Chronic intermittent hypobaric hypoxia protects the heart against ischemia/reperfusion injury through upregulation of antioxidant enzymes in adult guinea pigs.
OBJECTIVE
To investigate the protection and the anti-oxidative mechanism afforded by chronic intermittent hypobaric hypoxia (CIHH) against ischemia/reperfusion (I/R) injury in guinea pig hearts.


METHODS
Adult male guinea pigs were exposed to CIHH by mimicking a 5000 m high altitude (p(B)=404 mmHg, p(O2)=84 mmHg) in a hypobaric chamber for 6 h/day for 28 days. Langendorff-perfused isolated guinea pig hearts were used to measure variables of left ventricular function during baseline perfusion, ischemia and the reperfusion period. The activity and protein expression of antioxidant enzymes in the left myocardium were evaluated using biochemical methods and Western blotting, respectively. Intracellular reactive oxygen species (ROS) were assessed using ROS-sensitive fluorescence.


RESULTS
After 30 min of global no-flow ischemia followed by 60 min of reperfusion, myocardial function had better recovery rates in CIHH guinea pig hearts than in control hearts. The activity and protein expression of superoxide dismutase (SOD) and catalase (CAT) were significantly increased in the myocardium of CIHH guinea pigs. Pretreatment of control hearts with an antioxidant mixture containing SOD and CAT exerted cardioprotective effects similar to CIHH. The irreversible CAT inhibitor aminotriazole (ATZ) abolished the cardioprotection of CIHH. Cardiac contractile dysfunction and oxidative stress induced by exogenous hydrogen peroxide (H(2)O(2)) were attenuated by CIHH and CAT.


CONCLUSIONS
These data suggest that CIHH protects the heart against I/R injury through upregulation of antioxidant enzymes in guinea pig.Acta Pharmacologica Sinica (2009) 30: 947-955; doi: 10.1038/aps.2009.57; published online 22 June 2009.
Guo
Hui-Cai
HC
Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China.
Zhang
Zhe
Z
Zhang
Li-Nan
LN
Xiong
Chen
C
Feng
Chen
C
Liu
Qian
Q
Liu
Xu
X
Shi
Xiao-Lu
XL
Wang
Yong-Li
YL
D000640:Amitrole / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001835:Body Weight; D002374:Catalase / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000378:metabolism; D000860:Hypoxia; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000201:enzymology* / Q000473:pathology*; D009929:Organ Size; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D000099156:Superoxide Dismutase 2
D000640:Amitrole; D000975:Antioxidants; D002374:Catalase; D004791:Enzyme Inhibitors; D006861:Hydrogen Peroxide; D008315:Malondialdehyde; D016877:Oxidants; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2