Intermittent Hypoxia Severity in Animal Models of Sleep Apnea

Farré, Ramón; Montserrat, Josep M.; Gozal, David; Almendros, Isaac; Navajas, Daniel

doi:10.3389/fphys.2018.01556

Cited by 49 publications

(42 citation statements)

References 38 publications

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“…Abundant literature states that obstructive sleep apnoea (OSA) syndrome is an independent risk factor for metabolic and vascular disturbances, such as insulin resistance and atherosclerosis [16,17], and IH-induced adipose tissue dysfunction probably plays a key role in the pathogenesis. The effects of IH have been dissected in rodent experiments in which animals were exposed to cyclic and repetitive episodes of reduced inspiratory oxygen fraction (FiO 2 ), with the most frequently used protocol consisting of cyclic reduction of FiO 2 in animal cages from 21% FiO 2 (room air) to 4-6% FiO 2 , mimicking hypoxaemic conditions found in patients with severe OSA [18]. This IH condition, applied for at least 2 weeks, induces vascular dysfunctions and reproduces glucose and lipid homeostasis disturbances similar to those observed in OSA patients.…”

Section: Adipose Tissue and Ih: Insight From Rodent And Reductionist mentioning

confidence: 99%

Adipose tissue as a key player in obstructive sleep apnoea

et al. 2019

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Obstructive sleep apnoea (OSA) is a major health concern worldwide and adversely affects multiple organs and systems. OSA is associated with obesity in >60% of cases and is independently linked with the development of numerous comorbidities including hypertension, arrhythmia, stroke, coronary heart disease and metabolic dysfunction. The complex interaction between these conditions has a significant impact on patient care and mortality. The pathophysiology of cardiometabolic complications in OSA is still incompletely understood; however, the particular form of intermittent hypoxia (IH) observed in OSA, with repetitive short cycles of desaturation and re-oxygenation, probably plays a pivotal role. There is fast growing evidence that IH mediates some of its detrimental effects through adipose tissue inflammation and dysfunction. This article aims to summarise the effects of IH on adipose tissue in experimental models in a comprehensive way. Data from well-designed controlled trials are also reported with the final goal of proposing new avenues for improving phenotyping and personalised care in OSA.

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Section: Adipose Tissue and Ih: Insight From Rodent And Reductionist mentioning

confidence: 99%

Adipose tissue as a key player in obstructive sleep apnoea

et al. 2019

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“…Finally, we implemented a very severe hypoxia/reoxygenation challenge mimicking severe OSA (a subpopulation of 2–5% of all OSA patients), but this study did not address situations where the level of IH is either mild or moderate. However, it is of note that as a result of the inter‐species differences in O 2 dissociation curves, lower oxygen saturation levels are required in mice to elicit an equivalent reduction in oxygen partial pressure among humans . Given the dichotomous effect of CIH, future studies investigating the impact of IH at different ages according to the severity of hypoxia and the experimental protocol are needed.…”

Section: Discussionmentioning

confidence: 99%

“…However, it is of note that as a result of the inter-species differences in O 2 dissociation curves, lower oxygen saturation levels are required in mice to elicit an equivalent reduction in oxygen partial pressure among humans. 43 Given the dichotomous effect of CIH, 39 future studies investigating the impact of IH at different ages according to the severity of hypoxia and the experimental protocol are needed. The main strengths of our work include the use of older mice that were 18 months of age and the use of a conventional mouse strain, which allowed us to assess the cardiovascular consequences associated with IH exposure without other confounding factors or co-morbidities.…”

Section: Discussionmentioning

confidence: 99%

Effect of age on the cardiovascular remodelling induced by chronic intermittent hypoxia as a murine model of sleep apnoea

et al. 2019

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Background and objective Chronic intermittent hypoxia (CIH) is a major determinant of the cardiovascular morbidity associated with obstructive sleep apnoea (OSA), and the magnitude of CIH impact may be influenced by ageing. Here, we assessed the role of ageing in the early cardiovascular structural remodelling induced by severe CIH in a murine model of OSA. Methods Cardiovascular remodelling was assessed in young (2 months old, n = 20) and aged (18 months old, n = 20) C57BL/6 female mice exposed to CIH (20% O2 for 40 s, 5% O2 for 20 s) or normoxia (room air) for 8 weeks (6 h/day). Results Early vascular remodelling was observed in young mice exposed to CIH as illustrated by intima‐media thickening (mean change: 4.6 ± 2.6 μm; P = 0.02), elastin fibre disorganization (mean change: 9.2 ± 4.5%; P = 0.02) and fragmentation (mean change: 2.5 ± 0.8%; P = 0.03), and collagen (mean change: 3.2 ± 0.6%; P = 0.001) and mucopolysaccharide accumulation (mean change: 2.4 ± 0.8%; P = 0.01). In contrast, vascular remodelling was not apparent in aged mice exposed to CIH. Furthermore, left ventricular perivascular fibrosis (mean change: 0.71 ± 0.1; P < 0.001) and hypertrophy (mean change: 0.17 ± 0.1; P = 0.038) were increased by CIH exposure in young mice, but not in aged mice. Principal component analysis identified similar cardiovascular alterations among the young mice exposed to CIH and both older mouse groups, suggesting that CIH induces premature cardiovascular senescence. Conclusion Cardiovascular remodelling induced by severe CIH is affected by the age at which CIH onset occurs, suggesting that the deleterious cardiovascular effects associated with CIH may be more pronounced in younger populations, and such changes resemble chronological age‐related declines in cardiovascular structural integrity.

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“…has some limitations, many of which have already been acknowledged by the authors. IH may be an overly reductionist simulation of OSA, and the severity of IH that realistically simulates OSA is also debated . In addition, the study examined only female mice.…”

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confidence: 99%

“…IH may be an overly reductionist simulation of OSA, and the severity of IH that realistically simulates OSA is also debated. 14,15 In addition, the study examined only female mice. While authors should be commended for studying this neglected field, questions remain about the role of sex hormones in their findings and the generalizability of their results to male sex.…”

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confidence: 99%