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. 2023 Nov 14:14:1270787.
doi: 10.3389/fphar.2023.1270787. eCollection 2023.

The protective effect of vagus nerve stimulation against myocardial ischemia/reperfusion injury: pooled review from preclinical studies

Yu-Peng Xu #  1 , Xin-Yu Lu #  1 , Zheng-Qi Song  1 , Hui Lin  2 , Yi-He Chen  3
Affiliations

The protective effect of vagus nerve stimulation against myocardial ischemia/reperfusion injury: pooled review from preclinical studies

Yu-Peng Xu et al. Front Pharmacol. .

Abstract

Aims: Myocardial ischemia-reperfusion (I/R) injury markedly undermines the protective benefits of revascularization, contributing to ventricular dysfunction and mortality. Due to complex mechanisms, no efficient ways exist to prevent cardiomyocyte reperfusion damage. Vagus nerve stimulation (VNS) appears as a potential therapeutic intervention to alleviate myocardial I/R injury. Hence, this meta-analysis intends to elucidate the potential cellular and molecular mechanisms underpinning the beneficial impact of VNS, along with its prospective clinical implications. Methods and Results: A literature search of MEDLINE, PubMed, Embase, and Cochrane Database yielded 10 articles that satisfied the inclusion criteria. VNS was significantly correlated with a reduced infarct size following myocardial I/R injury [Weighed mean difference (WMD): 25.24, 95% confidence interval (CI): 32.24 to 18.23, p < 0.001] when compared to the control group. Despite high heterogeneity (I2 = 95.3%, p < 0.001), sensitivity and subgroup analyses corroborated the robust efficacy of VNS in limiting infarct expansion. Moreover, meta-regression failed to identify significant influences of pre-specified covariates (i.e., stimulation type or site, VNS duration, condition, and species) on the primary estimates. Notably, VNS considerably impeded ventricular remodeling and cardiac dysfunction, as evidenced by improved left ventricular ejection fraction (LVEF) (WMD: 10.12, 95% CI: 4.28; 15.97, p = 0.001) and end-diastolic pressure (EDP) (WMD: 5.79, 95% CI: 9.84; -1.74, p = 0.005) during the reperfusion phase. Conclusion: VNS offers a protective role against myocardial I/R injury and emerges as a promising therapeutic strategy for future clinical application.

Keywords: cardioprotection; meta-analysis; molecular mechanisms; myocardial I/R injury; vagus nerve stimulation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow chart of the literature screening.
FIGURE 2
FIGURE 2
Forest plot of infarct size for VNS treatment against myocardial I/R injury. VNS, vagus nerve stimulation.
FIGURE 3
FIGURE 3
Forest plot of LVEF for VNS treatment in myocardial I/R injury. LVEF: left ventricular eject fraction; VNS, vagus nerve stimulation.
FIGURE 4
FIGURE 4
Forest plot of LVEDP for VNS treatment in myocardial I/R injury. LVEDP, left ventricular end-diastolic pressure; VNS, vagus nerve stimulation.
See this image and copyright information in PMC

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