High levels of fatty acids increase contractile function of neonatal rabbit hearts during reperfusion following ischemia

Abstract

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) μmol 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) μmol·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.