Intracellular parameters were measured in isolated rat hearts by NMR spectroscopy and biochemical methods during 30 min of graded LFI and reperfusion as compared to continuous perfusion (control). Oxygen pressure was set to reach maximal oxygen extraction at 70% coronary flow rate (CFR), therefore oxygen limitation was proportional to coronary underperfusion. At 69, 38 and 10% CFR left ventricular pressures decreased to 71, 43 and 25% of pre-ischemic values respectively (P<0.005 v 97% in control) without an increase in diastolic tone, and recovered to 92+/-3% after 30 min of reperfusion. Despite hydrolysis of high energy phosphates and cellular acidification, ADP concentrations were stable in underperfused hearts. At 69, 38 and 10% CFR, cytosolic phosphorylation potentials (PP) decreased from 74+/-10 m M(-1)during pre-ischemia to 40+/-6, 25+/-4 and 14+/-4 m M(-1)respectively (P<0.05 v 63+/-9 m M(-1)in control), and lactate efflux increased to 256+/-18, 386+/-22 and 490+/-43 micromol /gdw respectively (P<0.005 v 186+/-22 micromol/gdw in control). Glycogen contents decreased (P<0.005 v control) and accounted for 27-30% of lactate efflux. These results indicate: (a) proportionate depression of contraction force and glycogen contents, and increased glucose uptake and anaerobic energy production in the underperfused myocardium. Coordinated modulation of these parameters attributes cytosolic PP a regulatory function; (b) resetting of cytosolic PP to lower levels mediates perfusion-contraction coupling during graded LFI. The data are consistent with the concept that glycolytic energy production improves myocardial tolerance to ischemia.
实验证据表明，在心脏工作负荷增加期间，收缩 - 灌注偶联存在代谢基础。本研究旨在描述心肌能量代谢对急性低流量缺血（LFI）的适应性变化，并确定其在灌注 - 收缩偶联中的作用。与持续灌注（对照）相比，在分级LFI和再灌注的30分钟内，通过核磁共振光谱和生化方法测量离体大鼠心脏的细胞内参数。将氧分压设定为在70%冠状动脉血流速度（CFR）时达到最大氧摄取量，因此氧限制与冠状动脉灌注不足成正比。在69%、38%和10% CFR时，左心室压力分别降至缺血前值的71%、43%和25%（与对照中的97%相比，P<0.005），舒张期张力未增加，再灌注30分钟后恢复至92±3%。尽管高能磷酸盐水解和细胞酸化，但灌注不足的心脏中ADP浓度保持稳定。在69%、38%和10% CFR时，胞质磷酸化电位（PP）分别从缺血前的74±10 mM⁻¹降至40±6、25±4和14±4 mM⁻¹（与对照中的63±9 mM⁻¹相比，P<0.05），乳酸流出分别增加至256±18、386±22和490±43 μmol/gdw（与对照中的186±22 μmol/gdw相比，P<0.005）。糖原含量降低（与对照相比，P<0.005），占乳酸流出的27 - 30%。这些结果表明：（a）灌注不足的心肌中收缩力和糖原含量成比例降低，葡萄糖摄取增加和无氧能量产生增加。这些参数的协调调节赋予胞质PP调节功能；（b）在分级LFI期间，将胞质PP重置为较低水平介导灌注 - 收缩偶联。这些数据与糖酵解能量产生改善心肌缺血耐受性的概念一致。
