scholarly journals A new rodent model for obstructive sleep apnea: effects on ATP-mediated dilations in cerebral arteries

2013 ◽  
Vol 305 (4) ◽  
pp. R334-R342 ◽  
Author(s):  
Randy F. Crossland ◽  
David J. Durgan ◽  
Eric E. Lloyd ◽  
Sharon C. Phillips ◽  
Anilkumar K. Reddy ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Rat Model ◽  
Cerebral Arteries ◽  
Upper Airway ◽  
Sleep Cycle ◽  
Control Group ◽  
Obstructive Sleep ◽  
Middle Cerebral Arteries ◽  
Sham Control Group

Obstructive sleep apnea (OSA), a condition in which the upper airway collapses during sleep, is strongly associated with metabolic and cardiovascular diseases. Little is known how OSA affects the cerebral circulation. The goals of this study were 1) to develop a rat model of chronic OSA that involved apnea and 2) to test the hypothesis that 4 wk of apneas during the sleep cycle alters endothelium-mediated dilations in middle cerebral arteries (MCAs). An obstruction device, which was chronically implanted into the trachea of rats, inflated to obstruct the airway 30 times/h for 8 h during the sleep cycle. After 4 wk of apneas, MCAs were isolated, pressurized, and exposed to luminally applied ATP, an endothelial P2Y2 receptor agonist that dilates through endothelial-derived nitric oxide (NO) and endothelial-dependent hyperpolarization (EDH). Dilations to ATP were attenuated ∼30% in MCAs from rats undergoing apneas compared with those from a sham control group ( P < 0.04 group effect; n = 7 and 10, respectively). When the NO component of the dilation was blocked to isolate the EDH component, the response to ATP in MCAs from the sham and apnea groups was similar. This finding suggests that the attenuated dilation to ATP must occur through reduced NO. In summary, we have successfully developed a novel rat model for chronic OSA that incorporates apnea during the sleep cycle. Using this model, we demonstrate that endothelial dysfunction occurred by 4 wk of apnea, likely increasing the vulnerability of the brain to cerebrovascular related accidents.

scholarly journals Increased Cerebrovascular Sensitivity to Endothelin-1 in a Rat Model of Obstructive Sleep Apnea: A Role for Endothelin Receptor B

2015 ◽  
Vol 35 (3) ◽  
pp. 402-411 ◽  
Author(s):  
David J Durgan ◽  
Randy F Crossland ◽  
Eric E Lloyd ◽  
Sharon C Phillips ◽  
Robert M Bryan
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Transient Receptor Potential ◽  
Cerebral Arteries ◽  
Receptor Potential ◽  
Fold Increase ◽  
Sleep Cycle ◽  
Rock Inhibitor ◽  
Endothelin 1 ◽  
Obstructive Sleep

Obstructive sleep apnea (OSA) is associated with cerebrovascular diseases. However, little is known regarding the effects of OSA on the cerebrovascular wall. We tested the hypothesis that OSA augments endothelin-1 (ET-1) constrictions of cerebral arteries. Repeated apneas (30 or 60 per hour) were produced in rats during the sleep cycle (8 hours) by remotely inflating a balloon implanted in the trachea. Four weeks of apneas produced a 23-fold increase in ET-1 sensitivity in isolated and pressurized posterior cerebral arteries (PCAs) compared with PCAs from sham-operated rats (EC50=10−9.2 mol/L versus 10−10.6 mol/L; P<0.001). This increased sensitivity was abolished by the ET-B receptor antagonist, BQ-788. Constrictions to the ET-B receptor agonist, IRL-1620, were greater in PCAs from rats after 2 or 4 weeks of apneas compared with that from sham-operated rats ( P=0.013). Increased IRL-1620 constrictions in PCAs from OSA rats were normalized with the transient receptor potential channel (TRPC) blocker, SKF96365, or the Rho kinase (ROCK) inhibitor, Y27632. These data show that OSA increases the sensitivity of PCAs to ET-1 through enhanced ET-B activity, and enhanced activity of TRPCs and ROCK. We conclude that enhanced ET-1 signaling is part of a pathologic mechanism associated with adverse cerebrovascular outcomes of OSA.

scholarly journals Novel proteins associated with chronic intermittent hypoxia and obstructive sleep apnea: From rat model to clinical evidence

