Open Access

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

  • Authors:
    • Yuhan Zhang
    • Yue Song
    • Tingting Shu
    • Licai Liang
    • Weijing Shao
    • Lang Guo
    • Peng Sun
  • View Affiliations

  • Published online on: July 25, 2019     https://doi.org/10.3892/mmr.2019.10527
  • Pages: 2675-2684
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.

References

1 

Adrie C, Adib-Conquy M, Laurent I, Monchi M, Vinsonneau C, Fitting C, Fraisse F, Dinh-Xuan AT, Carli P, Spaulding C, et al: Successful cardiopulmonary resuscitation after cardiac arrest as a ‘sepsis-like’ syndrome. Circulation. 106:562–568. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW and Tracey KJ: Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 405:458–462. 2000. View Article : Google Scholar : PubMed/NCBI

3 

Zhao M, He X, Bi XY, Yu XJ, Gil Wier W and Zang WJ: Vagal stimulation triggers peripheral vascular protection through the cholinergic anti-inflammatory pathway in a rat model of myocardial ischemia/reperfusion. Basic Res Cardiol. 108:3452013. View Article : Google Scholar : PubMed/NCBI

4 

Sun Z, Baker W, Hiraki T and Greenberg JH: The effect of right vagus nerve stimulation on focal cerebral ischemia: An experimental study in the rat. Brain Stimul. 5:1–10. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Inoue T, Abe C, Sung SS, Moscalu S, Jankowski J, Huang L, Ye H, Rosin DL, Guyenet PG and Okusa MD: Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through α7nAChR+ plenocytes. J Clin Invest. 126:1939–1952. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Sun P, Wang J, Zhao S, Yang Z, Tang Z, Ravindra N, Bradley J, Ornato JP, Peberdy MA and Tang W: Improved outcomes of cardiopulmonary resuscitation in rats treated with vagus nerve stimulation and its potential mechanism. Shock. 49:698–703. 2018. View Article : Google Scholar : PubMed/NCBI

7 

Hougardy JM, Sadis C and Le Moine A: Ultrasonic stimulation of the cholinergic anti-inflammatory pathway for renal protection. J Am Soc Nephrol. 24:1340–1342. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Gigliotti JC, Huang L, Ye H, Bajwa A, Chattrabhuti K, Lee S, Klibanov AL, Kalantari K, Rosin DL and Okusa MD: Ultrasound prevents renal ischemia-reperfusion injury by stimulating the splenic cholinergic anti-inflammatory pathway. J Am Soc Nephrol. 24:1451–1460. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Research NRCU: Guide for the Care and Use of Laboratory Animals. National Academies Press; Washington, DC: 1996

10 

Lin JY, Liao XX, Li H, Wei HY, Liu R, Hu CL, Huang GQ, Dai G and Li X: Model of cardiac arrest in rats by transcutaneous electrical epicardium stimulation. Resuscitation. 81:1197–1204. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Gong P, Zhao S, Wang J, Yang Z, Qian J, Wu X, Cahoon J and Tang W: Mild hypothermia preserves cerebral cortex microcirculation after resuscitation in a rat model of cardiac arrest. Resuscitation. 97:109–114. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Ye S, Weng Y, Sun S, Chen W, Wu X, Li Z, Weil MH and Tang W: Comparison of the durations of mild therapeutic hypothermia on outcome after cardiopulmonary resuscitation in the rat. Circulation. 125:123–129. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Gigliotti JC, Huang L, Bajwa A, Ye H, Mace EH, Hossack JA, Kalantari K, Inoue T, Rosin DL and Okusa MD: Ultrasound modulates the splenic neuroimmune axis in attenuating AKI. J Am Soc Nephrol. 26:2470–2481. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Niemann JT, Garner D and Lewis RJ: Tumor necrosis factor-alpha is associated with early postresuscitation myocardial dysfunction. Crit Care Med. 32:1753–1758. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Niemann JT, Youngquist ST, Shah AP, Thomas JL and Rosborough JP: TNF-α blockade improves early post-resuscitation survival and hemodynamics in a swine model of ischemic ventricular fibrillation. Resuscitation. 84:103–107. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Oda Y, Tsuruta R, Kasaoka S, Inoue T and Maekawa T: The cutoff values of intrathecal interleukin 8 and 6 for predicting the neurological outcome in cardiac arrest victims. Resuscitation. 80:189–193. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Vaahersalo J, Skrifvars MB, Pulkki K, Stridsberg M, Røsjø H, Hovilehto S, Tiainen M, Varpula T, Pettilä V and Ruokonen E; FINNRESUSCI Laboratory Study Group, : Admission interleukin-6 is associated with post resuscitation organ dysfunction and predicts long-term neurological outcome after out-of-hospital ventricular fibrillation. Resuscitation. 85:1573–1579. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Van Kempen MJ, Fromaget C, Gros D, Moorman AF and Lamers WH: Spatial distribution of connexin 43, the major cardiac gap junction protein, in the developing and adult rat heart. Circ Res. 68:1638–1651. 1991. View Article : Google Scholar : PubMed/NCBI

