Intrapulmonary shunt and alveolar dead space in a cohort of patients with acute COVID-19 pneumonitis and early recovery.

BACKGROUND: Pathological evidence suggests that coronavirus disease 2019 (COVID-19) pulmonary infection involves both alveolar damage (causing shunt) and diffuse microvascular thrombus formation (causing alveolar dead space). We propose that measuring respiratory gas exchange enables detection and quantification of these abnormalities. We aimed to measure shunt and alveolar dead space in moderate COVID-19 during acute illness and recovery. METHODS: We studied 30 patients (22 males; mean±sd age 49.9±13.5 years) 3-15 days from symptom onset and again during recovery, 55±10 days later (n=17). Arterial blood (breathing ambient air) was collected while exhaled oxygen and carbon dioxide concentrations were measured, yielding alveolar-arterial differences for each gas (P A-aO2 and P a-ACO2 , respectively) from which shunt and alveolar dead space were computed. RESULTS: For acute COVID-19 patients, group mean (range) for P A-aO2 was 41.4 (-3.5-69.3) mmHg and for P a-ACO2 was 6.0 (-2.3-13.4) mmHg. Both shunt (% cardiac output) at 10.4% (0-22.0%) and alveolar dead space (% tidal volume) at 14.9% (0-32.3%) were elevated (normal: <5% and <10%, respectively), but not correlated (p=0.27). At recovery, shunt was 2.4% (0-6.1%) and alveolar dead space was 8.5% (0-22.4%) (both p<0.05 versus acute). Shunt was marginally elevated for two patients; however, five patients (30%) had elevated alveolar dead space. CONCLUSIONS: We speculate impaired pulmonary gas exchange in early COVID-19 pneumonitis arises from two concurrent, independent and variable processes (alveolar filling and pulmonary vascular obstruction). For most patients these resolve within weeks; however, high alveolar dead space in ∼30% of recovered patients suggests persistent pulmonary vascular pathology.

Retinal abnormalities, although relatively common in sleep clinic patients referred for polysomnography, are largely unrelated to sleep-disordered breathing.

STUDY OBJECTIVES: There has been long-standing interest in potential links between obstructive sleep apnea (OSA) and eye disease. This study used retinal photography to identify undiagnosed retinal abnormalities in a cohort of sleep clinic patients referred for polysomnography (PSG) and then determined associations with PSG-quantified sleep-disordered breathing (SDB) severity. METHODS: Retinal photographs (n = 396 patients) were taken of each eye prior to polysomnography and graded according to validated, standardized, grading scales. SDB was quantified via in-laboratory polysomnography (PSG; n = 385) using standard metrics. A questionnaire (n = 259) documented patient-identified pre-existing eye disease. Within-group prevalence rates were calculated on a per patient basis. Data were analyzed using multivariate logistic regression models to determine independent predictors for retinal abnormalities. P < 0.05 was considered significant. RESULTS: Main findings were (1) 76% of patients reported no pre-existing "eye problems"; (2) however, 93% of patients had at least one undiagnosed retinal photograph-identified abnormality; (3) most common abnormalities were drusen (72%) and peripapillary atrophy (PPA; 47%); (4) age was the most common risk factor; (5) diabetes history was an expected risk factor for retinopathy; (6) patients with very severe levels of SDB (apnea hypopnea index ≥ 50 events/h) were nearly three times more likely to have PPA. CONCLUSION: Retinal photography in sleep clinic settings will likely detect a range of undiagnosed retinal abnormalities, most related to patient demographics and comorbidities and, except for PPA, not associated with SDB. PPA may be indicative of glaucoma, and any association with severe SDB should be confirmed in larger prospective studies.

Cancer sleep symptom-related phenotypic clustering differs across three cancer specific patient cohorts.

