Increased Oxidative Stress, Loop Gain And The Arousal Threshold Are Clinical Predictors Of Increased Apnea Severity Following Exposure To Intermittent Hypoxia
Gino S Panza,1,2,* Raichel M Alex,1,2,* Sanar S Yokhana,1,2 Dorothy S Lee Pioszak,1,2 M Safwan Badr,1–3 Jason H Mateika1–3 1Research and Development, John D. Dingell Veterans Affairs Medical Center, Detroit, MI 48201, USA; 2Department of Physiology, Wayne State University School...
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Dove Medical Press
2019
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oai:doaj.org-article:76acbf0cee534cb8b56ca1893bd01bba2021-12-02T04:44:52ZIncreased Oxidative Stress, Loop Gain And The Arousal Threshold Are Clinical Predictors Of Increased Apnea Severity Following Exposure To Intermittent Hypoxia1179-1608https://doaj.org/article/76acbf0cee534cb8b56ca1893bd01bba2019-10-01T00:00:00Zhttps://www.dovepress.com/increased-oxidative-stress-loop-gain-and-the-arousal-threshold-are-cli-peer-reviewed-article-NSShttps://doaj.org/toc/1179-1608Gino S Panza,1,2,* Raichel M Alex,1,2,* Sanar S Yokhana,1,2 Dorothy S Lee Pioszak,1,2 M Safwan Badr,1–3 Jason H Mateika1–3 1Research and Development, John D. Dingell Veterans Affairs Medical Center, Detroit, MI 48201, USA; 2Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA; 3Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA*These authors contributed equally to this workCorrespondence: Jason H MateikaJohn D. Dingell VA Medical Center, 4646 John R (11R), Room 4333, Detroit, MI 48201, USATel +1 313 576 4481Fax +1 313 576 1112Email jmateika@med.wayne.eduPurpose: We determined if oxidative stress prior to sleep onset is correlated to loop gain (LG) and the arousal threshold (AT) during non‐rapid eye movement (NREM) sleep. We also explored if LG and AT are correlated with apnea severity and indices of upper airway collapsibility during NREM sleep.Methods: Thirteen male participants with obstructive sleep apnea (apnea–hypopnea index > 5 events/hr) were administered an antioxidant or placebo cocktail while exposed to mild intermittent hypoxia in the awake state. Thereafter, loop gain and measures of arousal, apnea severity and upper airway collapsibility were ascertained during NREM sleep.Results: Modification in oxidative stress (i.e., 8-hydroxy-2-deoxyguanosine) prior to sleep onset was correlated to LG (r = 0.8, P = 0.003), the number (r = 0.71, P = 0.01) and duration (r = 0.63, P = 0.04) of apneic events and the percentage of time breathing was stable (r = −0.66, P = 0.03) during sleep. Using a forward stepwise regression analysis, our results showed that LG, AT, the ventilatory response to arousal and nadir end-tidal carbon dioxide were determinants of the apnea–hypopnea index (P value range = 0.04–0.001). In addition, the AT was a predictor of measures of upper airway collapsibility, including the hypopnea/apnea + hypopnea ratio and the degree of flow reduction that accompanied hypopneic events (P < 0.001).Conclusion: Modifications in oxidative stress following exposure to intermittent hypoxia during wakefulness are positively associated with loop gain and apnea severity during NREM sleep. Moreover, an increase in the arousal threshold is a predictor of increased upper airway collapsibility.Keywords: mild intermittent hypoxia, non-rapid eye movement sleep, arousal, oxidative stress, loop gainPanza GSAlex RMYokhana SSLee Pioszak DSBadr MSMateika JHDove Medical Pressarticlemild intermittent hypoxianon-rapid eye movement sleeparousaloxidative stressloop gainPsychiatryRC435-571Neurophysiology and neuropsychologyQP351-495ENNature and Science of Sleep, Vol Volume 11, Pp 265-279 (2019) |
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mild intermittent hypoxia non-rapid eye movement sleep arousal oxidative stress loop gain Psychiatry RC435-571 Neurophysiology and neuropsychology QP351-495 |
