Nocturnal swallowing augments arousal intensity and arousal tachycardia.

Cortical arousal from sleep is associated with autonomic activation and acute increases in heart rate. Arousals vary considerably in their frequency, intensity/duration, and physiological effects. Sleep and arousability impact health acutely (daytime cognitive function) and long-term (cardiovascular outcomes). Yet factors that modify the arousal intensity and autonomic activity remain enigmatic. In this study of healthy human adults, we examined whether reflex airway defense mechanisms, specifically swallowing or glottic adduction, influenced cardiac autonomic activity and cortical arousal from sleep. We found, in all subjects, that swallows trigger rapid, robust, and patterned tachycardia conserved across wake, sleep, and arousal states. Tachycardia onset was temporally matched to glottic adduction-the first phase of swallow motor program. Multiple swallows increase the magnitude of tachycardia via temporal summation, and blood pressure increases as a function of the degree of tachycardia. During sleep, swallows were overwhelmingly associated with arousal. Critically, swallows were causally linked to the intense, prolonged cortical arousals and marked tachycardia. Arousal duration and tachycardia increased in parallel as a function of swallow incidence. Our findings suggest that cortical feedback and tachycardia are integrated responses of the swallow motor program. Our work highlights the functional influence of episodic, involuntary airway defense reflexes on sleep and vigilance and cardiovascular function in healthy individuals.

Changes in the length and three-dimensional orientation of muscle fascicles and aponeuroses with passive length changes in human gastrocnemius muscles.

The mechanisms by which skeletal muscles lengthen and shorten are potentially complex. When the relaxed human gastrocnemius muscle is at its shortest in vivo lengths it falls slack (i.e. it does not exert any passive tension). It has been hypothesised that when the muscle is passively lengthened, slack is progressively taken up, first in some muscle fascicles then in others. Two-dimensional imaging methods suggest that, once the slack is taken up, changes in muscle length are mediated primarily by changes in the lengths of the tendinous components of the muscle. The aims of this study were to test the hypothesis that there is progressive engagement of relaxed muscle fascicles, and to quantify changes in the length and three-dimensional orientation of muscle fascicles and tendinous structures during passive changes in muscle length. Ultrasound imaging was used to determine the location, in an ultrasound image plane, of the proximal and distal ends of muscle fascicles at 14 sites in the human gastrocnemius muscle as the ankle was rotated passively through its full range. A three-dimensional motion analysis system recorded the location and orientation of the ultrasound image plane and the leg. These data were used to generate dynamic three-dimensional reconstructions of the architecture of the muscle fascicles and aponeuroses. There was considerable variability in the measured muscle lengths at which the slack was taken up in individual muscle fascicles. However, that variability was not much greater than the error associated with the measurement procedure. An analysis of these data which took into account the possible correlations between errors showed that, contrary to our earlier hypothesis, muscle fascicles are not progressively engaged during passive lengthening of the human gastrocnemius. Instead, the slack is taken up nearly simultaneously in all muscle fascicles. Once the muscle is lengthened sufficiently to take up the slack, about half of the subsequent increase in muscle length is due to elongation of the tendinous structures and half is due to elongation of muscle fascicles, at least over the range of muscle-tendon lengths that was investigated (up to ∼60 or 70% of the range of in vivo lengths). Changes in the alignment of muscle fascicles and flattening of aponeuroses contribute little to the total change in muscle length.

Measuring anisotropic muscle stiffness properties using elastography.

