Treatment with a copper-selective chelator causes substantive improvement in cardiac function of diabetic rats with left-ventricular impairment.

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dc.contributor.author Lu, Jun en
dc.contributor.author Pontré, Beau en
dc.contributor.author Pickup, Stephen en
dc.contributor.author Choong, Soon Y en
dc.contributor.author Li, Mingming en
dc.contributor.author Xu, Hong en
dc.contributor.author Gamble, Gregory en
dc.contributor.author Phillips, Anthony en
dc.contributor.author Cowan, Brett en
dc.contributor.author Young, Alistair en
dc.contributor.author Cooper, Garth en
dc.date.accessioned 2018-11-13T03:43:09Z en
dc.date.issued 2013-01-31 en
dc.identifier.issn 1475-2840 en
dc.identifier.uri http://hdl.handle.net/2292/44190 en
dc.description.abstract BACKGROUND: Defective copper regulation is implicated as a causative mechanism of organ damage in diabetes. Treatment with trientine, a divalent-copper-selective chelator, improves arterial and renal structure/function in diabetes, wherein it also ameliorates left-ventricular (LV) hypertrophy. However, direct in vivo evidence that trientine can improve cardiac function in heart failure has hitherto been lacking. METHODS: To determine whether trientine treatment could improve in vivo outcome, we measured cardiac function in groups of trientine-treated diabetic (TETA-DIA), non-drug-treated diabetic (DIA) and sham-treated control (SHAM) rats, by using in vivo high-field cardiac magnetic-resonance imaging (cMRI) and an ex vivo isolated-perfused working heart method. Forty age-matched animals underwent a cMRI scan after which 12 were randomized to the SHAM group and 28 underwent streptozotocin-injection; of these, 25 developed stable diabetes, and 12 were then randomized to receive no treatment for 16 weeks (DIA) and the other 13 to undergo 8-weeks' untreated diabetes followed by 8-weeks' drug treatment (TETA-DIA). Animals were studied again by cMRI at 8 and 16 weeks following disease induction, and finally by measurement of ex vivo cardiac function. RESULTS: After eight weeks diabetes, rats (DIA/TETA-DIA) had developed significant impairment of LV function, as judged by impairment of ejection fraction (LVEF), cardiac output (CO), and LV mass (LVM)/body-mass (all P < 0.001), as well as other functional indexes. LVEF, CO (both P < 0.001) and the other indexes deteriorated further at 16 weeks in DIA, whereas trientine (TETA-DIA) improved cardiac function by elevating LVEF and CO (both P < 0.001), and also partially reversed the increase in LVM/body-mass (P < 0.05). In ex vivo hearts from DIA, the CO response to increasing preload pressure was deficient compared with SHAM (P < 0.001) whereas the preload-CO relationship was significantly improved in TETA-DIA animals (P < 0.001). CONCLUSIONS: Trientine treatment significantly improved cardiac function in diabetic rats with substantive LV impairment. These results implicate impaired copper regulation in the pathogenesis of impaired cardiac function caused by diabetic cardiomyopathy, and support ongoing studies of trientine treatment in patients with heart failure. en
dc.format.medium Electronic en
dc.language eng en
dc.relation.ispartofseries Cardiovascular diabetology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.subject Heart en
dc.subject Animals en
dc.subject Rats en
dc.subject Rats, Wistar en
dc.subject Ventricular Dysfunction, Left en
dc.subject Diabetes Mellitus, Experimental en
dc.subject Copper en
dc.subject Chelating Agents en
dc.subject Heart Function Tests en
dc.subject Treatment Outcome en
dc.subject Male en
dc.subject Trientine en
dc.title Treatment with a copper-selective chelator causes substantive improvement in cardiac function of diabetic rats with left-ventricular impairment. en
dc.type Journal Article en
dc.identifier.doi 10.1186/1475-2840-12-28 en
pubs.begin-page 28 en
pubs.volume 12 en
dc.rights.holder Copyright: The author en
dc.identifier.pmid 23368770 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Research Support, Non-U.S. Gov't en
pubs.subtype research-article en
pubs.subtype Journal Article en
pubs.elements-id 375488 en
pubs.org-id Bioengineering Institute en
pubs.org-id ABI Associates en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Anatomy and Medical Imaging en
pubs.org-id School of Medicine en
pubs.org-id Medicine Department en
pubs.org-id Science en
pubs.org-id Biological Sciences en
pubs.org-id Science Research en
pubs.org-id Maurice Wilkins Centre (2010-2014) en
dc.identifier.eissn 1475-2840 en
pubs.record-created-at-source-date 2013-03-27 en
pubs.dimensions-id 23368770 en


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