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Although rats are a useful scientific tool, their hearts, unlike larger species, usually do not respond to torsadogenic drugs. Consequently, their resistance to drug\u2010induced arrhythmias is poorly understood. Here, we challenged rats with rapid delayed rectifier current (Ikr)\u2010inhibiting antibiotic clarithromycin (CLA), loop diuretic furosemide (FUR) or their combination (CLA\u2009+\u2009FUR), and examined functional and molecular abnormalities after stimulation with isoproterenol. Clarithromycin and furosemide were administered orally at 12\u2010h intervals for 7\u2009days. To evaluate electrical instability, electrocardiography (ECG) was recorded either in vivo or ex vivo using the Langendorff\u2010perfused heart method under basal conditions and subsequently under beta\u2010adrenergic stimulation. Gene expression was measured using real\u2010time quantitative PCR in left ventricular tissue. Indeed, FUR and CLA\u2009+\u2009FUR rats exhibited hypokalemia. CLA and CLA\u2009+\u2009FUR treatment resulted in drug\u2010induced LQTS and even an episode of TdP in one CLA\u2009+\u2009FUR rat. The combined treatment dysregulated gene expression of several ion channels subunits, including KCNQ1, calcium channels and Na+\/K\u2009+\u2009\u2010ATPase subunits, while both monotherapies had no impact. The rat with recorded TdP exhibited differences in the expression of ion channel genes compared to the rest of rats within the CLA\u2009+\u2009FUR group. The ECG changes were not detected in isolated perfused hearts. Hence, we report rapid orchestration of ion channel reprogramming of hearts with QT prolongation induced by simultaneous administration of clarithromycin and furosemide in rats, which may account for their ability to avoid arrhythmias triggered by beta\u2010adrenergic stimulation.<\/jats:p>","DOI":"10.1002\/prp2.1134","type":"journal-article","created":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T04:31:50Z","timestamp":1694838710000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rapid changes of mRNA expressions of cardiac ion channels affected by Torsadogenic drugs influence susceptibility of rat hearts to arrhythmias induced by Beta\u2010Adrenergic stimulation"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7055-9561","authenticated-orcid":false,"given":"Katarina","family":"Hadova","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, 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