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Activation of mitochondrial STAT-3 and reduced mitochondria damage during hypothermia treatment for post-cardiac arrest myocardial dysfunction

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Abstract

While therapeutic hypothermia improves the outcomes of individuals in cardiac arrest, the hemodynamic responses and mechanisms which underlie hypothermia-induced cardioprotection are not fully understood. Therefore, we investigated the mechanism by which induced hypothermia preserves cardiac function and protects against mitochondrial damage following cardiac arrest. Cardiac arrest was induced in adult male Wistar rats by asphyxiation for 8.5 min. Following resuscitation, the animals were randomly assigned to a hypothermia (32 °C) or normothermia (37 °C) group. Monitoring results showed that cardiac output at the fourth hour after resuscitation was significantly better in rats treated with hypothermia when compared to rats treated with normothermia (P < 0.01). Examinations by transmission electron microscopy showed that mitochondria in the left ventricle of rats in the hypothermia group were significantly less swollen compared to such mitochondria in the normothermia group (P < 0.001). Additionally, opening of mitochondrial permeability transition pores occurred less frequently in the hypothermic group. While complex I/III activity in the electron transport reaction was damaged after cardiac arrest and resuscitation, the degree of injury was ameliorated by hypothermia treatment (P < 0.05). The amount of STAT-3 phosphorylated at tyrosine 705 and its expression in mitochondria were significantly higher under hypothermia treatment compared to normothermia treatment. In vitro studies showed that inhibition STAT-3 activation abolished the ability of hypothermia to protect H9C2 cardiomyocytes against injury produced by simulated ischemia and reperfusion. Therapeutic hypothermia treatment can ameliorate cardiac dysfunction and help preserve both mitochondrial integrity and electron transport activity.

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Acknowledgments

The study was supported by grants from the National Science Council (101-2628-B-002-004-MY3) and National Taiwan University Hospital (101MSN04).

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Authors and Affiliations

  1. Department of Emergency Medicine, National Taiwan University Medical College and Hospital, No. 7 Chung-Shan S. Rd., 10002, Taipei, Taiwan

    Chien-Hua Huang, Min-Shan Tsai, Yu-Jen Su, Wei-Tien Chang & Wen-Jone Chen

  2. Division of Cardiology, Department of Internal Medicine, National Taiwan University Medical College and Hospital, Taipei, Taiwan

    Chien-Hua Huang, Tzung-Dau Wang & Wen-Jone Chen

  3. Division of Cardiology, Department of Internal Medicine, Cardinal Tien Hospital Yunghe Branch, New Taipei City, Taiwan

    Chih-Yen Chiang

  4. Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan

    Huei-Wen Chen

  5. Department of Internal Medicine, Lotung Poh-Ai Hospital, Yilan County, Taiwan

    Wen-Jone Chen

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  1. Chien-Hua Huang
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Huang, CH., Tsai, MS., Chiang, CY. et al. Activation of mitochondrial STAT-3 and reduced mitochondria damage during hypothermia treatment for post-cardiac arrest myocardial dysfunction. Basic Res Cardiol 110, 59 (2015). https://doi.org/10.1007/s00395-015-0516-3

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