Ultrasound improves the outcomes of cardiopulmonary resuscitation in rats by stimulating the cholinergic anti-inflammatory pathway

Abstract

The present study investigated the effects of the ultrasound (US), a noninvasive technique, on ischemia-reperfusion injury (IRI) following cardiopulmonary resuscitation (CPR). The animals used in the present study were randomized into five groups (n=8 per group) as follows: i) The CPR group, where the rats underwent 6 min of untreated ventricular fibrillation (VF) followed by CPR and defibrillation; ii) the US group, in which the treatment was identical to the CPR group with the exception that rats were exposed to US treatment 24 h prior to CPR; iii) the MLA group, in which the treatment was identical to the US group with the exception that the a7 nicotinic acetylcholine receptor (a7nAC hR) antagonist MLA (4 mg/kg) was administered 30 min prior to US and VF respectively; iv) the GTS group, in which the treatment was identical to the CPR group with the exception that the a7nAC hR agonist GTS-21 (4 mg/kg) was injected 30 min prior to VF; and v) the SHAM group, in which the rats were exposed to surgical preparation without CPR and US application. At 1 day prior to CPR, the US treatment was administered to the left kidney by US pulses (contrast general mode with 9 MHz) with a bursting mechanical index of 0.72 for 2 min. Following treatment of the left kidney, the right kidney was exposed to identical US treatment for an additional 2 min. The results demonstrated that US preconditioning decreased the number of defibrillations required and shortened the duration of CPR. US also suppressed tumor necrosis factor-a and interleukin-6 levels following resuscitation (P<0.05), and a significantly longer overall survival time was observed in the US-treated animals (P<0.01). In addition, US attenuated neuronal injury and promoted the expression of a7nAChR in hippocampal neurons (P<0.05). However, the protective effects of US were abolished by MLA and imitated by GTS-21. The results of the present study demonstrated that prior exposure to US may improve animal outcomes following CPR, and the protective effects of US may be dependent on the cholinergic anti-inflammatory pathway (CAP) via a7nAChR.