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mild intermittent hypoxia non-rapid eye movement sleep arousal oxidative stress loop gain Psychiatry RC435-571 Neurophysiology and neuropsychology QP351-495 Panza GS Alex RM Yokhana SS Lee Pioszak DS Badr MS Mateika JH Increased Oxidative Stress, Loop Gain And The Arousal Threshold Are Clinical Predictors Of Increased Apnea Severity Following Exposure To Intermittent Hypoxia |
description |
Gino S Panza,1,2,* Raichel M Alex,1,2,* Sanar S Yokhana,1,2 Dorothy S Lee Pioszak,1,2 M Safwan Badr,1–3 Jason H Mateika1–3 1Research and Development, John D. Dingell Veterans Affairs Medical Center, Detroit, MI 48201, USA; 2Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA; 3Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA*These authors contributed equally to this workCorrespondence: Jason H MateikaJohn D. Dingell VA Medical Center, 4646 John R (11R), Room 4333, Detroit, MI 48201, USATel +1 313 576 4481Fax +1 313 576 1112Email jmateika@med.wayne.eduPurpose: We determined if oxidative stress prior to sleep onset is correlated to loop gain (LG) and the arousal threshold (AT) during non‐rapid eye movement (NREM) sleep. We also explored if LG and AT are correlated with apnea severity and indices of upper airway collapsibility during NREM sleep.Methods: Thirteen male participants with obstructive sleep apnea (apnea–hypopnea index > 5 events/hr) were administered an antioxidant or placebo cocktail while exposed to mild intermittent hypoxia in the awake state. Thereafter, loop gain and measures of arousal, apnea severity and upper airway collapsibility were ascertained during NREM sleep.Results: Modification in oxidative stress (i.e., 8-hydroxy-2-deoxyguanosine) prior to sleep onset was correlated to LG (r = 0.8, P = 0.003), the number (r = 0.71, P = 0.01) and duration (r = 0.63, P = 0.04) of apneic events and the percentage of time breathing was stable (r = −0.66, P = 0.03) during sleep. Using a forward stepwise regression analysis, our results showed that LG, AT, the ventilatory response to arousal and nadir end-tidal carbon dioxide were determinants of the apnea–hypopnea index (P value range = 0.04–0.001). In addition, the AT was a predictor of measures of upper airway collapsibility, including the hypopnea/apnea + hypopnea ratio and the degree of flow reduction that accompanied hypopneic events (P < 0.001).Conclusion: Modifications in oxidative stress following exposure to intermittent hypoxia during wakefulness are positively associated with loop gain and apnea severity during NREM sleep. Moreover, an increase in the arousal threshold is a predictor of increased upper airway collapsibility.Keywords: mild intermittent hypoxia, non-rapid eye movement sleep, arousal, oxidative stress, loop gain |
format |
article |
author |
Panza GS Alex RM Yokhana SS Lee Pioszak DS Badr MS Mateika JH |
author_facet |
Panza GS Alex RM Yokhana SS Lee Pioszak DS Badr MS Mateika JH |
author_sort |
Panza GS |
title |
Increased Oxidative Stress, Loop Gain And The Arousal Threshold Are Clinical Predictors Of Increased Apnea Severity Following Exposure To Intermittent Hypoxia |
title_short |
Increased Oxidative Stress, Loop Gain And The Arousal Threshold Are Clinical Predictors Of Increased Apnea Severity Following Exposure To Intermittent Hypoxia |
title_full |
Increased Oxidative Stress, Loop Gain And The Arousal Threshold Are Clinical Predictors Of Increased Apnea Severity Following Exposure To Intermittent Hypoxia |
title_fullStr |
Increased Oxidative Stress, Loop Gain And The Arousal Threshold Are Clinical Predictors Of Increased Apnea Severity Following Exposure To Intermittent Hypoxia |
title_full_unstemmed |
Increased Oxidative Stress, Loop Gain And The Arousal Threshold Are Clinical Predictors Of Increased Apnea Severity Following Exposure To Intermittent Hypoxia |
title_sort |
increased oxidative stress, loop gain and the arousal threshold are clinical predictors of increased apnea severity following exposure to intermittent hypoxia |
publisher |
Dove Medical Press |
publishDate |
2019 |
url |
https://doaj.org/article/76acbf0cee534cb8b56ca1893bd01bba |
work_keys_str_mv |
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