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.