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Effects of sildenafil on cardiac repolarization.
Chern-En Chiang1, Hsiang-Ning Luk, Tsui-Min Wang
1Division of Cardiology, Taipei Veterans General Hospital and National Yang-Ming University, 201, Sec 2, Shih-Pai Road, 112, Taipei, Taiwan. cechiang@vghtpe.gov.tw
Cardiovascular Research
|July 19, 2002
Summary
Sildenafil does not prolong cardiac repolarization. Instead, high concentrations accelerate it by blocking calcium channels, potentially explaining rare sudden death reports.
Area of Science:
- Cardiovascular Pharmacology
- Electrophysiology
- Drug Safety
Background:
- Sudden cardiac death reports in patients using sildenafil necessitate investigation.
- Understanding sildenafil's impact on cardiac repolarization is crucial for patient safety.
Purpose of the Study:
- To investigate the effect of sildenafil on cardiac repolarization.
- To determine if sildenafil contributes to QT interval prolongation or shortening.
Main Methods:
- Utilized microelectrode recordings in guinea pig papillary muscles and canine Purkinje fibers.
- Employed whole-cell patch clamp in guinea pig ventricular myocytes.
- Conducted in vivo ECG measurements in guinea pigs.
Main Results:
- Sildenafil shortened action potential duration at higher concentrations (>10 microM) and abolished QT prolongation by D-sotalol and amiodarone.
- Sildenafil blocked L-type calcium current (I(Ca,L)) but did not affect potassium currents (I(Kr), I(Ks)).
- In vivo ECG showed significant QTc interval shortening with sildenafil administration.
Conclusions:
- Sildenafil does not prolong cardiac repolarization.
- Supra-therapeutic sildenafil concentrations accelerate repolarization, likely via I(Ca,L) blockade.
- Findings suggest sildenafil's effect on repolarization is not proarrhythmic.