Tadalafil prevents acute heart failure with reduced ejection fraction in mice.

Abstract

PURPOSE:

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.

CONCLUSIONS:

Tadalafil attenuates ischemic cardiomyopathy in mice and preserves LV function.

• Authors: Fadi N Salloum, Vinh Q Chau, Nicholas N Hoke, Rakesh C Kukreja
• Journal: Cardiovascular drugs and therapy (Cardiovasc Drugs Ther) Vol. 28 Issue 6 Pg. 493-500 (Dec 2014) ISSN: 1573-7241 [Electronic] United States
• PMID: 25322707 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Carbolines
• Phosphodiesterase Inhibitors
• Tadalafil

Topics

• Animals
• Apoptosis (drug effects)
• Carbolines (pharmacology)
• Cardiomegaly (diet therapy, drug therapy)
• Cardiomyopathies (drug therapy)
• Coronary Vessels (drug effects)
• Heart Failure (drug therapy, prevention & control)
• Male
• Mice
• Mice, Inbred ICR
• Myocardial Infarction (drug therapy)
• Phosphodiesterase Inhibitors (pharmacology)
• Pulmonary Edema (drug therapy)
• Tadalafil
• Ventricular Dysfunction, Left (drug therapy)
• Ventricular Function, Left (drug effects)
• Ventricular Remodeling (drug effects)