Ultrasound Improves The Outcomes After Cardiopulmonary Resuscitation By Stimulating The Cholinergic Anti-Inflammatory Pathway

Introduction: Recently it was shown that the ultrasound (US) treatment prevented renal ischemia- reperfusion injury (IRI) in mice. In the present study, we investigated the effects of the US treatment against IRI after CPR . Hypothesis: US would improve the outcomes after resuscitation in a rat model of CPR, and the protective effect of US would be dependent on the cholinergic anti-inflammatory pathway (CAP) via α7nAChR. Methods: The animals were randomized into 5 groups (n=8 each): (1) CPR group: the rats underwent 6 mins of untreated ventricular fibrillation (VF) followed by CPR and defibrillation; (2) US group: the treatment was identical to the CPR group except that rats were exposed to US treatment 24h before CPR; (3) MLA group: the treatment was identical to the US group except thatα7nAChR antagonist MLA (4mg/kg) was administered 30 mins prior to US treatment and VF respectively; (4) GTS group: the treatment was identical to the CPR group except that α7nAChR agonist GTS-21(4mg/kg) was injected 30 mins before VF. (5) SHAM group: the rats were exposed to surgical preparation without CPR and US application. One day before CPR, the US treatment was delivered to the left kidney by US pulses (contrast general mode with 9 MHz) with a bursting mechanical index of 0.72. US pulses were 1 second in duration and were applied once every 6 seconds for 2 mins. After the treatment of the left kidney, the right kidney was exposed to US treatment for another 2 mins. Results: Significantly longer duration of survival was observed in US-treated animals. And US treatment also suppressed the TNF-α and IL-6 following resuscitation, and improved neurological function. The expression of α7nAChR were promoted in hippocampal neurons in US group. Moreover, the protective effect of US treatment could be abolished by MLA and imitated by GTS-21. Conclusions: US treatment before IRI improves the outcomes after CPR, and CAP via α7nAChR plays an important role during CPR.