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Volume 14 Issue 3
May  2023
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Article Navigation >  Medical Journal of Peking Union Medical College Hospital  > 2023  >  14(3): 520-527
LI Feng, WU Xinjie, CHEN Qijiang, LIU Ying, XU Jiefeng, ZHOU Guangju, ZHANG Mao. Effects of Artesunate on Lung Injury After Cardiac Arrest and Resuscitation in Pigs and Its Mechanism[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(3): 520-527. doi: 10.12290/xhyxzz.2022-0730
Citation: LI Feng, WU Xinjie, CHEN Qijiang, LIU Ying, XU Jiefeng, ZHOU Guangju, ZHANG Mao. Effects of Artesunate on Lung Injury After Cardiac Arrest and Resuscitation in Pigs and Its Mechanism[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(3): 520-527. doi: 10.12290/xhyxzz.2022-0730
shu

Effects of Artesunate on Lung Injury After Cardiac Arrest and Resuscitation in Pigs and Its Mechanism

doi: 10.12290/xhyxzz.2022-0730
  • 1.

    Department of Emergency Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province, Zhejiang Province Clinical Research Center for Emergency and Critical Care Medicine, Hangzhou 310009, China

  • 2.

    Department of Emergency Medicine, Linping Campus, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 311100, China

  • 3.

    Department of Emergency Medicine, The First Hospital of Ninghai, Ninghai, Zhejiang 315600, China

  • 4.

    Department of Intensive Care Unit, The First Hospital of Ninghai, Ninghai, Zhejiang 315600, China

  • 5.

    Department of Emergency Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China

Funds:

Natural Science Foundation of China 82072126

Zhejiang Provincial Key Research and Development Program 2021C03073

Zhejiang Provincial Key Research and Development Program 2021C03036

Zhejiang Provincial Medical Science Foundation 2023KY305

More Information
  • Corresponding author: ZHANG Mao, E-mail: z2jzk@zju.edu.cn
  • Received Date: 2022-12-29
  • Accepted Date: 2023-02-15
  • Publish Date: 2023-05-30
    Abstract
  •   Objective  To explore whether artesunate (Art) has protective effect on lung tissue after cardiopulmonary resuscitation (CPR) and its potential mechanism based on animal experiment.  Methods  Twenty-four healthy male white pigs were randomly divided into sham group (n=6), CPR group (n=10), and Art group (n=8). The sham group only underwent the surgical preparation, and the CPR and Art groups established the CPR model by the method of ventricular fibrillation induction. After restoration of spontaneous circulation, the Art group was infused a dose of 4.8 mg/kg of Art via the femoral vein within 2 h. The same volume of vehicle was similarly infused in the sham and CPR groups. The changes of lung injury at baseline and after resuscitation, lung injury score, and lung tissue inflammation and its high mobility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-κB p65 (NF-κB p65) inflammatory pathway after resuscitation were compared among the three groups.  Results  (1) Lung injury: the levels of extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI), and oxygenation index (OI) at baseline were not significantly different among the three groups (all P > 0.05). The values of ELWI and PVPI at 1 h, 2 h, and 4 h after resuscitation were significantly increased while the values of OI at 1 h and 2 h after resuscitation were significantly decreased in the CPR group compared with the sham group (all P < 0.05). The values of ELWI, PVPI, and OI were better at each time point after resuscitation in the Art group than in the CPR group, in which the differences in ELWI and PVPI at 2 h and 4 h after resuscitation were significant between the two groups (all P < 0.05). (2)Lung injury score: the score of lung injury at 24 h after resuscitation was significantly increased in the CPR and Art groups compared with the sham group (all P < 0.05). However, the score of lung injury at 24 h after resuscitation was significantly decreased in the Art group compared with the CPR group (P < 0.05). (3)Lung tissue inflammation: the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the lung at 24 h after resuscitation were significantly increased in the CPR and Art groups compared with the sham group (all P < 0.05). However, the levels of TNF-α, IL-1β, and IL-6 in the lung at 24 h after resuscitation were significantly decreased in the Art group compared to the CPR group (all P < 0.05). (4) HMGB1/TLR4/NF-κB inflammatory pathway: the protein expression levels of HMGB1, TLR4, and NF-κB p65 in the lung at 24 h after resuscitation were significantly increased in the CPR and Art groups compared with the sham group (all P < 0.05). However, the protein expression levels of HMGB1, TLR4, and NF-κB p65 in the lung at 24 h after resuscitation were significantly decreased in the Art group compared with the CPR group (all P < 0.05).  Conclusions  Art could alleviate lung inflammatory injury after cardiac arrest and resuscitation, possibly through inhibiting the activation of HMGB1/TLR4/NF-κB signaling pathway.
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