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

Abstract

Background: Adequate pharmacologic cardiac support in acute myocardial infarction (MI), as well as in chronic MI patients under beta-blocker therapy, is problematic due to the impaired cardiac response to beta-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 beta-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, beta-adrenergic blockade inhibited the inotropic action of DOB, without altering the effect of ISTA. Surprisingly, beta-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 beta-adrenergic blockade.