Specific sleep disorders have been linked to disease progression in different cancers. We hypothesised sleep symptom clusters would differ between cancer types. The aim of this study was to compare sleep symptom clusters in post-treatment melanoma, breast and endometrial cancer patients. Data were collected from 124 breast cancer patients (1 male, 60 ± 15 years, 28.1 ± 6.6 kg/m2 ), 82 endometrial cancer patients (64.0 ± 12.5 years, 33.5 ± 10.4 kg/m2 ) and 112 melanoma patients (59 male, 65.0 ± 18.0 years, 29.1 ± 6.6 kg/m2 ). All patients completed validated questionnaires to assess sleep symptoms, including the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10). Snoring, tiredness, observed apneas, age, BMI, and gender data were also collected. Binary values (PSQI, ISI, FOSQ), or continuous variables for sleepiness (ESS) and perceived sleep quality (PSQI), were created and sleep symptom clusters were identified and compared across cancer cohorts. Four distinct sleep symptom clusters were identified: minimally symptomatic (n = 152, 47.7%); insomnia-predominant (n = 87, 24.9%); very sleepy with upper airway symptoms (n = 51, 16.3%), and severely symptomatic with severe dysfunction (n = 34, 11.1%). Breast cancer patients were significantly more likely to be in the insomnia predominant or severely symptomatic with severe dysfunction clusters, whereas melanoma patients were more likely to be minimally symptomatic or sleepy with upper airway symptoms (p <0.0001). Endometrial cancer patients were equally distributed across symptom clusters. Sleep symptom clusters vary across cancer patients. A more personalised approach to the management of sleep-related symptoms in these patients may improve the long term quality of life and survival.

Anthropometric and craniofacial sexual dimorphism in obstructive sleep apnea patients: is there male-female phenotypical convergence?

Obstructive sleep apnea (OSA) is more common in men than women. Body size is greater in males (sexual dimorphism), but large body habitus is associated with OSA for both genders. We speculated that male-female phenotypical convergence (reduced sexual dimorphism via identical phenotype acquisition) occurs with OSA and tested hypotheses: (1) phenotypical features pathogenic for OSA differ between OSA and healthy subjects irrespective of gender; and (2) such characteristics exhibit phenotypical convergence. Utilizing an existing database, we calculated male-female (group average) ratios for eight anthropometric and 33 surface cephalometric variables from 104 Caucasian OSA patients [72 males; apnea-hypopnea index (events h(-1) ): males: 42.3 ± 24.7 versus females: 42.6 ± 26.1 (P > 0.9)] and 85 Caucasian, healthy, non-OSA, community volunteers (36 males). Log-transformed data were analysed using a general linear model with post-hoc unpaired t-tests and significance at P < 0.0012 (Bonferroni multiple-comparison correction). OSA patients were older (56.9 ± 14.4 versus 38.0 ± 13.8 years), but there were no within-group gender-based age differences. All anthropometric variables (except height), plus cranial base width, mandibular breadth and retromandibular width diagonal were larger in gender-matched OSA versus healthy comparisons; thus satisfying hypothesis (1). Male-female ratios were mostly >1.0 across groups, but with no significant group × gender interactions no variable satisfied hypothesis (2). Thus, in this exploratory study, OSA patients had gender-common phenotypical differences to healthy subjects, but sexual dimorphism was preserved. Lack of complete phenotypical convergence may indicate gender-based critical phenotype-level attainment for OSA and/or gender-based OSA prevalence arises from factors other than those in this study.

Surface cephalometric and anthropometric variables in OSA patients: statistical models for the OSA phenotype.

STUDY OBJECTIVE: We used statistical modelling to probe the contributions of anthropometric and surface cephalometric variables to the OSA phenotype. DESIGN: The design is prospective cohort study. SETTING: The setting is community-based and sleep disorder laboratory. PATIENTS OR PARTICIPANTS: Study #1-Model development study: 147 healthy asymptomatic volunteers (62.6 % Caucasian; age, 18-76 years; 81 females; median multivariable apnea prediction index=0.15) and 140 diagnosed OSA patients (84.3 % Caucasian; age, 18-83 years; 41 females; polysomnography [PSG] determined apnea-hypopnea index >10 events/h). Study #2-Model test study: 345 clinic patients (age, 18-86 years; 129 females) undergoing PSG for diagnosis of OSA. INTERVENTION: We measured 10 anthropometric and 34 surface cephalometric dimensions (calipers) and calculated mandibular enclosure volumes for study #1 and recorded age and neck circumference for study #2. Statistical modelling included principal component (PC), logistic regression, and receiver-operator curve analyses. MEASUREMENTS AND RESULTS: Model development study: A regression model incorporating three identified PC predicted OSA with 88 % sensitivity and specificity. However, a simplified model based on age and NC alone was equally effective (87 % sensitivity and specificity). Model test study: The simplified model predicted OSA with high sensitivity (93 %) but poor specificity (21 %). CONCLUSION: We conclude that in our clinic-based cohort, craniofacial bony and soft tissue structures (excluding neck anatomy) do not play a substantial role in distinguishing patients with OSA from those without. This may be because craniofacial anatomy does not contribute greatly to the pathogenesis of OSA in this group or because referral bias has created a relatively homogeneous phenotypic population.

