Intermittent hypoxia improves atrial tolerance to subsequent anoxia and reduces stress protein expression

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Abstract
We tested the hypothesis that 21 days of intermittent hypoxia (IH) increases the tolerance of the spontaneously beating guinea‐pig double atria preparation to acute in‐vitro hypoxia, and reduces cardiac stress protein expression. A total of 28 guinea‐pigs were divided into four groups: (i) IH; (ii) IH + in‐vitro hypoxia (IH + IV); (iii) control (CON); (iv) control + in‐vitro hypoxia (CON + IV). The IH animals were exposed to 8% O2/0.3% CO2 for 12 h day–1 for 21 days. Normoxic controls were exposed to room air for the same duration. Acute in‐vitro hypoxia (20, 10, 5 and 0% O2 in 5% CO2) was introduced into the atrial preparation. Heat shock protein (Hsp) 70 and Hsp90 content were determined by Western blotting. Intermittent hypoxia groups demonstrated typical responses to chronic hypoxic exposure, characterized by significantly (P < 0.05) lower body weights, reduced growth rates and increased heart weight/body weight ratios. In the CON + IV group, in‐vitro hypoxia reduced heart rate (20% O2, –30 ± 8 beats min–1; 10% O2, –34 ± 8 beats min–1; 5% O2, –37 ± 9 beats min–1 and 0% O2, –51 ± 9* beats min–1: *P < 0.05 vs. 20% O2). At 0% O2, the decrease in the rate response was significantly attenuated in the IH + IV (–30 ± 8 beats min–1; n=10) compared with the CON + IV (–51 ± 9 beats min–1; n=10). IH significantly reduced atrial Hsp70 and Hsp90 expression, however, levels of both proteins were unchanged in the ventricle. Furthermore, Hsp90 and to a lesser degree Hsp70 in the atria remained suppressed following in‐vitro hypoxia in the IH group. Our results show that the increased resistance of the isolated atria to anoxia following IH may contribute to the concomitant reductions in basal and hypoxia‐induced Hsp expression as the overall stress response is reduced.

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