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  • http://hdl.handle.net/10402/era.25301
  • Neonatal Cardiac Fatty Acid Metabolism
  • Lam, Victoria Hol Mun
  • English
  • Neonatal, newborn, cardiac, heart, congenital heart defect, fatty acid beta oxidation, metabolism, PPARalpha, cardiac hypertrophy
    1 Introduction
    2 Supra-physiological Insulin Levels Elevate Palmitate Oxidation to Improve Neonatal Rabbit Heart Ischemia-Reperfusion Recovery
    3 Neonatal Rabbit Aorto-Caval Shunt Volume-Overload Cardiac Hypertrophy Model
    4 Cardiac Hypertrophy in the Newborn Delays the Maturation of Fatty Acid β-Oxidation and Compromises Post-ischemic Functional Recovery
    5 Activating Peroxisome Proliferator-Activated Receptor  Prevents Post-Ischemic Contractile Dysfunction in the Hypertrophied Neonatal Heart
    6 General discussion
  • Jan 29, 2012 6:52 PM
  • Thesis
  • English
  • Adobe PDF
  • 9526408 bytes
  • The surgical repair of congenital heart defects (CHDs) often requires a bloodless/motionless field achieved by arresting the neonatal heart and exposing it to a period of ischemia. Metabolic manipulation, such as suppression of fatty acid (FA) oxidation, improves post-ischemic functional recovery in adult hearts. However, the metabolic profile of a neonatal heart differs dramatically from that of an adult. The neonatal heart is highly dependent on FA oxidation while glucose metabolic rates remain low until weaning. Since the neonatal myocardium is a FA-centered metabolism, then, unlike the adult heart, augmenting FA oxidation may improve its post-ischemic function recovery by increasing ATP available to the myocardium. In these studies, hearts were isolated from relevant neonatal rabbit models to study insulin’s effect, neonatal volume-overload hypertrophy, neonatal cardiac hypertrophy treated with a peroxisome proliferator activated-receptor-Α (PPARΑ) agonist. The hearts were perfused ex vivo to assess changes in cardiac metabolism and post-ischemic functional recovery associated with each treatment. The results demonstrate that high fat alters the neonatal heart’s response to insulin to increase FA oxidation and improve post-ischemic functional recovery. In contrast, neonatal cardiac hypertrophy downregulates FA metabolism and is associated with poor post-ischemic functional recovery. The administration of a PPARΑ agonist upregulated the FA metabolic pathway; therefore, FA metabolism increased and rescued the metabolic phenotype associated with cardiac hypertrophy and normalized post-ischemic functional recovery. In conclusion, augmenting FA oxidation with clinical levels of insulin in the normal neonatal heart and or a PPARΑ agonist in hypertrophied neonatal hearts improves post-ischemic functional recovery and may be a viable therapy of ischemia-reperfusion protection.
  • Doctoral
  • Doctor of Philosophy
  • Medical Sciences-Paediatrics
  • Spring 2012
  • Dr. Gary D Lopaschuk, Pediatrics
    Dr. Ivan M Rebeyka, Surgery
  • Dr. Jason R Dyck, Pediatrics
    Dr. Thomas D Scholz, Pediatrics
    Dr. Zamaneh Kassiri, Physiology
    Dr. Peter E Light, Pharmacology