Departments of Pediatrics and Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, 423 Heritage Medical Research Centre, Edmonton, AB, Canada.
Am J Physiol Heart Circ Physiol. 2010 May;298(5):H1426-37. doi: 10.1152/ajpheart.00284.2009. Epub 2010 Feb 12.
In the neonatal heart the transition from using carbohydrates to using fatty acids has not fully matured and oxidative metabolism/ATP generation may be limiting contractile function after ischemia. This study tested the hypothesis that increasing fatty acid availability increases recovery of left ventricular (LV) work by increasing palmitate oxidation, tricarboxylic acid (TCA) cycle activity, and ATP generation. Isolated working hearts from 7-day-old rabbits were perfused with Krebs solution containing low (0.4 mM) or high (2.4 mM) palmitate and 5.5 mM glucose. Hearts were subjected to 35-min global ischemia before 40-min reperfusion, and rates of glycolysis, glucose oxidation, and palmitate oxidation were assessed. LV work was similar before ischemia but was greater during reperfusion in hearts perfused with 2.4 mM palmitate compared with hearts perfused with 0.4 mM palmitate [6.98 +/- 0.14 (n = 15) vs. 3.01 +/- 0.23 (n = 16) mJ.beat(-1).g dry wt(-1); P < 0.05]. This was accompanied by increased LV energy expenditure during reperfusion [35.98 +/- 0.16 (n = 8) vs. 19.92 +/- 0.18 (n = 6) mJ.beat(-1).g dry wt(-1); P < 0.05]. During reperfusion the rates of palmitate oxidation [237.5 +/- 28.10 (n = 7) vs. 86.0 +/- 9.7 (n = 6) nmol.g dry wt(-1).min(-1); P < 0.05], total TCA cycle activity [2.65 +/- 0.39 (n = 7) vs. 1.36 +/- 0.14 (n = 6) micromol acetyl-CoA.g dry wt(-1).min(-1); P < 0.05], and ATP generation attributable to palmitate oxidation [26.6 +/- 3.1 (n = 7) vs. 12.6 +/- 1.7 (n = 6) micromol.g dry wt(-1).min(-1); P < 0.05] were greater in hearts perfused with 2.4 mM palmitate. These data indicate that the neonatal heart has decreased energy reserve, and, in contrast to the mature heart, increasing availability of fatty acid substrate increases energy production and improves recovery of function after ischemia.
在新生儿心脏中，从使用碳水化合物到使用脂肪酸的转变尚未完全成熟，氧化代谢/ATP 生成可能会限制缺血后的收缩功能。本研究假设增加脂肪酸的可用性可以通过增加棕榈酸氧化、三羧酸 (TCA) 循环活性和 ATP 生成来增加左心室 (LV) 工作的恢复。从 7 天大的兔子中分离出工作心脏，并用含有低 (0.4 mM) 或高 (2.4 mM) 棕榈酸和 5.5 mM 葡萄糖的 Krebs 溶液灌注。心脏在 40 分钟再灌注前经历 35 分钟的全缺血，评估糖酵解、葡萄糖氧化和棕榈酸氧化的速率。缺血前 LV 工作相似，但在灌注 2.4 mM 棕榈酸的心脏中，再灌注期间的 LV 工作更大[6.98 +/- 0.14 (n = 15) 比 3.01 +/- 0.23 (n = 16) mJ.beat(-1).g 干重(-1); P < 0.05]。这伴随着再灌注期间 LV 能量消耗的增加[35.98 +/- 0.16 (n = 8) 比 19.92 +/- 0.18 (n = 6) mJ.beat(-1).g 干重(-1); P < 0.05]。在再灌注期间，棕榈酸氧化的速率[237.5 +/- 28.10 (n = 7) 比 86.0 +/- 9.7 (n = 6) nmol.g 干重(-1).min(-1); P < 0.05]、总 TCA 循环活性[2.65 +/- 0.39 (n = 7) 比 1.36 +/- 0.14 (n = 6) micromol 乙酰辅酶 A.g 干重(-1).min(-1); P < 0.05]和归因于棕榈酸氧化的 ATP 生成[26.6 +/- 3.1 (n = 7) 比 12.6 +/- 1.7 (n = 6) micromol.g 干重(-1).min(-1); P < 0.05]在灌注 2.4 mM 棕榈酸的心脏中更高。这些数据表明，新生儿心脏的能量储备减少，与成熟心脏相反，增加脂肪酸底物的可用性可增加能量产生并改善缺血后功能的恢复。