Sleep disordered breathing has minimal association with retinal microvascular diameters in a non-diabetic sleep clinic cohort.

INTRODUCTION: Obstructive sleep apnea (OSA) may increase stroke risk; retinal arteriolar (central retinal arteriolar equivalent, CRAE) diameter narrowing and/or retinal venular (central retinal venule equivalent, CRVE) widening may predict stroke. We examined relationships between sleep disordered breathing (SDB) and CRAE and CRVE and in a diabetes-free sleep clinic cohort. METHODS: Patients for SDB assessment were recruited (Main Group, n = 264, age: 58.5 ± 8.9 yrs [mean ± SD]; males: 141) for in-laboratory polysomnography (standard metrics, eg apnea hypopnea index, AHI) and retinal photographs (evening and morning). A more severe SDB sub-group (n = 85) entered a 12-month cardiovascular risk factor minimisation (hypertension/hypercholesterolemia control; RFM) and continuous positive airway pressure (CPAP) intervention (RFM/CPAP Sub-Group); successfully completed by n = 66 (AHI = 32.4 [22.1-45.3] events/hour, median[IQR]). Univariate (Spearman's correlation, t-test) and multiple linear regression models examined non-SDB and SDB associations with CRAE and CRVE measures. RESULTS: Main Group: Evening CRAE predictors were: systolic blood pressure (0.18µm decrease per mmHg, p = 0.001), age (2.47µm decrease per decade, p = 0.012), Caucasian ethnicity (4.45 µm versus non-Caucasian, p = 0.011), height (0.24 µm decrease per cm increase, p = 0.005) and smoking history (3.08 µm increase, p = 0.052). Evening CRVE predictors were: Caucasian ethnicity (11.52 µm decrease versus non-Caucasian, p>0.001), diastolic blood pressure (0.34 µm increase in CRVE per mmHg, p = 0.001), hypertension history (6.5 µm decrease, p = 0.005), and smoking history (4.6 µm increase, p = 0.034). No SDB metric (all p>0.08) predicted CRAE or CRVE measures. RFM/CPAP Sub-Group: A one-unit increase in ln(AHI+1) was associated with a 0.046µm increase in CRAE (n = 85; p = 0.029). Mean evening CRAE and CRVE values did not change across the intervention (n = 66), but evening CRVE decreased ~6.0 µm for individuals with AHI >30 events/hr. CONCLUSION: No major SDB associations with CRAE or CRVE were identified, although the RFM/CPAP intervention reduced evening CRVE for severe OSA patients. Implications for cerebro-vascular disease risk remain uncertain. TRIAL REGISTRATION: The protocol was registered with the Australian New Zealand Clinical Trials Registry (Trial Id: ACTRN12620000694910).

Increased intrapulmonary shunt and alveolar dead space post-COVID-19.

