Chronic intermittent hypoxia increases the CO2 reserve in sleeping dogs

Chronic intermittent hypoxia increases the CO2 reserve in sleeping dogs. J Appl Physiol 103: 1942-1949, 2007. First published October 11, 2007; doi: 10.1152/japplphysiol.00735.2007.-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 (PETCO2) 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 PETO2 = 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 center dot min(-1)center dot 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.