Left-sided vagus nerve stimulation improves cardiopulmonary resuscitation outcomes in rats as effectively as right-sided vagus nerve stimulation

Abstract

BACKGROUND: Our group previously reported that right-sided vagus nerve stimulation (RVNS) signifi cantly improved outcomes after cardiopulmonary resuscitation (CPR) in a rat model of cardiac arrest (CA). However, whether left-sided vagus nerve stimulation (LVNS) could achieve the same eff ect as RVNS in CPR outcomes remains unknown.METHODS: A rat model of CA was established using modified percutaneous epicardial electrical stimulation to induce ventricular fi brillation (VF). Rats were treated with LVNS or RVNS for 30 minutes before the induction of VF. All animals were observed closely within 72 hours after return of spontaneous circulation (ROSC), and their health and behavior were evaluated every 24 hours. RESULTS: Compared with those in the RVNS group, the hemodynamic measurements in the LVNS group decreased more notably. Vagus nerve stimulation (VNS) decreased the serum levels of tumor necrosis factor-alpha (TNF-α) and the arrhythmia score, and attenuated inflammatory infiltration in myocardial tissue after ROSC, regardless of the side of stimulation, compared with fi ndings in the CPR group. Both LVNS and RVNS ameliorated myocardial function and increased the expression of α-7 nicotinic acetylcholine receptor in the myocardium after ROSC. Moreover, a clear improvement in 72-hour survival was shown with VNS pre-treatment, with no signifi cant diff erence in effi cacy when comparing the laterality of stimulation.CONCLUSIONS: LVNS may have similar eff ects as RVNS on improving outcomes after CPR.

VNS‐mediated α7nAChR signaling promotes SPM synthesis via regulation of netrin‐1 expression during LPS‐induced ALI

“…In our study, we chose to stimulate the left cervical vagus nerve due to its lesser impact on heart rate and its preference among clinical patients 49 . This is despite evidence suggesting that stimulation of either the left or right side yields similar improvements in cardiopulmonary resuscitation (CPR) outcomes in rats 50 . Researchers have discovered that mesenchymal stromal cells (MSCs) can induce lung protection by activating the vagal anti‐inflammatory pathway, as evidenced by the detection of Ach in the BALF 47 …”

Threshold adjusted vagus nerve stimulation after asphyxial cardiac arrest results in neuroprotection and improved survival

“…This result is consistent with a previous study by Sun et al, 2017, who demonstrated that after 8 min of ventricular fibrillation (VF) CA in rats, right cervical VNS initiated for 4 h at the beginning of chest compression with 10% reduction in HR, improved cerebral function, and 72 h survival (Sun et al, 2018 ). While pre-treatment studies present a range of difficulties, nevertheless, Shao et al demonstrated that 30 min of VNS to right or left cervical vagus nerve before inducing VF in rats significantly improved 72 h survival (Shao et al, 2021 ), suggesting that stimulation of either cervical vagus nerve can confer a protective effect. Thus, to activate the array of cervical vagus nerve fibers (afferent and efferent) and achieve optimal effect (Ahmed et al, 2021 ; Chang et al, 2020 ), we applied electrical tVNS after 12 min CA and resuscitation, and observed a substantial survival benefit as compared to control (87.5% v 37.5%, respectively; P < 0.05; Fig.…”

“…The threshold chosen for effective left cervical VNS was a 15–20% reduction of basal HR for stimulating maximal cervical vagus nerve fibers (afferent and efferent) and getting an optimal effect (Ahmed et al, 2021 ; Chang et al, 2020 ). Various studies have used different settings to stimulate either right or left cervical vagus nerve for survival and neuroprotection (Kim et al, 2019 ; Sun et al, 2018 ; Shao et al, 2021 ), preventing cardiac damage (Xue et al, 2017 ) and protecting kidney injury (Inoue et al, 2016 ). These studies suggest that VNS may have differential effects with different stimulation parameters.…”

“…VNS has also been approved for clinical use by the Food and Drug Administration in 1997 and is currently recognized as a safe and effective treatment modality for epilepsy, depression, and stroke (Nemeroff et al, 2006 ; Koo et al, 2001 ; Dawson et al, 2021 ). Furthermore, improved VNS-mediated survival, neuroprotection and improved myocardial function after cardiac arrest have been recently reported (Kim et al, 2019 ; Sun et al, 2018 ; Shao et al, 2021 ).…”

“…By contrast, Sun et al used 10% reduction in HR as an optimized threshold by stimulating right vagus nerve in rats and demonstrated improved myocardial and cerebral function and longer duration of survival (Sun et al, 2018 ). Shao et al recently used a pulse width of 1.2 ms, a frequency of 4 Hz, and an intensity of 6 V to stimulate both right and left vagus nerve in rats (Shao et al, 2021 ) to produce a survival and neuroprotective effect. Xue et al used electrical voltage pulses ranging from 2 to 4 V to obtain a 10% reduction in basal heart rate for attenuating isoproterenol-induced cardiac damage in rats (Xue et al, 2017 ), while Inoue et al used electrical stimulation (square wave; 50 μA intensity; frequency, 5 Hz; duration, 1 ms) for VNS to mitigate kidney injury following ischemia reperfusion injury in mice (Inoue et al, 2016 ).…”