Collins-Nakai R L, Noseworthy D, Lopaschuk G D
Department of Pediatrics and Pharmacology, University of Alberta, Edmonton, Canada.
Am J Physiol. 1994 Nov;267(5 Pt 2):H1862-71. doi: 10.1152/ajpheart.1994.267.5.H1862.
Although epinephrine is widely used clinically, its effect on myocardial energy substrate preference in the intact heart has yet to be clearly defined. We determined the effects of epinephrine on glucose and fatty acid metabolism in isolated working rat hearts perfused with 11 mM glucose, 0.4 mM palmitate, and 100 muU/ml insulin at an 11.5-mmHg left atrial preload and a 60-mmHg aortic afterload. Glycolysis and glucose oxidation were measured in hearts perfused with [5-3H]glucose and [U-14C]glucose, whereas fatty acid oxidation was measured in hearts perfused with [1-14C]palmitate. Addition of 1 microM epinephrine resulted in a 53% increase in the heart rate-developed pressure product. Glycolysis increased dramatically following addition of epinephrine (a 272% increase), as did glucose oxidation (a 410% increase). In contrast, fatty acid oxidation increased by only 10%. Epinephrine treatment did not increase the amount of oxygen required to produce an equivalent amount of ATP; however, epinephrine did increase the uncoupling between glycolysis and glucose oxidation in these fatty acid-perfused hearts, resulting in a significant increase in H+ production from glucose metabolism. Overall ATP production in epinephrine-treated hearts increased 59%. The contribution of glucose (glycolysis and glucose oxidation) to ATP production increased from 13 to 36%, which was accompanied by a reciprocal decrease in the contribution of fatty acid oxidation to ATP production from 83 to 63%. The increase in glucose oxidation was accompanied by a significant increase in pyruvate dehydrogenase complex activity in the active form. We conclude that the increase in ATP required for contractile function following epinephrine treatment occurs through a preferential increase in glucose use.
尽管肾上腺素在临床上被广泛使用，但其对完整心脏中心肌能量底物偏好的影响尚未明确界定。我们测定了肾上腺素对在11.5 mmHg左心房前负荷和60 mmHg主动脉后负荷下，用11 mM葡萄糖、0.4 mM棕榈酸酯和100 μU/ml胰岛素灌注的离体工作大鼠心脏中葡萄糖和脂肪酸代谢的影响。在用[5-³H]葡萄糖和[U-¹⁴C]葡萄糖灌注的心脏中测量糖酵解和葡萄糖氧化，而在用[1-¹⁴C]棕榈酸酯灌注的心脏中测量脂肪酸氧化。添加1 μM肾上腺素导致心率-压力乘积增加53%。添加肾上腺素后糖酵解显著增加（增加272%），葡萄糖氧化也是如此（增加410%）。相比之下，脂肪酸氧化仅增加10%。肾上腺素处理并未增加产生等量ATP所需的氧量；然而，肾上腺素确实增加了这些脂肪酸灌注心脏中糖酵解与葡萄糖氧化之间的解偶联，导致葡萄糖代谢产生的H⁺显著增加。肾上腺素处理的心脏中总的ATP产生增加了59%。葡萄糖（糖酵解和葡萄糖氧化）对ATP产生的贡献从13%增加到36%，同时脂肪酸氧化对ATP产生的贡献相应地从83%减少到63%。葡萄糖氧化的增加伴随着活性形式的丙酮酸脱氢酶复合物活性的显著增加。我们得出结论，肾上腺素处理后收缩功能所需的ATP增加是通过优先增加葡萄糖利用而发生的。