Physiological and pathological changes to the anisotropic mechanical properties of skeletal muscle are still largely unknown, with only a few studies quantifying changes in vivo. This study used the noninvasive MR elastography (MRE) technique, in combination with diffusion tensor imaging (DTI), to measure shear modulus anisotropy in the human skeletal muscle in the lower leg. Shear modulus measurements parallel and perpendicular to the fibre direction were made in 10 healthy subjects in the medial gastrocnemius, soleus and tibialis anterior muscles. The results showed significant differences in the medial gastrocnemius (µâ€– = 0.86 ± 0.15 kPa; µâŠ¥ = 0.66 ± 0.19 kPa, P < 0.001), soleus (µâ€– = 0.83 ± 0.22 kPa; µâŠ¥ = 0.65 ± 0.13 kPa, P < 0.001) and the tibialis anterior (µâ€– = 0.78 ± 0.24 kPa; µâŠ¥ = 0.66 ± 0.16 kPa, P = 0.03) muscles, where the shear modulus measured in the direction parallel is greater than that measured in the direction perpendicular to the muscle fibres. No significant differences were measured across muscle groups. This study provides the first direct estimates of the anisotropic shear modulus in the triceps surae muscle group, and shows that the technique may be useful for the probing of mechanical anisotropy changes caused by disease, aging and injury.

Measuring changes in muscle stiffness after eccentric exercise using elastography.

Muscle stiffness has been reported to increase following eccentric muscle exercise, but to date only indirect methods have been used to measure it. This study aimed to use Magnetic Resonance Elastography (MRE), a noninvasive imaging technique, to assess the time-course of passive elasticity changes in the medial gastrocnemius and soleus muscles before and after a bout of eccentric exercise. Shear storage modulus (G') and loss modulus (G'') measurements were made in eight healthy subjects for both muscles in vivo before, one hour after, 48 hours after and 1 week after eccentric exercise. The results show a 21% increase in medial gastrocnemius storage modulus following eccentric exercise with a peak occurring ~48 hours after exercise (before exercise 1.15 ± 0.23 kPa, 48 hours after 1.38 ± 0.27 kPa). No significant changes in soleus muscle storage modulus were measured for the exercise protocol used in this study, and no significant changes in loss modulus were observed. This study provides the first direct measurements in skeletal muscle before and after eccentric exercise damage and suggests that MRE can be used to detect the time course of changes to muscle properties.

Movement of the tongue during normal breathing in awake healthy humans.

Electromyographic (EMG) activity of the airway muscles suggest that genioglossus is the primary upper airway dilator muscle. However, EMG data do not necessarily translate into tissue motion and most imaging modalities are limited to assessment of the surfaces of the upper airway. In this study, we hypothesized that genioglossus moves rhythmically during the respiratory cycle and that the motion within is inhomogeneous. A 'tagged' magnetic resonance imaging technique was used to characterize respiratory-related tissue motions around the human upper airway in quiet breathing. Motion of airway tissues at different segments of the eupnoeic respiratory cycle was imaged in six adult subjects by triggering the scanner at the end of inspiration. Displacements of the 'tags' were analysed using the harmonic phase method (HARP). Respiratory timing was monitored by a band around the upper abdomen. The genioglossus moved during the respiratory cycle. During expiration, the genioglossus moved posteriorly and during inspiration, it moved anteriorly. The degree of motion varied between subjects. The maximal anteroposterior movement of a point tracked on the genioglossus was 1.02 +/- 0.54 mm (mean +/- s.d.). The genioglossus moved over the geniohyoid muscle, with minimal movement in other muscles surrounding the airway at the level of the soft palate. Local deformation of the tongue was analysed using two-dimensional strain maps. Across the respiratory cycle, positive strains within genioglossus reached peaks of 17.5 +/- 9.3% and negative strains reached peaks of -16.3 +/- 9.3% relative to end inspiration. The patterns of strains were consistent with elongation and compression within a constant volume structure. Hence, these data suggest that even during respiration, the tongue behaves as a muscular hydrostat.

Age-specific parental knowledge of restraint transitions influences appropriateness of child occupant restraint use.

