Cardiac consequences of intermittent hypoxia: a matter of dose? A systematic review and meta-analysis in rodents

Belaidi, Élise; Khouri, Charles; Harki, Olfa; Baillieul, Sébastien; Faury, Gilles; Briançon‐Marjollet, Anne; Pépin, Jean‐Louis; Arnaud, Claire

doi:10.1183/16000617.0269-2021

Cited by 25 publications

(18 citation statements)

References 50 publications

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“…These studies demonstrate different oxidative stress responses to IH among vascular beds that depend on the duration of total IH exposure as well as characteristics (number of cycles per hour, depth) of IH [ 56 ]. In recent meta-analyses performed on rodents, we demonstrated that the duration (acute exposure of few hours vs. chronic exposure of several days) and the depth of hypoxia (10% vs. 5%) impact the response to ischemia-reperfusion [ 57 ]. Since IH did not impact superoxide anion content or pro/anti-oxidant balance in the aorta, we cannot say that vascular oxidative stress is the main driver of an increase in BP under IH.…”

Section: Discussionmentioning

confidence: 99%

L-Citrulline Supplementation Reduces Blood Pressure and Myocardial Infarct Size under Chronic Intermittent Hypoxia, a Major Feature of Sleep Apnea Syndrome

et al. 2022

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Intermittent hypoxia (IH) is a landmark of obstructive sleep apnea (OSA) at the core of the cardiovascular consequences of OSA. IH triggers oxidative stress, a major underlying mechanism for elevated blood pressure (BP) and increased infarct size. L-citrulline is an amino acid that has been demonstrated to be protective of the cardiovascular system and exert pleiotropic effects. Therefore, we tested the impact of citrulline supplementation on IH-induced increase in BP and infarct size. Four groups of rats exposed to normoxia (N) or IH [14 days (d), 8 h/day, 30 s-O2 21%/30 s-O2 5%] and were supplemented or not with citrulline (1 g·kg−1·d−1). After 14 d, BP was measured, and hearts were submitted to global ischemia-reperfusion to measure infarct size. Histological and biochemical analyses were conducted on hearts and aorta to assess oxidative stress. Citrulline significantly reduced BP (–9.92%) and infarct size (–18.22%) under IH only. In the aorta, citrulline supplementation significantly decreased superoxide anion and nitrotyrosine levels under IH and abolished the IH-induced decrease in nitrite. Citrulline supplementation significantly decreased myocardial superoxide anion levels and xanthine oxidase enzyme activity under IH. Citrulline shows a cardioprotective capacity by limiting IH-induced pro-oxidant activity. Our results suggest that citrulline might represent a new pharmacological strategy in OSA patients with high cardiovascular risk.

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Section: Discussionmentioning

confidence: 99%

L-Citrulline Supplementation Reduces Blood Pressure and Myocardial Infarct Size under Chronic Intermittent Hypoxia, a Major Feature of Sleep Apnea Syndrome

et al. 2022

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“…Conversely, chronic HIF-1 activation is recognized to induce deleterious effects. Indeed, sustained HIF-1α overexpression leads to cardiac hypertrophy [ 19 ], and we demonstrated that chronic IH is a potent inducer of its adverse effects on infarct size [ 20 , 21 ]. In line, we and others demonstrated an important cooperation between HIF-1 and ER stress in these detrimental effects.…”

Section: Introductionmentioning

confidence: 99%

Intermittent Hypoxia-Induced Cardiomyocyte Death Is Mediated by HIF-1 Dependent MAM Disruption

