Abstract 2952: Comparison of a Combination of β1-Adrenergic Receptor (AR) Blocker and β2AR Agonist vs. a Combination of β1AR Blocker and Angiotensin Converting Enzyme Inhibitor for the Treatment of Chronic Heart Failure
We have previously demonstrated the efficiency of long-term (12 months) treatment of rats in chronic heart failure (CHF) post myocardial infarction (MI) with a combination of a β2AR agonist and a β1AR blocker. Here, in the same model, we report the effects of long-term treatment (12 months) with a combination of β1AR blocker and β2AR agonist vs. a combination of β1AR blocker and angiotensin converting enzyme inhibitor (ACEI), the current therapy of choice for the treatment of CHF. Two weeks after coronary artery ligation, rats were divided into four groups (n=27 each) similar in average MI size and left ventricular (LV) chamber size measured by echocardiography (Echo): Non-treated (C); treated, with fenoterol, a β2AR agonist, and metoprolol, a β1AR blocker, (β1/β2); with metoprolol and enalapril, a ACEI, (β1/A); and with all three drugs (β1/β2/A). The mortality was significantly but similarly reduced in all treatment groups (44% in β1/β2, 56% in β1/β2/A and 59% in β1/A vs. 81% in C). Monthly Echo revealed significant attenuation of the LV chamber remodeling, functional deterioration, and MI expansion in all treatment groups compared to C. Significantly better effects, however, were observed in β1/β2 and β1/β2/A compared to β1/A. For example, while the LV ejection fraction was reduced by 36% in β1/A from pre-treatment baseline, it was reduced significantly lesser, by 30%, in β1/β2 and, by 13%, in β1/β2/A. The therapeutic effectiveness of combination of β1AR blocker and β2AR agonist exceeds that of combination of β1AR blocker and ACEI with respect to cardiac remodeling and MI expansion. Thus, the addition of a β2AR agonist to the standard therapy may further improve the treatment of CHF.