Effects of the new ultra-long-acting β2-AR agonist indacaterol in chronic treatment alone or in combination with the β1-AR blocker metoprolol on cardiac remodelling

Abstract

Aim: The role and the mechanism of a chronic treatment with indacaterol, a new ultra-long-acting a β 2 -AR agonist on the reverse cardiac remodelling and its effects in combination with metoprolol, a selective β 1 -AR antagonist, have been investigated in an experimental model of heart failure (HF). Methods: We investigated the effects of indacaterol and metoprolol, administered alone or in combination, on myocardial histology, β-receptors pathway, markers of remodelling and hemodynamic parameters in a HF rat model. Animals were randomized in five groups: SHAM; HF rats; HF+indacaterol 0.3mg/Kg/day (I); HF+metoprolol 100mg/kg/day (M); HF+M+I (M+I). The treatments continued for 15 weeks. Results: The I and M treatments significantly reduced the infarct size (8.50±0.87% and 12.50±1.44%, respectively; P 1 andβ 2 mRNA expression as well as cardiac cAMP levels and reduced cardiac GRK2 expression, compared with HF group. Conclusions: Our study documented an additive interaction between indacaterol and metoprolol in normalizing and reversing cardiac remodelling. The translation of these findings to clinical practice suggest that this combination could be safe and more effective in patients with a coexisting HF and COPD.