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Delayed anesthetic preconditioning protects against myocardial infarction via activation of nuclear factor-κB and upregulation of autophagy

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Abstract

Purpose

Delayed volatile anesthetic preconditioning (APC) can protect against myocardial ischemia/reperfusion (I/R) injury; the delayed phase is called the second window of protection (SWOP), but the underlying mechanism is unclear. Nuclear factor-κB (NF-κB) is involved in the myocardial protection conferred by APC in the acute phase; autophagy has been reported to confer apoptosis inhibition and infarction reduction. We hypothesized that APC initiates delayed cardioprotection against I/R injury via the activation of NF-kB and upregulation of autophagy, thus attenuating the inflammatory response and apoptosis

Methods

After a rat I/R model was set up, left ventricular samples were obtained before I/R to assess NF-κB-DNA binding activity and microtubule-associated protein 1 light chain 3 (LC3) and cathepsin B protein expression, and to examine autophagosomes with a transmission electron microscope. Infarct size and the expressions of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and caspase-3 were measured at the end of 2-h reperfusion.

Results

The infarct size was significantly reduced in the SWOP group (30 ± 3 %) when compared with that in the I/R group (47 ± 7 %, P < 0.05), and this finding was associated with increased NF-κB-DNA binding activity and autophagosomes. In addition, the expressions of LC3-II and cathepsin B were also up-regulated, and the expressions of TNF-α, IL-1β, and caspase-3 were attenuated in the SWOP group when compared with the findings in the I/R group. However, this protection was abolished by the administration of parthenolide (PTN) before sevoflurane inhalation, which resulted in an infarct size that was significantly increased (47 ± 5 %, P < 0.05 PTN + SWOP vs. SWOP group).

Conclusion

Delayed APC protected the rat heart from I/R injury. The underlying mechanisms may include NF-κB activation, upregulation of autophagy, and the attenuation of TNF-α, IL-1β, and caspase-3 expressions.

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Acknowledgments

This work was supported by Grant No. 30872453 (to Dr. Wang) from the National Natural Science Foundation of China, and by Grants No. SYS201130 (to Dr. Wang) and No. SYS201038 (to Dr. Xie) from the Technology Bureau of Suzhou, China. Dr. Wang also received support from the Revitalizing the Key Talent’s Subsidy Project in Science and Education, Jiangsu Province, China).

Conflict of interest

None of the authors has any conflict of interest.

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Authors and Affiliations

  1. Department of Anesthesiology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, People’s Republic of China

    Shigang Qiao, Hong Xie, Chen Wang & Xuemei Wu

  2. Institute of Neuroscience, Soochow University, Suzhou, 215004, People’s Republic of China

    Chen Wang & Chunfeng Liu

  3. Department of Anesthesiology and Pain Medicine, University of California Davis Health System, Davis, CA, 95616, USA

    Hong Liu

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  1. Shigang Qiao
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  2. Hong Xie
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  3. Chen Wang
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  4. Xuemei Wu
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  5. Hong Liu
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  6. Chunfeng Liu
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Corresponding author

Correspondence to Chen Wang.

Additional information

S. Qiao and H. Xie contributed equally to this manuscript.

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Qiao, S., Xie, H., Wang, C. et al. Delayed anesthetic preconditioning protects against myocardial infarction via activation of nuclear factor-κB and upregulation of autophagy. J Anesth 27, 251–260 (2013). https://doi.org/10.1007/s00540-012-1494-3

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  • DOI: https://doi.org/10.1007/s00540-012-1494-3

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