The Magnitude of Long‐Term Facilitation is Influenced by Modifications to Mild Intermittent Hypoxia Protocols in Participants with OSA

Abstract

IntroductionMild intermittent hypoxia (MIH) with sustained hypercapnia initiates long‐term facilitation (LTF) of minute ventilation in humans. To date the impact of different protocols administered acutely, and repeatedly for a select number of days, on the magnitude of LTF in humans with obstructive sleep apnea (OSA) has not been investigated. Thus, the primary aim of this study was to investigate the impact of two different MIH protocols administered over 10 days on the magnitude of LTF.MethodsTwenty‐seven males with OSA participated in the investigation. Both protocols were characterized by 12 episodes of hypoxia of similar intensity (PETO2 ≍ 50 mmHg). However, one protocol (P1) was comprised of 2‐minute hypoxic episodes and the other protocol (P2) was comprised of 4‐minute hypoxic episodes. In addition, during P1 PETCO2 was maintained 2 mmHg above baseline throughout the protocol, while PETCO2 was sustained 4 mmHg above baseline during the completion of P2. During the completion of both protocols, minute ventilation was measured initially under conditions of normoxia and hypercapnia (i.e. 2 mmHg or 4 mmHg above baseline) prior to exposure to MIH. Following exposure to MIH, minute ventilation was recorded for an additional 30 minutes (i.e. end recovery period). Data was averaged for the initial 2 days and final 2 days of the protocol. Absolute measures of minute ventilation, and measures standardized to baseline measures on the initial days, were compared between protocols.ResultsThirteen participants completed P1and 14 participants completed P2. Absolute measures showed that minute ventilation during end‐recovery was greater than baseline on the initial and final days of both protocols (P < 0.01). However, minute ventilation during end‐recovery on the initial and final days was greater after the completion of P2 compared to P1 (P < 0.01). This difference remained after measures of minute ventilation were standardized relative to baseline (P < 0.05). Minute ventilation during end‐recovery on the final days was also greater compared to the initial days after completion of P2 (P < 0.05). This was not the case following completion of P1 (P > 0.3). This difference remained after the data was standardized to baseline measures (P < 0.05).ConclusionOur results showed that LTF of minute ventilation can be initiated using two different protocols that varied in regard to episode duration and the degree to which PETCO2is maintained above baseline. We also showed that increases in episode duration and sustained PETCO2 results in a greater magnitude of LTF on a given day. Moreover, these modifications appear to enhance the magnitude of LTF following repeated daily exposure.