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Permanent link (DOI): https://doi.org/10.7939/R33D0X

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Long-term cardiovascular and metabolic effects of hypoxia-induced intrauterine growth restriction Open Access

Descriptions

Other title
Subject/Keyword
Syndrome
Obesity
Metabolic
Iron
Resistance
Resveratrol
Fetal
Metabolism
Hypoxia
Cardiac
Programming
Ischemia
Glucose
Intolerance
Insulin
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Rueda-Clausen, Christian Federico
Supervisor and department
Davidge, Sandra T. (Physiology/Obstetrics and Gynecology)
Examining committee member and department
Lopaschuk, Gary D. (Pharmacology)
Giussani, Dino A. (Physiology, Development & Neuroscience (PDN) University of Cambridge)
Seubert, John M. (Pharmacy and Pharmaceutical Sciences)
Kassiri, Zamaneh (Physiology)
Department
Department of Physiology
Specialization

Date accepted
2011-01-27T18:55:57Z
Graduation date
2011-06
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
Cardiovascular and metabolic diseases are still the primary cause of death and disability in modern society. Although genetic factors play a fundamental role in the development of these chronic conditions, the remarkable variability in an individual’s susceptibility to develop these pathologies cannot be completely explained by genetics. The early programming of adult diseases theory became established in the 1980’s, and is now supported by a growing body of evidence demonstrating that exposure to suboptimal environmental conditions during crucial periods of time can predispose an individual to the development of chronic conditions (including cardiovascular and metabolic diseases) later in life. Among the multitude of factors that can cause early programming, we have focused on the study of pregnancy complications leading to fetal hypoxia and causing intrauterine growth restriction (IUGR). To this end, we have used an animal model in which pregnant Sprague Dawley rats were exposed to either normal (∼21% O2) or hypoxic (∼11.5% O2) conditions during the last third of pregnancy. We then followed and studied the cardiovascular and metabolic characteristics of the offspring later in life. The studies presented in this thesis demonstrate that hypoxic prenatal insults have long-term consequences on cardiac structure, function and susceptibility to ischemia. We also demonstrated that programmed susceptibility to myocardial ischemia was associated with changes in cardiac energy metabolism and increased levels of myocardial oxidative stress. Moreover, we described the interaction between prenatal hypoxic insults, aging and sex differences in the later development of cardiovascular conditions. Additional studies presented in this thesis demonstrate that offspring born IUGR are more susceptible to develop most components of the metabolic syndrome when exposed to a high-fat (HF) diet. Furthermore, we also demonstrated that the exacerbated deleterious response to a HF diet described in offspring born IUGR can be prevented by postnatal administration of Resveratrol, which is a natural compound with anti-oxidant and anti-aging properties. In conclusion, the results presented in this thesis are an important contribution to the understanding of the long-term cardiovascular and metabolic effects of prenatal hypoxic insults causing IUGR and provide evidence regarding possible mechanisms and treatment alternatives that could be considered.
Language
English
DOI
doi:10.7939/R33D0X
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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