RT Journal Article
SR Electronic
T1 Cardioprotective and Survival Benefits of Long-Term Combined Therapy with β<sub>2</sub> Adrenoreceptor (AR) Agonist and β<sub>1</sub> AR Blocker in Dilated Cardiomyopathy Postmyocardial Infarction
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 491
OP 499
DO 10.1124/jpet.107.135335
VO 325
IS 2
A1 Ismayil Ahmet
A1 Melissa Krawczyk
A1 Weizhong Zhu
A1 Anthony Yiu-Ho Woo
A1 Christopher Morrell
A1 Suresh Poosala
A1 Riu-ping Xiao
A1 Edward G. Lakatta
A1 Mark I. Talan
YR 2008
UL http://jpet.aspetjournals.org/content/325/2/491.abstract
AB 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 β2 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 &lt; 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. The American Society for Pharmacology and Experimental Therapeutics