Cardioprotective and survival benefits of long-term combined therapy with β2 adrenoreceptor (AR) agonist and β1 AR blocker in dilated cardiomyopathy postmyocardial infarction

Ismayil Ahmet, Melissa Krawczyk, Weizhong Zhu, Anthony Yiu Ho Woo, Christopher Morrell, Suresh Poosala, Riu Ping Xiao, Edward G. Lakatta, Mark I. Talan

Research output: Contribution to journalArticle

Abstract

We have reported therapeutic effectiveness of pharmacological stimulation of β2 adrenoreceptors (ARs) to attenuate the cardiac remodeling and myocardial infarction (MI) expansion in a rat model of dilated cardiomyopathy (DCM) post-MI. Furthermore, the combination of β2 AR stimulation with β1 AR blockade exceeded the therapeutic effectiveness of β1 AR blockade. However, these studies were relatively short (6 weeks). In this study, in the same experimental model, we compared different effects, including survival benefit, of combined therapy with the β1 AR blocker, metoprolol, plus the β1 AR agonist, fenoterol (β1-β2 +), and either therapy alone (β1- or β2+) during the 1-year study. Therapy was started 2 weeks after permanent ligation of the left coronary artery. Cardiac remodeling, MI expansion, and left ventricular function were assessed by serial echocardiography and compared with untreated animals (nT). Sixty-seven percent mortality in nT was reduced to 33% in the β1 -β2+ (p < 0.01). Progressive cardiac remodeling observed in nT and β1- was significantly attenuated in β1-β2+, during the first 6 months of treatment. In β1 -β2+, MI expansion was completely prevented, and functional decline was significantly attenuated during the entire year. Myocardial apoptosis was significantly reduced in both β1-β2+ and β1-. A reduction of cardiac β1 AR density and decreases in chronotropic and contractile responses to β2 AR-specific stimulation in the absence of a reduction of β2 AR density in nT were precluded in rats receiving combined therapy. The results demonstrate the cardioprotective and survival benefit of long-term combination therapy of β2 AR agonists and β1 AR blockers in a model of DCM.

Original languageEnglish (US)
Pages (from-to)491-499
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume325
Issue number2
DOIs
StatePublished - May 1 2008
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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