Transcutaneous spinal cord stimulation and its impact on cardiovascular autonomic regulation after spinal cord injury.

Individuals with spinal cord injury (SCI) have significant dysfunction in cardiovascular autonomic regulation. Although recent findings postulate that spinal cord stimulation improves autonomic regulation, limited scope of past methods have tested only above level sympathetic activation, leaving significant uncertainty. To identify whether transcutaneous spinal cord stimulation improves cardiovascular autonomic regulation, two pairs of well-matched individuals with and without high thoracic, complete SCI were recruited. Baseline autonomic regulation was characterized with multiple tests of sympathoinhibition and above/below injury level sympathoexcitation. At three subsequent visits, testing was repeated with the addition submotor threshold transcutaneous spinal cord stimulation at three previously advocated frequencies. Uninjured controls demonstrated no autonomic deficits at baseline and had no changes with any frequency of stimulation. As expected, individuals with SCI had baseline autonomic dysfunction. In a frequency-dependent manner, spinal cord stimulation enhanced sympathoexcitatory responses, normalizing previously impaired Valsalva's maneuvers. However, stimulation exacerbated already impaired sympathoinhibitory responses, resulting in significantly greater mean arterial pressure increases with the same phenylephrine doses compared with baseline. Impaired sympathoexcitatory response below the level of injury were also further exacerbated with spinal cord stimulation. At baseline, neither individual with SCI demonstrated autonomic dysreflexia with the noxious foot cold pressor test; the addition of stimulation led to a dysreflexic response in every trial, with greater relative hypertension and bradycardia indicating no improvement in cardiovascular autonomic regulation. Collectively, transcutaneous spinal cord stimulation demonstrates no improvements in autonomic regulation after SCI, and instead likely generates tonic sympathoexcitation which may lower the threshold for dangerous autonomic dysreflexia.NEW & NOTEWORTHY Spinal cord stimulation increases blood pressure after spinal cord injury, though it is unclear if this restores natural autonomic regulation or induces a potentially dangerous pathological reflex. We performed comprehensive autonomic testing batteries, with and without transcutaneous spinal cord stimulation at multiple frequencies. Across 96 independent tests, stimulation did not change uninjured control responses, though all frequencies facilitated pathological reflexes without improved autonomic regulation for those with spinal cord injuries.

Nitric oxide-mediated vasodilation in human bone.

OBJECTIVE: Regulation of blood flow to bone is critical but poorly understood, particularly in humans. This study aims to determine whether nitric oxide (NO), a major regulator of vascular tone to other tissues, contributes also to the regulation of blood flow to bone. METHODS: In young healthy adults (n = 16, 8F, 8M), we characterized NO-mediated vasodilation in the tibia in response to sublingual nitroglycerin and contrasted it to lower leg. Blood flow responses were assessed in supine individuals by continuously measuring tibial total hemoglobin (tHb) via near-infrared spectroscopy and lower leg blood flow (LBF) as popliteal flow velocity via Doppler ultrasound in the same leg. RESULTS: LBF increased by Δ9.73 ± 0.66 cm/s and peaked 4.4 min after NO administration and declined slowly but remained elevated (Δ3.63 ± 0.60 cm/s) at 10 min. In contrast, time to peak response was longer and smaller in magnitude in the tibia as tHb increased Δ2.08 ± 0.22 µM and peaked 5.3 min after NO administration and declined quickly but remained elevated (Δ0.87±0.22 µM) at 10 min (p = .01). CONCLUSIONS: In young adults, the tibial vasculature demonstrates robust NO-mediated vasodilation, but tHb is delayed and diminishes faster compared to LBF, predominately reflective of skeletal muscle responses. Thus, NO-mediated vasodilation in bone may be characteristically different from other vascular beds.

Paradoxical breathing during sleep is associated with increased sleep apnea and reduced ventilatory capacities in high-level spinal cord injury.

Sleep-disordered breathing is highly prevalent in individuals with high-level spinal cord injury. In addition, chest mechanics are known to be altered, leading to paradoxical breathing. Here we investigated the interaction between paradoxical breathing and sleep quality in these patients, and its association with measurements of respiratory function, hypercapnic ventilatory response and peak exercise ventilation. Home-based polysomnography was performed in 13 patients with spinal cord injury (C4 to T4) untreated for sleep-disordered breathing. We defined paradoxical breathing as counterphase between thoracic and abdominal movements during slow-wave and rapid eye movement sleep. Sleep quality, pulmonary function, hypercapnic ventilatory responses and peak exercise ventilation were compared between those with and without paradoxical breathing. Half of individuals presented with nocturnal paradoxical breathing. Despite similar age, body mass index, injury level, time since injury, and respiratory function, those with paradoxical breathing had higher apnea-hypopnea index (13 ± 8 versus 5 ± 3 events per hr) and average sleep heart rate (67 ± 12 versus 54 ± 4 bpm; p < 0.05). Moreover, paradoxical breathing was associated with lower hypercapnic ventilatory response (slope: 0.35 ± 0.17 versus 0.96 ± 0.38) and lower peak exercise ventilation (33 ± 4 versus 48 ± 12 L min-1 ; p < 0.05). Nocturnal respiratory muscle desynchronization could play a role in the pathophysiology of sleep apnea, and could relate to low ventilatory responses to both hypercapnia and exercise in high-level spinal cord injury. Polysomnography may be an important diagnostic tool for these patients for whom therapeutic approaches should be considered to treat this abnormality.

Valsalva maneuver pressure recovery time is prolonged following spinal cord injury with correlations to autonomically-influenced secondary complications.

