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Background: Adequate pharmacologic cardiac support in acute myocardial infarction (MI), as well as in chronic MI patients under β-blocker therapy, is problematic due to the impaired cardiac response to β-adrenergic agonists. New therapeutic approaches could resolve this problem. Istaroxime (ISTA) is a new Na + ,K + -ATPase inhibitor and SERCA 2 agonist. Aims: To evaluate: 1) the effects of dobutamine (DOB) on left ventricular function in early (48-72 h) and late (14 days) phases of a post-MI canine model, compared to ISTA, and 2) the efficacy of DOB in chronic left ventricular dysfunction (6 months post-MI) in dogs pre-treated or not with a β-blocker, compared with ISTA and milrinone (MIL). Results: When compared to the effects in healthy animals, DOB increased contractility only slightly in the first 48-72 h post-MI, whereas its efficacy recovered partially by day 14 and fully by 6 months after MI. ISTA had a greater effect on contractility than DOB and improved relaxation, while DOB did not. Moreover, ß-adrenergic blockade inhibited the inotropic action of DOB, without altering the effect of ISTA. Surprisingly, ß-adrenergic blockade blunted the effects of MIL. Conclusion: ISTA may represent a novel strategy for enhancing left ventricular performance even in the context of acute MI and/or concomitant β-adrenergic blockade.

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