Differences in myocardial ischemic tolerance between 1- and 7-day-old rabbits

Abstract

Between 1 and 7 days of life, the newborn rabbit heart shifts from predominantly using carbohydrates to predominantly using fatty acids as an energy substrate. We therefore used isolated working hearts from 1- or 7-day-old rabbits to determine the effects of fatty acids on myocardial glucose use and the ability of hearts to recover following various periods of transient no-flow ischemia. One-day-old hearts were perfused via the inferior vena cava and ejected buffer through the cannulated aorta and pulmonary artery. Seven-day-old hearts were perfused via the left atrium and ejected buffer through the cannulated aorta. To measure glucose use, hearts were perfused with 11 mM [3H, 14C]glucose, 3% albumin, and 500 microU insulin/mL, in the presence or absence of 0.4 mM palmitate. In the absence of fatty acids, glycolytic rates were similar in 1- and 7-day-old hearts, whereas glucose oxidation rates were 5 times greater in 7-day-old hearts. Palmitate did not have any major effects on overall glucose use in 1-day-old hearts, but did markedly inhibit glycolysis and glucose oxidation in 7-day-old hearts. A series of hearts were also subjected to periods (25-60 min) of no-flow ischemia, followed by 30 min of aerobic reperfusion. In the absence of palmitate, 1-day-old hearts subjected to ischemic periods of up to 60 min recovered some degree of mechanical function during reperfusion, whereas 7-day-old rabbit hearts failed to recover if hearts were subjected to ischemic periods of 35 min or longer.(ABSTRACT TRUNCATED AT 250 WORDS)

Comprehensive Analysis of the Transcriptome-Wide m6A Methylome of Heart via MeRIP After Birth: Day 0 vs. Day 7

“…Cellular metabolism in the heart is dynamic at different stages of cardiac myocytes. Glycolysis and fatty acid oxidation change from fetal to mature tissue (50). Pfkfb2 has been reported to play a special role in regulating glycolysis and proliferation in pancreatic cancer cells (51).…”

Energy Metabolic Phenotype of the Cardiomyocyte During Development, Differentiation, and Postnatal Maturation

“…76,83,84 Despite this increase in fatty acid levels, fatty acid oxidation rates remain low in the immediate newborn period, providing less than 15% of the heart's ATP requirements, 82,85 due in part to an inhibition of mitochondrial fatty acid uptake. 36,65,86,87 Within days of birth, a dramatic increase in fatty acid b-oxidation occurs (a 10-fold increase), which is accompanied by a parallel decrease in glycolytic rates. 82 Studies in newborn pigs have also shown an increase in fatty acid oxidation with age.…”

Pyruvate Augments Mechanical Function via Activation of the Pyruvate Dehydrogenase Complex in Reperfused Ischemic Immature Rabbit Hearts

“…Following ischemia, the presence of increased fatty acid oxidation rates is thought to result in a reduction in glucose oxidation via inhibition of the pyruvate dehydrogenase complex [4,7]. These low rates of glucose oxidation, relative to rates of glycolysis, contribute to poor cardiac efficiency during reperfusion, secondary to the production of protons from glycolysis uncoupled from glucose oxidation [19]. Proton clearance from the myocytes redirects ATP away from contractile function resulting in a decrease in cardiac efficiency.…”