High-throughput Flow Cytometry Cell-based Assay to Detect Antibodies to N-Methyl-D-aspartate Receptor or Dopamine-2 Receptor in Human Serum

Over the recent years, antibodies against surface and conformational proteins involved in neurotransmission have been detected in autoimmune CNS diseases ...

The University of Sydney

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.

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

We studied the impact of wall strain and surrounding pressure on the onset of airflow limitation in a thin-walled "floppy" tube model. A vacuum source-generated steady-state (baseline) airflow (0-350 ml/s) through a thin-walled latex tube (length 80 mm, wall thickness 0.23 mm) enclosed within a rigid, sealed, air-filled, cylindrical chamber while upstream minus downstream pressure, chamber pressure (Pc), and lumen geometry [in-line digital camera; segmentation (Amira 5.2.2) and analysis (Rhinoceros 4) software] were monitored. Longitudinal strain (S; 0-62.5%) and Pc (0-20 cmH(2)O) combinations were imposed, and Pc associated with onset of 1) reduced airflow and 2) fully developed airflow limitation recorded. At any strain, increasing Pc resulted in a decrease in airflow. Across all baseline airflow, threshold pressure was 1-7 cmH(2)O for S < 25%, 6-8 cmH(2)O at S = 25% and 37.5%, and 5-7 cmH(2)O at S = 50% and 62.5%. Pc associated with fully developed airflow limitation was 4-6 cmH(2)O for S < 25%, >20 cmH(2)O at S = 25% (i.e., no flow limitation), 18 cmH(2)O at S = 37.5%, and 8-12 cmH(2)O at S = 50% and 62.5%. Lumen area decreased with increasing Pc but was 1) larger at S = 25% and 2) characterized by bifold narrowing at S < 25% and trifold narrowing at S ≥ 25%. In conclusion, tube function was modulated by Pc vs. S interactions, with S = 25% producing trifold lumen narrowing, maximal patency, and no airflow limitation. Findings may have implications for understanding peripharyngeal tissue pressure and pharyngeal wall strain effects on passive pharyngeal airway function in humans.

Onset of airflow limitation in a collapsible tube model: impact of surrounding pressure, longitudinal strain, and wall folding geometry.

Increasing lung volume improves upper airway airflow dynamics via passive mechanisms such as reducing upper airway extraluminal tissue pressures (ETP) and increasing longitudinal tension via tracheal displacement. We hypothesized a threshold lung volume for optimal mechanical effects on upper airway airflow dynamics. Seven supine, anesthetized, spontaneously breathing New Zealand White rabbits were studied. Extrathoracic pressure was altered, and lung volume change, airflow, pharyngeal pressure, ETP laterally (ETPlat) and anteriorly (ETPant), tracheal displacement, and sternohyoid muscle activity (EMG%max) monitored. Airflow dynamics were quantified via peak inspiratory airflow, flow limitation upper airway resistance, and conductance. Every 10-ml lung volume increase resulted in caudal tracheal displacement of 2.1 ± 0.4 mm (mean ± SE), decreased ETPlat by 0.7 ± 0.3 cmH(2)O, increased peak inspiratory airflow of 22.8 ± 2.6% baseline (all P < 0.02), and no significant change in ETPant or EMG%max. Flow limitation was present in most rabbits at baseline, and abolished 15.7 ± 10.5 ml above baseline. Every 10-ml lung volume decrease resulted in cranial tracheal displacement of 2.6 ± 0.4 mm, increased ETPant by 0.9 ± 0.2 cmH(2)O, ETPlat was unchanged, increased EMG%max of 11.1 ± 0.3%, and a reduction in peak inspiratory airflow of 10.8 ± 1.0%baseline (all P < 0.01). Lung volume, resistance, and conductance relationships were described by exponential functions. In conclusion, increasing lung volume displaced the trachea caudally, reduced ETP, abolished flow limitation, but had little effect on resistance or conductance, whereas decreasing lung volume resulted in cranial tracheal displacement, increased ETP and increased resistance, and reduced conductance, and flow limitation persisted despite increased muscle activity. We conclude that there is a threshold for lung volume influences on upper airway airflow dynamics.

A threshold lung volume for optimal mechanical effects on upper airway airflow dynamics: studies in an anesthetized rabbit model.

Baroreflex sensitivity (BRS) is reduced in humans during snoring, however the mechanisms are unknown. We used an anaesthetised rabbit induced snoring (IS) model, to test: (1) whether IS was associated with reduced BRS; and (2) if snoring related vibration transmission to peri-carotid tissues influenced BRS levels. BRS was quantified using the spontaneous sequence technique. During IS, BRS fell by 40%, without any associated change in blood pressure (BP) but accompanied by an increase in heart rate (HR). Direct application of a snore frequency and intensity matched vibratory stimulus to the peri-carotid tissues of non-snoring tracheostomised rabbits had no effect on BRS, HR or BP. In conclusion, IS induced depression of BRS is likely mediated via a HR driven change in BRS operating point that is unrelated to snoring-related vibration transmission to carotid baroreceptors. The anaesthetised IS rabbit provides a model in which mechanistic interactions between snoring and BRS can be further explored.

Snoring effects on the baroreflex: an animal model.

Baroreflex sensitivity (BRS) is reduced during snoring in humans and animal models. We utilised our rabbit model to examine the contribution of increased upper airway resistance to baroreflex resetting during snoring, by comparing BRS and baroreflex operating point (OP) values during IS to those obtained during tracheostomised breathing through an external resistive load (RL) titrated to match IS levels of peak inspiratory pleural pressure (Ppl). During both IS and RL, BRS decreased by 45% and 49%. There was a linear relationship between the change in Ppl and the decrease in BRS, which was similar for IS and RL. During both RL and IS, there was a shift in OP driven by ~16% increase in HR and no change in arterial pressure. Snoring related depression of BRS is likely mediated via a HR driven change in OP, which itself may be the outcome of negative intra-thoracic pressure mediated effects on right atrial wall stretch reflex control of heart rate.

Mazen Amatoury

Institute for Neuroscience and Muscle Research,
The Kids Research Institute at the Children's Hospital at Westmead,
Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children's Hospital at Westmead

The University of Sydney

High-throughput Flow Cytometry Cell-based Assay to Detect Antibodies to N-Methyl-D-aspartate Receptor or Dopamine-2 Receptor in Human Serum