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 α7 nicotinic acetylcholine receptor (α7nAChR) 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 α7nAChR 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-α 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 α7nAChR 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 α7nAChR.

Cooling Down Inflammation in the Cardiovascular System via the Nicotinic Acetylcholine Receptor

“…200 VNS has been shown to exert protective effects against acute cerebral, cardiac, and renal I/R injury by suppressing inflammation by a7-nAChR activation. [201][202][203] Based on the beneficial effects of VNS in regional I/R injury, the role of VNS during global I/R injury of cardiac arrest and cardiopulmonary resuscitation has also been investigated. In a rat model of cardiopulmonary resuscitation, both VNS and GTS-21 were tested.…”

The role of (¹⁸F)-fluoro-D-glucose positron emission tomography/computed tomography in the surveillance of abnormal myocardial energy metabolism and cardiac dysfunction in a rat model of cardiopulmonary resuscitation

“…Post-resuscitation myocardial injury is evidently due to oxidative stress, calcium overload, neutrophil accumulation, microvascular damage, and abnormal energy metabolism, among other causes. 1 , 2 , 3 As one of the most common pathological mechanisms after the ROSC, energy metabolism disorder in the myocardium leads to a series of detrimental changes in the energy supply and substrate metabolism related to the regulation of mitochondrial function, oxidative stress, and inflammation. 4 , 5 …”