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Ischemic limb preconditioning-induced anti-arrhythmic effect in reperfusion-induced myocardial injury: is it mediated by the RISK or SAFE pathway?

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Abstract

The mechanism for limb ischemic precondition (RLIPC)-induced suppression of reperfusion arrhythmia remains unknown. The purpose of this study was to examine the roles of the pro-survival reperfusion injury salvage kinase (RISK) and survivor activating factor enhancement (SAFE) pathways in this RLIPC-mediated antiarrhythmic activity. Male Sprague Dawley rats were assigned to sham-operated, control, or RLIPC groups. All rats except for the sham rats had 5 min of left main coronary artery occlusion with another 20 min of reperfusion. RLIPC was initiated by four cycles of limb ischemia (5 min) and reperfusion (5 min) on the bilateral femoral arteries. Hearts in every group were taken for protein phosphorylation analysis. RLIPC ameliorated reperfusion-induced arrhythmogenesis and reduced the incidence of sudden cardiac death during the entire 20-min reperfusion period (66.7% of control rats had SCD vs. only 16.7% of RLIPC-treated rats). RLIPC enhances ventricular ERK1/2 phosphorylation after reperfusion. RLIPC-induced antiarrhythmic action and ERK1/2 phosphorylation are abolished in the presence of the ERK1/2 inhibitor U0126. Limb ischemic preconditioning protects the heart against myocardial reperfusion injury-induced lethal arrhythmia. These beneficial effects may involve the activation of ERK1/2 in the RISK signaling pathway.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by Sichuan University West China Hospital setup funding to ZH.

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Authors and Affiliations

  1. Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

    Xu Cheng & Jin Liu

  2. Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

    Huan Li, Zhibing Yan & Zhaoyang Hu

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Contributions

ZH designed the study. XC, HL, ZY, and ZH performed the experiments. XC, HL, ZY, JL, and ZH conducted acquisition, analysis, or interpretation of data for the work. ZH drafted the manuscript. All the authors read, revised, and approved the final manuscript.

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Correspondence to Zhaoyang Hu.

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This study was reviewed and approved by the Institutional Animal Care and Use Committee of Sichuan University (Approval No. 2015035A).

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The authors declare no competing interests.

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Cheng, X., Li, H., Yan, Z. et al. Ischemic limb preconditioning-induced anti-arrhythmic effect in reperfusion-induced myocardial injury: is it mediated by the RISK or SAFE pathway?. Pflugers Arch - Eur J Physiol 474, 979–991 (2022). https://doi.org/10.1007/s00424-022-02716-5

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