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  • Mechanisms and Clinical Utility of Sustained Ligand-Activated Preconditioning

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    See Hoe_2016_01Thesis.pdf (11.09Mb)
    Author(s)
    See Hoe, Louise
    Primary Supervisor
    Headrick, John
    Other Supervisors
    Du Toit, Eugene
    Year published
    2016
    Metadata
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    Abstract
    Ischaemic heart disease (IHD) remains a leading cause of global morbidity and mortality, with persistent prevalence in Western populations, and a growing incidence in the developing world. Myocardial ischaemic injury is alleviated through surgical intervention, detrimentally exposing the heart to reperfusion injury. This inevitable and paradoxical injury has driven a field of cardioprotective research aimed at limiting cell death, enhancing standard reperfusion protocols and improving long-term patient outcomes from ischaemia/reperfusion (I/R) injury. Despite promising laboratory results, clinical translation of cardioprotective ...
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    Ischaemic heart disease (IHD) remains a leading cause of global morbidity and mortality, with persistent prevalence in Western populations, and a growing incidence in the developing world. Myocardial ischaemic injury is alleviated through surgical intervention, detrimentally exposing the heart to reperfusion injury. This inevitable and paradoxical injury has driven a field of cardioprotective research aimed at limiting cell death, enhancing standard reperfusion protocols and improving long-term patient outcomes from ischaemia/reperfusion (I/R) injury. Despite promising laboratory results, clinical translation of cardioprotective interventions remains an unrealised goal. Notably, age, co-morbidities and chronic pharmacotherapy negatively influence the efficacy of cardioprotective interventions aimed at limiting I/R injury. Thus, effective interventions that reduce myocardial I/R injury in the settings of ageing and disease are fundamental. Based upon this fundamental premise, this doctoral project investigates a novel opioid therapy termed sustained ligand-activated preconditioning (SLP). Previous work demonstrated that SLP is superior to conventional cardioprotection through engagement of alternative signalling pathways, and exhibits potent and prolonged efficacy in young to aged hearts. Studies executed in this doctorate aimed to further delineate the specific mechanisms involved in generation of the protected SLP phenotype, and determine the clinical utility of SLP using other relevant models of disease and chronic pharmacotherapy.
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    Thesis Type
    Thesis (PhD Doctorate)
    Degree Program
    Doctor of Philosophy (PhD)
    School
    School of Medical Science
    DOI
    https://doi.org/10.25904/1912/926
    Copyright Statement
    The author owns the copyright in this thesis, unless stated otherwise.
    Item Access Status
    Public
    Subject
    Ischaemic heart disease
    Myocardial ischaemic injury
    Sustained ligand-activated preconditioning
    Heart disease
    Publication URI
    http://hdl.handle.net/10072/365566
    Collection
    • Theses - Higher Degree by Research

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