Improved Outcomes of Cardiopulmonary Resuscitation in Rats Treated with Vagus Nerve Stimulation and its Potential Mechanism
Studies have demonstrated that vagus nerve stimulation (VNS) reduces ischemia/reperfusion (I/R) injury. In this study, we investigated the protective effects of VNS in a rat model of cardiopulmonary resuscitation (CPR). We further investigated whether the beneficial effects of VNS were dependent on the alpha 7 nicotinic acetylcholine receptor (α7nAChR). Forty animals were randomized into 4 groups and all underwent CPR (n = 10 each): (1) CPR alone (control); (2) VNS during CPR; (3) α7nAChR antagonist methyllycaconitine citrate (MLA) with VNS; (4) α7nAChR agonist 3-(2, 4-dimethoxybenzylidene) anabaseine (GTS-21) without VNS. The right vagus nerve was exteriorized in all animals. Ventricular fibrillation (VF) was induced and untreated for 8 minutes. Defibrillation was attempted after 8 minutes of CPR. VNS was initiated at the beginning of precordial chest compressions and continued for 4 hours after return of spontaneous circulation (ROSC) in both the VNS and MLA groups. Hemodynamic measurements and myocardial function, including ejection fraction and myocardial performance index, were assessed at baseline, 1 and 4 hours after ROSC. The neurological deficit score was measured at 24-hour intervals for a total of 72 hours. The heart rate was reduced in the VNS and MLA groups, while no difference was found in mean arterial pressure between the four groups. Better post-resuscitation myocardial and cerebral function and longer duration of survival were observed in the VNS-treated animals. The protective effects of VNS could be abolished by MLA and imitated by GTS-21. In addition, VNS decreased the number of electrical shocks and the duration of CPR required. VNS improves multiple outcomes after CPR.