Long-Term Facilitation Of Ventilation Following Acute Continuous Hypoxia In Awake Humans During Sustained Hypercapnia

Key points In awake humans, when CO2 is maintained above normal levels, exposure to acute intermittent hypoxia causes a sustained elevation in ventilation that persists when normoxic breathing is resumed. In this study we have demonstrated that when CO2 is maintained above normal levels, exposure to acute continuous hypoxia also causes a sustained elevation in ventilation when normoxic breathing is resumed. This sustained elevation in ventilation following both acute intermittent hypoxia and acute continuous hypoxia is maintained by mechanisms other than increased activity of the carotid body. These results help develop our understanding of respiratory control in humans and may aid future development of treatments for respiratory control disorders, such as obstructive sleep apnoea. Abstract In awake humans, long-term facilitation of ventilation (vLTF) following acute intermittent hypoxia (AIH) is only expressed if CO2 is maintained above normocapnic levels. vLTF has not been reported following acute continuous hypoxia (ACH) and it is not known whether this might be unmasked by elevated CO2. Twelve healthy participants completed three trials. In all trials end-tidal pressure of CO2 was elevated 45 mmHg above normocapnic levels. During Trial 1 (AIH) participants were exposed to eight 4 min episodes of hypoxia. During Trial 2 (ACH) participants were exposed to continuous hypoxia for 32 min. In Trial 3 (Control) participants were exposed to euoxia throughout. To assess the contribution of the carotid body (CB) in observed ventilatory responses, CB afferent discharge before and after each trial was transiently inhibited with hyperoxia. Minute ventilation () increased following all trials, but was significantly greater in Trials 1 and 2 when compared with Trial 3 (Trial 1: 4.96 +/- 0.87, Trial 2: 5.07 +/- 0.7, Trial 3: 2.55 +/- 0.98 l min-1, P < 0.05). Hyperoxia attenuated to a similar extent in baseline and recovery in all trials (Trial 1: 3.0 +/- 0.57 vs. 3.27 +/- 0.68, Trial 2: 1.97 +/- 0.62 vs. 2.56 +/- 0.62, Trial 3: 2.23 +/- 0.49 vs. 2.15 +/- 0.55 l min-1, P > 0.05). Data are means +/- SEM. In awake humans with elevated CO2, ACH evokes a sustained increase in ventilation that is comparable to that evoked by AIH. However, a gradual positive drift in ventilation in response to elevated CO2 accounts for approximately half of this apparent vLTF. Additionally, our data support the view that the CB is not directly involved in maintaining vLTF.