{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T04:36:08Z","timestamp":1767414968487,"version":"3.37.3"},"reference-count":52,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2017,7,5]],"date-time":"2017-07-05T00:00:00Z","timestamp":1499212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Several rabbit proarrhythmia models have been developed using genetic or pharmacological methods to suppress the slow component of delayed rectifier K<jats:sup>+<\/jats:sup> currents in the ventricle, leading to reduction of the repolarization reserve. Here we have characterized a novel rabbit <jats:italic>in vivo<\/jats:italic> proarrhythmia model with severe bradycardia caused by acute atrioventricular block (AVB).<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Bradycardia was induced in isoflurane\u2010anaesthetized rabbits by inducing AVB with catheter ablation, and the ventricle was electrically driven at 60 beats min<jats:sup>\u22121<\/jats:sup> throughout the experiment except when extrasystoles appeared. We assessed the effects of two antiarrhythmics, two quinolone antibiotics and one antipsychotic drug, which were chosen as positive drugs (dofetilide, sparfloxacin and haloperidol) and negative drugs (amiodarone and moxifloxacin) for induction of Torsades de Pointes (TdP).<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In our model, TdP arrhythmias appeared with high reproducibility after i.v. dofetilide (10\u2013100 \u03bcg\u00b7kg<jats:sup>\u22121<\/jats:sup>) in five out of six rabbits, sparfloxacin (30 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>) in three out of six rabbits and haloperidol (0.3\u20133 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>) in two out of six rabbits. The lethal arrhythmias repeatedly appeared and were accompanied with prolongation of the QT interval and early afterdepolarization\u2010like phenomena. Neither amiodarone (0.3\u201310 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>, <jats:italic>n<\/jats:italic>\u00a0=\u00a06) nor moxifloxacin (3\u201330 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>, <jats:italic>n<\/jats:italic>\u00a0=\u00a06) induced such arrhythmias, even when QT intervals were prolonged.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>These results suggest that our model of the unremodelled and bradycardic heart of the anaesthetized rabbit is a useful test system for the detection of drug\u2010induced TdP arrhythmias.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13870","type":"journal-article","created":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T09:02:44Z","timestamp":1495789364000},"page":"2591-2605","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The anaesthetized rabbit with acute atrioventricular block provides a new model for detecting 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