Increased intrapulmonary shunt (QS/Qt) and alveolar dead space (VD/VT) are present in early recovery from 2019 Novel Coronavirus (COVID-19). We hypothesized patients recovering from severe critical acute illness (NIH category 3-5) would have greater and longer lasting increased QS/Qt and VD/VT than patients with mild-moderate acute illness (NIH 1-2). Fifty-nine unvaccinated patients (33 males, aged 52 [38-61] yr, body mass index [BMI] 28.8 [25.3-33.6] kg/m2; median [IQR], 44 previous mild-moderate COVID-19, and 15 severe-critical disease) were studied 15-403 days postacute severe acute respiratory syndrome coronavirus infection. Breathing ambient air, steady-state mean alveolar Pco2, and Po2 were recorded simultaneously with arterial Po2/Pco2 yielding aAPco2, AaPo2, and from these, QS/Qt%, VD/VT%, and relative alveolar ventilation (40 mmHg/[Formula: see text], VArel) were calculated. Median [Formula: see text] was 39.4 [35.6-41.1] mmHg, [Formula: see text] 92.3 [87.1-98.2] mmHg; [Formula: see text] 32.8 [28.6-35.3] mmHg, [Formula: see text] 112.9 [109.4-117.0] mmHg, AaPo2 18.8 [12.6-26.8] mmHg, aAPco2 5.9 [4.3-8.0] mmHg, QS/Qt 4.3 [2.1-5.9] %, and VD/VT16.6 [12.6-24.4]%. Only 14% of patients had normal QS/Qt and VD/VT; 1% increased QS/Qt but normal VD/VT; 49% normal QS/Qt and elevated VD/VT; 36% both abnormal QS/Qt and VD/VT. Previous severe critical COVID-19 predicted increased QS/Qt (2.69 [0.82-4.57]% per category severity [95% CI], P < 0.01), but not VD/VT. Increasing age weakly predicted increased VD/VT (1.6 [0.1-3.2]% per decade, P < 0.04). Time since infection, BMI, and comorbidities were not predictors (all P > 0.11). VArel was increased in most patients. In our population, recovery from COVID-19 was associated with increased QS/Qt in 37% of patients, increased VD/VT in 86%, and increased alveolar ventilation up to ∼13 mo postinfection. NIH severity predicted QS/Qt but not elevated VD/VT. Increased VD/VT suggests pulmonary microvascular pathology persists post-COVID-19 in most patients.NEW & NOTEWORTHY Using novel methodology quantifying intrapulmonary shunt and alveolar dead space in COVID-19 patients up to 403 days after acute illness, 37% had increased intrapulmonary shunt and 86% had elevated alveolar dead space likely due to independent pathology. Elevated shunt was partially related to severe acute illness, and increased alveolar dead space was weakly related to increasing age. Ventilation was increased in the majority of patients regardless of previous disease severity. These results demonstrate persisting gas exchange abnormalities after recovery.

Mass loading of the upper airway extraluminal tissue space in rabbits: effects on tissue pressure and pharyngeal airway lumen geometry.

Lateral pharyngeal fat pad compression of the upper airway (UA) wall is thought to influence UA size in patients with obstructive sleep apnea. We examined interactions between acute mass/volume loading of the UA extra-luminal tissue space and UA patency. We studied 12 supine, anesthetized, spontaneously breathing, head position-controlled (50 degrees ), New Zealand White rabbits. Submucosal extraluminal tissue pressures (ETP) in the anterolateral (ETPlat) and anterior (ETPant) pharyngeal wall were monitored with surgically inserted pressure transducer-tipped catheters (Millar). Tracheal pressure (Ptr) and airflow (V) were measured via a pneumotachograph and pressure transducer inserted in series into the intact trachea, with hypopharyngeal cross-sectional area (CSA) measured via computed tomography, while graded saline inflation (0-1.5ml) of a compliant tissue expander balloon in the anterolateral subcutaneous tissue was performed. Inspiratory UA resistance (Rua) at 20 ml/s was calculated from a power function fitted to Ptr vs. V data. Graded expansion of the anterolateral balloon increased ETPlat from 2.3 +/- 0.5 cmH(2)O (n = 11, mean +/- SEM) to 5.0 +/- 1.1 cmH(2)O at 1.5-ml inflation (P < 0.05; ANOVA). However, ETPant was unchanged from 0.5 +/- 0.5 cmH(2)O (n = 9; P = 0.17). Concurrently, Rua increased to 119 +/- 4.2% of baseline value (n = 12; P < 0.001) associated with a significant reduction in CSA between 10 and 70% of airway length to a minimum of 82.2 +/- 4.4% of baseline CSA at 40% of airway length (P < 0.05). We conclude that anterolateral loading of the upper airway extraluminal tissue space decreases upper airway patency via an increase in ETPlat, but not ETPant. Lateral pharyngeal fat pad size may influence UA patency via increased tissue volume and pressure causing UA wall compression.

Pharyngeal muscle contraction modifies peri-pharyngeal tissue pressure in rabbits.

We examined the influence of pharyngeal dilator muscle activity on upper airway extraluminal tissue pressure (ETP) distribution and upper airway patency. We studied seven anaesthetised, supine, spontaneously breathing NZ white rabbits. ETP was measured via pressure transducer tipped catheters in lateral (ETP(lat)) and anterior (ETP(ant)) pharyngeal wall tissues. Airflow (V) and tracheal pressure (P) were monitored and upper airway resistance (RUA) calculated. Genioglossus (GG) or bilateral sternohyoid (SH) muscles were electrically stimulated. Tongue protrusion (TP) during GG stimulation was measured. With GG stimulation, RUA decreased to 57.8+/-10.9% (mean+/-S.E.M.) of baseline and TP increased to 4.8+/-0.5mm (both p<0.05), but ETP(lat) (2.6+/-1.5 cm H(2)O) and ETP(ant) (1.4+/-0.8 cm H(2)O) were unchanged. SH stimulation reduced RUA to 53.6+/-6.8%, and ETP(lat) fell by 1.0+/-0.4 cm H(2)O (both p<0.05). ETP(ant) was unchanged. GG muscle contraction decreased RUA without altering ETP, whereas SH contraction altered RUA and ETP(lat), but not ETP(ant). Contraction of the upper airway dilator muscles results in improvements in upper airway patency associated with changes in peri-pharyngeal tissue pressure.

