{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T16:34:21Z","timestamp":1778776461060,"version":"3.51.4"},"reference-count":14,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2000,7,18]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014Several 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.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014Studies were undertaken in 10 isolated guinea pig hearts that demonstrated prolongation of cardiac repolarization in a reverse use-dependent manner by sildenafil 30 \u03bcmol\/L. Action potential duration increased 15% from baseline 117\u00b13 to 134\u00b12 ms with sildenafil during pacing at 250 ms cycle length, whereas a 6% increase from 99\u00b12 to 105\u00b12 ms was seen with pacing at 150 ms cycle length. Experiments in human\n            <jats:italic>ether-a-go-go<\/jats:italic>\n            \u2013related gene (HERG)\u2013transfected HEK293 cells (n=30) demonstrated concentration-dependent block of the rapid component (I\n            <jats:sub>Kr<\/jats:sub>\n            ) of the delayed rectifier potassium current: activating current was 50% decreased at 100 \u03bcmol\/L. This effect was confirmed using HERG-transfected Chinese hamster ovary (CHO) cells, which exhibit no endogenous I\n            <jats:sub>K<\/jats:sub>\n            -like current.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014Sildenafil 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.\n          <\/jats:p>","DOI":"10.1161\/01.cir.102.3.275","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:42:29Z","timestamp":1339461749000},"page":"275-277","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":73,"title":["Sildenafil (Viagra) Prolongs Cardiac Repolarization by Blocking the Rapid Component of the Delayed Rectifier Potassium Current"],"prefix":"10.1161","volume":"102","author":[{"given":"Peter","family":"Geelen","sequence":"first","affiliation":[{"name":"From the Institut de Cardiologie de Que\u0301bec, Ho\u0302pital Laval (P.G., B.D., J.R., J.B., P.D., G.E.O., J.T.) et Faculte\u0301s de Pharmacie (B.D., J.R., J.T.) et de Me\u0301decine (P.G., J.B., P.D., G.E.O., J.T.), Universite\u0301 Laval, Sainte-Foy, Que\u0301bec; and Centre de Recherche, Ho\u0302pital du Sacre\u0301-C\u0153ur de Montre\u0301al (B.D., G.R., R.C., J.T.), De\u0301partement de Pharmacologie, Faculte\u0301 de Me\u0301decine (G.R., R.C., J.T.) et Faculte\u0301 de Pharmacie (J.T.), Universite\u0301 de Montre\u0301al, Montre\u0301al, Que\u0301bec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benoit","family":"Drolet","sequence":"additional","affiliation":[{"name":"From the Institut de Cardiologie de Que\u0301bec, Ho\u0302pital Laval (P.G., B.D., J.R., J.B., P.D., G.E.O., J.T.) et Faculte\u0301s de Pharmacie (B.D., J.R., J.T.) et de Me\u0301decine (P.G., J.B., P.D., G.E.O., J.T.), Universite\u0301 Laval, Sainte-Foy, Que\u0301bec; and Centre de Recherche, Ho\u0302pital du Sacre\u0301-C\u0153ur de Montre\u0301al (B.D., G.R., R.C., J.T.), De\u0301partement de Pharmacologie, Faculte\u0301 de Me\u0301decine (G.R., R.C., J.T.) et Faculte\u0301 de Pharmacie (J.T.), Universite\u0301 de Montre\u0301al, Montre\u0301al, Que\u0301bec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jimmy","family":"Rail","sequence":"additional","affiliation":[{"name":"From the Institut de Cardiologie de Que\u0301bec, Ho\u0302pital Laval (P.G., B.D., J.R., J.B., P.D., G.E.O., J.T.) et Faculte\u0301s de Pharmacie (B.D., J.R., J.T.) et de Me\u0301decine (P.G., J.B., P.D., G.E.O., J.T.), Universite\u0301 Laval, Sainte-Foy, Que\u0301bec; and Centre de Recherche, Ho\u0302pital du Sacre\u0301-C\u0153ur de Montre\u0301al (B.D., G.R., R.C., J.T.), De\u0301partement de Pharmacologie, Faculte\u0301 de Me\u0301decine (G.R., R.C., J.T.) et Faculte\u0301 de Pharmacie (J.T.), Universite\u0301 de Montre\u0301al, Montre\u0301al, Que\u0301bec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jocelyn","family":"Be\u0301rube\u0301","sequence":"additional","affiliation":[{"name":"From the Institut de Cardiologie de Que\u0301bec, Ho\u0302pital Laval (P.G., B.D., J.R., J.B., P.D., G.E.O., J.T.) et Faculte\u0301s de Pharmacie (B.D., J.R., J.T.) et de Me\u0301decine (P.G., J.B., P.D., G.E.O., J.T.), Universite\u0301 Laval, Sainte-Foy, Que\u0301bec; and Centre de Recherche, Ho\u0302pital du Sacre\u0301-C\u0153ur de Montre\u0301al (B.D., G.R., R.C., J.T.), De\u0301partement de Pharmacologie, Faculte\u0301 de Me\u0301decine (G.R., R.C., J.T.) et Faculte\u0301 de Pharmacie (J.T.), Universite\u0301 de Montre\u0301al, Montre\u0301al, Que\u0301bec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascal","family":"Daleau","sequence":"additional","affiliation":[{"name":"From the Institut de Cardiologie de Que\u0301bec, Ho\u0302pital Laval (P.G., B.D., J.R., J.B., P.D., G.E.O., J.T.) et Faculte\u0301s de Pharmacie (B.D., J.R., J.T.) et de Me\u0301decine (P.G., J.B., P.D., G.E.O., J.T.), Universite\u0301 Laval, Sainte-Foy, Que\u0301bec; and Centre de Recherche, Ho\u0302pital du Sacre\u0301-C\u0153ur de Montre\u0301al (B.D., G.R., R.C., J.T.), De\u0301partement de Pharmacologie, Faculte\u0301 de Me\u0301decine (G.R., R.C., J.T.) et Faculte\u0301 de Pharmacie (J.T.), Universite\u0301 de Montre\u0301al, Montre\u0301al, Que\u0301bec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy","family":"Rousseau","sequence":"additional","affiliation":[{"name":"From the Institut de Cardiologie de Que\u0301bec, Ho\u0302pital Laval (P.G., B.D., J.R., J.B., P.D., G.E.O., J.T.) et Faculte\u0301s de Pharmacie (B.D., J.R., J.T.) et de Me\u0301decine (P.G., J.B., P.D., G.E.O., J.T.), Universite\u0301 Laval, Sainte-Foy, Que\u0301bec; and Centre de Recherche, Ho\u0302pital du Sacre\u0301-C\u0153ur de Montre\u0301al (B.D., G.R., R.C., J.T.), De\u0301partement de Pharmacologie, Faculte\u0301 de Me\u0301decine (G.R., R.C., J.T.) et Faculte\u0301 de Pharmacie (J.T.), Universite\u0301 de Montre\u0301al, Montre\u0301al, Que\u0301bec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rene\u0301","family":"Cardinal","sequence":"additional","affiliation":[{"name":"From the Institut de Cardiologie de Que\u0301bec, Ho\u0302pital Laval (P.G., B.D., J.R., J.B., P.D., G.E.O., J.T.) et Faculte\u0301s de Pharmacie (B.D., J.R., J.T.) et de Me\u0301decine (P.G., J.B., P.D., G.E.O., J.T.), Universite\u0301 Laval, Sainte-Foy, Que\u0301bec; and Centre de Recherche, Ho\u0302pital du Sacre\u0301-C\u0153ur de Montre\u0301al (B.D., G.R., R.C., J.T.), De\u0301partement de Pharmacologie, Faculte\u0301 de Me\u0301decine (G.R., R.C., J.T.) et Faculte\u0301 de Pharmacie (J.T.), Universite\u0301 de Montre\u0301al, Montre\u0301al, Que\u0301bec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilles E.","family":"O\u2019Hara","sequence":"additional","affiliation":[{"name":"From the Institut de Cardiologie de Que\u0301bec, Ho\u0302pital Laval (P.G., B.D., J.R., J.B., P.D., G.E.O., J.T.) et Faculte\u0301s de Pharmacie (B.D., J.R., J.T.) et de Me\u0301decine (P.G., J.B., P.D., G.E.O., J.T.), Universite\u0301 Laval, Sainte-Foy, Que\u0301bec; and Centre de Recherche, Ho\u0302pital du Sacre\u0301-C\u0153ur de Montre\u0301al (B.D., G.R., R.C., J.T.), De\u0301partement de Pharmacologie, Faculte\u0301 de Me\u0301decine (G.R., R.C., J.T.) et Faculte\u0301 de Pharmacie (J.T.), Universite\u0301 de Montre\u0301al, Montre\u0301al, Que\u0301bec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques","family":"Turgeon","sequence":"additional","affiliation":[{"name":"From the Institut de Cardiologie de Que\u0301bec, Ho\u0302pital Laval (P.G., B.D., J.R., J.B., P.D., G.E.O., J.T.) et Faculte\u0301s de Pharmacie (B.D., J.R., J.T.) et de Me\u0301decine (P.G., J.B., P.D., G.E.O., J.T.), Universite\u0301 Laval, Sainte-Foy, Que\u0301bec; and Centre de Recherche, Ho\u0302pital du Sacre\u0301-C\u0153ur de Montre\u0301al (B.D., G.R., R.C., J.T.), De\u0301partement de Pharmacologie, Faculte\u0301 de Me\u0301decine (G.R., R.C., J.T.) et Faculte\u0301 de Pharmacie (J.T.), Universite\u0301 de Montre\u0301al, Montre\u0301al, Que\u0301bec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199805143382001"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(01)63100-8"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/clc.4960210902"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.99.1.168"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.97.2.204"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(98)77782-3"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004240050930"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19980601)52:5<612::AID-JNR13>3.0.CO;2-3"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.1998.tb00889.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(99)00046-6"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-199607000-00035"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijir.3900354"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.91.12.3010"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.76.1.110"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.CIR.102.3.275","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T13:08:07Z","timestamp":1715519287000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.CIR.102.3.275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,7,18]]},"references-count":14,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2000,7,18]]}},"alternative-id":["10.1161\/01.CIR.102.3.275"],"URL":"https:\/\/doi.org\/10.1161\/01.cir.102.3.275","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,7,18]]},"assertion":[{"value":"2000-04-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-05-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-07-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}