Journal Article Ppublish
PubMed: 41747235 DOI: 10.1139/cjpp-2025-0245
Early treatment with pyridostigmine alleviates the isoprenaline-induced model of heart failure with preserved ejection fraction (HFpEF) in rats.
Can J Physiol Pharmacol 104:1-11
Authors: Sonja T Marinković, Tanja Šobot, Žana M Maksimović, Ðorđe Ðukanović, Snežana Uletilović, Nebojša Mandić-Kovačević, Sanja Jovičić, Milka Matičić, Milica Gajić Bojić, Aneta Stojmenovski, Anđela Bojanić, Dragana Lončar-Stojiljković, Ranko Škrbić, Miloš P Stojiljković
Affiliations
- Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina.
- Paediatric Clinic, University Clinical Centre of the Republic of Srpska, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina.
- Department of Physiology, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina.
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina.
- Department of Pharmaceutical Chemistry, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina.
- Department of Medical Biochemistry and Chemistry, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina.
- Department of Pharmacy, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina.
- Department of Histology and Embryology, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina.
- Department of Anaesthesiology and Reanimatology, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina.
- Academy of Sciences and Arts of the Republic of Srpska, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina.
- Department of Pathologic Physiology, I.M. Sechenov First Moscow State Medical University, Moscow 119435, Russia.
Abstract
Acetylcholinesterase (AChE) inhibitors constitute a large and chemically diverse group of compounds that inhibit the enzyme AChE. Some of these compounds that are used to treat Alzheimer's 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 mg/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 mg/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 (↑ EF), coupled with a decrease in chamber wall thinning (↑ PWDd, ↑ PWDs) and dilatation progression (↓ LVIDd, ↓ 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.
MeSH
Research Design, Physiology, Acetylcholinesterase, Heart Failure, Heart, Cardiovascular Diseases, Heart Failure, Diastolic, Pharmacology, Therapeutics, Isoproterenol