Early treatment with pyridostigmine alleviates heart failure with preserved ejection fraction (HFpEF) in rats

Acetylcholinesterase (AChE) inhibitors constitute a group of compounds that inhibit the enzyme AChE. Some of these 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. Due to their ability to correct the autonomic imbalance, a key component in the development of heart failure (HF), they have been proposed as a potential therapeutic approach. 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). Afterwards, rats were treated with pyridostigmine (20 mg/kg/day for 14 days) or received no treatment. 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, pathohistological 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.