iScience. 2026 Jan 9;29(2):114657. doi: 10.1016/j.isci.2026.114657. eCollection 2026 Feb 20.
ABSTRACT
Vagus nerve stimulation (VNS), as a neuromodulation therapy, has shown promising prospects in the treatment of myocardial ischemia-reperfusion injury (MIRI) following myocardial infarction (MI). MIRI can exacerbate secondary damage to post-ischemic myocardial tissue. VNS can alleviate MIRI by enhancing vagal nerve activity. In preclinical studies, VNS exerts cardioprotective effects through multi-target synergistic regulation: inhibiting inflammatory cascades through the cholinergic anti-inflammatory pathway (CAP) and vagus nerve-spleen pathway, improving mitochondrial function, resisting oxidative stress, suppressing cardiomyocyte apoptosis, and regulating autonomic nerves to reduce arrhythmias risk. This review explores the interactions between the aforementioned mechanisms, rarely addressed in prior studies. Furthermore, this review summarizes relevant clinical studies, where VNS significantly reduces myocardial injury markers and arrhythmia incidence. However, VNS still faces clinical application challenges including unstandardized parameter and operation standards and insufficient clinical evidence. This review aims to bridge preclinical and clinical research, providing a reference for VNS clinical application in MIRI.
PMID:41716993 | PMC:PMC12915268 | DOI:10.1016/j.isci.2026.114657