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Specifically, in adult murine cardiomyocytes, metoprolol, a cardioselective \u03b2<jats:sub>1<\/jats:sub>-adrenergic receptor blocker, when given with triiodothyronine (T3, a thyroid hormone) accentuates the ability of T3 to stimulate ERK1\/2 phosphorylation and proliferative signaling by inhibiting expression of the nuclear phospho-ERK1\/2-specific phosphatase, dual-specificity phosphatase-5. While short-duration metoprolol plus T3 therapy generates new heart muscle in healthy mice, in mice with myocardial infarction-induced left ventricular dysfunction and pathological remodeling, it remuscularizes the heart, restores contractile function and reverses chamber dilatation; outcomes that are enduring. 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