OBJECTIVE: To determine the factors that influence appropriate restraint usage by child occupants across the age range for which any type of child restraint may be appropriate (0-10 years). DESIGN: Randomized household telephone survey. SETTING: Statewide survey, New South Wales, Australia. SUBJECTS: Parents or carers of children aged 0-10 years. MAIN OUTCOME MEASURES: Parental reporting of appropriateness of child restraint. METHODS: Demographic information and data on age, size, restraint practices, parental knowledge of child occupant safety, and attitude to restraint use was collected using a structured interview. Data were analysed using logistic regression after cluster adjustment. RESULTS: Inappropriate restraint use by children was widespread, particularly in children aged 2+ years. Overall, parental knowledge of appropriate ages for restraint transitions was associated with increased likelihood of appropriate restraint use. Lower levels of formal parental education, larger families, parental restraint non-use, and parent/child negotiability of restraint use were predictors of inappropriate restraint use. For particular child age subgroups, the parental knowledge that predicted appropriate restraint use was specific to that age group. Most parents felt that they knew enough to safely restrain their child, despite widespread inappropriate restraint use. CONCLUSIONS: Parents are more likely to make appropriate restraint choices for their children if they possess restraint knowledge specific to their children's age and size. Educational campaigns may be most effective when they provide information for specific ages and transition points. Strategies to overcome parents' misplaced confidence that they know enough to restrain their children safely are also indicated.

Models of the pulsatile hydrodynamics of cerebrospinal fluid flow in the normal and abnormal intracranial system.

Images obtained from magnetic resonance imaging have helped to ascertain that both the cerebrospinal fluid (CSF) and brain move in a pulsatile manner within the cranium. However, these images are not able to reveal any quantitative information on the physiological forces that are associated with pulsatile motion. Understanding both the pressure and velocity flow field of CSF in the ventricles is important to help understand the mechanics of hydrocephalus. Four separate fluid structure interaction models of the ventricular system in the sagittal plane were created for this purpose. The first model was of a normal brain. The second and third models were pathological brain models with aqueductal stenosis at various locations along the fluid pathway. The fourth model was of a hydrocephalic brain. Results revealed the hydrodynamics of CSF pulsatile flow in the ventricles of these models. Most importantly, it has also revealed the different changes in CSF pulsatile hydrodynamics caused by the various locations of fluid flow obstructions.

Focal spinal arachnoiditis increases subarachnoid space pressure: a computational study.

BACKGROUND: Enlarging fluid filled cystic cavitations form within the spinal cord in up to 28% of spinal cord injured patients. These post-traumatic syrinxes can cause neurological deterioration and current treatment results are unsatisfactory. Localized scar tissue (arachnoiditis) within the subarachnoid space at the level of injury has been suggested to be involved in the pathogenesis of syrinx formation. This study tests the hypothesis that pressure pulses in the subarachnoid space are accentuated adjacent to regions of arachnoiditis, which may drive fluid into the spinal cord and contribute to syrinx formation. METHODS: An axisymmetric, cylindrical computational fluid dynamics model was developed to represent the subarachnoid space under normal physiological conditions and in the presence of arachnoiditis. Cerebrospinal fluid flow into the model was estimated from magnetic resonance imaging flow studies. Arachnoiditis was modelled as a porous obstruction in the subarachnoid space. FINDINGS: Peak fluid pressures were higher above the obstruction than in the absence of obstruction. The peak pressures were strongly dependent on the permeability of the obstruction. INTERPRETATION: Elevations in subarachnoid space pressures due to arachnoiditis may facilitate fluid flow into the spinal cord, enhancing syrinx formation. This suggests that it may be worthwhile to investigate strategies that inhibit arachnoiditis or minimize systolic pressure peaks for treating or preventing syringomyelia.

Inwardly rectifying potassium channel 4.1 expression in post-traumatic syringomyelia.

Post-traumatic syringomyelia (PTS) is a serious neurological disorder characterized by fluid filled cavities that develop in the spinal cord. PTS is thought to be caused by an imbalance between fluid inflow and outflow in the spinal cord, but the underlying mechanisms are unknown. The ion channel Kir4.1 plays an important role in the uptake of K(+) ions from the extracellular space and release of K(+) ions into the microvasculature, generating an osmotic gradient that drives water movement. Changes in Kir4.1 expression may contribute to disturbances in K(+) homeostasis and subsequently fluid imbalance. Here we investigated whether changes in Kir4.1 protein expression occur in PTS. Western blotting and immunohistochemistry were used to evaluate Kir4.1 and glial fibrillary acidic protein (GFAP) expression in a rodent model of PTS at 3 days, 1, 6 or 12 weeks post-surgery. In Western blotting experiments, Kir4.1 expression increased 1 week post-surgery at the level of the cavity. Immunohistochemical analysis examined changes in the spinal parenchyma directly in contact with the syrinx cavity. In these experiments, there was a significant decrease in Kir4.1 expression in PTS animals compared to controls at 3 days and 6 weeks post-surgery, while an up-regulation of GFAP in PTS animals was observed at 1 and 12 weeks. This suggests that while overall Kir4.1 expression is unchanged at these time-points, there are many astrocytes surrounding the syrinx cavity that are not expressing Kir4.1. The results demonstrate a disturbance in the removal of K(+) ions in tissue surrounding a post-traumatic syrinx cavity. It is possible this contributes to water accumulation in the injured spinal cord leading to syrinx formation or exacerbation of the underlying pathology.

