title: Tadalafil prevents acute heart failure with reduced ejection fraction in mice.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Tadalafil attenuates ischemic cardiomyopathy in mice and preserves LV function.
authors.affiliation: Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, 1101 East Marshall Street, Room 7-020A, Richmond, VA, 23298-0204, USA, fnsalloum@vcu.edu.
authors.forename: Fadi N
authors.initials: FN
authors.lastname: Salloum
authors.forename: Vinh Q
authors.initials: VQ
authors.lastname: Chau
authors.forename: Nicholas N
authors.initials: NN
authors.lastname: Hoke
authors.forename: Rakesh C
authors.initials: RC
authors.lastname: Kukreja
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology*; D006332:Cardiomegaly / Q000178:diet therapy / Q000188:drug therapy; D009202:Cardiomyopathies / Q000188:drug therapy; D003331:Coronary Vessels / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009203:Myocardial Infarction / Q000188:drug therapy; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011654:Pulmonary Edema / Q000188:drug therapy; D000068581:Tadalafil; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D002243:Carbolines; D010726:Phosphodiesterase Inhibitors; D000068581:Tadalafil