Correction to: Objective and Subjective Effects of a Prototype Nasal Dilator Strip on Sleep in Subjects with Chronic Nocturnal Nasal Congestion.

The article "Objective and Subjective Effects of a Prototype Nasal Dilator Strip on Sleep in Subjects with Chronic Nocturnal Nasal Congestion", written by John R. Wheatley, Terence C. Amis, Sharon A. Lee, Renee Ciesla, Gilbert Shanga was originally published electronically on the publisher's internet portal (currently SpringerLink) on May, 22, 2019 without Open Access. The article has now been made Open Access.

Objective and Subjective Effects of a Prototype Nasal Dilator Strip on Sleep in Subjects with Chronic Nocturnal Nasal Congestion.

INTRODUCTION: This exploratory study characterized the performance of a nasal dilator strip with improved spring forces in lowering nasal resistance during sleep and reducing sleep-disordered breathing in subjects with difficulty sleeping due to chronic nocturnal nasal congestion. METHODS: Subjects applied the strip at bedtime for 28 days (active phase; n = 70). Objective assessments included snoring variables, breathing route during sleep, and polysomnography measures compared with baseline. Nasal breathing, congestion, and sleep were measured subjectively using rating scales and questionnaires. During a crossover nasal resistance phase (n = 55), nasal resistance was measured using posterior rhinomanometry with the strip applied on one of two nights. RESULTS: In the active phase, breathing and sleep were perceived to improve, with less daytime sleepiness (P < 0.04) and increased ease of breathing, sleep quality, staying asleep, and feeling refreshed in the morning (all P < 0.0001). However, while objective polysomnography metrics were generally similar with and without the strip, median wake after sleep onset time was numerically reduced by ~ 11 min, and the spontaneous arousal rate fell by ~ 37%. In the nasal resistance phase (n = 55), median resistance (at 0.2-0.25 l/s) while asleep was 39.1% lower with (n = 37) versus without (n = 36) the strip (1.34 vs. 2.20 cmH2O/l/s; P = 0.048). CONCLUSIONS: This exploratory study supports a role for the improved spring force nasal dilator strip in alleviating sleep-related symptoms in subjects with chronic nasal congestion, potentially via lowering nasal resistance and reducing nocturnal awakenings. A larger study is indicated to confirm these preliminary data. CLINICALTRIALS. GOV IDENTIFIER: NCT03105297. FUNDING: GlaxoSmithKline Consumer Healthcare. Plain language summary available for this article.

Heavy snoring as a cause of carotid artery atherosclerosis.

STUDY OBJECTIVES: Previous studies have suggested that snoring and obstructive sleep apnea hypopnea syndrome may be important risk factors for the development of carotid atherosclerosis and stroke. However, it is not clear if snoring per se is independently related to the risk of developing carotid atherosclerotic plaque. DESIGN: Observational cohort study. SETTING: Volunteer sample examined in a sleep laboratory. PARTICIPANTS: One hundred ten volunteers (snorers and nonsnorers with only mild, nonhypoxic obstructive sleep apnea hypopnea syndrome) underwent polysomnography with quantification of snoring, bilateral carotid and femoral artery ultrasound with quantification of atherosclerosis, and cardiovascular risk factor assessment. Subjects were categorized into 3 snoring groups: mild (0%-25% night snoring), moderate (> 25%-50% night snoring), and heavy (> 50% night snoring). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The prevalence of carotid atherosclerosis was 20% with mild snoring, 32% with moderate snoring, and 64% with heavy snoring (P < 0.04, X2). Logistic regression analysis was used to determine the independent effect of snoring on the prevalence of carotid and femoral atherosclerosis. After adjustment for age, sex, smoking history, and hypertension, heavy snoring was significantly associated with carotid atherosclerosis (odds ratio 10.5; 95% confidence interval 2.1-51.8; P = 0.004) but not with femoral atherosclerosis. CONCLUSIONS: Heavy snoring significantly increases the risk of carotid atherosclerosis, and the increase is independent of other risk factors, including measures of nocturnal hypoxia and obstructive sleep apnea severity. Considering the high prevalence of snoring in the community, these findings have substantial public health implications for the management of carotid atherosclerosis and the prevention of stroke.

