Carbon Monoxide-Saturated Hemoglobin-Based Oxygen Carriers Attenuate High-Altitude-Induced Cardiac Injury by Amelioration of the Inflammation Response and Mitochondrial Oxidative Damage.
Cardiology
; 136(3): 180-191, 2017.
Article
em En
| MEDLINE
| ID: mdl-27728906
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.CONCLUSION:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxigênio
/
Monóxido de Carbono
/
Estresse Oxidativo
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Altitude
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Inflamação
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Hipóxia
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Mitocôndrias Cardíacas
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article