{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T03:39:31Z","timestamp":1778211571706,"version":"3.51.4"},"reference-count":56,"publisher":"American Physiological Society","issue":"4","funder":[{"DOI":"10.13039\/501100011725","name":"Servier","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100011725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fonds de Recherche du Quebec - Sante"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2016,10,1]]},"abstract":"<jats:p> While heart rate reduction (HRR) is a target for the management of patients with heart disease, contradictory results were reported using ivabradine, which selectively inhibits the pacemaker I<jats:sub>f<\/jats:sub> current, vs. \u03b2-blockers like metoprolol. This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB<jats:sup>+\/+<\/jats:sup>;LDLR<jats:sup>\u2212\/\u2212<\/jats:sup>). Following a longitudinal study design, we used 3- and 6-mo-old mice, untreated or treated for 3 mo with ivabradine or metoprolol. Cardiac function was evaluated in vivo and ex vivo in working hearts perfused with <jats:sup>13<\/jats:sup>C-labeled substrates to assess substrate fluxes through energy metabolic pathways. Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired ( P &lt; 0.001) contractile function (aortic flow: \u221245%; cardiac output: \u221234%; stroke volume: \u221235%) and glycolysis (\u221224%) ex vivo. Despite inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine ( O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. Despite similar HRR, ivabradine, but not metoprolol, preserved cardiac function and glucose metabolism during disease progression. <\/jats:p>","DOI":"10.1152\/ajpheart.00789.2015","type":"journal-article","created":{"date-parts":[[2016,8,6]],"date-time":"2016-08-06T02:59:07Z","timestamp":1470452347000},"page":"H991-H1003","source":"Crossref","is-referenced-by-count":13,"title":["Ivabradine and metoprolol differentially affect cardiac glucose metabolism despite similar heart rate reduction in a mouse model of dyslipidemia"],"prefix":"10.1152","volume":"311","author":[{"given":"Fanny","family":"Vaillant","sequence":"first","affiliation":[{"name":"Montreal Heart Institute, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada;"},{"name":"Department of Nutrition, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Lauzier","sequence":"additional","affiliation":[{"name":"Montreal Heart 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