Tissue oxygenation in brain, muscle, and fat in a rat model of sleep apnea: differential effect of obstructive apneas and intermittent hypoxia

Abstract

Study objectives: To test the hypotheses that the dynamic changes in brain oxygen partial pressure (PtO(2)) in response to obstructive apneas or to intermittent hypoxia differ from those in other organs and that the changes in brain PtO(2) in response to obstructive apneas is a source of oxidative stress.

Design: Prospective controlled animal study.

Setting: University laboratory.

Participants: 98 Sprague-Dawley rats.

Interventions: Cerebral cortex, skeletal muscle, or visceral fat tissues were exposed in anesthetized animals subjected to either obstructive apneas or intermittent hypoxia (apneic and hypoxic events of 15 s each and 60 events/h) for 1 h.

Measurements and results: Arterial oxygen saturation (SpO(2)) presented a stable pattern, with similar desaturations during both stimuli. The PtO(2) was measured by a microelectrode. During obstructive apneas, a fast increase in cerebral PtO(2) was observed (38.2 ± 3.4 vs. 54.8 ± 5.9 mm Hg) but not in the rest of tissues. This particular cerebral response was not found during intermittent hypoxia. The cerebral content of reduced glutathione was decreased after obstructive apneas (46.2% ± 15.2%) compared to controls (100.0% ± 14.7%), but not after intermittent hypoxia. This antioxidant consumption after obstructive apneas was accompanied by increased cerebral lipid peroxidation under this condition. No changes were observed for these markers in the other tissues.

Conclusions: These results suggest that cerebral cortex could be protected in some way from hypoxic periods caused by obstructive apneas. The increased cerebral PtO(2) during obstructive apneas may, however, cause harmful effects (oxidative stress). The obstructive apnea model appears to be more adequate than the intermittent hypoxia model for studying brain changes associated with OSA.

Keywords: Tissue oxygenation; animal model; intermittent hypoxia; obstructive apnea; oxidative stress.

Figure 1

Experimental setup. Anesthetized animals were subjected to recurrent obstructive apneas (A) or to intermittent hypoxia test (B). EV, electrovalves. See text for explanation.

Figure 2

Time course of the maximum (Δ) and minimum (▾) values of arterial oxygen saturation (SpO₂) (A) and oxygen partial pressure (PtO₂) in cerebral cortex (B), skeletal muscle (C), and visceral fat (D) during application of recurrent obstructive apneas or intermittent hypoxia. Baseline value is represented by an open circle. Results are shown as mean ± SE. Time dependence within obstructive apneas or intermittent hypoxia groups: *P < 0.05 respect with to baseline, †P < 0.05 respect with to the first apneic event. Comparisons between obstructive apneas vs. intermittent hypoxia for corresponding values in each tissue: ^#P < 0.05.

Figure 3

Glutathione (GSH) levels in cerebral cortex (A), skeletal muscle (B), and visceral fat (C) tissues in control animals and in animals subjected to recurrent obstructive apneas or intermittent hypoxia. Results are shown as mean ± SE. *P < 0.05.

Figure 4

Lipid peroxidation (LPO) levels in cerebral cortex (A) and skeletal muscle (B) tissues for all groups (control, obstructive apneas, and intermittent hypoxia). Results are shown as mean ± SE. *P < 0.05.