title: Carbon Monoxide-Saturated Hemoglobin-Based Oxygen Carriers Attenuate High-Altitude-Induced Cardiac Injury by Amelioration of the Inflammation Response and Mitochondrial Oxidative Damage.
abstract: OBJECTIVE
  To investigate the therapeutic effect of carbon monoxide (CO) on high-altitude hypoxia-induced cardiac damage.
  
  
  METHODS
  Forty male C57BL/6 mice were randomly divided into 4 groups. The mice were exposed to normoxia or simulated 5,500-meter high-altitude hypoxia in a hypobaric chamber for 7 days. During the first 3 days, the mice were pretreated with CO-saturated hemoglobin (Hb)-based oxygen carrier (CO-HBOC), oxygen-saturated hemoglobin-based oxygen carrier (O2-HBOC) at a dose of 0.3 g Hb/kg/day or an equivalent volume of saline. The in vivo left ventricle function, cardiac enzyme release, histopathological changes, apoptosis and inflammation were also measured.
  
  
  RESULTS
  High-altitude hypoxia induced significant cardiac damage, as demonstrated by impaired cardiac function and increased proapoptotic, proinflammatory and pro-oxidant markers. Pretreatment with CO-HBOC significantly improved cardiac performance, reduced cardiac enzyme release and limited myocardial apoptosis. The increased inflammatory response was also suppressed. In addition to the preserved mitochondrial structure, hypobaric hypoxia-induced mitochondrial oxidative damage was remarkably attenuated. Moreover, these antiapoptotic and antioxidative effects were accompanied by an upregulated phosphorylation of Akt, ERK and STAT3.
  
  
  CONCLUSIONS
  This study demonstrated that CO-HBOC provides a promising protective effect on high-altitude hypoxia-induced myocardial injury, which is mediated by the inhibition of inflammation and mitochondrial oxidative damage.
authors.affiliation: Department of Anesthesiology, General Hospital of Chengdu Military Area Command, Chengdu, China.
authors.forename: Qingshu
authors.initials: Q
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Hu
authors.forename: Yu
authors.initials: Y
authors.lastname: Hu
authors.forename: Gu
authors.initials: G
authors.lastname: Gong
authors.forename: Hua
authors.initials: H
authors.lastname: Tan
authors.forename: Li
authors.initials: L
authors.lastname: Deng
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Sun
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Yi
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Tao
authors.initials: T
authors.lastname: Li
mesh_terms: D000531:Altitude; D000818:Animals; D017209:Apoptosis; D002248:Carbon Monoxide / Q000494:pharmacology*; D006352:Heart Ventricles / Q000473:pathology; D006454:Hemoglobins; D000860:Hypoxia / Q000503:physiopathology*; D007249:Inflammation / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000187:drug effects*; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects*; D010100:Oxygen / Q000494:pharmacology*; D011897:Random Allocation; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D006454:Hemoglobins; D002248:Carbon Monoxide; D010100:Oxygen