Tadalafil Prevents Acute Heart Failure with Reduced Ejection Fraction in Mice
Phosphodiesterase-5 (PDE5) inhibitors were shown to exert powerful protection in various animal models of cardiomyopathy. Tadalafil is a long-acting and highly specific PDE5 inhibitor, which makes it the most attractive in its class for long-term management of patients with heart failure. We studied the effects of tadalafil in attenuating ischemic cardiomyopathy in mice.
Methods and Results
Adult male mice underwent myocardial infarction (MI) by permanent left coronary artery ligation and were treated daily with tadalafil (1 mg/kg; ip) or volume-matched 10 % DMSO for 4 weeks. Twenty four hours after coronary ligation, infarct size, measured by TTC staining, was reduced from 70.1 ± 3.1 % in DMSO-treated group to 49.3 ± 2.6 % with tadalafil (P < 0.05). Similarly, tadalafil treatment yielded a smaller fibrotic area (8.8 ± 2.8 % of LV), assessed by Masson’s trichrome staining, as compared to DMSO group (21.9 ± 3.9 %, P < 0.05). Apoptosis, measured by TUNEL assay, also declined with tadalafil (2.1 ± 0.2 %) as compared to DMSO (6.7 ± 0.4 %, P < 0.05) at 28 days post MI. Tadalafil also attenuated the increase in cardiac hypertrophy and pulmonary edema following infarction. These parameters reflect diminished left ventricular (LV) adverse remodeling and preserved fractional shortening with tadalafil at 7 and 28 days post infarction.
Tadalafil attenuates ischemic cardiomyopathy in mice and preserves LV function.
KeywordsInfarct size Apoptosis LV function Cardiomyopathy Phosphodiesterase-5 inhibitors
This work was supported by grants from the American Heart Association (10SDG3770011 and 14GRNT20010003) and the Virginia Commonwealth University Presidential Research Quest Fund to Fadi N. Salloum and grants from the National Institutes of Health (HL-51045, HL-79424, and HL-93685) to Rakesh C. Kukreja.
Tadalafil was kindly provided by Lily ICOS.
Conflict of Interest
The authors declare that they have no conflict of interest.
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