Acta Pharmacologica Sinica (2009) 30: 947-955; doi: 10.1038/aps.2009.57; published online 22 June 2009

Aim: 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 (H₂O₂) were attenuated by CIHH and CAT. 

Conclusion: These data suggest that CIHH protects the heart against I/R injury through upregulation of antioxidant enzymes in guinea pig.

Keywords: chronic intermittent hypobaric hypoxia; cardioprotection; antioxidant enzymes; ischemia/reperfusion; guinea pig