Enforced mouth breathing decreases lung function in mild asthmatics.

BACKGROUND AND OBJECTIVE: Nasal breathing provides a protective influence against exercise-induced asthma. We hypothesized that enforced oral breathing in resting mild asthmatic subjects may lead to a reduction in lung function. METHODS: Asymptomatic resting mild asthmatic volunteers (n = 8) were instructed to breathe either nasally only (N; tape over lips) or orally only (O; nose clip) for 1 h each, on separate days. Lung function (% predicted FEV(1)) was measured using standard spirometry at baseline and every 10 min for 1 h. 'Difficulty in breathing' was rated using a Borg scale at the conclusion of the N and O periods. RESULTS: Baseline FEV(1) on the N (101.2 +/- 3.8% predicted) and O (102.7 +/- 3.9% predicted) days was not significantly different (P > 0.3). At 60 min, FEV(1) on the O day (96.5 +/- 4.1% predicted) was significantly less than on the N day (101.0 +/- 3.5% predicted; P < 0.009). On the N day, FEV(1) did not change with time (P > 0.3), whereas on the O day, FEV(1) fell progressively (slope = -0.06 +/- 0.01% FEV(1)/min, P < 0.0001; linear mixed effects modelling). Three subjects experienced coughing/wheezing at the end of the O day but none experienced symptoms at the end of the N day. Subjects perceived more 'difficulty breathing in' at the end of the O day (1.5 +/- 0.4 arbitrary units) than on the N day (0.4 +/- 0.3 arbitrary unit; P < 0.05). CONCLUSIONS: Enforced oral breathing causes a decrease in lung function in mild asthmatic subjects at rest, initiating asthma symptoms in some. Oral breathing may play a role in the pathogenesis of acute asthma exacerbations.

Pupil Dilation May Affect Retinal Vessel Caliber Measures.

PURPOSE: To assess the effect of pupil dilation on measures of retinal vessel caliber. DESIGN: Observational study with self-comparisons Methods: Retinal photographs were taken for both eyes of 25 subjects before and after pupil dilation. Three photographic graders, masked to pupil dilation status, measured the same set of images using a computer-assisted, semi-automatic method. We compared means (standard deviations) of retinal arteriolar caliber equivalent (CRAE) and retinal venular caliber equivalent (CRVE) of the same eyes between pre- and post-dilation images. We assessed concordance correlation coefficients (CC), Bland Altman limits-of-agreements, and used linear mixed models to assess CRAE and CRVE measures associated with pupil dilation (influencing image quality), graders (observers) and right-left eye variation. RESULTS: We found high CCs for CRAE (0.82-0.94) and CRVE (0.87-0.94) between pre- and post-dilation images of the same eyes across the graders. Bland Altman plots showed that mean differences ranged from 0.55-3.42µm for CRAE and 1.56-2.29µm for CRVE. After adjusting for right-left eye random variation, a significant fixed effect of dilation was evident in mean CRAE in two of the three graders. There was no significant fixed effect of dilation in mean CRVE across all graders. In models including data of both eyes' measures from pre- and post-dilation images by three graders, the fixed effect for dilation status contributed significantly to CRAE and CRVE variances whereas random effects for graders and dilation status contributed minimally. CONCLUSIONS: Contrary to our hypothesis, we found a systematic effect of pupil dilation on retinal vessel caliber measures.

Tracheal traction effects on upper airway patency in rabbits: the role of tissue pressure.

