Ventilatory and waking responses to hypoxia in sleeping dogs

Abstract

We examined waking and ventilatory responses to acute hypoxia in four dogs during natural sleep. Progressive hypoxia was induced by a rebreathing technique in which alveolar CO2 pressure (PACO2) was held at the eucapnic level. Arterial O2 saturation (SaO2) was measured with an ear oximeter, and sleep stage was determined by electroencephalographic and behavioral criteria. Arousal from eucapnic hypoxia occurred at a SaO2 of 87.5 +/- 2.6% (mean +/- SE) during slow-wave sleep (SWS), and at a SaO2 of 70.5 +/- 3.4% during rapid-eye-movement (REM) sleep (P less than 0.005). The irregular pattern of breathing typical of REM sleep persisted during hypoxia. However linear regression analysis of breath-by-breath instantaneous minute volume of ventilation (VI) against SaO2 revealed regression coefficients in REM sleep that were similar to those found in SWS and wakefulness. This finding contrasts with earlier observations of a decreased response of VI to CO2 during REM sleep. The results indicate that although waking responses to hypoxia are delayed in REM sleep, ventilatory responses remain intact and therefore may be of importance in maintaining adequate ventilation during this stage of sleep.

Central serotonin neurons are required for arousal to CO 2

“…Acute hypercapnia is a potent stimulus for arousal from sleep (19,20) and can also activate limbic structures, leading to the experience of dyspnea (21) and panic (22). Functional MRI studies have shown that hypercapnia and hypoxia induced by brief apnea cause an increase in activity within the thalamus and cerebral cortex (23).…”

Effect of route of breathing on the ventilatory and arousal responses to hypercapnia in awake and sleeping dogs.

“…As in most studies, the greatest depression in the ventilatory response to hypercapnia occurred during REM sleep (Phillipson et al 1977;Gothe et al 1981; Hedemark & Kronenberg 1982;Berthon-Jones & Sullivan, 1984). The mechanism of sleep-induced reduction of CO2 chemosensitivity is still not well understood.…”

“…Phillipson et al (1976Phillipson et al ( , 1977 introduced the chronic dog model to study the influence of sleep on respiration. Measurement of breathing pattern was performed in these studies using a chronic tracheostoma.…”

“…The mechanism of sleep-induced reduction of CO2 chemosensitivity is still not well understood. Depression of chemosensitivity during sleep may reflect changes at a peripheral level, a reduced sensitivity of the medullary chemoreceptors, increased brain blood flow, or may be due to changes in cholinergic mechanisms controlling respiration during sleep (Phillipson et al 1977;Berthon-Jones & Sullivan, 1984;Parisi, Neubauer, Frank, Santiago & Edelman, 1988;Lydic, Baghdoyan, Wertz & White, 1991).…”

“…Hypoxaemia, hypercapnia, stimuli arising from chest wall and airways (both upper and lower airways), or from contracting respiratory muscles (Bowes, Townsend, Bromley, Kozar & Phillipson, 1981;Berthon-Jones & Sullivan, 1982Issa et al 1987;Vincken, Guilleminault, Silvestri, Cosio & Grassino 1987;Gleeson, Zwillich & White, 1990) are known respiratory stimuli that induce arousal. A number of studies have investigated the arousal threshold to CO2 (Phillipson, Kozar, Rebuck & Murphy, 1977;Gothe, Altose, Goldman & Cherniack, 1981;Douglas, White, Weil, Pickett, & Zwillich, 1982; Hedemark & Kronenberg 1982; Berthon-Jones & Sullivan, 1984). The results of these studies indicated that the arousal threshold to hypercapnia is variable, with some studies reporting no difference between rapid eye movement (REM) and non-REM (NREM) sleep, while others demonstrated a higher threshold in REM sleep.…”