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Changes of Endothelin-1 and Nitric Oxide Systems in Brain Tissue During Mild Hypothermia in a Porcine Model of Cardiac Arrest

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Abstract

Background

Our previous study found that mild hypothermia (MH) after resuscitation reduced cerebral microcirculation, but the mechanism was not elucidated. The aim of this study was to clarify changes of endothelin-1 (ET-1) and nitric oxide (NO) systems in brain tissue during hypothermia after resuscitation.

Methods

Twenty-six domestic male Beijing Landrace pigs were used in this study. MH was intravascularly induced 1 h after resuscitation from 8-min ventricular fibrillation. Core temperature was reduced to 33 °C and maintained until 8 h after resuscitation, and then animals were euthanized. ET-1 and NO levels in brain tissue and peripheral plasma were measured. Expression of endothelin-converting enzyme-1 (ECE-1), endothelin A receptor (ET-AR), endothelin-B receptor, and nitric oxide synthase (NOS) in brain tissue was determined by Western blot analysis.

Results

Compared with non-hypothermia (NH) treatment, MH after resuscitation significantly increased the level of endothelin-1 and reduced the level of NO in peripheral blood and brain tissue. Cerebral expression of ECE-1 and ET-AR was significantly increased during MH after resuscitation. Moreover, MH significantly decreased inducible NOS expression compared with the NH group.

Conclusions

The ET-1 system is activated, while inducible NOS is inhibited in brain tissue during MH after resuscitation.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81801882) and Foundation for Training Excellent Talents of Beijing (No. 2017000021469G219). We thank Liwen Bianji, Edanz Group, China, for editing the English text of a draft of this manuscript.

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Authors and Affiliations

  1. Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China

    Junyuan Wu, Wei Yuan, Yongzhen Zhao & Chunsheng Li

  2. Department of Neurology, Beijing First Hospital of Integrated Chinese and Western Medicine, Beijing, 100000, China

    Zhiwei Li

  3. Department of Emergency Medicine, Beijing Fuxing Hospital, Capital Medical University, Beijing, 100038, China

    Jie Li

  4. Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China

    Zhenhua Li

  5. Department of Emergency Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China

    Jiebin Li

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  1. Junyuan Wu
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  3. Wei Yuan
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  4. Yongzhen Zhao
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  5. Jie Li
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  6. Zhenhua Li
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  8. Chunsheng Li
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Contributions

CL and JW designed the experiment protocol, and reviewed the final manuscript. JW took part in the animal experiment, analyzed experimental data and drafted the manuscript. ZW-L helped draft the manuscript. WY, YZ, JL, ZH-L and JB-L took part in the animal experiment and interpreted the results.

Corresponding author

Correspondence to Chunsheng Li.

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This study conformed to ethical standards.

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Wu, J., Li, Z., Yuan, W. et al. Changes of Endothelin-1 and Nitric Oxide Systems in Brain Tissue During Mild Hypothermia in a Porcine Model of Cardiac Arrest. Neurocrit Care 33, 73–81 (2020). https://doi.org/10.1007/s12028-019-00855-9

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