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253943
Author(s):  
Xiaojun Tang ◽  
Shisheng Li ◽  
Xinming Yang ◽  
Qinglai Tang ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Rat Model ◽  
Intermittent Hypoxia ◽  
Mapk Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Chronic Intermittent Hypoxia ◽  
Control Group ◽  
Obstructive Sleep ◽  
And Control

Objective To screen for obstructive sleep apnea (OSA) biomarkers, isobaric tags for relative and absolute quantitation (iTRAQ)-labeled quantitative proteomics assay was used to identify differentially expressed proteins (DEPs) during chronic intermittent hypoxia (CIH). Method The iTRAQ technique was applied to compare DEPs in the serum of a CIH rat model and control group. Biological analysis of DEPs was performed using Gene Ontology and Kyoto Encyclopedia to explore related biological functions and signaling pathways. Enzyme-linked immunosorbent assay (ELISA) was performed to validate their expression in sera from patients with OSA and CIH rats. Results Twenty-three DEPs (fold change ≥1.2 or ≤0.833, p<0.05) were identified, and two DEPs (unique peptides>3 and higher coverage) were further verified by ELISA in the CIH rat model and OSA subject: apolipoprotein A-IV (APOA4, p<0.05) and Tubulin alpha-1A chain (TUBA1A, p<0.05). Both groups showed significant differences in the expression levels of DEPs between the CIH and control groups and the severe OSA and non-OSA groups. APOA4 was found to be upregulated and TUBA1A downregulated in both the sera from OSA patients and CIH rats, on comparing proteomics results with clinical results. There were two pathways that involved three DEPs, the mitogen-activated protein kinase (MAPK) signaling pathway (p<0.05) and cytokine-cytokine receptor interaction (p<0.05). Conclusion APOA4 and TUBA1A may be potential novel biomarkers for CIH and OSA, and may play an important role in the development of OSA complications.

scholarly journals Muscular Assessment in Patients With Severe Obstructive Sleep Apnea Syndrome: Protocol for a Case-Control Study (Preprint)

2021 ◽  
Author(s):  
Paz Francisca Borrmann ◽  
Carlos O'Connor-Reina ◽  
Jose M Ignacio ◽  
Elisa Rodriguez Ruiz ◽  
Laura Rodriguez Alcala ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Muscle Tone ◽  
Therapeutic Option ◽  
Sleep Apnea Syndrome ◽  
Upper Airway ◽  
Case Control ◽  
Control Group ◽  
Myofunctional Therapy ◽  
Obstructive Sleep

BACKGROUND Myofunctional therapy is currently a reasonable therapeutic option to treat obstructive sleep apnea-hypopnea syndrome (OSAHS). This therapy is based on performing regular exercises of the upper airway muscles to increase their tone and prevent their collapse. Over the past decade, there has been an increasing number of publications in this area; however, to our knowledge, there are no studies focused on patients who can most benefit from this therapy. OBJECTIVE This protocol describes a case-control clinical trial aimed at determining the muscular features of patients recently diagnosed with severe OSAHS compared with those of healthy controls. METHODS Patients meeting set criteria will be sequentially enrolled up to a sample size of 40. Twenty patients who meet the inclusion criteria for controls will also be evaluated. Patients will be examined by a qualified phonoaudiologist who will take biometric measurements and administer the Expanded Protocol of Orofacial Myofunctional Evaluation with Scores (OMES), Friedman Staging System, Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index questionnaires. Measures of upper airway muscle tone will also be performed using the Iowa Oral Performance Instrument and tongue digital spoon devices. Evaluation will be recorded and reevaluated by a second specialist to determine concordance between observers. RESULTS A total of 60 patients will be enrolled. Both the group with severe OSAHS (40 patients) and the control group (20 subjects) will be assessed for differences between upper airway muscle tone and OMES questionnaire responses. CONCLUSIONS This study will help to determine muscle patterns in patients with severe OSAHS and can be used to fill the gap currently present in the assessment of patients suitable to be treated with myofunctional therapy. CLINICALTRIAL ISRCTN Registry ISRCTN12596010; https://www.isrctn.com/ISRCTN12596010 INTERNATIONAL REGISTERED REPORT PRR1-10.2196/30500

scholarly journals The The relationship between NLRP3 rs10159239 and Vaspin rs2236242 gene variants and obstructive sleep apnea

