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  • Chronic β1-adrenoceptor blockade impairs ischaemic tolerance and preconditioning in murine myocardium

    Author(s)
    Hoe, Louise E See
    Schilling, Jan M
    Busija, Anna R
    Haushalter, Kristofer J
    Ozberk, Victoria
    Keshwani, Malik M
    Roth, David M
    Du Toit, Eugene
    Headrick, John P
    Patel, Hemal H
    Peart, Jason N
    Griffith University Author(s)
    Peart, Jason N.
    Du Toit, Eugene
    Ozberk, Victoria
    Year published
    2016
    Metadata
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    Abstract
    β-adrenoceptor antagonists are commonly used in ischaemic heart disease (IHD) patients, yet may impair signalling and efficacy of ‘cardioprotective’ interventions. We assessed effects of chronic β1-adrenoceptor antagonism on myocardial resistance to ischaemia-reperfusion (IR) injury and the ability of cardioprotective interventions [classic ischaemic preconditioning (IPC); novel sustained ligand-activated preconditioning (SLP)] to reduce IR injury in murine hearts. Young male C57Bl/6 mice were untreated or received atenolol (0.5 g/l in drinking water) for 4 weeks. Subsequently, two cardioprotective stimuli were evaluated: ...
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    β-adrenoceptor antagonists are commonly used in ischaemic heart disease (IHD) patients, yet may impair signalling and efficacy of ‘cardioprotective’ interventions. We assessed effects of chronic β1-adrenoceptor antagonism on myocardial resistance to ischaemia-reperfusion (IR) injury and the ability of cardioprotective interventions [classic ischaemic preconditioning (IPC); novel sustained ligand-activated preconditioning (SLP)] to reduce IR injury in murine hearts. Young male C57Bl/6 mice were untreated or received atenolol (0.5 g/l in drinking water) for 4 weeks. Subsequently, two cardioprotective stimuli were evaluated: morphine pellets implanted (to induce SLP, controls received placebo) 5 days prior to Langendorff heart perfusion, and IPC in perfused hearts (3×1.5 min ischaemia/2 min reperfusion). Atenolol significantly reduced in vivo heart rate. Untreated control hearts exhibited substantial left ventricular dysfunction (~50% pressure development recovery, ~20 mmHg diastolic pressure rise) with significant release of lactate dehydrogenase (LDH, tissue injury indicator) after 25 min ischaemia/45 min reperfusion. Contractile dysfunction and elevated LDH were reduced >50% with IPC and SLP. While atenolol treatment did not modify baseline contractile function, post-ischaemic function was significantly depressed compared to untreated hearts. Atenolol pre-treatment abolished beneficial effects of IPC, whereas SLP protection was preserved. These data indicate that chronic β1-adrenoceptor blockade can exert negative effects on functional IR tolerance and negate conventional IPC (implicating β1-adrenoceptors in IR injury and IPC signalling). However, novel morphine-induced SLP is resistant to inhibition by β1-adrenoceptor antagonism.
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    Journal Title
    European Journal of Pharmacology
    Volume
    789
    DOI
    https://doi.org/10.1016/j.ejphar.2016.06.054
    Subject
    Artificial intelligence
    Pharmacology and pharmaceutical sciences
    Pharmacology and pharmaceutical sciences not elsewhere classified
    Psychology
    Cognitive and computational psychology
    Zoology
    Social and personality psychology
    Publication URI
    http://hdl.handle.net/10072/100466
    Collection
    • Journal articles

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