Effects of short- and long-term hypobaric hypoxia on Bcl2 family in rat heart

Background: Controversial effects of intermittent hypobaric hypoxia such as cardiac damage or cardiac protection are still mysterious. It is unclear if short-term and long-term intermittent hypobaric hypoxic challenges exert different effects on cytochrome c oxidase and Bcl-2 family in rat heart. Methods: Sixty Sprague-Dawley rats were randomized assigned into two groups: first, short-term intermittent hypobaric hypoxia (STIHH)-normobaric normoxia (n = 10), hypobaric hypoxia (380 mmHg, 12% O₂, 8 hr/day) for 1 day (n = 10), and for 4 days (n = 10) and second, long-term intermittent hypobaric hypoxia (LTIHH)-normobaric normoxia (n = 10), hypobaric hypoxia for 1 week (n = 10) and 2 weeks (n = 10). After STIHH or LTIHH challenge, myocardial morphology, cytochrome c oxidase and pro-apoptotic Bcl-2 family in the excised left ventricle were determined by histological analysis, Western blotting, and RT-PCR. Results: Increased wall thickness and abnormal myocardial architecture were observed after LTIHH. Cytochrome c oxidase and anti-apoptotic Bcl-2 protein were significantly increased after STIHH, but were decreased after LTIHH. Pro-apoptotic BNIP3 and Bad proteins were significantly decreased after STIHH but increased after LTIHH. Conclusions: STIHH appeared to exert protective effects on hearts whereas LTIHH appeared to exert deleterious effects, which imply that deleterious or advantageous effect of cardiac adaptation after intermittent hypobaric hypoxia is tightly time-course dependent.