Barak C, Reed M K, Maniscalco S P, Sherry A D, Malloy C R, Jessen M E
Department of Surgery, University of Texas Southwestern Medical Center at Dallas, 75235-8879, USA.
J Cardiovasc Pharmacol. 1998 Mar;31(3):336-44. doi: 10.1097/00005344-199803000-00002.
The effects of dichloroacetate (DCA) on fatty acid oxidation and flux through pyruvate dehydrogenase (PDH) were studied in ischemic, reperfused myocardium supplied with glucose, long-chain fatty acids, lactate, pyruvate, and acetoacetate. The oxidation rates of all substrates were determined by combined 13C nuclear magnetic resonance (NMR) spectroscopy and oxygen-consumption measurements, and PDH flux was assessed by lactate plus pyruvate oxidation. In nonischemic control hearts, DCA increased PDH flux more than eightfold (from 0.68 +/- 0.28 to 5.81 +/- 1.16 micromol/min/g dry weight; n = 8 each group; p < 0.05) and significantly inhibited the oxidation of acetoacetate and fatty acids. DCA also improved mechanical recovery after 30 min of ischemia plus 30 min of reperfusion but did not significantly increase PDH flux measured at the end of the reperfusion period (1.35 +/- 0.42 micromol/min/g dry weight) compared with untreated ischemic hearts (0.87 +/- 0.28 micromol/min/g dry weight; n = 8 each group; p = NS). Although DCA had a modest effect on functional recovery in the reperfused myocardium, this beneficial effect was not associated with either marked stimulation of PDH flux or inhibition of fatty acid oxidation.
在供应葡萄糖、长链脂肪酸、乳酸、丙酮酸和乙酰乙酸的缺血再灌注心肌中，研究了二氯乙酸（DCA）对脂肪酸氧化和通过丙酮酸脱氢酶（PDH）的通量的影响。所有底物的氧化速率通过13C核磁共振（NMR）光谱和耗氧量测量相结合来确定，PDH通量通过乳酸加丙酮酸氧化来评估。在非缺血对照心脏中，DCA使PDH通量增加了八倍多（从0.68±0.28增加到5.81±1.16微摩尔/分钟/克干重；每组n = 8；p < 0.05），并显著抑制乙酰乙酸和脂肪酸的氧化。DCA还改善了30分钟缺血加30分钟再灌注后的机械恢复，但与未处理的缺血心脏相比，在再灌注期结束时测量的PDH通量（1.35±0.42微摩尔/分钟/克干重）没有显著增加（0.87±0.28微摩尔/分钟/克干重；每组n = 8；p = 无显著性差异）。尽管DCA对再灌注心肌的功能恢复有适度影响，但这种有益作用与显著刺激PDH通量或抑制脂肪酸氧化均无关。