19 

Niemann JT, Rosborough J, Youngquist S, Lewis RJ, Phan QT and Filler S: The proinflammatory cytokine response following resuscitation in the swine model depends on the method of ventricular fibrillation induction. Acad Emerg Med. 15:939–944. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Fernandez-Cobo M, Gingalewski C, Drujan D and De Maio A: Downregulation of connexin 43 gene expression in rat heart during inflammation. The role of tumour necrosis factor. Cytokine. 11:216–224. 1999. View Article : Google Scholar : PubMed/NCBI

21 

Sims JJ, Schoff KL, Loeb JM and Wiegert NA: Regional gap junction inhibition increases defibrillation thresholds. Am J Physiol Heart Circ Physiol. 285:H10–H16. 2003. View Article : Google Scholar : PubMed/NCBI

22 

Pavlov VA, Ochani M, Yang LH, Gallowitsch-Puerta M, Ochani K, Lin X, Levi J, Parrish WR, Rosas-Ballina M, Czura CJ, et al: Selective a7-nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe sepsis. Crit Care Med. 35:1139–1144. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Norman GJ, Morris JS, Karelina K, Weil ZM, Zhang N, Al-Abed Y, Brothers HM, Wenk GL, Pavlov VA, Tracey KJ and Devries AC: Cardiopulmonary arrest and resuscitation disrupts cholinergic anti-inflammatory processes: A role for cholinergic a7 nicotinic receptors. J Neurosci. 31:3446–3452. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Khraiche ML, Phillips WB, Jackson N and Muthuswamy J: Ultrasound induced increase in excitability of single neurons. Conf Proc IEEE Eng Med Biol Soc. 2008:4246–4249. 2008.PubMed/NCBI

25 

Mihran RT, Lineaweaver S, Barnes FS and Wachtel H: Effects of pulsed acoustic and mechanical stimuli on the excitability of isolated neuronal and cardiac cells. Appl Occup Environ. Hyg. 11:271–274. 1996.

26 

Lu T, Loh TM, El-Sayed HF and Davies MG: Single-center retrospective review of ultrasound-accelerated versus traditional catheter-directed thrombolysis for acute lower extremity deep venous thrombosis. Vascular. 25:525–532. 2017. View Article : Google Scholar : PubMed/NCBI

27 

Nazer B, Gerstenfeld EP, Hata A, Crum LA and Matula TJ: Cardiovascular applications of therapeutic ultrasound. J Interv Card Electrophysiol. 39:287–294. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Miller DL, Smith NB, Bailey MR, Czarnota GJ, Hynynen K and Makin IR; Bioeffects Committee of the American Institute of Ultrasound in Medicine, : Overview of therapeutic ultrasound applications and safety considerations. J Ultrasound Med. 31:623–634. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

September 2019
Volume 20 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Zhang, Y., Song, Y., Shu, T., Liang, L., Shao, W., Guo, L., & Sun, P. (2019). Ultrasound improves the outcomes of cardiopulmonary resuscitation in rats by stimulating the cholinergic anti‑inflammatory pathway. Molecular Medicine Reports, 20, 2675-2684. https://doi.org/10.3892/mmr.2019.10527
MLA
Zhang, Y., Song, Y., Shu, T., Liang, L., Shao, W., Guo, L., Sun, P."Ultrasound improves the outcomes of cardiopulmonary resuscitation in rats by stimulating the cholinergic anti‑inflammatory pathway". Molecular Medicine Reports 20.3 (2019): 2675-2684.
Chicago
Zhang, Y., Song, Y., Shu, T., Liang, L., Shao, W., Guo, L., Sun, P."Ultrasound improves the outcomes of cardiopulmonary resuscitation in rats by stimulating the cholinergic anti‑inflammatory pathway". Molecular Medicine Reports 20, no. 3 (2019): 2675-2684. https://doi.org/10.3892/mmr.2019.10527