Abstract
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.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
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
Substances
-
Cardiotonic Agents
-
Piperazines
-
Purines
-
Sulfones
-
Sildenafil Citrate
-
3',5'-Cyclic-GMP Phosphodiesterases
-
Cyclic GMP