et al. 2022

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Rationale: Intermittent hypoxia (IH) is one of the main features of sleep-disordered breathing (SDB). Recent findings indicate that hypoxia inducible factor-1 (HIF-1) promotes cardiomyocytes apoptosis during chronic IH, but the mechanisms involved remain to be elucidated. Here, we hypothesize that IH-induced ER stress is associated with mitochondria-associated ER membrane (MAM) alteration and mitochondrial dysfunction, through HIF-1 activation. Methods: Right atrial appendage biopsies from patients with and without SDB were used to determine HIF-1α, Grp78 and CHOP expressions. Wild-type and HIF-1α+/− mice were exposed to normoxia (N) or IH (21–5% O2, 60 cycles/h, 8 h/day) for 21 days. Expressions of HIF-1α, Grp78 and CHOP, and apoptosis, were measured by Western blot and immunochemistry. In isolated cardiomyocytes, we examined structural integrity of MAM by proximity ligation assay and their function by measuring ER-to-mitochondria Ca2+ transfer by confocal microscopy. Finally, we measured mitochondrial respiration using oxygraphy and calcium retention capacity (CRC) by spectrofluorometry. MAM structure was also investigated in H9C2 cells incubated with 1 mM CoCl2, a potent HIF-1α inducer. Results: In human atrial biopsies and mice, IH induced HIF-1 activation, ER stress and apoptosis. IH disrupted MAM, altered Ca2+ homeostasis, mitochondrial respiration and CRC. Importantly, IH had no effect in HIF-1α+/− mice. Similar to what observed under IH, HIF-1α overexpression was associated with MAM alteration in H9C2. Conclusion: IH-induced ER stress, MAM alterations and mitochondrial dysfunction were mediated by HIF-1; all these intermediate mechanisms ultimately inducing cardiomyocyte apoptosis. This suggests that HIF-1 modulation might limit the deleterious cardiac effects of SDB.

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“…The clinical significance of periodic breathing and exposure to mild intermittent hypoxia in neonates is not well established [ 1 , 32 ]. In animal models, mild intermittent hypoxia has shown both negative and positive effects on neurodevelopment and cardiovascular function [ 32 , 33 ]. However, in general, intermittent hypoxia is considered detrimental for neurodevelopment [ 1 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Supplemental Oxygen Treats Periodic Breathing without Effects on Sleep in Late-Preterm Infants

Seppä-Moilanen¹,

Andersson²,

Kirjavainen³

2022

Neonatology

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Background: The effect of supplemental oxygen on sleep has not been studied in preterm infants. Methods: We studied 18 stable late-preterm infants with observed periodic breathing at a median gestational age of 36 weeks. Polysomnography was performed on room air and on 25% oxygen-enriched ambient air. Results: Supplemental oxygen did not affect sleep stage distribution, sleep efficiency, the frequency of sleep stage transitions, the appearance of rapid-eye movement (REM) sleep periods, or the high number of spontaneous arousals. The percentage in periodic breathing out of total sleep time decreased from 10% (interquartile range [IQR] 5–9%) on room air to 1% (IQR 0–3%) (p < 0.001) on supplemental oxygen. Also, the number of central apneas decreased from 48 (IQR 32–68) to 23 (IRQ 15–32) per hour (p < 0.001), and the number of oxygen desaturations of a minimum 3% from 38 (IQR 29–74) to 10 (IQR 5–24) per hour (p < 0.001). On room air in non-REM sleep, the median end-tidal carbon dioxide values were systematically lower during periodic breathing at 5.1 (IQR 4.6–6.4) kPa than during stable breathing at 5.5 (4.9–5.9) kPa (p < 0.0001). Conclusions: In late-preterm infants, supplemental oxygen effectively reduces periodic breathing and the number of oxygen desaturations while having no significant effect on sleep. The results support the importance of carotid body over-reactivity on the genesis of periodic breathing in preterm infants.

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Cardiac consequences of intermittent hypoxia: a matter of dose? A systematic review and meta-analysis in rodents

Cited by 25 publications

References 50 publications

L-Citrulline Supplementation Reduces Blood Pressure and Myocardial Infarct Size under Chronic Intermittent Hypoxia, a Major Feature of Sleep Apnea Syndrome

L-Citrulline Supplementation Reduces Blood Pressure and Myocardial Infarct Size under Chronic Intermittent Hypoxia, a Major Feature of Sleep Apnea Syndrome

Intermittent Hypoxia-Induced Cardiomyocyte Death Is Mediated by HIF-1 Dependent MAM Disruption

Supplemental Oxygen Treats Periodic Breathing without Effects on Sleep in Late-Preterm Infants

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