STUDY OBJECTIVES: To investigate the mechanisms via which lung volume related caudal tracheal traction decreases upper airway collapsibility. DESIGN: Acute physiological study. PARTICIPANTS: 20 male, supine, anesthetised, tracheostomised, spontaneously breathing, NZ white rabbits fitted with a sealed face mask. SETTING: N/A. MEASUREMENTS AND RESULTS: Upper airway extraluminal tissue pressure (ETP) was measured in the lateral (ETPlat) and anterior (ETPant) pharyngeal walls (pressure transducer tipped catheters). Graded traction was applied to the isolated upper airway (n = 17, 0-140 g). Subsequently, inflation and deflation was performed (with and without traction, 48 g, n = 13) with measurement of intraluminal pressure. Upper airway transmural pressure (PTM) was calculated (at closure and reopening) for both ETP sites (PTMlat and PTMant, respectively). A traction force of 144 g decreased ETPlat from 2.6 +/- 0.7 cm H2O (mean +/- SEM) to 2.1 +/- 0.7 cm H2O and ETPant from 1.1 +/- 0.4 cm H2O to 0.8 +/- 0.4 cm H2O (both P < 0.001). Increasing traction decreased closing and reopening pressures by 1.4 +/- 0.2 cm H2O for 48 g of traction (n = 13, P < 0.0001). In addition, 48 g of traction decreased ETPlat (at closure and reopening) by 0.2 +/- 0.05 cm H2O (P < 0.0001), and decreased ETPant by 0.5 +/- 0.1 cm H2O at closing pressure and 0.8 +/- 0.1 cm H2O at reopening (both p < 0.0001). Thus, for 48 g of traction, PTMlat (at closure and reopening) fell by 1.1 +/- 0.2 cm H2O and PTMant (reopening only) fell by 0.9 +/- 0.3 cm H2O (all P < 0.0001). CONCLUSIONS: Since tracheal traction decreased PTMlat and PTMant by a greater amount than ETPlat and ETPant, we conclude that the decrease in upper airway collapsibility mediated by lung volume related caudal tracheal traction is partially explained by reductions in ETP.

Oscillatory pressure wave transmission from the upper airway to the carotid artery.

Snoring-associated vibration energy transmission from the upper airway to the carotid artery has been hypothesized as a potential atherosclerotic plaque initiating/rupturing event that may provide a pathogenic mechanism linking snoring and embolic stroke. We examined transmission of oscillatory pressure waves from the pharyngeal lumen to the common carotid artery wall and lumen in seven male, anesthetized, spontaneously breathing New Zealand White rabbits. Airflow was monitored via a pneumotachograph inserted in series in the intact trachea. Fifteen 20-s runs of, separately, 40-, 60-, and 90-Hz oscillatory pressure waves [pressure amplitude in the trachea (Ptr(amp)), amplitude 2-20 cmH(2)O] were generated by a loudspeaker driven by a sine wave generator and amplifier and superimposed on tidal breathing via the cranial tracheal connector. Pressure transducer-tipped catheters measured pressure amplitudes in the tissues adjacent to the common carotid artery bifurcation (Pcti(amp)) and within the lumen (carotid sinus; Pcs(amp)). Data were analyzed using power spectrum analysis and linear mixed-effects statistical modeling. Both the frequency (f) and amplitude of the injected pressure wave influenced Pcti(amp) and Pcs(amp), in that ln Pcti(amp) = 1.2(Ptr(amp)) + 0.02(f) - 5.2, and ln Pcs(amp) = 0.6(Ptr(amp)) + 0.02(f) - 4.9 (both P < 0.05). Across all frequencies tested, transfer of oscillatory pressure across the carotid artery wall was associated with an amplitude gain, as expressed by a Pcs(amp)-to-Pcti(amp) ratio of 1.8 +/- 0.3 (n = 6). Our findings confirm transmission of oscillatory pressure waves from the upper airway lumen to the peripharyngeal tissues and across the carotid artery wall to the lumen. Further studies are required to establish the role of this incident energy in the pathogenesis of carotid artery vascular disease.

Mandibular advancement decreases pressures in the tissues surrounding the upper airway in rabbits.

