Cardiovascular Research Group and Departments of Pharmacology and Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
J Mol Cell Cardiol. 2009 Jul;47(1):142-8. doi: 10.1016/j.yjmcc.2009.03.005. Epub 2009 Mar 19.
It is unknown what effects high levels of fatty acids have on energy metabolism and cardiac efficiency during milder forms of ischemia. To address this issue, isolated working rat hearts perfused with Krebs-Henseleit solution (5 mM glucose, 100 muU/mL insulin, and 0.4 (Normal Fat) or 1.2 mM palmitate (High Fat)) were subjected to 30 min of aerobic perfusion followed by 30 min of mild ischemia (39% reduction in coronary flow). Both groups had similar aerobic function and rates of glycolysis, however the High Fat group had elevated rates of palmitate oxidation (150%), and decreased rates of glucose oxidation (51%). Mild ischemia decreased cardiac work (56% versus 40%) and efficiency (29% versus 11%) further in High Fat hearts. Palmitate oxidation contributed a greater percent of acetyl-CoA production during mild ischemia in the High Fat group (81% versus 54%). During mild ischemia glycolysis remained at aerobic levels in the Normal Fat group, but was accelerated in the High Fat group. Triglyceride, glycogen and adenine nucleotide content did not differ at the end of mild ischemia, however glycogen turnover was double in the High Fat group (248%). Addition of the pyruvate dehydrogenase inhibitor dichloroacetate to the High Fat group resulted in a doubling of the rate of glucose oxidation and improved cardiac efficiency during mild ischemia. We demonstrate that fatty acid oxidation dominates as the main source of residual oxidative metabolism during mild ischemia, which is accompanied by suppressed cardiac function and efficiency in the presence of high fat.
目前尚不清楚在轻度缺血的情况下，高水平的脂肪酸对能量代谢和心脏效率有何影响。为了解决这个问题，用 Krebs-Henseleit 溶液（5mM 葡萄糖、100mU/mL 胰岛素和 0.4（正常脂肪）或 1.2mM 棕榈酸（高脂））灌注的分离工作大鼠心脏进行了 30 分钟的有氧灌注，然后进行 30 分钟的轻度缺血（冠状动脉流量减少 39%）。两组的有氧功能和糖酵解率相似，但高脂组的棕榈酸氧化率升高（150%），葡萄糖氧化率降低（51%）。轻度缺血进一步降低了高脂心脏的心脏工作（56%对 40%）和效率（29%对 11%）。在高脂组中，轻度缺血期间，棕榈酸氧化对乙酰辅酶 A 生成的贡献率更大（81%对 54%）。在轻度缺血期间，正常脂肪组的糖酵解仍保持在有氧水平，但高脂组加速了糖酵解。轻度缺血结束时，甘油三酯、糖原和腺嘌呤核苷酸含量没有差异，但高脂组的糖原周转率是正常脂肪组的两倍（248%）。向高脂组中添加丙酮酸脱氢酶抑制剂二氯乙酸可使葡萄糖氧化率增加一倍，并改善轻度缺血期间的心脏效率。我们证明，在轻度缺血期间，脂肪酸氧化占据主导地位，成为残留氧化代谢的主要来源，同时伴有高脂血症时心脏功能和效率降低。