2021 ◽  
Vol 126 (1) ◽  
Author(s):  
Buğra Kerget ◽  
Ferhan Kerget ◽  
Çiğdem Yüce Kahraman ◽  
Alperen Aksakal ◽  
Ömer Araz
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Upper Airway ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Obstructive Sleep ◽  
And Control ◽  
The Relationship ◽  
Increased Susceptibility

Background: In obstructive sleep apnea (OSA), recurrent upper airway obstruction and apnea/hypopnea episodes result in endothelial dysfunction, which leads to the release of many proinflammatory cytokines and reactive oxygen species (ROS). ROS induces NLRP3, a protein involved in the synthesis of interleukin (IL)-1 and IL-18; vaspin is a serine protease inhibitor that has an important role in suppressing the activation of NLRP3 inflammasome. In this study, we aimed to investigate the effect of NLRP3 rs10159239 (rs9239) and vaspin rs2236242 (rs6242) single nucleotide polymorphisms (SNPs) on OSA development. Methods: This study included 220 individuals who underwent polysomnography (118 patients with OSA and 102 healthy controls). NLRP3 rs9239 and vaspin rs6242 mutation frequencies were analyzed. Results: The NLRP3 rs9239 SNP genotype analysis revealed no statistically significant differences between the OSA and control groups. In the vaspin gene analysis, the rs6242 AA genotype was significantly more frequent in the OSA group compared with the control group, while the AT genotype was more frequent in controls (P = 0.004, P = 0.02). Comparison of rs6242 allele levels showed that the A allele was significantly more frequent in OSA patients than in controls (P = 0.03). The AA genotype was significantly more frequent in patients with severe OSA than in patients with mild or moderate OSA and the control group (P = 0.001 for all). Serum vaspin levels were significantly lower in carriers of the AA genotype than those with AT and TT genotypes (P = 0.001). Conclusion: The vaspin rs6242 SNP AA genotype increased susceptibility to OSA, while the AT genotype appeared to be protective. The lower plasma vaspin levels in OSA compared with the control group and in patients with the AA genotype suggest that vaspin may be a protective biomarker for OSA.

scholarly journals Three-dimensional analyses of palatal morphology and its relation to upper airway area in obstructive sleep apnea

2016 ◽  
Vol 87 (2) ◽  
pp. 300-306 ◽  
Author(s):  
Defne Kecik
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Three Dimensional ◽  
Upper Airway ◽  
Control Group ◽  
Pharyngeal Airway ◽  
Obstructive Sleep ◽  
Lateral Cephalograms ◽  
Airway Morphology ◽  
Pharyngeal Area

ABSTRACT Objective: To evaluate the relationship between palatal morphology and pharyngeal airway morphology in patients who have obstructive sleep apnea (OSA) and compare with a nonsnoring and nonapneic control group. Materials and Methods: Three-dimensional maxillary dental cast measurements from 25 OSA patients (6 women, 19 men) with a mean age of 41.5 (4.8) years, and 25 control group participants (14 women, 11 men) without any symptom of OSA with a mean age of 38.3 (3.7) were correlated with an analysis of pharyngeal area evaluated with lateral cephalograms. Intermolar and intercanine widths and palatal volumes were calculated on the dental casts, and the upper airway area measurements were performed on lateral cephalograms. Results: OSA patients had smaller oropharyngeal volume and upper airway when compared with controls (P &lt; .001). Palatal area measurements were significantly smaller in OSA (P &lt; .001). OSA patients had significantly narrower maxilla with smaller intermolar and intercanine widths (P &lt; .001). A positive correlation was found between the palatal morphology and pharyngeal dimensions. Conclusions: A significant correlation exists between palatal morphology and pharyngeal airway.

