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

Drugs Exp Clin Res. 2002;28(6):213-9.

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