MR Elastography Can Be Used to Measure Brain Stiffness Changes as a Result of Altered Cranial Venous Drainage During Jugular Compression.

BACKGROUND AND PURPOSE: Compressing the internal jugular veins can reverse ventriculomegaly in the syndrome of inappropriately low pressure acute hydrocephalus, and it has been suggested that this works by "stiffening" the brain tissue. Jugular compression may also alter blood and CSF flow in other conditions. We aimed to understand the effect of jugular compression on brain tissue stiffness and CSF flow. MATERIALS AND METHODS: The head and neck of 9 healthy volunteers were studied with and without jugular compression. Brain stiffness (shear modulus) was measured by using MR elastography. Phase-contrast MR imaging was used to measure CSF flow in the cerebral aqueduct and blood flow in the neck. RESULTS: The shear moduli of the brain tissue increased with the percentage of blood draining through the internal jugular veins during venous compression. Peak velocity of caudally directed CSF in the aqueduct increased significantly with jugular compression (P < .001). The mean jugular venous flow rate, amplitude, and vessel area were significantly reduced with jugular compression, while cranial arterial flow parameters were unaffected. CONCLUSIONS: Jugular compression influences cerebral CSF hydrodynamics in healthy subjects and can increase brain tissue stiffness, but the magnitude of the stiffening depends on the percentage of cranial blood draining through the internal jugular veins during compression­that is, subjects who maintain venous drainage through the internal jugular veins during jugular compression have stiffer brains than those who divert venous blood through alternative pathways. These methods may be useful for studying this phenomenon in patients with the syndrome of inappropriately low-pressure acute hydrocephalus and other conditions.

A vertebral dislocation model of spinal cord injury in rats.

A new model of spinal cord injury (SCI) has been developed in the rat, which produces axonal and vascular injury within the spinal cord through lateral displacement of the vertebral column. An electromechanical feedback-controlled device produces the injury by displacing the vertebral column to the left hand side. The speed and lateral displacement is controllable by the user, and the resulting injury ranges from no histologically evident injury, to total disruption of the vertebral column with associated widespread axonal and vascular damage. Histological and immunohistological techniques were employed to correlate mechanical parameters with the extent of pathological injury of spinal cord. Axonal injury was most severe in the left lateral white matter, and vascular injury was concentrated in the gray matter.

Zoledronic acid improves the mechanical properties of normal and healing bone.

OBJECTIVE: To determine the effects of the bisphosphonate zoledronic acid on the mechanical properties of normal and regenerating bone in a rabbit model of distraction osteogenesis. BACKGROUND: Bisphosphonate therapy is used for treating osteoporosis and, more recently, to enhance bone healing and reduce stress-shielding osteoporosis in distraction osteogenesis. METHODS: Thirty eight rabbits underwent 14 days of distraction osteogenesis on the right rear limb. They received either zero, one or two doses of intravenous zoledronic acid. Four point bending tests were performed to collect mechanical data. RESULTS: The peak load capacity of the regenerating bone was significantly increased by bisphosphonate therapy, but a similar trend in normal bone was not significant. The energy absorbed to failure did not vary significantly in either group. CONCLUSIONS: These data suggest that bisphosphonate therapy has a beneficial effect on the load capacity of regenerating bone, without increasing the brittleness of either new or existing bone. RELEVANCE: Zoledronic acid administration may be a potentially valuable adjunct to distraction osteogenesis treatment, to enhance bone strength, thus reducing refracture complications.

Large strain behaviour of brain tissue in shear: some experimental data and differential constitutive model.

In this paper, some experimental measurements of the behaviour of bovine brain tissue under large shear strains in vitro are reported, and a constitutive model which is consistent with the data is developed. It was determined that brain tissue is not strain-time separable, showing slower relaxation at higher strains, and that the stresses in shear are not linear with increasing shear strain. The new constitutive model is a differential model, including both an "elastic" term, of the Mooney type and a nonlinear viscoelastic term. The latter allows for the change in relaxation behaviour with strain, by modifying an upper convected multimode Maxwell model with a damping function. The model shows good agreement with the experimental shear results and could be used to describe other types of data.

Linear viscoelastic properties of bovine brain tissue in shear.

We report the results from a series of rheological tests of fresh bovine brain tissue. Using a standard Bohlin VOR shear rheometer, shear relaxation and oscillating strain sweep experiments were performed on disks of brain tissue 30 mm in diameter, with a thickness of 1.5-2 mm. The strain sweep experiment showed that the viscoelastic strain limit is of the order of 0.1% strain. Shear relaxation data do not indicate the presence of a long-term elastic modulus, indicating fluid-like behavior. A relaxation spectrum was calculated by inverting the experimental data and used to predict oscillatory response, which agreed well with measured data.

Viscoelastic properties of the tongue and soft palate using MR elastography.

Biomechanical properties of the human tongue are needed for finite element models of the upper airway and may be important to elucidate the pathophysiology of obstructive sleep apneoa. Tongue viscoelastic properties have not been characterized previously. Magnetic resonance elastography (MRE) is an emerging imaging technique that can measure the viscoelastic properties of soft tissues in-vivo. In this study, MRE was used to measure the viscoelastic properties of the tongue and soft palate in 7 healthy volunteers during quiet breathing. Results show that the storage shear modulus of the tongue and soft palate is 2.67±0.29 and 2.53±0.31 kPa (mean ± SD), respectively. This is the first study to investigate the mechanical properties of the tongue using MRE, and it provides necessary data for future studies of patient groups with altered upper airway function.

Movement of the human upper airway during inspiration with and without inspiratory resistive loading.

The electromyographic (EMG) activity of human upper airway muscles, particularly the genioglossus, has been widely measured, but the relationship between EMG activity and physical movement of the airway muscles remains unclear. We aimed to measure the motion of the soft tissues surrounding the airway during normal and loaded inspiration on the basis of the hypothesis that this motion would be affected by the addition of resistance to breathing during inspiration. Tagged MR imaging of seven healthy subjects was performed in a 3-T scanner. Tagged 8.6-mm-spaced grids were used, and complementary spatial modulation of magnetization images were acquired beginning ∼200 ms before inspiratory airflow. Deformation of tag line intersections was measured. The genioglossus moved anteriorly during normal and loaded inspiration, with less movement during loaded inspiration. The motion of tissues at the anterior border of the upper airway was nonuniform, with larger motions inferiorly. At the level of the soft palate, the lateral dimension of the airway decreased significantly during loaded inspiration (-0.15 ± 0.09 and -0.48 ± 0.09 mm during unloaded and loaded inspiration, respectively, P < 0.05). When resistance to inspiratory flow was added, genioglossus motion and lateral dimensions of the airway at the level of the soft palate decreased. Our results suggest that genioglossus motion begins early to dilate the airway prior to airflow and that inspiratory loading reduces the anterior motion of the genioglossus and increases the collapse of the lateral airway walls at the level of the soft palate.

Using static preload with magnetic resonance elastography to estimate large strain viscoelastic properties of bovine liver.

Traditional magnetic resonance elastography (MRE) applies small amplitude vibration to tissues. Thus currently MRE measures only the small deformation behaviour of tissues. MRE has the potential to estimate the strain-varying shear modulus of soft tissues, if applied at different static strains, which may allow prediction of the large-strain behaviour of tissues. This study uses MRE of bovine liver specimens under various levels of static compressive pre-strain up to 30%. Storage and loss moduli measured using MRE increased non-linearly with static compressive pre-strain, and exponential models fit well to these data to describe this relationship (R(2)>0.93). Based on these models, a 10% linear compression of liver would result in a 47% overestimate of the 'true' storage modulus of the uncompressed tissue. The results of this study have implications for MRE transducer design and interpretation of results from in vivo MRE studies.

Spinal injury in motor vehicle crashes: elevated risk persists up to 12 years of age.

OBJECTIVE: To determine whether age is associated with serious spinal injury in paediatric motor vehicle occupants, after controlling for crash-related factors. DESIGN AND SETTING: Retrospective record review. PATIENTS AND OUTCOME MEASURES: All motor vehicle passengers aged 0-16 years treated at two major children's hospitals from 1999 to 2004 with ICD-10 codes for spinal trauma. Injury outcomes were categorised as minor and serious. Minor injuries were analogous to AIS 1 injuries. Serious injuries were those that posed some risk to the integrity of the spinal column or cord. RESULTS: 72 cases were identified (58 <12 years of age, 14 > or = 12 years of age). Using logistic regression to adjust for confounders, including crash severity and crash type, age <12 years was found to be significantly associated with serious spinal injury. Compared to older children, children aged less than 12 years were more likely to sustain serious spinal injury (OR 7.1, 95% CI 1.2 to 42.9). CONCLUSION: Children up to age 12 have an elevated risk of serious spinal injury in car crashes. This age breakpoint may reflect the adequacy of seat belt fit, and use of adult seatbelts alone before age 12 may increase a child's risk of serious spinal injury. An association between age and serious spinal injury should also be considered in the triage of paediatric motor vehicle occupants.

Accuracy of medical and ambulance record restraint and crash data information for child occupants.

OBJECTIVE: To correlate the accuracy of information on children's restraint usage and crash characteristics recorded with medical data using in-depth crash investigation. Restraint and crash information within the medical and ambulance records is often available, but information on the accuracy of this data is limited. METHODS: Comparison of restraint and crash characteristic data from medical and ambulance records with that obtained from in-depth crash investigation studies, for a case series of child occupants aged 2-8 years involved in motor vehicle crashes. RESULTS: When restraint type, seating position, impact severity, and impact direction data were recorded in either the medical record or ambulance records, it tended to be at least partially correct. However, incompleteness or absence of specifics of restraint use and crash information in the medical record (7-17%) was common. Ambulance records were often not available (39%), but this data was more often complete (78-100%) and accurate (52-89%), when available, possibly due to the use of a standardized pro-forma. CONCLUSIONS: Ambulance and hospital records data can provide information on restraint type and usage for child occupants in motor vehicle crashes, as well as crash information. The use of a standardized pro-forma may encourage more complete and accurate reporting of restraint and crash data.

Tensile radial stress in the spinal cord related to arachnoiditis or tethering: a numerical model.

Spinal arachnoiditis comprises fibrous scarring of the subarachnoid space, following spinal trauma or inflammation, and is often associated with syringomyelia. We hypothesised that cord-to-dura attachments could cause transient tensile cord radial stress, as pressure waves propagate. This was tested in a fluid-structure interaction model, simulating three types of cord tethering, with 'arachnoiditis' confined to a short mid-section of the cord. The annular system was excited abdominally with a short transient, and the resulting Young and Lamb waves and reflections were analysed. Radial mid-section tethering was less significant than axial tethering, which gave rise to tensile radial stress locally when the cord was not fixed cranially. Simulated as inextensible string connections to the dura, arachnoiditis caused both localised tensile radial stress and localised low pressure in the cord as the transient passed. The extent of these effects was sensitive to the relative stiffness of the dura and cord. Tensile radial stress may create a syrinx in previously normal cord tissue, and transiently lowered pressure may draw in interstitial fluid, causing the syrinx to enlarge if fluid exit is inhibited. The suggested mechanism could also explain the juxtaposition of syrinxes to regions of arachnoiditis.