Dataset Information

A novel mouse model of obstructive sleep apnea by bulking agent-induced tongue enlargement results in left ventricular contractile dysfunction.

ABSTRACT: Aims: Obstructive sleep apnea (OSA) is a widespread disease with high global socio-economic impact. However, detailed pathomechanisms are still unclear, partly because current animal models of OSA do not simulate spontaneous airway obstruction. We tested whether polytetrafluoroethylene (PTFE) injection into the tongue induces spontaneous obstructive apneas.

Methods and results: PTFE (100 ?l) was injected into the tongue of 31 male C57BL/6 mice and 28 mice were used as control. Spontaneous apneas and inspiratory flow limitations were recorded by whole-body plethysmography and mRNA expression of the hypoxia marker KDM6A was quantified by qPCR. Left ventricular function was assessed by echocardiography and ventricular CaMKII expression was measured by Western blotting. After PTFE injection, mice showed features of OSA such as significantly increased tongue diameters that were associated with significantly and sustained increased frequencies of inspiratory flow limitations and apneas. Decreased KDM6A mRNA levels indicated chronic hypoxemia. 8 weeks after surgery, PTFE-treated mice showed a significantly reduced left ventricular ejection fraction. Moreover, the severity of diastolic dysfunction (measured as E/e') correlated significantly with the frequency of apneas. Accordingly, CaMKII expression was significantly increased in PTFE mice and correlated significantly with the frequency of apneas.

Conclusions: We describe here the first mouse model of spontaneous inspiratory flow limitations, obstructive apneas, and hypoxia by tongue enlargement due to PTFE injection. These mice develop systolic and diastolic dysfunction and increased CaMKII expression. This mouse model offers great opportunities to investigate the effects of obstructive apneas.

SUBMITTER: Lebek S

PROVIDER: S-EPMC7728202 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A novel mouse model of obstructive sleep apnea by bulking agent-induced tongue enlargement results in left ventricular contractile dysfunction.

Lebek Simon S Hegner Philipp P Schach Christian C Reuthner Kathrin K Tafelmeier Maria M Maier Lars Siegfried LS Arzt Michael M Wagner Stefan S

PloS one 20201210 12

<h4>Aims</h4>Obstructive sleep apnea (OSA) is a widespread disease with high global socio-economic impact. However, detailed pathomechanisms are still unclear, partly because current animal models of OSA do not simulate spontaneous airway obstruction. We tested whether polytetrafluoroethylene (PTFE) injection into the tongue induces spontaneous obstructive apneas.<h4>Methods and results</h4>PTFE (100 μl) was injected into the tongue of 31 male C57BL/6 mice and 28 mice were used as control. Spont ...[more]

PMID: 33301470

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Project description:Study objectivesObstructive sleep apnea (OSA) is associated with cardiovascular comorbidities such as left ventricular (LV) hypertrophy. Whether OSA is an independent etiological factor for this hypertrophic remodeling is yet unknown. Continuous positive airway pressure partially reverses this hypertrophy, but data regarding the effect of mandibular advancement devices on LV remodeling are scarce. The aim of this prospective trial is to evaluate the effect of mandibular advancement device therapy on LV geometry and function in patients with OSA.MethodsAt baseline and 6-month follow-up, participants underwent a home sleep apnea test, 24-hour ambulatory blood pressure monitoring and a 2-dimensional Doppler and tissue Doppler echocardiography.ResultsSixty-three patients (age: 49 ± 11 years; body mass index: 27.0 ± 3.4 kg/m2; baseline apnea-hypopnea index home sleep apnea test: 11.7 [8.2; 24.9] events/h) completed the 6-month follow-up visit. Overall, blood pressure values and parameters of LV function were within normal ranges at baseline and did not change under mandibular advancement device therapy. In contrast, the interventricular septum thickness was at the upper limits of normal at baseline and showed a significant decrease at 6-month follow-up (11.1 ± 2.1 mm vs 10.6 ± 2.0 mm, P = .03). This significant improvement is only found in responders but not in nonresponders. There was no correlation between the decrease of interventricular septum thickness and the change in blood pressure.ConclusionsIn mildly obese, normotensive patients with OSA we observed significant reverse hypertrophic remodeling after 6 months of successful mandibular advancement device therapy, with maintained normotensive systemic blood pressure. This suggests that OSA is an independent factor in the pathophysiology of LV hypertrophy in these patients.Clinical trial registrationRegistry: ClinicalTrials.gov; Name: Evaluation of the Cardiovascular Effects of the MAS in the Treatment of Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT02320877; Identifier: NCT02320877.CitationDieltjens M, Vanderveken OM, Shivalkar B, et al. Mandibular advancement device treatment and reverse left ventricular hypertrophic remodeling in patients with obstructive sleep apnea. J Clin Sleep Med. 2022;18(3):903-909.

