Sauer F D, Kramer J K, Forester G V, Butler K W
Animal Research Centre, Research Branch, Central Experimental Farm, Ottawa, Canada.
Biochim Biophys Acta. 1989 Aug 8;1004(2):205-14. doi: 10.1016/0005-2760(89)90269-5.
Hearts from 4 week-old weanling pigs were capable of continuous work output when perfused with Krebs-Henseleit buffer containing 11 mM glucose. Perfused hearts metabolized either glucose or fatty acids, but optimum work output was achieved by a combination of glucose plus physiological concentrations (0.1 mM) of either palmitate or erucate. Higher concentrations of free fatty acids increased their rate of oxidation but also resulted in a large accumulation of neutral lipids in the myocardium, as well as a tendency to increased acetylation and acylation of coenzyme A and carnitine. When hearts were perfused with 1 mM fatty acids, the work output declined below control values. Erucic acid is known to be poorly oxidized by isolated rat heart mitochondria and, to a lesser degree, by perfused rat hearts. In addition, it has been reported that erucic acid acts as an uncoupler of oxidative phosphorylation. In isolated perfused pig hearts used in the present study, erucic acid oxidation rates were as high as palmitate oxidation rates. When energy coupling was measured by 31P-NMR, the steady-state levels of ATP and phosphocreatine during erucic acid perfusion did not change noticeably from those during glucose perfusion. It was concluded that the severe decrease in oxidation rates and ATP production resulting from the exposure of isolated pig and heart mitochondria to erucic acid are not replicated in the intact pig heart.
当用含有11 mM葡萄糖的克氏-亨氏缓冲液灌注时，4周龄断奶仔猪的心脏能够持续输出功。灌注的心脏能够代谢葡萄糖或脂肪酸，但葡萄糖与生理浓度（0.1 mM）的棕榈酸或芥酸组合可实现最佳的功输出。较高浓度的游离脂肪酸会提高其氧化速率，但也会导致心肌中中性脂质大量积累，以及辅酶A和肉碱的乙酰化和酰化增加的趋势。当心脏用1 mM脂肪酸灌注时，功输出下降至低于对照值。已知芥酸被分离的大鼠心脏线粒体氧化的能力较差，在灌注的大鼠心脏中氧化能力稍弱。此外，有报道称芥酸可作为氧化磷酸化的解偶联剂。在本研究中使用的分离灌注猪心脏中，芥酸的氧化速率与棕榈酸的氧化速率一样高。当通过31P-NMR测量能量偶联时，在芥酸灌注期间ATP和磷酸肌酸的稳态水平与葡萄糖灌注期间相比没有明显变化。得出的结论是，分离的猪心脏线粒体暴露于芥酸导致的氧化速率和ATP生成的严重下降在完整的猪心脏中并未重现。
