© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Effects of sildenafil on cardiac repolarization
aDivision of Cardiology, Taipei Veterans General Hospital and National Yang-Ming University, 201, Sec 2, Shih-Pai Road, Taipei 112, Taiwan
bDepartment of Anesthesiology, Chang-Gung Memorial Hospital, Taipei, Taiwan
cGraduate Institute of Medical Science, Taipei Medical University, Taipei, Taiwan
cechiang{at}vghtpe.gov.tw
* Corresponding author. Tel.: +886-2-2875-7602; fax: +886-2-2874-5422
Objectives: Sudden death has occasionally been reported in patients taking sildenafil. The objective of this study was to investigate the effect of sildenafil on cardiac repolarization. Methods: We used conventional microelectrode recording technique in isolated guinea pig papillary muscles and canine Purkinje fibers, whole-cell patch clamp techniques in guinea pig ventricular myocytes, and in vivo ECG measurements in guinea pigs. Results: Action potential duration at 90% repolarization (APD90) was not affected by sildenafil in the therapeutic ranges (
1 µM), but shortened by higher concentration (
10 µM) in both guinea pig papillary muscles and canine Purkinje fibers. D-Sotalol prolonged APD90 in the same preparations with concentrations 1 µM in a reverse frequency-dependent manner. Co-administration of sildenafil (10 and 30 µM) abolished the APD-prolonging effects of D-sotalol (30 µM) and amiodarone (100 µM). Sildenafil, with concentrations up to 30 µM, had no significant effect on both the rapid (IKr) and the slow (IKs) components of the delayed rectifier potassium currents in guinea pig ventricular myocytes. Sildenafil dose-dependently blocked L-type Ca2+ current (ICa,L), but had no effect on persistent Na+ current in guinea pig ventricular myocytes. ECG recordings in intact guinea pigs revealed significant shortening of QTc interval by sildenafil (10 and 30 mg/kg orally). The QT-prolonging effects by D,L-sotalol (50 mg/kg) and amiodarone (100 mg/kg) were abolished by sildenafil (30 mg/kg). Conclusions: Sildenafil does not prolong cardiac repolarization. Instead, in supra-therapeutic concentrations, it accelerates cardiac repolarization, presumably through its blocking effect on ICa,L.
KEYWORDS K-Channel; Long QT syndrome; Membrane potential; Myocytes; Purkinje fiber; Repolarization
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. E. Werner, A. L. Meredith, R. W. Aldrich, and M. T. Nelson Hypercontractility and impaired sildenafil relaxations in the BKCa channel deletion model of erectile dysfunction Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2008; 295(1): R181 - R188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-E. Chiang, H.-N. Luk, and T.-M. Wang Swelling-activated chloride current is activated in guinea pig cardiomyocytes from endotoxic shock Cardiovasc Res, April 1, 2004; 62(1): 96 - 104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Reffelmann and R. A. Kloner Effects of sildenafil on myocardial infarct size, microvascular function, and acute ischemic left ventricular dilation Cardiovasc Res, August 1, 2003; 59(2): 441 - 449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Reffelmann and R. A. Kloner Therapeutic Potential of Phosphodiesterase 5 Inhibition for Cardiovascular Disease Circulation, July 15, 2003; 108(2): 239 - 244. [Full Text] [PDF]
|
|