Abstract 151: The Effects of Obstructive Sleep Apnea on the Cerebral Vascular Wall

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Robert M Bryan ◽  
Randy F Crossland ◽  
David J Durgan
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Cerebral Arteries ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Vascular Wall ◽  
Sleep Cycle ◽  
No Production ◽  
No Donor ◽  
Obstructive Sleep

Obstructive sleep apnea (OSA) is a significant risk factor for stroke. However, little is known regarding how OSA affects the cerebrovascular wall. We hypothesized that (A) OSA will attenuate dilations of cerebral arteries by agonist-induced NO release from cerebrovascular endothelium and (B) OSA will upregulate endothelin-1 (ET-1)-mediated constrictions in cerebral arteries. Airway obstructions were induced by chronically implanting inflatable endotracheal obstruction devices (ODs). The ODs were remotely controlled by a computer to produce 30 apneas/hr (10 sec each) during 8 hrs of the sleep cycle in free-ranging rats. During apnea pO 2 decreased from 122±3 to 67±3 mm Hg; pCO 2 increased from 43±1 to 51±1 mm Hg; pH decreased from 7.46±0.00 to 7.38±0.01; and hemoglobin O 2 saturation decreased from 94±1 to 82±1 % (n=5 and p<0.003 for each). After 4 weeks of apnea blood pressure in OSA rats were similar to that in sham rats (108±1 and 103±1 mmHg respectively). Cerebral arteries were isolated after 4 weeks from sham and OSA rats, mounted on pipettes, and pressurized. Diameter changes of the cerebral arteries were measured after the addition of various agents. Dilations to ATP, a P2Y 2 agonist which stimulates NO production in the endothelium, were attenuated in cerebral arteries from OSA rats by 40% (n=5-8, P<0.05). However, the dilations to the NO donor, MAHMA-NOnoate, were similar between groups. Sensitivity to ET-1, an agonist for ET A and ET B , was increased ~20 fold in OSA arteries. EC 50 s for ET-1 constrictions in cerebral arteries from sham and OSA rats were 10.7 ± 4.3 nM and 0.5 ± 0.4 nM respectively (n=5-6, p=0.01). Constrictions to IRL-1620, a selective ET B agonist, were enhanced 11-fold in OSA compared to sham cerebral arteries (n=3-4, p<0.01). In preliminary studies, the increased sensitivity to ET-1in cerebral arteries from OSA rats was attenuated by the ET B antagonist, BQ-788. We conclude that OSA produces pathological changes involving decreased endothelial-derived NO production and enhances constrictor responses to ET-1 as a result of ET B upregulation. Since blood pressures were similar in the OSA and sham rats, we conclude that cerebrovascular dysfunction can occur with OSA in the absence of coexisting hypertension.

Aerodynamics Analysis of the Impact of Nasal Surgery on Patients with Obstructive Sleep Apnea and Nasal Obstruction

ORL ◽  
2021 ◽  
pp. 1-8
Author(s):  
Lifeng Li ◽  
Demin Han ◽  
Hongrui Zang ◽  
Nyall R. London
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Nasal Obstruction ◽  
Upper Airway ◽  
Apnea Hypopnea Index ◽  
Nasal Surgery ◽  
Subjective Sleep Quality ◽  
Obstructive Sleep ◽  
Significant Difference ◽  
The Impact

<b><i>Objective:</i></b> The purpose of this study was to evaluate the effects of nasal surgery on airflow characteristics in patients with obstructive sleep apnea (OSA) by comparing the alterations of airflow characteristics within the nasal and palatopharyngeal cavities. <b><i>Methods:</i></b> Thirty patients with OSA and nasal obstruction who underwent nasal surgery were enrolled. A pre- and postoperative 3-dimensional model was constructed, and alterations of airflow characteristics were assessed using the method of computational fluid dynamics. The other subjective and objective clinical indices were also assessed. <b><i>Results:</i></b> By comparison with the preoperative value, all postoperative subjective symptoms statistically improved (<i>p</i> &#x3c; 0.05), while the Apnea-Hypopnea Index (AHI) changed little (<i>p</i> = 0.492); the postoperative airflow velocity and pressure in both nasal and palatopharyngeal cavities, nasal and palatopharyngeal pressure differences, and total upper airway resistance statistically decreased (all <i>p</i> &#x3c; 0.01). A significant difference was derived for correlation between the alteration of simulation metrics with subjective improvements (<i>p</i> &#x3c; 0.05), except with the AHI (<i>p</i> &#x3e; 0.05). <b><i>Conclusion:</i></b> Nasal surgery can decrease the total resistance of the upper airway and increase the nasal airflow volume and subjective sleep quality in patients with OSA and nasal obstruction. The altered airflow characteristics might contribute to the postoperative reduction of pharyngeal collapse in a subset of OSA patients.

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