Impact of anaerobic glycolysis and oxidative substrate selection on contractile function and mechanical efficiency during moderate severity ischemia.
Impact of anaerobic glycolysis and oxidative substrate selection on contractile function and mechanical efficiency during moderate severity ischemia.
复制标题
中度严重缺血期间无氧糖酵解和氧化底物选择对收缩功能和机械效率的影响。
DOI：
10.1152/ajpheart.00561.2008
复制
发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Stanley,WilliamC
中科院分区：
文献类型：
--
作者：
Zhou,Lufang;Huang,Hazel;McElfresh,TracyA;Prosdocimo,DomenickA;Stanley,WilliamC
在中度严重心肌缺血期间，无氧糖酵解和氧化底物选择对收缩功能和机械效率的作用尚不清楚。我们假设：1）防止无氧糖酵解会恶化收缩功能和机械效率，2）增加糖酵解和葡萄糖氧化，同时抑制游离脂肪酸氧化可改善缺血期间的收缩功能。实验在麻醉猪中进行，左冠状动脉前降支血流减少 60%，持续 40 分钟，引起局部缺血。研究了三组：1) 不治疗，2) 用碘乙酸盐抑制糖酵解 (IAA)，或 3) 高胰岛素血症和高血糖 (HI + HG)。使用放射性同位素和来自净乳酸流出和心肌乳酸含量的无氧糖酵解来测量葡萄糖和游离脂肪酸氧化。根据左心室压力和前壁节段长度评估区域收缩力。我们发现，在没有游离脂肪酸和葡萄糖氧化改变的情况下，在缺血期间用 IAA 预防无氧糖酵解不会对心肌缺血期间的收缩功能或机械效率产生不利影响，这表明无氧糖酵解对于维持残余收缩功能并不是必需的。用 HI + HG 增加糖酵解和葡萄糖氧化可抑制游离脂肪酸氧化并改善收缩功能和机械效率。总之，这些结果表明，在体内中度严重缺血期间，心肌功能与无氧糖酵解之间存在分离，这表明代谢治疗的目的不应该是抑制无氧糖酵解本身，而是激活胰岛素信号传导和/或增强碳水化合物氧化和/或减少脂肪酸氧化。
The role of anaerobic glycolysis and oxidative substrate selection on contractile function and mechanical efficiency during moderate severity myocardial ischemia is unclear. We hypothesize that1) preventing anaerobic glycolysis worsens contractile function and mechanical efficiency and2) increasing glycolysis and glucose oxidation while inhibiting free fatty acid oxidation improves contractile function during ischemia. Experiments were performed in anesthetized pigs, with regional ischemia induced by a 60% decrease in left anterior descending coronary artery blood flow for 40 min. Three groups were studied:1) no treatment,2) inhibition of glycolysis with iodoacetate (IAA), or3) hyperinsulinemia and hyperglycemia (HI + HG). Glucose and free fatty acid oxidation were measured using radioisotopes and anaerobic glycolysis from net lactate efflux and myocardial lactate content. Regional contractile power was assessed from left ventricular pressure and segment length in the anterior wall. We found that preventing anaerobic glycolysis with IAA during ischemia in the absence of alterations in free fatty acid and glucose oxidation did not adversely affect contractile function or mechanical efficiency during myocardial ischemia, suggesting that anaerobic glycolysis is not essential for maintaining residual contractile function. Increasing glycolysis and glucose oxidation with HI + HG inhibited free fatty acid oxidation and improved contractile function and mechanical efficiency. In conclusion, these results show a dissociation between myocardial function and anaerobic glycolysis during moderate severity ischemia in vivo, suggesting that metabolic therapies should not be aimed at inhibiting anaerobic glycolysis per se, but rather activating insulin signaling and/or enhancing carbohydrate oxidation and/or decreasing fatty acid oxidation.