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Neonatal Cardiac Fatty Acid Metabolism Open Access

Descriptions

Other title

Subject/Keyword

Neonatal, newborn, cardiac, heart, congenital heart defect, fatty acid beta oxidation, metabolism, PPARalpha, cardiac hypertrophy
3 Neonatal Rabbit Aorto-Caval Shunt Volume-Overload Cardiac Hypertrophy Model
6 General discussion
2 Supra-physiological Insulin Levels Elevate Palmitate Oxidation to Improve Neonatal Rabbit Heart Ischemia-Reperfusion Recovery
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
1 Introduction

Type of item

Thesis

Degree grantor

University of Alberta

Author or creator

Lam, Victoria Hol Mun

Supervisor and department

Dr. Ivan M Rebeyka, Surgery
Dr. Gary D Lopaschuk, Pediatrics

Examining committee member and department

Dr. Peter E Light, Pharmacology
Dr. Jason R Dyck, Pediatrics
Dr. Zamaneh Kassiri, Physiology
Dr. Thomas D Scholz, Pediatrics

Department

Medical Sciences-Paediatrics

Specialization

Date accepted

2012-01-29T18:52:41Z

Graduation date

2012-06

Degree

Doctor of Philosophy

Degree level

Doctoral

Abstract

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.

Language

English

DOI

doi:10.7939/R3G03B

Rights

Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.

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2012-01-26T02:06:12.000Z

Date Modified

2014-05-01T02:20:40.637+00:00

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