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Chronic intermittent hypoxia increases the CO₂ reserve in sleeping dogs

¹The John Rankin Laboratory of Pulmonary Medicine, Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin; and ²Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya, Japan

Submitted 9 July 2007 ; accepted in final form 5 October 2007

We hypothesized that chronic intermittent hypoxia (CIH) would induce a predisposition to apnea in response to induced hypocapnia. To test this, we used pressure support ventilation to quantify the difference in end-tidal partial pressure of CO₂ (PET_CO2) between eupnea and the apneic threshold ("CO₂ reserve") as an index of the propensity for apnea and unstable breathing during sleep, both before and following up to 3-wk exposure to chronic intermittent hypoxia in dogs. CIH consisted of 25 s of PET_O2 = 35–40 Torr followed by 35 s of normoxia, and this pattern was repeated 60 times/h, 7–8 h/day for 3 wk. The CO₂ reserve was determined during non-rapid eye movement sleep in normoxia 14–16 h after the most recent hypoxic exposure. Contrary to our hypothesis, the slope of the ventilatory response to CO₂ below eupnea progressively decreased during CIH (control, 1.36 ± 0.18; week 2, 0.94 ± 0.12; week 3, 0.73 ± 0.05 l·min^–1·Torr^–1, P < 0.05). This resulted in a significant increase in the CO₂ reserve relative to control (P < 0.05) following both 2 and 3 wk of CIH (control, 2.6 ± 0.6; week 2, 3.7 ± 0.8; week 3, 4.5 ± 0.9 Torr). CIH also 1) caused no change in eupneic, air breathing Pa_CO2; 2) increased the slope of the ventilatory response to hypercapnia after 2 wk but not after 3 wk compared with control; and 3) had no effect on the ventilatory response to hypoxia. We conclude that 3-wk CIH reduced the sensitivity of the ventilatory response to transient hypocapnia and thereby increased the CO₂ reserve, i.e., the propensity for apnea was reduced.

hypocapnia; sleep apnea; sleep-disordered breathing

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