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  • Sarcolemmal dependence of cardiac protection and stress-resistance: Roles in aged or diseased hearts

    Author(s)
    Hoe, Louise E See
    May, Lauren T
    Headrick, John P
    Peart, Jason N
    Griffith University Author(s)
    Peart, Jason N.
    Year published
    2016
    Metadata
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    Abstract
    Disruption of the sarcolemmal membrane is a defining feature of oncotic death in cardiac ischaemia–reperfusion (I-R), and its molecular makeup not only fundamentally governs this process but also affects multiple determinants of both myocardial I-R injury and responsiveness to cardioprotective stimuli. Beyond the influences of membrane lipids on the cytoprotective (and death) receptors intimately embedded within this bilayer, myocardial ionic homeostasis, substrate metabolism, intercellular communication and electrical conduction are all sensitive to sarcolemmal makeup, and critical to outcomes from I-R. As will be outlined ...
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    Disruption of the sarcolemmal membrane is a defining feature of oncotic death in cardiac ischaemia–reperfusion (I-R), and its molecular makeup not only fundamentally governs this process but also affects multiple determinants of both myocardial I-R injury and responsiveness to cardioprotective stimuli. Beyond the influences of membrane lipids on the cytoprotective (and death) receptors intimately embedded within this bilayer, myocardial ionic homeostasis, substrate metabolism, intercellular communication and electrical conduction are all sensitive to sarcolemmal makeup, and critical to outcomes from I-R. As will be outlined in this review, these crucial sarcolemmal dependencies may underlie not only the negative effects of age and common co-morbidities on myocardial ischaemic tolerance but also the on-going challenge of implementing efficacious cardioprotection in patients suffering accidental or surgically induced I-R. We review evidence for the involvement of sarcolemmal makeup changes in the impairment of stress-resistance and cardioprotection observed with ageing and highly prevalent co-morbid conditions including diabetes and hypercholesterolaemia. A greater understanding of membrane changes with age/disease, and the inter-dependences of ischaemic tolerance and cardioprotection on sarcolemmal makeup, can facilitate the development of strategies to preserve membrane integrity and cell viability, and advance the challenging goal of implementing efficacious ‘cardioprotection’ in clinically relevant patient cohorts.
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    Journal Title
    British Journal of Pharmacology
    Volume
    173
    DOI
    https://doi.org/10.1111/bph.13552
    Subject
    Pharmacology and pharmaceutical sciences
    Pharmacology and pharmaceutical sciences not elsewhere classified
    Publication URI
    http://hdl.handle.net/10072/100233
    Collection
    • Journal articles

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