This study examined whether time of day and repeated exposure to intermittent hypoxia have an impact on the hypoxic ventilatory response (HVR) and ventilatory long-term facilitation (vLTF). Thirteen participants with sleep apnea were exposed to twelve 4-min episodes of isocapnic hypoxia followed by a 30-min recovery period each day for 10 days. On days 1 (initial day) and 10 (final day) participants completed the protocol in the evening (PM); on the remaining days the protocol was completed in the morning (AM). The HVR was increased in the morning compared with evening on the initial (AM 0.83 ± 0.08 vs. PM 0.64 ± 0.11 l·min⁻¹·%SaO₂⁻¹; P ≤ 0.01) and final days (AM 1.0 ± 0.08 vs. PM 0.81 ± 0.09 l·min⁻¹·%SaO₂⁻¹; P ≤ 0.01, where %SaO₂ refers to percent arterial oxygen saturation). Moreover, the magnitude of the HVR was enhanced following daily exposure to intermittent hypoxia in the morning (initial day 0.83 ± 0.08 vs. final day 1.0 ± 0.08 l·min⁻¹·%SaO₂⁻¹; P ≤ 0.03) and evening (initial day 0.64 ± 0.11 vs. final day 0.81 ± 0.09 l·min⁻¹·%SaO₂⁻¹; P ≤ 0.03). vLTF was reduced in the morning compared with the evening on the initial (AM 19.03 ± 0.35 vs. PM 22.30 ± 0.49 l/min; P ≤ 0.001) and final (AM 20.54 ± 0.32 vs. PM 23.11 ± 0.54 l/min; P ≤ 0.01) days. Following daily exposure to intermittent hypoxia, vLTF was enhanced in the morning (initial day 19.03 ± 0.35 vs. final day 20.54 ± 0.32 l/min; P ≤ 0.01). We conclude that the HVR is increased while vLTF is decreased in the morning compared with the evening in individuals with sleep apnea and that the magnitudes of these phenomena are enhanced following daily exposure to intermittent hypoxia.

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We examined whether exposure to intermittent hypoxia (IH) during wakefulness impacted on the apnea/hypopnea index (AHI) during sleep in individuals with sleep apnea. Participants were exposed to twelve 4-min episodes of hypoxia in the presence of sustained mild hypercapnia each day for 10 days. A control group was exposed to sustained mild hypercapnia for a similar duration. The intermittent hypoxia protocol was completed in the evening on day 1 and 10 and was followed by a sleep study. During all sleep studies, the change in esophageal pressure (ΔPes) from the beginning to the end of an apnea and the tidal volume immediately following apneic events were used to measure respiratory drive. Following exposure to IH on day 1 and 10, the AHI increased above baseline measures (day 1: 1.95 ± 0.42 fraction of baseline, P ≤ 0.01, vs. day 10: 1.53 ± 0.24 fraction of baseline, P < 0.06). The indexes were correlated to the hypoxic ventilatory response (HVR) measured during the IH protocol but were not correlated to the magnitude of ventilatory long-term facilitation (vLTF). Likewise, ΔPes and tidal volume measures were greater on day 1 and 10 compared with baseline (ΔPes: -8.37 ± 0.84 vs. -5.90 ± 1.30 cmH(2)0, P ≤ 0.04; tidal volume: 1,193.36 ± 101.85 vs. 1,015.14 ± 119.83 ml, P ≤ 0.01). This was not the case in the control group. Interestingly, the AHI on day 10 (0.78 ± 0.13 fraction of baseline, P ≤ 0.01) was significantly less than measures obtained during baseline and day 1 in the mild hypercapnia control group. We conclude that enhancement of the HVR initiated by exposure to IH may lead to increases in the AHI during sleep and that initiation of vLTF did not appear to impact on breathing stability. Lastly, our results suggest that repeated daily exposure to mild sustained hypercapnia may lead to a decrease in breathing events.