Project description:ObjectivesThe aim of this study was to identify correlations between sleep apnea severity and tongue volume or posterior airway space measured via three-dimensional reconstruction of volumetric computerized tomography (CT) images in patients with obstructive sleep apnea (OSA) for use in predicting OSA severity and in surgical treatment. We also assessed associations between tongue volume and Mallampati score.MethodsSnoring/OSA male patients (n = 64) who underwent polysomnography, cephalometry, and CT scans were enrolled in this retrospective study. OSA was diagnosed when the apnea-hypopnea index (AHI) was greater than 5 (mild 5-14; moderate 15-29; severe>30). The patients were also categorized into the normal-mild group (n = 22) and the moderate-severe group (n = 42). Using volumetric CT images with the three-dimensional reconstruction technique, the volume of the tongue, posterior airway space volume, and intra-mandibular space were measured. The volumes, polysomnographic parameters, and physical examination findings were compared, and independent factors that are related to OSA were analysed.ResultsNo associations between tongue volume or posterior airway space and the AHI were observed. However, multivariate linear analyses showed that tongue volume had significantly negative association with lowest O2 saturation (r = 0.365, p = 0.027). High BMI was related to an increase in tongue volume. Modified Mallampati scores showed borderline significant positive correlations with absolute tongue volume (r = 0.251, p = 0.046) and standardized tongue volume (absolute tongue volume / intramandibular area; r = 0.266, p = 0.034). Between the normal-mild and moderate-severe groups, absolute tongue volumes were not different, although the standardized tongue volume in the moderate-severe group was significantly higher.ConclusionAbsolute tongue volume showed stronger associations with lowest O2 saturation during sleep than with the severity of AHI. We also found that high BMI was a relevant factor for an increase in absolute tongue volume and modified Mallampati grading was a useful physical examination to predict tongue size.

Project description:BackgroundLeft ventricular geometry and left atrium (LA) enlargement are risk factors for cardiovascular disease. However, reports on the relationship between left ventricular geometry and LA volume yielded contradictory findings, and LA phasic function remains unclear. Hence, this study aimed to investigate the influence of left ventricular geometry on LA volume and phasic function in patients with obstructive sleep apnea syndrome (OSAS) via a multimodal echocardiographic approach.MethodsIn this cross-sectional study, 221 patients with OSAS (age 20-68 years, mean age 45.27 ± 12.50 years) underwent clinical evaluation, polysomnography, and multimodal echocardiographic examination with two-dimensional echocardiography (2DE), two-dimensional speckle-tracking echocardiography (2D-STE) and three-dimensional echocardiography (3DE). Based on conventional classification of left ventricular geometry, patients with OSAS were divided into four groups: normal geometry (NG), concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH).ResultsBased on 2DE and 3DE, the LA volumes and indices gradually increased from NG to CH. Additionally, 2DE and 3DE LA maximum volume index (LAVImax) were higher in patients with CH and EH than in patients with NG and CR (P < 0.05). The reservoir function, estimated by LA total emptying fraction (LA TotEF) was lower in patients with CH than in patients with NG in 2DE and 3DE (both, P < 0.05). Also, LA conduit function, evaluated by LA passive emptying fraction (LA PassEF) was lower in patients with CH than in patients with NG and CR, and in patients with EH than in those with NG in 2DE and 3DE (all, P < 0.05). The LA booster pump function, evaluated by LA active emptying fraction (LA ActEF) showed no statistically significant difference in 2DE; however, it was greater in patients with CH than in those with NG in 3DE. Similar results were obtained by 2D-STE, and CH was significantly associated with LA strain during systole (LAS-S, β = - 0.546, 95%CI: - 6.371-(- 3.444); P < 0.001), early diastole (LAS-E, β = - 0.636, 95%CI: - 9.532-(- 5.710); P < 0.001), and late diastole (LAS-A, β = - 0.450, 95%CI: 1.518-3.909; P < 0.001) in multiple linear regression.ConclusionsThe LA phasic function changed with left ventricular geometry via multimodal echocardiography. CH had the most notable negative effect on the maximum volume and phasic function of the LA.

Dataset Information

A novel mouse model of obstructive sleep apnea by bulking agent-induced tongue enlargement results in left ventricular contractile dysfunction.

Publications

A novel mouse model of obstructive sleep apnea by bulking agent-induced tongue enlargement results in left ventricular contractile dysfunction.

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