Allard M F, Schönekess B O, Henning S L, English D R, Lopaschuk G D
Cardiovascular Research Laboratory, University of British Columbia, St. Paul's Hospital, Vancouver, Canada.
Am J Physiol. 1994 Aug;267(2 Pt 2):H742-50. doi: 10.1152/ajpheart.1994.267.2.H742.
The contribution of glycolysis and oxidative metabolism to ATP production was determined in isolated working hypertrophied hearts perfused with Krebs-Henseleit buffer containing 3% albumin, 0.4 mM palmitate, 0.5 mM lactate, and 11 mM glucose. Glycolysis and glucose oxidation were directly measured by perfusing hearts with [5-3H/U-14C]glucose and by measuring 3H2O and 14CO2 production, respectively. Palmitate and lactate oxidation were determined by simultaneous measurement of 3H2O and 14CO2 in hearts perfused with [9,10-3H]palmitate and [U-14C]lactate. At low workloads (60 mmHg aortic after-load), rates of palmitate oxidation were 47% lower in hypertrophied hearts than in control hearts, but palmitate oxidation remained the primary energy source in both groups, accounting for 55 and 69% of total ATP production, respectively. The contribution of glycolysis to ATP production was significantly higher in hypertrophied hearts (19%) than in control hearts (7%), whereas that of glucose and lactate oxidation did not differ between groups. During conditions of high work (120 mmHg aortic afterload), the extra ATP production required for mechanical function was obtained primarily from an increase in the oxidation of glucose and lactate in both groups. The contribution of palmitate oxidation to overall ATP production decreased in hypertrophied and control hearts (to 40 and 55% of overall ATP production, respectively) and was no longer significantly depressed in hypertrophied hearts. Glycolysis, on the other hand, was accelerated in control hearts to rates seen in the hypertrophied hearts. Thus a reduced contribution of fatty acid oxidation to energy production in hypertrophied rat hearts is accompanied by a compensatory increase in glycolysis during low work conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
在灌注含3%白蛋白、0.4 mM棕榈酸酯、0.5 mM乳酸盐和11 mM葡萄糖的Krebs-Henseleit缓冲液的离体工作肥大心脏中，测定了糖酵解和氧化代谢对ATP生成的贡献。通过用[5-³H/U-¹⁴C]葡萄糖灌注心脏并分别测量³H₂O和¹⁴CO₂的生成，直接测定糖酵解和葡萄糖氧化。通过同时测量灌注[9,10-³H]棕榈酸酯和[U-¹⁴C]乳酸盐的心脏中的³H₂O和¹⁴CO₂，测定棕榈酸酯和乳酸盐氧化。在低工作负荷（60 mmHg主动脉后负荷）下，肥大心脏中棕榈酸酯氧化速率比对照心脏低47%，但棕榈酸酯氧化在两组中仍是主要能量来源，分别占总ATP生成的55%和69%。肥大心脏中糖酵解对ATP生成的贡献（19%）显著高于对照心脏（7%），而葡萄糖和乳酸盐氧化的贡献在两组间无差异。在高工作状态（120 mmHg主动脉后负荷）下，两组机械功能所需的额外ATP生成主要来自葡萄糖和乳酸盐氧化的增加。肥大心脏和对照心脏中棕榈酸酯氧化对总ATP生成的贡献均降低（分别降至总ATP生成的40%和55%），且肥大心脏中不再显著降低。另一方面，对照心脏中的糖酵解加速至肥大心脏中的速率。因此，在低工作条件下，肥大大鼠心脏中脂肪酸氧化对能量生成的贡献降低，同时糖酵解会代偿性增加。（摘要截短于250字）
