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Comparison of the protective effects of direct ischemic preconditioning and remote ischemic preconditioning in a rabbit model of transient spinal cord ischemia

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Abstract

Introduction

This study aimed to determine the relative potency of direct ischemic preconditioning (DIPC) and remote ischemic preconditioning (RIPC) for protection against ischemic spinal cord injury in rabbits and to explore the mechanisms involved.

Methods

In experiment 1, we compared the neurological and histopathological outcomes of DIPC, kidney RIPC, and limb RIPC. The DIPC and kidney RIPC groups received two cycles of 5-min occlusion/15-min reperfusion of the abdominal aorta and left renal artery, respectively. The limb RIPC group received two cycles of 10-min occlusion/10-min reperfusion of the femoral arteries bilaterally. Thirty minutes after the conditioning ischemia, spinal cord ischemia was produced by occluding the abdominal aorta for 15 min. In experiments 2 and 3, we investigated whether pretreatment using a free-radical scavenger, dimethylthiourea (DMTU), an adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), or a mitochondrial ATP-sensitive potassium channel antagonist, 5-hydroxydecanoate (5HD), could attenuate the protective effects of DIPC. In experiment 4, comprehensive analysis of phosphorylated proteins in the spinal cord was performed using a Proteome Profiler Array followed by immunoblotting to elucidate the signal pathway activated by DIPC.

Results

In experiment 1, DIPC improved the neurological and histopathological outcomes, whereas kidney and limb RIPC had no protective effects. In experiments 2 and 3, strong protective effects of DIPC were reconfirmed but were not attenuated by DMTU, DPCPX, or 5HD. In experiment 4, DIPC induced phosphorylation of Akt2.

Conclusions

DIPC, but not kidney or limb RIPC, protected against ischemic spinal cord injury in rabbits. Akt2 might contribute to this protective effect.

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Acknowledgements

This study was supported by a Grant-in-Aid for Scientific Research (C) (No. 25462437) from the Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Department of Anesthesiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan

    Takehiko Fukui, Kazuyoshi Ishida, Kiyotaka Shiramoto, Hidenori Harada, Atsuo Yamashita, Satoshi Yamashita & Mishiya Matsumoto

  2. Center for Gene Research, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan

    Yoichi Mizukami

Authors
  1. Takehiko Fukui
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  2. Kazuyoshi Ishida
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  3. Yoichi Mizukami
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  4. Kiyotaka Shiramoto
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  5. Hidenori Harada
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  6. Atsuo Yamashita
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  7. Satoshi Yamashita
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  8. Mishiya Matsumoto
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Correspondence to Mishiya Matsumoto.

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The authors declare no conflicts of interest.

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Fukui, T., Ishida, K., Mizukami, Y. et al. Comparison of the protective effects of direct ischemic preconditioning and remote ischemic preconditioning in a rabbit model of transient spinal cord ischemia. J Anesth 32, 3–14 (2018). https://doi.org/10.1007/s00540-017-2420-5

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  • DOI: https://doi.org/10.1007/s00540-017-2420-5

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