title: Activation of mitochondrial STAT-3 and reduced mitochondria damage during hypothermia treatment for post-cardiac arrest myocardial dysfunction.
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.
authors.affiliation: Department of Emergency Medicine, National Taiwan University Medical College and Hospital, No. 7 Chung-Shan S. Rd., 10002, Taipei, Taiwan.|Division of Cardiology, Department of Internal Medicine, National Taiwan University Medical College and Hospital, Taipei, Taiwan.
authors.forename: Chien-Hua
authors.initials: CH
authors.lastname: Huang
authors.affiliation: Department of Emergency Medicine, National Taiwan University Medical College and Hospital, No. 7 Chung-Shan S. Rd., 10002, Taipei, Taiwan.
authors.forename: Min-Shan
authors.initials: MS
authors.lastname: Tsai
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Cardinal Tien Hospital Yunghe Branch, New Taipei City, Taiwan.
authors.forename: Chih-Yen
authors.initials: CY
authors.lastname: Chiang
authors.affiliation: Department of Emergency Medicine, National Taiwan University Medical College and Hospital, No. 7 Chung-Shan S. Rd., 10002, Taipei, Taiwan.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Su
authors.affiliation: Division of Cardiology, Department of Internal Medicine, National Taiwan University Medical College and Hospital, Taipei, Taiwan.
authors.forename: Tzung-Dau
authors.initials: TD
authors.lastname: Wang
authors.affiliation: Department of Emergency Medicine, National Taiwan University Medical College and Hospital, No. 7 Chung-Shan S. Rd., 10002, Taipei, Taiwan.
authors.forename: Wei-Tien
authors.initials: WT
authors.lastname: Chang
authors.affiliation: Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Huei-Wen
authors.initials: HW
authors.lastname: Chen
authors.affiliation: Department of Emergency Medicine, National Taiwan University Medical College and Hospital, No. 7 Chung-Shan S. Rd., 10002, Taipei, Taiwan. wjchen1955@ntu.edu.tw.|Division of Cardiology, Department of Internal Medicine, National Taiwan University Medical College and Hospital, Taipei, Taiwan. wjchen1955@ntu.edu.tw.|Department of Internal Medicine, Lotung Poh-Ai Hospital, Yilan County, Taiwan. wjchen1955@ntu.edu.tw.
authors.forename: Wen-Jone
authors.initials: WJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D002302:Cardiac Output; D002460:Cell Line; D042967:Electron Transport Complex I / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D006323:Heart Arrest / Q000628:therapy*; D007036:Hypothermia, Induced; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000648:ultrastructure; D011897:Random Allocation; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III
keywords: Cardiopulmonary resuscitation; Hypothermia; Mitochondria; Post-cardiac arrest myocardial dysfunction; Rat; STAT-3