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  • Opioid Receptors and Cardioprotection - 'Opioidergic Conditioning' of the Heart

    Author(s)
    Headrick, John P
    Hoe, Louise E See
    Du Toit, Eugene F
    Peart, Jason N
    Griffith University Author(s)
    Headrick, John P.
    Peart, Jason N.
    Du Toit, Eugene
    Year published
    2015
    Metadata
    Show full item record
    Abstract
    Ischaemic heart disease (IHD) remains a lead cause of morbidity/mortality globally, firmly established in Westernised or 'developed' countries and rising in prevalence in developing nations. Cardioprotective therapies to limit myocardial damage with associated ischaemia-reperfusion (I-R), during infarction or surgical ischaemia, are thus a very important though still elusive clinical goal. The opioid receptor (OPR) system, encompassing the d (vas deferens), ? (ketocyclazocine) and 堨morphine) OPRs and their endogenous opioid ligands (endorphins, dynorphins, enkephalins), appears a logical candidate for such exploitation. This ...
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    Ischaemic heart disease (IHD) remains a lead cause of morbidity/mortality globally, firmly established in Westernised or 'developed' countries and rising in prevalence in developing nations. Cardioprotective therapies to limit myocardial damage with associated ischaemia-reperfusion (I-R), during infarction or surgical ischaemia, are thus a very important though still elusive clinical goal. The opioid receptor (OPR) system, encompassing the d (vas deferens), ? (ketocyclazocine) and 堨morphine) OPRs and their endogenous opioid ligands (endorphins, dynorphins, enkephalins), appears a logical candidate for such exploitation. This regulatory system may orchestrate organism and organ responses to stress, induces mammalian hibernation and associated metabolic protection, triggers powerful adaptive stress-resistance in response to ischaemia/hypoxia (preconditioning), and mediates cardiac benefit stemming from physical activity. In addition to direct myocardial actions, central OPR signalling may also enhance the ability of the heart to withstand I-R injury. The d- and ?-OPR sub-types are strongly implicated in cardioprotection across models and species (including anti-infarct and anti-arrhythmic actions), with mixed evidence for 孏PR dependent protection in animal and human tissues. A small number of clinical trials evidence cardiac benefit via morphine or remifentanil in cardiopulmonary by-pass or coronary angioplasty patients, though further trials of sub-type specific OPR agonists are needed. The precise roles and utility of this G-protein coupled receptor (GPCR) family in healthy and diseased human myocardium, and in mediating central and peripheral survival responses, warrant further investigation, as do the putative negative influences of ageing, IHD co-morbidities, and relevant drugs on OPR signalling and protective responses.
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    DOI
    https://doi.org/10.1111/bph.13042
    Subject
    Pharmacology and pharmaceutical sciences
    Medical physiology not elsewhere classified
    Publication URI
    http://hdl.handle.net/10072/68402
    Collection
    • Reports

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