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European Journal of Heart Failure 2008 10(10):990-996; doi:10.1016/j.ejheart.2008.07.007
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© 2008 European Society of Cardiology

Sympathomimetic inefficiency in restoring contractility in the acute or chronic β-blocker-treated ischaemic heart: Comparison with a new agent

Giovan Giuseppe Matteraa,*, Emilio Vanolib, Jean-Pierre Gagnolc, Francesca Maria Paola Loia, Franco Borsinia and Paolo Carminatia

a Research & Development Sigma-Tau S.p.A. Pomezia Italy
b Cardiology Department, Universita di Pavia, IRCCS Policlinico S. Matteo Pavia Italy
c Universite de Montpellier 1 et CRNS UPIR5232 France

* Corresponding author. R & D-General Pharmacology Department, Sigma-Tau S.p.A., Via Pontina km 30.400, 00040 Pomezia, Roma, Italy. Tel. +39 0691393882; fax: +39 0691393988. E-mail address: giovanni.mattera{at}sigma-tau.it (G.G. Mattera).


  Abstract

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 SERCA2 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.

Key Words: Acute myocardial infarction • β-blockers • Contractility • Dobutamine • Milrinone • Istaroxime

Received January 22, 2008; Revised May 21, 2008; Accepted July 14, 2008


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