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Some of these compounds that are used to treat Alzheimer\u2019s disease have been reported to have favourable cardiovascular effects, i.e., a 35% reduction of the risk for cardiovascular disease. There has been a growing interest in AchE inhibitors as a potential therapeutic approach for cardiovascular diseases, especially heart failure (HF), since they correct the autonomic imbalance, a key component in the development of heart failure. In the present study, HF was induced in male Wistar albino rats using an isoprenaline model (85\u00a0mg\/kg\/day s.c. for 2 days, followed by 3 weeks of HF development) of heart failure with preserved ejection fraction. Afterwards, rats were treated with pyridostigmine (20\u00a0mg\/kg\/day in tap water for 14 days), while the controls received no treatment. Electrocardiographic and echosonographic measurements were obtained, and samples were taken for antioxidative status measurement and histopathological analysis. Administration of pyridostigmine resulted in preservation of cardiac contractile function (\u2191 EF), coupled with a decrease in chamber wall thinning (\u2191 PWDd, \u2191 PWDs) and dilatation progression (\u2193 LVIDd, \u2193 LVIDs). Additionally, histopathological findings showed significantly reduced tissue damage score and attenuation of cardiac fibrosis development, indicating the cardioprotective potential of pyridostigmine when used as treatment for the early stages of heart failure; however, further investigations are needed to fully investigate the interplay between the several proposed mechanisms through which AChE inhibitors express their protective effects.<\/jats:p>","DOI":"10.1139\/cjpp-2025-0245","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T21:35:07Z","timestamp":1772141707000},"page":"1-11","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Early treatment with pyridostigmine alleviates the isoprenaline-induced model of heart failure with preserved ejection fraction (HFpEF) in rats"],"prefix":"10.1139","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4512-9428","authenticated-orcid":false,"given":"Sonja T.","family":"Marinkovi\u0107","sequence":"first","affiliation":[{"name":"University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]},{"name":"University Clinical Centre of the Republic of Srpska","place":["Banja Luka, Bosnia and Herzegovina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"\u0160obot","sequence":"additional","affiliation":[{"name":"University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u017dana M.","family":"Maksimovi\u0107","sequence":"additional","affiliation":[{"name":"University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]},{"name":"University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9887-9695","authenticated-orcid":false,"given":"\u00d0or\u0111e","family":"\u00d0ukanovi\u0107","sequence":"additional","affiliation":[{"name":"University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]},{"name":"University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sne\u017eana","family":"Uletilovi\u0107","sequence":"additional","affiliation":[{"name":"University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]},{"name":"University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neboj\u0161a","family":"Mandi\u0107-Kova\u010devi\u0107","sequence":"additional","affiliation":[{"name":"University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]},{"name":"University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanja","family":"Jovi\u010di\u0107","sequence":"additional","affiliation":[{"name":"University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]},{"name":"University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milka","family":"Mati\u010di\u0107","sequence":"additional","affiliation":[{"name":"University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milica","family":"Gaji\u0107 Boji\u0107","sequence":"additional","affiliation":[{"name":"University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]},{"name":"University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta","family":"Stojmenovski","sequence":"additional","affiliation":[{"name":"University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An\u0111ela","family":"Bojani\u0107","sequence":"additional","affiliation":[{"name":"University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragana","family":"Lon\u010dar-Stojiljkovi\u0107","sequence":"additional","affiliation":[{"name":"University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranko","family":"\u0160krbi\u0107","sequence":"additional","affiliation":[{"name":"University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]},{"name":"University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]},{"name":"Academy of Sciences and Arts of the Republic of Srpska","place":["Banja Luka, Bosnia and Herzegovina"]},{"name":"I.M. 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