Abstract 15520: Tadalafil Attenuates Ischemic Cardiomyopathy and Improves Left Ventricular Function in Mice
Background: Phosphodiesterase-5 inhibitors including sildenafil, vardenafil and tadalafil induce anti-ischemic effect in the heart in various animal species. Since tadalafil is a long-acting and more specific PDE-5 inhibitor, we contemplated that it would be an attractive drug for long-term management of patients with heart failure. Therefore, we studied its effect in attenuation of ischemic cardiomyopathy following infarction in a mouse model.
Methods and Results: Adult male ICR mice underwent myocardial infarction (MI) by permanent ligation of the left anterior descending coronary artery (LAD) and were treated with tadalafil (1 mg/kg; ip) or volume-matched 10% DMSO for 4 weeks. Infarct size, measured by TTC staining, was smaller in tadalafil-treated group as compared to DMSO control 24 h after LAD ligation. The fibrotic area (% of LV), assessed by Masson’s trichrome staining was reduced to 8.6±2.6% with tadalafil as compared to 19.1±3.6% with DMSO at 28 days post MI. The apoptotic index, measured by TUNEL assay, was 6.7 ± 0.4% in the DMSO group vs. 2.1 ± 0.2% in tadalafil-treated mice (P<0.05) on day 28 post MI. Fractional shortening (FS) decreased significantly on days 7 and 28 post-MI in DMSO-treated group; however, the decrease in FS in with tadalafil was less pronounced (Figure B). Baseline FS was 47 ± 2%. Also, cardiac hypertrophy (mg/cm) and pulmonary edema (mg/cm), calculated as heart-to-body and lung-to-body weight ratios, respectively, normalized with tibia length, were significantly attenuated with tadalafil (90.1±9.1 and 85.3±3.3, respectively) compared to vehicle (108.5±4.4 and 104.0±5.1, respectively). Heart-to-body and lung-to-body weight ratios for sham animals were 66.1 ± 2.9 and 85.7 ± 1.3, respectively.
Conclusion: Tadalafil attenuates ischemic cardiomyopathy in mice by limiting necrosis, apoptosis and preserving LV function. We propose that tadalafil can be a promising novel strategy for treatment of heart failure in patients with MI.
- © 2012 by American Heart Association, Inc.