The pharyngeal airway can be considered as an airway luminal shape formed by surrounding tissues, contained within a bony enclosure formed by the mandible, skull base, and cervical vertebrae. Mandibular advancement (MA), a therapy for obstructive sleep apnea, is thought to increase the size of this bony enclosure and to decrease the pressure in the upper airway extraluminal tissue space (ETP). We examined the effect of MA on upper airway airflow resistance (Rua) and ETP in a rabbit model. We studied 11 male, supine, anesthetized, spontaneously breathing New Zealand White rabbits in which ETP was measured via pressure transducer-tipped catheters inserted into the tissues surrounding the lateral (ETPlat) and anterior (ETPant) pharyngeal wall. Airflow, measured via surgically inserted pneumotachograph in series with the trachea, and tracheal pressure were recorded while graded MA at 75 degrees and 100 degrees to the horizontal was performed using an external traction device. Data were analyzed using a linear mixed-effects statistical model. We found that MA at 100 degrees increased mouth opening from 4.7 +/- 0.4 to 6.6 +/- 0.4 (SE) mm (n = 7; P < 0.004), whereas mouth opening did not change from baseline (4.0 +/- 0.2 mm) with MA at 75 degrees . MA at both 75 degrees and 100 degrees decreased mean ETPlat and ETPant by approximately 0.1 cmH2O/mm MA (n = 7-11; all P < 0.0005). However, the fall in Rua (measured at 20 ml/s) with MA was greater for MA at 75 degrees (approximately 0.03 mmH2O.ml(-1).s.mm(-1)) than at 100 degrees (approximately 0.01 mmH2O.ml(-1).s.mm(-1); P < 0.02). From these findings, we conclude that MA decreases ETP and is more effective in reducing Rua without mouth opening.

Snoring-related energy transmission to the carotid artery in rabbits.

Epidemiological studies link habitual snoring and stroke, but mechanisms involved are poorly understood. One previously advanced hypothesis is that transmitted snoring vibration energy may promote carotid atheromatous plaque formation or rupture. To test whether vibration energy is present in carotid artery walls during snoring we developed an animal model in which we examined induced snoring (IS)-associated tissue energy levels. In six male, supine, anesthetized, spontaneously breathing New Zealand White rabbits, we surgically inserted pressure transducer-tipped catheters (Millar) to monitor tissue pressure at the carotid artery bifurcation (PCT) and within the carotid sinus lumen (PCS; artery ligated). Snoring was induced via external compression (sandbag) over the pharyngeal region. Data were analyzed using power spectral analysis for frequency bands above and below 50 Hz. For frequencies below 50 Hz, PCT energy was 2.2 (1.1-12.3) cmH2O2 [median (interquartile range)] during tidal breathing (TB) increasing to 39.0 (2.5-95.0) cmH2O2 during IS (P = 0.05, Wilcoxon's signed-rank test). For frequencies > 50 Hz, PCT energy increased from 9.2 (8.3-10.4) x 10(-4) cmH2O2 during TB to 172.0 (118.0-569.0) x 10(-4) cmH2O2 during IS (P = 0.03). Concurrently, PCS energy was 13.4 (8.5-18.0) x 10(-4) cmH2O2 during TB and 151.0 (78.2-278.8) x 10(-4) cmH2O2 during IS (P < 0.03). The PCS energy was greater than PCT energy for the 100-275 Hz bandwidth. In conclusion, during IS there is increased energy around and within the carotid artery, including lower frequency amplification for PCS. These findings may have implications for carotid atherogenesis and/or plaque rupture.

Development and validation of a computational finite element model of the rabbit upper airway: simulations of mandibular advancement and tracheal displacement.

The mechanisms leading to upper airway (UA) collapse during sleep are complex and poorly understood. We previously developed an anesthetized rabbit model for studying UA physiology. On the basis of this body of physiological data, we aimed to develop and validate a two-dimensional (2D) computational finite element model (FEM) of the passive rabbit UA and peripharyngeal tissues. Model geometry was reconstructed from a midsagittal computed tomographic image of a representative New Zealand White rabbit, which included major soft (tongue, soft palate, constrictor muscles), cartilaginous (epiglottis, thyroid cartilage), and bony pharyngeal tissues (mandible, hard palate, hyoid bone). Other UA muscles were modeled as linear elastic connections. Initial boundary and contact definitions were defined from anatomy and material properties derived from the literature. Model parameters were optimized to physiological data sets associated with mandibular advancement (MA) and caudal tracheal displacement (TD), including hyoid displacement, which featured with both applied loads. The model was then validated against independent data sets involving combined MA and TD. Model outputs included UA lumen geometry, peripharyngeal tissue displacement, and stress and strain distributions. Simulated MA and TD resulted in UA enlargement and nonuniform increases in tissue displacement, and stress and strain. Model predictions closely agreed with experimental data for individually applied MA, TD, and their combination. We have developed and validated an FEM of the rabbit UA that predicts UA geometry and peripharyngeal tissue mechanical changes associated with interventions known to improve UA patency. The model has the potential to advance our understanding of UA physiology and peripharyngeal tissue mechanics.