Influence of arterial O₂ on the susceptibility to posthyperventilation apnea during sleep

Abstract

Xie, Ailiang, James B. Skatrud, Dominic S. Puleo, and Jerome A. Dempsey. Influence of arterial O2 on the susceptibility to posthyperventilation apnea during sleep. J Appl Physiol 100: 171-177, 2006. First published September 22, 2005 doi:10.1152/japplphysiol.00440.2005.-To investigate the contribution of the peripheral chemoreceptors to the susceptibility to posthyperventilation apnea, we evaluated the time course and magnitude of hypocapnia required to produce apnea at different levels of peripheral chemoreceptor activation produced by exposure to three levels of inspired PO 2. We measured the apneic threshold and the apnea latency in nine normal sleeping subjects in response to augmented breaths during normoxia (room air), hypoxia (arterial O 2 saturation ϭ 78 -80%), and hyperoxia (inspired O2 fraction ϭ 50 -52%). Pressure support mechanical ventilation in the assist mode was employed to introduce a single or multiple numbers of consecutive, sighlike breaths to cause apnea. The apnea latency was measured from the end inspiration of the first augmented breath to the onset of apnea. It was 12.2 Ϯ 1.1 s during normoxia, which was similar to the lung-to-ear circulation delay of 11.7 s in these subjects. Hypoxia shortened the apnea latency (6.3 Ϯ 0.8 s; P Ͻ 0.05), whereas hyperoxia prolonged it (71.5 Ϯ 13.8 s; P Ͻ 0.01). The apneic threshold end-tidal PCO 2 (PETCO 2 ) was defined as the PETCO 2 at the onset of apnea. During hypoxia, the apneic threshold PET CO 2 was higher (38.9 Ϯ 1.7 Torr; P Ͻ 0.01) compared with normoxia (35.8 Ϯ 1.1; Torr); during hyperoxia, it was lower (33.0 Ϯ 0.8 Torr; P Ͻ 0.05). Furthermore, the difference between the eupneic PET CO 2 and apneic threshold PET CO 2 was smaller during hypoxia (3.0 Ϯ 1.0 Torr P Ͻ 001) and greater during hyperoxia (10.6 Ϯ 0.8 Torr; P Ͻ 0.05) compared with normoxia (8.0 Ϯ 0.6 Torr). Correspondingly, the hypocapnic ventilatory response to CO 2 below the eupneic PETCO 2 was increased by hypoxia (3.44 Ϯ 0.63 l ⅐ min Ϫ1 ⅐ Torr Ϫ1 ; P Ͻ 0.05) and decreased by hyperoxia (0.63 Ϯ 0.04 l ⅐ min Ϫ1 ⅐ Torr Ϫ1 ; P Ͻ 0.05) compared with normoxia (0.79 Ϯ 0.05 l ⅐ min Ϫ1 ⅐ Torr Ϫ1 ). These findings indicate that posthyperventilation apnea is initiated by the peripheral chemoreceptors and that the varying susceptibility to apnea during hypoxia vs. hyperoxia is influenced by the relative activity of these receptors. apnea threshold THE RELATIVE CONTRIBUTION of peripheral vs. central chemoreception in initiating the posthyperventilation apneas remains an unresolved question. The importance of peripheral chemoreception in mediating the rapid ventilatory response to hypocapnia has been supported using animal models. Carotid body denervation either eliminated or prolonged the time course for the development of apnea after the administration of augmented breaths (6, 39). However, carotid body denervation profoundly alters central chemoreception as indicated by the substantial CO 2 retention after denervation. Our laboratory has previously demonstrated the complex effect of hypoxia in t...

Ventilatory Response to a Hyperoxic Test Is Related to the Frequency of Short Apneic Episodes in Late Preterm Neonates

“…Other mechanisms (especially central ones) may explain the variability by modulating chemoreceptor inputs, as reported by Xie et al (35). In particular, the ventral medullary surface and its adjacent areas play a key integrative role in central CO 2 chemosensitivity and the modulation of afferent inputs from carotid body and laryngeal afferents.…”

“…Indeed, the increase in carotid body activity can promote respiratory instability and apnea when the CO 2 partial pressure falls below the apneic threshold (10), thereby depressing inspiratory motor drive. This explanation is supported by studies performed in animals (34) or healthy sleeping adults (35), which have demonstrated the importance of critical O 2 -CO 2 blood gas combinations with high carotid body gain in the induction of periodic breathing (8 -10,36). Because the critical PaCO 2 thresholds that produce periodic breathing and apnea are closed (9), we can extend the assumption of an hypocapnia threshold to apnea (37).…”

Treatment of Central Sleep Apnea in US Veterans

“…To date, only small studies [15][16][17][18][19] conducted mostly in patients with underlying CHF, have demonstrated the effectiveness of adding O 2 for the management of CSA. However, no study has evaluated the effectiveness of a combination therapy of PAP and supplemental oxygen on the evolution of central apneas in an unselected population of patients with a mix of etiologies for CSA.…”

“…[23][24][25]29,30 The outcomes of therapy have also varied considerably, with limited evidence to establish the effectiveness of any therapy for CSA. [26][27][28][29]31,32 The majority of published literature has focused on the treatment of CSA secondary to congestive heart failure (CHF), [2][3][4][5][6][7][8][9][10][11][15][16][17][18][19][20][21][22][26][27][28][29] with very little data on patients with "primary" CSA 23,24 or CSA secondary to causes other than CHF. 33 In addition, there is very little data on the treatment of CSA related to opioid use and CSA that is concomitant with OSA.…”

Children at high altitude have less nocturnal periodic breathing than adults

“…Sighs were defined as large breaths with VTs greater than twice the previous stable VT amplitude [28]. The CO 2 apnoea threshold was defined as the value of PET,CO 2 of the last breath before an apnoea occurred [29]. The CO 2 reserve (DPET,CO 2 ) was calculated as the difference in PET,CO 2 during eupnoea and the CO 2 apnoea threshold.…”