{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T15:12:47Z","timestamp":1783091567978,"version":"3.54.6"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,4,21]],"date-time":"2019-04-21T00:00:00Z","timestamp":1555804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["C06 RR020128\u201001"],"award-info":[{"award-number":["C06 RR020128\u201001"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cardiovasc electrophysiol"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Higher progesterone concentrations are protective against drug\u2010induced prolongation of ventricular repolarization. We tested the hypothesis that pretreatment with progesterone reduces the incidence of drug\u2010induced torsades de pointes (TdP).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>Female New Zealand white rabbits (2.5\u20103.2\u2009kg) underwent ovariectomy and were randomized to undergo implantation with subcutaneous 21\u2010day sustained release pellets containing progesterone 50\u2009mg (n\u2009=\u200922) or placebo (n\u2009=\u200923). After 20 days, hearts were excised, mounted, and perfused with modified Krebs\u2010Henseleit solution. The atrioventricular (AV) node was destroyed manually. Following a 15\u2010minute equilibration period, hearts were perfused with dofetilide 100\u2009nM for 30\u2009minutes, during which the electrocardiogram was recorded continuously. Incidences of spontaneous TdP, other ventricular arrhythmias and mean QT<jats:sub>c<\/jats:sub> intervals were compared. Median serum progesterone concentrations were higher in progesterone vs placebo\u2010treated rabbits (3.8 [range, 2.8\u20105.1] vs 0.7 [0.4\u20101.7]\u2009ng\/mL, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001). Median serum estradiol concentrations were similar (58 [22\u201072] vs 53 [34\u201062]\u2009pg\/mL), <jats:italic>P<\/jats:italic>\u2009=\u20090.79). The incidence of TdP was lower in hearts from progesterone\u2010treated rabbits (27% vs 61%, <jats:italic>P<\/jats:italic>\u2009=\u20090.049). The incidences of bigeminy (36% vs 74%, <jats:italic>P<\/jats:italic>\u2009=\u20090.03) and trigeminy (18% vs 57%, <jats:italic>P<\/jats:italic>\u2009=\u20090.01) were also lower in hearts from progesterone\u2010treated rabbits. There was no significant difference between groups in incidence of couplets (59% vs 74%, <jats:italic>P<\/jats:italic>\u2009=\u20090.54) or monomorphic ventricular tachycardia (14% vs 30%, <jats:italic>P<\/jats:italic>\u2009=\u20090.28). Maximum QT\n<jats:sub>c<\/jats:sub> interval and short\u2010term beat\u2010to\u2010beat QT interval variability during dofetilide perfusion were significantly shorter in hearts from progesterone\u2010treated rabbits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Pretreatment with progesterone reduces the incidence of drug\u2010induced TdP, bigeminy, and trigeminy in isolated perfused AV node\u2010ablated rabbit hearts.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jce.13942","type":"journal-article","created":{"date-parts":[[2019,4,22]],"date-time":"2019-04-22T04:30:28Z","timestamp":1555907428000},"page":"941-949","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Progesterone pretreatment reduces the incidence of drug\u2010induced torsades de pointes in atrioventricular node\u2010ablated isolated perfused rabbit 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