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Sympathomimetic inefficiency in restoring contractility in the acute or chronic β‐blocker‐treated ischaemic heart: Comparison with a new agent
Author(s) -
Mattera Giovan Giuseppe,
Vanoli Emilio,
Gagnol JeanPierre,
Loi Francesca Maria Paola,
Borsini Franco,
Carminati Paolo
Publication year - 2008
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/j.ejheart.2008.07.007
Subject(s) - medicine , dobutamine , inotrope , cardiology , contractility , milrinone , blockade , myocardial infarction , heart failure , hemodynamics , receptor
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, β‐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.