Cardioprotection with sildenafil, a selective inhibitor of cyclic 3',5'-monophosphate-specific phosphodiesterase 5

• Published in: Drugs under experimental and clinical research Vol. 28; no. 6; p. 213
• Main Authors: Das, S, Maulik, N, Das, D K, Kadowitz, P J, Bivalacqua, T J
• Format: Journal Article
• Language: English
• Published: Switzerland 2002
• Subjects: 3',5'-Cyclic-GMP Phosphodiesterases - antagonists & inhibitors; Animals; Cardiotonic Agents - pharmacology; Cardiotonic Agents - therapeutic use; Cyclic GMP - metabolism; Disease Models, Animal; Dose-Response Relationship, Drug; Electrocardiography; In Vitro Techniques; Male; Myocardial Infarction - etiology; Myocardial Infarction - pathology; Myocardial Infarction - prevention & control; Myocardial Ischemia - complications; Myocardial Ischemia - drug therapy; Myocardial Ischemia - physiopathology; Myocardial Reperfusion Injury - prevention & control; Myocardium - metabolism; Piperazines - pharmacology; Piperazines - therapeutic use; Purines; Rats; Rats, Sprague-Dawley; Sildenafil Citrate; Sulfones; Ventricular Fibrillation - drug therapy; Ventricular Fibrillation - etiology; Ventricular Fibrillation - physiopathology; Ventricular Function - drug effects
• ISSN: 0378-6501

The effects of sildenafil (Viagra), a specific inhibitor of phosphodiesterase 5, on ischemic myocardium was examined using an isolated rat heart model. Rats were pretreated with sildenafil at doses ranging from 0.001 mg to 0.5 mg/kg body weight. After 60 min, isolated hearts were subjected to ischemia for 30 min followed by 2 h of reperfusion. The results demonstrated that at 0.05 mg/kg (and to some extent at 0.01 mg/kg), sildenafil provided significant cardioprotection as evidenced by improved ventricular recovery, a reduced incidence of ventricular fibrillation and decreased myocardial infarction. At higher doses, it caused a significant increase in the incidence of ventricular fibrillation while at very low doses it had no effect on cardiac function. As expected, sildenafil increased cyclic 3',5'-monophosphate (cGMP) content in the heart. The results demonstrate for the first time that within a narrow dose range, sildenafil can protect the heart from ischemia/reperfusion injury, probably through a cGMP-signaling pathway.