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Sildenafil (Viagra) prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current.
Circulation. 2000 Jul 18; 102(3):275-7.Circ

Abstract

BACKGROUND

-Several cases of unexpected death have been reported with sildenafil in patients predisposed to ischemic cardiac events. Although acute episodes of ischemia could account for some of these deaths, we hypothesized that sildenafil may have unsuspected electrophysiological effects predisposing some patients to proarrhythmia.

METHODS

AND

RESULTS

-Studies were undertaken in 10 isolated guinea pig hearts that demonstrated prolongation of cardiac repolarization in a reverse use-dependent manner by sildenafil 30 mcmol/L. Action potential duration increased 15% from baseline 117+/-3 to 134+/-2 ms with sildenafil during pacing at 250 ms cycle length, whereas a 6% increase from 99+/-2 to 105+/-2 ms was seen with pacing at 150 ms cycle length. Experiments in human ether-a-go-go-related gene (HERG)-transfected HEK293 cells (n=30) demonstrated concentration-dependent block of the rapid component (I(Kr)) of the delayed rectifier potassium current: activating current was 50% decreased at 100 mcmol/L. This effect was confirmed using HERG-transfected Chinese hamster ovary (CHO) cells, which exhibit no endogenous I(K)-like current.

CONCLUSIONS

-Sildenafil possesses direct cardiac electrophysiological effects similar to class III antiarrhythmic drugs. These effects are observed at concentrations that may be found in conditions of impaired drug elimination such as renal or hepatic insufficiency, during coadministration of another CYP3A substrate/inhibitor, or after drug overdose and offer a new potential explanation for sudden death during sildenafil treatment.

Authors+Show Affiliations

Institut de Cardiologie de Québec, Hôpital Laval, et Facultés de Médecine, Université Laval, Sainte-Foy, Québec.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10899088

Citation

Geelen, P, et al. "Sildenafil (Viagra) Prolongs Cardiac Repolarization By Blocking the Rapid Component of the Delayed Rectifier Potassium Current." Circulation, vol. 102, no. 3, 2000, pp. 275-7.
Geelen P, Drolet B, Rail J, et al. Sildenafil (Viagra) prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current. Circulation. 2000;102(3):275-7.
Geelen, P., Drolet, B., Rail, J., Bérubé, J., Daleau, P., Rousseau, G., Cardinal, R., O'Hara, G. E., & Turgeon, J. (2000). Sildenafil (Viagra) prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current. Circulation, 102(3), 275-7.
Geelen P, et al. Sildenafil (Viagra) Prolongs Cardiac Repolarization By Blocking the Rapid Component of the Delayed Rectifier Potassium Current. Circulation. 2000 Jul 18;102(3):275-7. PubMed PMID: 10899088.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sildenafil (Viagra) prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current. AU - Geelen,P, AU - Drolet,B, AU - Rail,J, AU - Bérubé,J, AU - Daleau,P, AU - Rousseau,G, AU - Cardinal,R, AU - O'Hara,G E, AU - Turgeon,J, PY - 2000/7/19/pubmed PY - 2000/8/6/medline PY - 2000/7/19/entrez SP - 275 EP - 7 JF - Circulation JO - Circulation VL - 102 IS - 3 N2 - BACKGROUND-Several cases of unexpected death have been reported with sildenafil in patients predisposed to ischemic cardiac events. Although acute episodes of ischemia could account for some of these deaths, we hypothesized that sildenafil may have unsuspected electrophysiological effects predisposing some patients to proarrhythmia. METHODS AND RESULTS-Studies were undertaken in 10 isolated guinea pig hearts that demonstrated prolongation of cardiac repolarization in a reverse use-dependent manner by sildenafil 30 mcmol/L. Action potential duration increased 15% from baseline 117+/-3 to 134+/-2 ms with sildenafil during pacing at 250 ms cycle length, whereas a 6% increase from 99+/-2 to 105+/-2 ms was seen with pacing at 150 ms cycle length. Experiments in human ether-a-go-go-related gene (HERG)-transfected HEK293 cells (n=30) demonstrated concentration-dependent block of the rapid component (I(Kr)) of the delayed rectifier potassium current: activating current was 50% decreased at 100 mcmol/L. This effect was confirmed using HERG-transfected Chinese hamster ovary (CHO) cells, which exhibit no endogenous I(K)-like current. CONCLUSIONS-Sildenafil possesses direct cardiac electrophysiological effects similar to class III antiarrhythmic drugs. These effects are observed at concentrations that may be found in conditions of impaired drug elimination such as renal or hepatic insufficiency, during coadministration of another CYP3A substrate/inhibitor, or after drug overdose and offer a new potential explanation for sudden death during sildenafil treatment. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/10899088/Sildenafil__Viagra__prolongs_cardiac_repolarization_by_blocking_the_rapid_component_of_the_delayed_rectifier_potassium_current_ L2 - http://www.ahajournals.org/doi/full/10.1161/01.cir.102.3.275?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -