Publications by authors named "Sevda Aslan"

24 Publications

  • Page 1 of 1

Characterization of Lower Urinary Tract Dysfunction after Thoracic Spinal Cord Injury in Yucatan Minipigs.

J Neurotrauma 2021 May 2;38(9):1306-1326. Epub 2021 Mar 2.

International Collaboration on Repair Discoveries (ICORD), Departments of Department of Orthopaedics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

There is an increasing need to develop approaches that will not only improve the clinical management of neurogenic lower urinary tract dysfunction (NLUTD) after spinal cord injury (SCI), but also advance therapeutic interventions aimed at recovering bladder function. Although pre-clinical research frequently employs rodent SCI models, large animals such as the pig may play an important translational role in facilitating the development of devices or treatments. Therefore, the objective of this study was to develop a urodynamics protocol to characterize NLUTD in a porcine model of SCI. An iterative process to develop the protocol to perform urodynamics in female Yucatan minipigs began with a group of spinally intact, anesthetized pigs. Subsequently, urodynamic studies were performed in a group of awake, lightly restrained pigs, before and after a contusion-compression SCI at the T2 or T9-T11 spinal cord level. Bladder tissue was obtained for histological analysis at the end of the study. All anesthetized pigs had bladders that were acontractile, which resulted in overflow incontinence once capacity was reached. Uninjured, conscious pigs demonstrated appropriate relaxation and contraction of the external urethral sphincter during the voiding phase. SCI pigs demonstrated neurogenic detrusor overactivity and a significantly elevated post-void residual volume. Relative to the control, SCI bladders were heavier and thicker. The developed urodynamics protocol allows for repetitive evaluation of lower urinary tract function in pigs at different time points post-SCI. This technique manifests the potential for using the pig as an intermediary, large animal model for translational studies in NLUTD.
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http://dx.doi.org/10.1089/neu.2020.7404DOI Listing
May 2021

Improvements in Bladder Function Following Activity-Based Recovery Training With Epidural Stimulation After Chronic Spinal Cord Injury.

Front Syst Neurosci 2020 5;14:614691. Epub 2021 Jan 5.

Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY, United States.

Spinal cord injury (SCI) results in profound neurologic impairment with widespread deficits in sensorimotor and autonomic systems. Voluntary and autonomic control of bladder function is disrupted resulting in possible detrusor overactivity, low compliance, and uncoordinated bladder and external urethral sphincter contractions impairing storage and/or voiding. Conservative treatments managing neurogenic bladder post-injury, such as oral pharmacotherapy and catheterization, are important components of urological surveillance and clinical care. However, as urinary complications continue to impact long-term morbidity in this population, additional therapeutic and rehabilitative approaches are needed that aim to improve function by targeting the recovery of underlying impairments. Several human and animal studies, including our previously published reports, have documented gains in bladder function due to activity-based recovery strategies, such as locomotor training. Furthermore, epidural stimulation of the spinal cord (scES) combined with intense activity-based recovery training has been shown to produce volitional lower extremity movement, standing, as well as improve the regulation of cardiovascular function. In our center, several participants anecdotally reported improvements in bladder function as a result of training with epidural stimulation configured for motor systems. Thus, in this study, the effects of activity-based recovery training in combination with scES were tested on bladder function, resulting in improvements in overall bladder storage parameters relative to a control cohort (no intervention). However, elevated blood pressure elicited during bladder distention, characteristic of autonomic dysreflexia, was not attenuated with training. We then examined, in a separate, large cross-sectional cohort, the interaction between detrusor pressure and blood pressure at maximum capacity, and found that the functional relationship between urinary bladder distention and blood pressure regulation is disrupted. Regardless of one's bladder emptying method (indwelling suprapubic catheter vs. intermittent catheterization), autonomic instability can play a critical role in the ability to improve bladder storage, with SCI enhancing the vesico-vascular reflex. These results support the role of intersystem stimulation, integrating scES for both bladder and cardiovascular function to further improve bladder storage.
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http://dx.doi.org/10.3389/fnsys.2020.614691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813989PMC
January 2021

Contribution of Trunk Muscles to Upright Sitting with Segmental Support in Children with Spinal Cord Injury.

Children (Basel) 2020 Dec 8;7(12). Epub 2020 Dec 8.

Department of Neurological Surgery, University of Louisville, Louisville, KY 40202, USA.

To investigate and compare trunk control and muscle activation during uncompensated sitting in children with and without spinal cord injury (SCI). Static sitting trunk control in ten typically developing (TD) children (5 females, 5 males, mean (SD) age of 6 (2)y) and 26 children with SCI (9 females, 17 males, 5(2)y) was assessed and compared using the Segmental Assessment of Trunk Control (SATCo) test while recording surface electromyography (EMG) from trunk muscles. The SCI group scored significantly lower on the SATCo compared to the TD group. The SCI group produced significantly higher thoracic-paraspinal activation at the lower-ribs, and, below-ribs support levels, and rectus-abdominus activation at below-ribs, pelvis, and no-support levels than the TD group. The SCI group produced significantly higher lumbar-paraspinal activation at inferior-scapula and no-support levels. Children with SCI demonstrated impaired trunk control with the ability to activate trunk muscles above and below the injury level.
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http://dx.doi.org/10.3390/children7120278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762575PMC
December 2020

Heart rate and blood pressure response improve the prediction of orthostatic cardiovascular dysregulation in persons with chronic spinal cord injury.

Physiol Rep 2020 10;8(20):e14617

Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY, USA.

Unstable blood pressure after spinal cord injury (SCI) is not routinely examined but rather predicted by level and completeness of injury (i.e., American Spinal Injury Association Impairment Scale AIS classification). Our aim was to investigate hemodynamic response to a sit-up test in a large cohort of individuals with chronic SCI to better understand cardiovascular function in this population. Continuous blood pressure and ECG were recorded from individuals with SCI (n = 159) and non-injured individuals (n = 48). We found orthostatic hypotension occurred within each level and AIS classification (n = 36). Moreover, 45 individuals with chronic SCI experienced a drop in blood pressure that did not meet the criteria for orthostatic hypotension, but was accompanied by dramatic increases in heart rate, reflecting orthostatic intolerance. A cluster analysis of hemodynamic response to a seated position identified eight distinct patterns of interaction between blood pressure and heart rate during orthostatic stress indicating varied autonomic responses. Algorithmic cluster analysis of heart rate and blood pressure is more sensitive to diagnosing orthostatic cardiovascular dysregulation. This indicates blood pressure instability cannot be predicted by level and completeness of SCI, and the consensus statement definition of orthostatic hypotension is insufficient to characterize the variability of blood pressure and heart rate responses during orthostatic stress. Both blood pressure and heart rate responses are needed to characterize autonomic function after SCI.
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http://dx.doi.org/10.14814/phy2.14617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575221PMC
October 2020

Muscle Activation Patterns During Movement Attempts in Children With Acquired Spinal Cord Injury: Neurophysiological Assessment of Residual Motor Function Below the Level of Lesion.

Front Neurol 2019 20;10:1295. Epub 2019 Dec 20.

Kosair Charities Center for Pediatric NeuroRecovery, University of Louisville, Louisville, KY, United States.

Characterization of residual neuromotor capacity after spinal cord injury (SCI) is challenging. The current gold standard for measurement of sensorimotor function after SCI, the International Society for Neurological Classification of Spinal Cord Injury (ISNCSCI) exam, seeks to determine isolated intentional muscle activation, however many individuals with SCI exhibit intentional movements and muscle activation patterns which are not confined to specific joint or muscle. Further, isolated muscle activation is a feature of the neuromuscular system that emerges during development, and thus may not be an appropriate measurement standard for children younger than 6. We utilized neurophysiological assessment methodology, long studied in adult SCI populations, to evaluate residual neuromotor capacity in 24 children with SCI, as well as 19 typically developing (TD) children. Surface electromyography (EMG) signals were recorded from 11 muscles bilaterally, representing spinal motor output from all regions (i.e., cervical, thoracic, and lumbosacral), during standardized movement attempts. EMG records were subjectively analyzed based on spatiotemporal muscle activation characteristics, while the voluntary response index (VRI) was utilized for objective analysis of unilateral leg movement tasks. Evidence of intentional leg muscle activation below the level of lesion was found in 11/24 children with SCI, and was classified based on activation pattern. Trace activation, bilateral (generalized) activation, and unilateral or isolated activation occurred in 32, 49, and 8% of movement tasks, respectively. Similarly, VRI analyses objectively identified significant differences between TD and SCI children in both magnitude ( < 0.01) and similarity index ( < 0.05) for all unilateral leg movement tasks. Activation of the erector spinae muscles, recorded at the T10-T12 vertebral level, was observed in all children with SCI, regardless of injury level or severity. Residual descending influence on spinal motor circuits may be present after SCI in children. Assessment of multi-muscle activation patterns during intentional movement attempts can provide objective evidence of the presence and extent of such residual muscle activation, and may provide an indicator of motor recovery potential following injury. The presence of residual intentional muscle activation has important implications for rehabilitation following pediatric-onset SCI.
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http://dx.doi.org/10.3389/fneur.2019.01295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933608PMC
December 2019

Respiratory muscle activation patterns during maximum airway pressure efforts are different in women and men.

Respir Physiol Neurobiol 2019 01 15;259:143-148. Epub 2018 Sep 15.

Department of Neurological Surgery, University of Louisville, Louisville, KY, USA; Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY, USA. Electronic address:

Maximum inspiratory and expiratory pressure values (PI and PE) are indirect measures of respiratory muscle strength that, in healthy adults, are known to be significantly lower in women compared to men. In part, sex differences in breathing kinematics, lung size, body composition, muscle mass, and muscle fiber composition are thought to be responsible for these effects. However, it is not known whether respiratory muscle activation during maximum respiratory efforts is also sex-specific. In this study, we addressed whether respiratory multi-muscle activation patterns during PI and PE efforts are different between healthy women and men. Forced vital capacity (FVC), forced expiratory volume in one second (FEV), PI, PE, and surface electromyographic (sEMG) activity recorded from respiratory muscles during these maximum airway pressure efforts were obtained in 13 women and 11 men. Percent predicted values of FVC and FEV were not significantly different in these two groups (women vs. men: 112 ± 14 vs. 105 ± 15%, p = 0.29; and 92 ± 12 vs. 93 ± 13, p = 0.82, Mean ± SD, respectively), while PI and PE measures were significantly lower in women compared to men (68 ± 16 vs. 88 ± 19 cmHO, p = 0.011; and 69 ± 13 vs. 94 ± 17, p = 0.0004, respectively). Using vector-based methodology, by calculating the Similarity Index (SI) as measure of the resemblance between two sEMG patterns and the Magnitude (Mag) representing the overall amount sEMG during motor task, we have found that although the Mag values for both PI and PE tasks were not significantly different in two groups, the SIs revealed significant sex-dependent differences in muscle activation patterns (0.89 ± 0.08 vs. 0.97 ± 0.02, p = 0.016; and 0.77 ± 0.11 vs. 0.92 ± 0.04, p = 0.0006, respectively). During the PI effort, presented as the percentage of total sEMG amplitude, activity of upper trapezius muscle was significantly larger (p = 0.001) while activation of rectus abdominus, oblique, and lower paraspinal muscles were significantly smaller (p = 0.002, p = 0.040, p = 0.005, respectively) in women when compared to the men (50 ± 21 vs. 22 ± 11%; 2 ± 2 vs. 8 ± 7; 4 ± 3 vs. 9 ± 7, 2 ± 3 vs. 7 ± 6, respectively). During PE effort, the percentage of sEMG activity were significantly larger in upper and lower trapezius, and intercostal muscles (p = 0.038, p = 0.049, p = 0.037, respectively) and were significantly smaller in pectoralis, rectus abdominus, and oblique muscles (p = 0.021, p < 0.0001, p = 0.048, respectively) in women compared to men (16 ± 10 vs. 9 ± 4%; 16 ± 9 vs. 8 ± 5; 36 ± 12 vs. 25 ± 9; 6 ± 3 vs. 15 ± 5; 14 ± 5 vs. 20 ± 7, respectively). These findings indicate that respiratory muscle activation patterns during maximum airway pressure efforts in healthy individuals are sex-specific. This information should be considered during respiratory motor control evaluation and treatment planning for people with compromised respiratory motor function.
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http://dx.doi.org/10.1016/j.resp.2018.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252128PMC
January 2019

Prediction of Maximal Oxygen Consumption from Rating of Perceived Exertion (RPE) using a Modified Total-body Recumbent Stepper.

Int J Exerc Sci 2015 1;8(4):414-424. Epub 2018 Aug 1.

Department of Health and Sport Sciences, University of Louisville, Louisville, KY, USA.

Exercise training is crucial to improve cardiovascular health and quality of life in people with spinal cord injuries (SCI). A key limitation is the lack of validated submaximal tests to evaluate and predict cardiovascular fitness in this population. The purpose of this study was to validate a submaximal test to predict maximal oxygen consumption for individuals with SCI. Ten able-bodied participants and two individuals with SCI completed a rating of perceived exertion (RPE)-based submaximal oxygen consumption test and a graded maximal oxygen consumption test on a NuStep T4 recumbent stepper. Prediction of VOmax from an RPE-based protocol is feasible and can produce reliable predicted VOmax values in the able bodied population. This study is a proof of concept to the implementation of a submaximal test protocol using a total body recumbent stepper to predict VO2max in able-bodied individuals. Additionally, this study shows evidence of feasibility of performing this test in SCI individuals.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108154PMC
August 2018

Epidural Spinal Cord Stimulation of Lumbosacral Networks Modulates Arterial Blood Pressure in Individuals With Spinal Cord Injury-Induced Cardiovascular Deficits.

Front Physiol 2018 18;9:565. Epub 2018 May 18.

Department of Neurological Surgery, University of Louisville, Louisville, KY, United States.

Disruption of motor and autonomic pathways induced by spinal cord injury (SCI) often leads to persistent low arterial blood pressure and orthostatic intolerance. Spinal cord epidural stimulation (scES) has been shown to enable independent standing and voluntary movement in individuals with clinically motor complete SCI. In this study, we addressed whether scES configured to activate motor lumbosacral networks can also modulate arterial blood pressure by assessing continuous, beat-by-beat blood pressure and lower extremity electromyography during supine and standing in seven individuals with C5-T4 SCI. In three research participants with arterial hypotension, orthostatic intolerance, and low levels of circulating catecholamines (group 1), scES applied while supine and standing resulted in increased arterial blood pressure. In four research participants without evidence of arterial hypotension or orthostatic intolerance and normative circulating catecholamines (group 2), scES did not induce significant increases in arterial blood pressure. During scES, there were no significant differences in electromyographic (EMG) activity between group 1 and group 2. In group 1, during standing assisted by scES, blood pressure was maintained at 119/72 ± 7/14 mmHg (mean ± SD) compared with 70/45 ± 5/7 mmHg without scES. In group 2 there were no arterial blood pressure changes during standing with or without scES. These findings demonstrate that scES configured to facilitate motor function can acutely increase arterial blood pressure in individuals with SCI-induced cardiovascular deficits.
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http://dx.doi.org/10.3389/fphys.2018.00565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968099PMC
May 2018

Respiratory functional and motor control deficits in children with spinal cord injury.

Respir Physiol Neurobiol 2018 01 28;247:174-180. Epub 2017 Oct 28.

Department of Physiology, University of Louisville, Louisville, KY, USA; Department of Neurological Surgery, University of Louisville, Louisville, KY, USA. Electronic address:

Children with spinal cord injury (SCI) are at high risk for developing complications due to respiratory motor control deficits. However, underlying mechanisms of these abnormalities with respect to age, development, and injury characteristics are unclear. To evaluate the effect of SCI and age on respiratory motor control in children with SCI, we compared pulmonary function and respiratory motor control outcome measures in healthy typically developing (TD) children to age-matched children with chronic SCI. We hypothesized that the deficits in respiratory functional performance in children with SCI are due to the abnormal and age-dependent respiratory muscle activation patterns. Fourteen TD (age 7±2 yrs., Mean±SD) and twelve children with SCI (age 6±1 yrs.) were evaluated by assessing Forced Vital Capacity (FVC); Forced Expiratory Volume in 1sec (FEV); and respiratory electromyographic activity during maximum inspiratory and maximum expiratory airway pressure measurements (PI and PE). The results indicate a significant reduction (p<.01) of FVC, FEV and PE values in children with SCI compared to TD controls. During PE assessment, children with SCI produced significantly decreased (p<.01) activation of respiratory muscles below the neurological level of injury (rectus abdominous and external oblique muscles). In addition, children with SCI had significantly increased (p<.05) compensatory muscle activation above the level of injury (upper trapezius muscle). In the TD group, age, height, and weight significantly (p<.05) contributed towards increase in FVC and FEV. In children with SCI, only age was significantly (p<.05) correlated with FVC and FEV values. These findings indicate the degree of SCI-induced respiratory functional and motor control deficits in children are age-dependent.
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http://dx.doi.org/10.1016/j.resp.2017.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698146PMC
January 2018

Effects of Respiratory Training on Heart Rate Variability and Baroreflex Sensitivity in Individuals With Chronic Spinal Cord Injury.

Arch Phys Med Rehabil 2018 03 9;99(3):423-432. Epub 2017 Aug 9.

Department of Physiology, University of Louisville, Louisville, KY; Department of Neurological Surgery, University of Louisville, Louisville, KY. Electronic address:

Objective: To evaluate the effects of pressure threshold respiratory training (RT) on heart rate variability and baroreflex sensitivity in persons with chronic spinal cord injury (SCI).

Design: Before-after intervention case-controlled clinical study.

Setting: SCI research center and outpatient rehabilitation unit.

Participants: Participants (N=44) consisted of persons with chronic SCI ranging from C2 to T11 who participated in RT (n=24), and untrained control subjects with chronic SCI ranging from C2 to T9 (n=20).

Interventions: A total of 21±2 RT sessions performed 5 days a week during a 4-week period using a combination of pressure threshold inspiratory and expiratory devices.

Main Outcome Measures: Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV), and beat-to-beat arterial blood pressure and heart rate changes during the 5-second-long maximum expiratory pressure maneuver (5s MEP) and the sit-up orthostatic stress test, acquired before and after the RT program.

Results: In contrast to the untrained controls, individuals in the RT group experienced significantly increased FVC and FEV (both P<.01) in association with improved quality of sleep, cough, and speech. Sympathetically (phase II) and parasympathetically (phase IV) mediated baroreflex sensitivity both significantly (P<.05) increased during the 5s MEP. During the orthostatic stress test, improved autonomic control over heart rate was associated with significantly increased sympathetic and parasympathetic modulation (low- and high-frequency change: P<.01 and P<.05, respectively).

Conclusions: Inspiratory-expiratory pressure threshold RT is a promising technique to positively affect both respiratory and cardiovascular dysregulation observed in persons with chronic SCI.
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http://dx.doi.org/10.1016/j.apmr.2017.06.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807237PMC
March 2018

Respiratory motor training and neuromuscular plasticity in patients with chronic obstructive pulmonary disease: A pilot study.

Respir Physiol Neurobiol 2016 07 29;229:59-64. Epub 2016 Apr 29.

Department of Medicine: Division of Pulmonary, Critical Care and Sleep Disorders, University of Louisville, Louisville, KY, USA; Department of Medicine: Division of Pulmonary, Critical Care and Sleep Medicine, University Hospitals and Case Western Reserve University, Cleveland, OH, USA.

The objective of this study was to examine the feasibility of a full-scale investigation of the neurophysiological mechanisms of COPD-induced respiratory neuromuscular control deficits. Characterization of respiratory single- and multi-muscle activation patterns using surface electromyography (sEMG) were assessed along with functional measures at baseline and following 21±2 (mean±SD) sessions of respiratory motor training (RMT) performed during a one-month period in four patients with GOLD stage II or III COPD. Pre-training, the individuals with COPD showed significantly increased (p<0.05) overall respiratory muscle activity and disorganized multi-muscle activation patterns in association with lowered spirometrical measures and decreased fast- and slow-twitch fiber activity as compared to healthy controls (N=4). Following RMT, functional and respiratory sEMG activation outcomes during quite breathing and forced expiratory efforts were improved suggesting that functional improvements, induced by task-specific RMT, are evidence respiratory neuromuscular networks re-organization.
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http://dx.doi.org/10.1016/j.resp.2016.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887410PMC
July 2016

Baroreceptor reflex during forced expiratory maneuvers in individuals with chronic spinal cord injury.

Respir Physiol Neurobiol 2016 07 30;229:65-70. Epub 2016 Apr 30.

Department of Physiology, University of Louisville, Louisville, KY, USA; Department of Neurological Surgery, University of Louisville, Louisville, KY, USA. Electronic address:

Pulmonary and cardiovascular dysfunctions are leading causes of morbidity and mortality in patients with chronic Spinal Cord Injury (SCI). Impaired respiratory motor function and decreased Baroreflex Sensitivity (BS) are predictors for the development of cardiopulmonary disease. This observational case-controlled clinical study was undertaken to investigate if respiratory motor control deficits in individuals with SCI affect their ability to perform the Valsalva maneuver, and to determine if a sustained Maximum Expiratory Pressure (MEP) effort can serve as an acceptable maneuver for determination of the BS in the event that the Valsalva maneuver cannot be performed. The BS outcomes (ms/mmHg) were obtained using continuous beat-to-beat arterial blood pressure (BP) and heart rate (HR) recordings during Valsalva or MEP maneuvers in thirty nine individuals with chronic C3-T12 SCI. Twenty one participants (54%) reported signs of intolerance during the Valsalva maneuver and only 15 individuals (39%) were able to complete this task. Cervical level of injury was a significant risk factor (p=0.001) for failing to complete the Valsalva maneuver, and motor-complete injury was a significant risk factor for symptoms of intolerance (p=0.04). Twenty eight participants (72%) were able to perform the MEP maneuver; the other 11 participants failed to exceed the standard airway pressure threshold of 27cm H2O. Neither level nor completeness of injury were significant risk factors for failure of MEP maneuver. When the required airway pressure was sustained, there were no significant differences between BS outcomes obtained during Valsalva and MEP maneuvers. The results of this study indicate that individuals with high-level and motor-complete SCI are at increased risk of not completing the Valsalva maneuver and that baroreflex-mediated responses can be evaluated by using sustained MEP maneuver when the Valsalva maneuver cannot be performed.
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http://dx.doi.org/10.1016/j.resp.2016.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887317PMC
July 2016

Respiratory Training Improves Blood Pressure Regulation in Individuals With Chronic Spinal Cord Injury.

Arch Phys Med Rehabil 2016 06 21;97(6):964-73. Epub 2015 Dec 21.

Department of Neurological Surgery, University of Louisville, Louisville, Kentucky. Electronic address:

Objective: To investigate the effects of respiratory motor training (RMT) on pulmonary function and orthostatic stress-mediated cardiovascular and autonomic responses in individuals with chronic spinal cord injury (SCI).

Design: Before-after intervention case-controlled clinical study.

Setting: SCI research center and outpatient rehabilitation unit.

Participants: A sample of (N=21) individuals with chronic SCI ranging from C3 to T2 diagnosed with orthostatic hypotension (OH) (n=11) and healthy, noninjured controls (n=10).

Interventions: A total of 21±2 sessions of pressure threshold inspiratory-expiratory RMT performed 5d/wk during a 1-month period.

Main Outcome Measures: Standard pulmonary function test: forced vital capacity, forced expiratory volume in one second, maximal inspiratory pressure, maximal expiratory pressure, beat-to-beat arterial blood pressure, heart rate, and respiratory rate were acquired during the orthostatic sit-up stress test before and after the RMT program.

Results: Completion of RMT intervention abolished OH in 7 of 11 individuals. Forced vital capacity, low-frequency component of power spectral density of blood pressure and heart rate oscillations, baroreflex effectiveness, and cross-correlations between blood pressure, heart rate, and respiratory rate during the orthostatic challenge were significantly improved, approaching levels observed in noninjured individuals. These findings indicate increased sympathetic activation and baroreflex effectiveness in association with improved respiratory-cardiovascular interactions in response to the sudden decrease in blood pressure.

Conclusions: Respiratory training increases respiratory capacity and improves orthostatic stress-mediated respiratory, cardiovascular, and autonomic responses, suggesting that this intervention can be an efficacious therapy for managing OH after SCI.
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http://dx.doi.org/10.1016/j.apmr.2015.11.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884550PMC
June 2016

Respiratory motor function in seated and supine positions in individuals with chronic spinal cord injury.

Respir Physiol Neurobiol 2014 Nov 27;203:9-14. Epub 2014 Aug 27.

Department of Neurological Surgery, University of Louisville, Louisville, KY, USA. Electronic address:

This case-controlled clinical study was undertaken to investigate to what extent pulmonary function in individuals with chronic spinal cord injury (SCI) is affected by posture. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), maximal inspiratory pressure (PImax) and maximal expiratory pressure (PEmax) were obtained from 27 individuals with chronic motor-complete (n=13, complete group) and motor-incomplete (n=14, incomplete group) C2-T12 SCI in both seated and supine positions. Seated-to-supine changes in spirometrical (FVC and FEV1) and airway pressure (PImax and PEmax) outcome measures had different dynamics when compared in complete and incomplete groups. Patients with motor-complete SCI had tendency to increase spirometrical outcomes in supine position showing significant increase in FVC (p=.007), whereas patients in incomplete group exhibited decrease in these values with significant decreases in FEV1 (p=.002). At the same time, the airway pressure values were decreased in supine position in both groups with significant decrease in PEmax (p=.031) in complete group and significant decrease in PImax (p=.042) in incomplete group. In addition, seated-to-supine percent change of PImax was strongly correlated with neurological level of motor-complete SCI (ρ=-.77, p=.002). These results indicate that postural effects on respiratory performance in patients with SCI can depend on severity and neurological level of SCI, and that these effects differ depending on respiratory tasks. Further studies with adequate sample size are needed to investigate these effects in clinically specific groups and to study the mechanisms of such effects on specific respiratory outcome measures.
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http://dx.doi.org/10.1016/j.resp.2014.08.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4179925PMC
November 2014

Local Wavelet-Based Filtering of Electromyographic Signals to Eliminate the Electrocardiographic-Induced Artifacts in Patients with Spinal Cord Injury.

J Biomed Sci Eng 2013 Jul;6(7B)

BioImaging laboratory, Bioengineering Department, University of Louisville, Louisville, KY 40292, USA.

Surface Electromyography (EMG) is a standard method used in clinical practice and research to assess motor function in order to help with the diagnosis of neuromuscular pathology in human and animal models. EMG recorded from trunk muscles involved in the activity of breathing can be used as a direct measure of respiratory motor function in patients with spinal cord injury (SCI) or other disorders associated with motor control deficits. However, EMG potentials recorded from these muscles are often contaminated with heart-induced electrocardiographic (ECG) signals. Elimination of these artifacts plays a critical role in the precise measure of the respiratory muscle electrical activity. This study was undertaken to find an optimal approach to eliminate the ECG artifacts from EMG recordings. Conventional global filtering can be used to decrease the ECG-induced artifact. However, this method can alter the EMG signal and changes physiologically relevant information. We hypothesize that, unlike global filtering, localized removal of ECG artifacts will not change the original EMG signals. We develop an approach to remove the ECG artifacts without altering the amplitude and frequency components of the EMG signal by using an externally recorded ECG signal as a mask to locate areas of the ECG spikes within EMG data. These segments containing ECG spikes were decomposed into 128 sub-wavelets by a custom-scaled Morlet Wavelet Transform. The ECG-related sub-wavelets at the ECG spike location were removed and a de-noised EMG signal was reconstructed. Validity of the proposed method was proven using mathematical simulated synthetic signals and EMG obtained from SCI patients. We compare the Root-mean Square Error and the Relative Change in Variance between this method, global, notch and adaptive filters. The results show that the localized wavelet-based filtering has the benefit of not introducing error in the native EMG signal and accurately removing ECG artifacts from EMG signals.
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http://dx.doi.org/10.4236/jbise.2013.67A2001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3845519PMC
July 2013

Locomotor step training with body weight support improves respiratory motor function in individuals with chronic spinal cord injury.

Respir Physiol Neurobiol 2013 Dec 31;189(3):491-7. Epub 2013 Aug 31.

Department of Exercise Physiology, University of Louisville, Louisville, KY, USA.

This prospective case-controlled clinical study was undertaken to investigate to what extent the manually assisted treadmill stepping locomotor training with body weight support (LT) can change respiratory function in individuals with chronic spinal cord injury (SCI). Pulmonary function outcomes (forced vital capacity /FVC/, forced expiratory volume one second /FEV1/, maximum inspiratory pressure /PImax/, maximum expiratory pressure /PEmax/) and surface electromyographic (sEMG) measures of respiratory muscles activity during respiratory tasks were obtained from eight individuals with chronic C3-T12 SCI before and after 62±10 (mean±SD) sessions of the LT. FVC, FEV1, PImax, PEmax, amount of overall sEMG activity and rate of motor unit recruitment were significantly increased after LT (p<0.05). These results suggest that these improvements induced by the LT are likely the result of neuroplastic changes in spinal neural circuitry responsible for the activation of respiratory muscles preserved after injury.
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http://dx.doi.org/10.1016/j.resp.2013.08.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3833892PMC
December 2013

Evaluation of respiratory muscle activation using respiratory motor control assessment (RMCA) in individuals with chronic spinal cord injury.

J Vis Exp 2013 Jul 19(77). Epub 2013 Jul 19.

Department of Neurological Surgery, University of Louisville, Louisville, USA.

During breathing, activation of respiratory muscles is coordinated by integrated input from the brain, brainstem, and spinal cord. When this coordination is disrupted by spinal cord injury (SCI), control of respiratory muscles innervated below the injury level is compromised leading to respiratory muscle dysfunction and pulmonary complications. These conditions are among the leading causes of death in patients with SCI. Standard pulmonary function tests that assess respiratory motor function include spirometrical and maximum airway pressure outcomes: Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1), Maximal Inspiratory Pressure (PImax) and Maximal Expiratory Pressure (PEmax). These values provide indirect measurements of respiratory muscle performance(6). In clinical practice and research, a surface electromyography (sEMG) recorded from respiratory muscles can be used to assess respiratory motor function and help to diagnose neuromuscular pathology. However, variability in the sEMG amplitude inhibits efforts to develop objective and direct measures of respiratory motor function. Based on a multi-muscle sEMG approach to characterize motor control of limb muscles, known as the voluntary response index (VRI), we developed an analytical tool to characterize respiratory motor control directly from sEMG data recorded from multiple respiratory muscles during the voluntary respiratory tasks. We have termed this the Respiratory Motor Control Assessment (RMCA). This vector analysis method quantifies the amount and distribution of activity across muscles and presents it in the form of an index that relates the degree to which sEMG output within a test-subject resembles that from a group of healthy (non-injured) controls. The resulting index value has been shown to have high face validity, sensitivity and specificity. We showed previously that the RMCA outcomes significantly correlate with levels of SCI and pulmonary function measures. We are presenting here the method to quantitatively compare post-spinal cord injury respiratory multi-muscle activation patterns to those of healthy individuals.
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http://dx.doi.org/10.3791/50178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740445PMC
July 2013

Quantitative and sensitive assessment of neurophysiological status after human spinal cord injury.

J Neurosurg Spine 2012 Sep;17(1 Suppl):77-86

Department of Neurological Surgery, Kentucky Spinal Cord Injury Research Center, Louisville, Kentucky, USA.

Object: This study was designed to develop an objective and sensitive spinal cord injury (SCI) characterization protocol based on surface electromyography (EMG) activity.

Methods: Twenty-four patients at both acute and chronic time points post-SCI, as well as 4 noninjured volunteers, were assessed using neurophysiological and clinical measures of volitional motor function. The EMG amplitude was recorded from 15 representative muscles bilaterally during standardized maneuvers as a neurophysiological assessment of voluntary motor function. International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) examinations were performed as a clinical assessment of lesion severity.

Results: Sixty-six functional neurophysiological assessments were performed in 24 patients with SCI and in 4 neurologically intact individuals. The collected EMG data were organized by quantitative parameters and statistically analyzed. The correlation between root mean square (RMS) of the EMG signals and ISNCSCI motor score was confirmed by Kendall correlation analysis. The Kendall correlation value between overall muscles/levels, motor scores, and the RMS of the EMG data is 0.85, with the 95% CI falling into the range of 0.76-0.95. Significant correlations were also observed for the soleus (0.51 [0.28-0.74]), tibialis anterior (TA) (0.53 [0.33-0.73]), tricep (0.52, [0.34-0.70]), and extensor carpi radialis (ECR) (0.80 [0.42-1.00]) muscles. Comparisons of RMS EMG values in groups defined by ISNCSCI motor score further confirmed these results. At the bicep and ECR, patients with motor scores of 5 had nearly significantly higher RMS EMG values than patients with motor scores of 0 (p = 0.059 and 0.052, respectively). At the soleus and TA, the RMS of the EMG value was significantly higher (p < 0.01) for patients with American Spinal Injury Association Impairment Scale motor scores of 5 than for those with ISNCSCI motor scores of 0. Those with C-7 ISNCSCI motor scores of 5 had significantly higher RMS EMG values at the tricep than those with motor scores of 4 (p = 0.008) and 0 (p = 0.02). Results also show that surface EMG signals recorded from trunk muscles allowed the examiner to pick up subclinical changes, even though no ISNCSCI scores were given.

Conclusions: Surface EMG signal is suitable for objective neurological SCI characterization protocol design. The quantifiable features of surface EMG may increase SCI characterization resolution by adding subclinical details to the clinical picture of lesion severity and distribution.
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http://dx.doi.org/10.3171/2012.6.AOSPINE12117DOI Listing
September 2012

Evaluation of respiratory muscle activation in individuals with chronic spinal cord injury.

Respir Physiol Neurobiol 2010 Sep 6;173(2):171-8. Epub 2010 Aug 6.

Department of Neurological Surgery, University of Louisville, Louisville, KY 40202, USA.

This study was undertaken to physiologically characterize respiratory muscle control in eighteen individuals with spinal cord injury (SCI) through comparison with 14 matched non-injured (NI) subjects. Standard pulmonary function measures (FVC, FEV(1), PI(max) and PE(max)) were obtained along with surface electromyographic (sEMG) recording from respiratory muscles. A vector analysis of sEMG was used to calculate Similarity Index (SI) values relating SCI subject sEMG patterns to those produced by NI subjects. SI values for inspiratory and expiratory tasks were very consistent within the NI group, 0.92±0.03 and 0.93±0.04 (mean±SD), respectively. Altered multi-muscle patterns in the SCI group produced SI values that trended lower 0.84±0.11 for inspiratory tasks and were significantly lower, 0.59±0.22 for expiratory tasks. SI values for expiratory tasks were also significantly correlated with SCI levels and pulmonary function measures. These results suggest that pulmonary function after SCI is dependent upon the degree to which multi-muscle activation patterns are disrupted.
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http://dx.doi.org/10.1016/j.resp.2010.07.013DOI Listing
September 2010

Blood pressure regulation in neurally intact human vs. acutely injured paraplegic and tetraplegic patients during passive tilt.

Am J Physiol Regul Integr Comp Physiol 2007 Mar 2;292(3):R1146-57. Epub 2006 Nov 2.

Center for Biomedical Engineering, Wenner-Gren Research Laboratory, University of Kentucky, Lexington, KY 40506-0070, USA.

We investigated autonomic control of cardiovascular function in able-bodied (AB), paraplegic (PARA), and tetraplegic (TETRA) subjects in response to head-up tilt following spinal cord injury. We evaluated spectral power of blood pressure (BP), baroreflex sensitivity (BRS), baroreflex effectiveness index (BEI), occurrence of systolic blood pressure (SBP) ramps, baroreflex sequences, and cross-correlation of SBP with heart rate (HR) in low (0.04-0.15 Hz)- and high (0.15-0.4 Hz)-frequency regions. During tilt, AB and PARA effectively regulated BP and HR, but TETRA did not. The numbers of SBP ramps and percentages of heartbeats involved in SBP ramps and baroreflex sequences increased in AB, were unchanged in PARA, and declined in TETRA. BRS was lowest in PARA and declined with tilt in all groups. BEI was greatest in AB and declined with tilt in all groups. Low-frequency power of BP and the peak of the SBP/HR cross-correlation magnitude were greatest in AB, increased during tilt in AB, remained unchanged in PARA, and declined in TETRA. The peak cross-correlation magnitude in HF decreased with tilt in all groups. Our data indicate that spinal cord injury results in decreased stimulation of arterial baroreceptors and less engagement of feedback control as demonstrated by lower 1) spectral power of BP, 2) number (and percentages) of SBP ramps and barosequences, 3) cross-correlation magnitude of SBP/HR, 4) BEI, and 5) changes in delay between SBP/HR. Diminished vasomotion and impaired baroreflex regulation may be major contributors to decreased orthostatic tolerance following injury.
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http://dx.doi.org/10.1152/ajpregu.00225.2006DOI Listing
March 2007

Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models.

Br J Pharmacol 2006 Feb;147(3):281-8

Pain Management Research Institute, Northern Clinical School, The University of Sydney, NSW, Australia.

While cannabinoid receptor agonists have analgesic activity in chronic pain states, they produce a spectrum of central CB(1) receptor-mediated motor and psychotropic side effects. The actions of endocannabinoids, such as anandamide are terminated by removal from the extracellular space, then subsequent enzymatic degradation by fatty-acid amide hydrolase (FAAH). In the present study, we compared the effect of a selective FAAH inhibitor, URB597, to that of a pan-cannabinoid receptor agonist HU210 in rat models of chronic inflammatory and neuropathic pain. Systemic administration of URB597 (0.3 mg kg(-1)) and HU210 (0.03 mg kg(-1)) both reduced the mechanical allodynia and thermal hyperalgesia in the CFA model of inflammatory pain. In contrast, HU210, but not URB597, reduced mechanical allodynia in the partial sciatic nerve-ligation model of neuropathic pain. HU210, but not URB597, produced a reduction in motor performance in unoperated rats. The effects of URB597 in the CFA model were dose dependent and were reduced by coadministration with the cannabinoid CB1 antagonist AM251 (1 mg kg(-1)), or the CB2 and SR144528 (1 mg kg(-1)). Coadministration with AM251 plus SR144528 completely reversed the effects of URB597. These findings suggest that the FAAH inhibitor URB597 produces cannabinoid CB1 and CB2 receptor-mediated analgesia in inflammatory pain states, without causing the undesirable side effects associated with cannabinoid receptor activation.
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http://dx.doi.org/10.1038/sj.bjp.0706510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1751298PMC
February 2006

Effect of the cannabinoid ajulemic acid on rat models of neuropathic and inflammatory pain.

Neurosci Lett 2005 Jul 8;382(3):231-5. Epub 2005 Apr 8.

Pain Management Research Institute, Northern Clinical School, Kolling Institute, The University of Sydney, NSW 2006, Australia.

There is increasing evidence that cannabinoid agonists alleviate the abnormal pain sensations associated with animal models of neuropathic and inflammatory pain. However, cannabinoids produce a number of motor and psychotropic side effects. In the present study we found that systemic administration of the cannabinoid acid derivative 1',1'-dimethylheptyl-delta-8-tetrahydrocannabinol-11-oic acid (ajulemic acid, IP-751) and the non-selective cannabinoid receptor agonist HU-210 reduced mechanical allodynia in a nerve-injury induced model of neuropathic pain and in the CFA-induced model of inflammatory pain. In contrast, HU-210, but not ajulemic acid reduced motor performance in the rotarod test. These findings suggest that ajulemic acid reduces abnormal pain sensations associated with chronic pain without producing the motor side effects associated with THC and other non-selective cannabinoid receptor agonists.
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http://dx.doi.org/10.1016/j.neulet.2005.03.019DOI Listing
July 2005
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