PURPOSE: This work's purpose was to quantify rapid sympathetic activation in individuals with spinal cord injury (SCI), and to identify associated correlations with symptoms of orthostatic hypotension and common autonomically mediated secondary medical complications. METHODS: This work was a cross-sectional study of individuals with SCI and uninjured individuals. Symptoms of orthostatic hypotension were recorded using the Composite Autonomic Symptom Score (COMPASS)-31 and Autonomic Dysfunction following SCI (ADFSCI) survey. Histories of secondary complications of SCI were gathered. Rapid sympathetic activation was assessed using pressure recovery time of Valsalva maneuver. Stepwise multiple linear regression models identified contributions to secondary medical complication burden. RESULTS: In total, 48 individuals (24 with SCI, 24 uninjured) underwent testing, with symptoms of orthostatic hypotension higher in those with SCI (COMPASS-31, 3.3 versus 0.6, p < 0.01; ADFSCI, 21.2 versus. 3.2, p < 0.01). Pressure recovery time was prolonged after SCI (7.0 s versus. 1.7 s, p < 0.01), though poorly correlated with orthostatic symptom severity. Neurological level of injury after SCI influenced pressure recovery time, with higher injury levels associated with more prolonged time. Stepwise multiple linear regression models identified pressure recovery time as the primary explanation for variance in number of urinary tract infections (34%), histories of hospitalizations (12%), and cumulative secondary medical complication burden (24%). In all conditions except time for bowel program, pressure recovery time outperformed current clinical tools for assessing such risk. CONCLUSIONS: SCI is associated with impaired rapid sympathetic activation, demonstrated here by prolonged pressure recovery time. Prolonged pressure recovery time after SCI predicts higher risk for autonomically mediated secondary complications, serving as a viable index for more "autonomically complete" injury.

Improved pulmonary function is associated with reduced inflammation after hybrid whole-body exercise training in persons with spinal cord injury.

NEW FINDINGS: What is the central question of this study? Does 12 weeks of functional electrical stimulation (FES) rowing exercise training lead to suppressed systemic inflammation and an improvement in pulmonary function in persons with sub-acute spinal cord injury (SCI)? What is the main finding and its importance? Twelve weeks of FES rowing exercise improves pulmonary function and the magnitude of improvement is associated with reductions in inflammatory biomarkers. Thus, interventions targeting inflammation may lead to better pulmonary outcomes for person with sub-acute SCI. ABSTRACT: The current study was designed to test the hypotheses that (1) reducing systemic inflammation via a 12-week functional electrical stimulation rowing exercise training (FESRT) prescription results in augmented pulmonary function, and (2) the magnitude of improvement in pulmonary function is inversely associated with the magnitude of systemic inflammation suppression in persons with sub-acute (≤2 years) spinal cord injury (SCI). We conducted a retrospective analysis of a randomized controlled trial (NCT#02139436). Twenty-one participants were enrolled (standard of care (SOC; n = 9) or FESRT (n = 12)). The exercise prescription was three sessions/week at 70-85% of peak heart rate. A two-way analysis of covariance and regression analysis was used to assess group differences and associations between pulmonary function, log transformed high-sensitivity C-reactive protein (hsCRPlog ) and white blood cell count (WBC). Following FESRT, clinically significant improvements in forced expiratory volume in 1 s (FEV1 ; 0.25 (0.08-0.43) vs. -0.06 (-0.26 to 0.15) litres) and forced vital capacity (0.22 (0.04-0.39) vs. 0.08 (-0.29 to 0.12) litres) were noted and systemic WBC (-1.45 (-2.48 to -0.50) vs. 0.41 (-0.74 to 1.56) µl) levels were suppressed compared to SOC (mean change (95% confidence interval); P < 0.05). Additionally, both ΔhsCRPlog and ΔWBC were predictors of ΔFEV1 (r2  = 0.89 and 0.43, respectively; P < 0.05). Twelve weeks of FESRT improves pulmonary function and reduces WBC in persons with sub-acute SCI. The potency of FESRT to augment pulmonary function may depend on adequate suppression of systemic inflammation.

Exercise Training Does Not Attenuate Cardiac Atrophy or Loss of Function in Individuals With Acute Spinal Cord Injury: A Pilot Study.

OBJECTIVE: To investigate the effects of 2 modes of exercise training, upper-body alone, and the addition of electrical stimulation of the lower body, to attenuate cardiac atrophy and loss of function in individuals with acute spinal cord injury (SCI). DESIGN: Randomized controlled trial. SETTING: Rehabilitation Hospital. PARTICIPANTS: Volunteers (N=27; 5 women, 22 men) who were <24 months post SCI. INTERVENTIONS: Volunteers completed either 6 months of no structured exercise (Control), arm rowing (AO), or a combination of arm rowing with electrical stimulation of lower body paralyzed muscle (functional electrical stimulation [FES] rowing). MAIN OUTCOME MEASURES: Transthoracic echocardiography was performed on each subject prior to and 6 months after the intervention. The relations between time since injury and exercise type to cardiac structure and function were assessed via 2-way repeated-measures analysis of variance and with multilevel linear regression. RESULTS: Time since injury was significantly associated with a continuous decline in cardiac structure and systolic function, specifically, a reduction in left ventricular mass (0.197 g/month; P=.049), internal diameter during systole (0.255 mm/month; P<.001), and diastole (0.217 mm/month; P=.019), as well as cardiac output (0.048 L/month, P=.019), and left ventricular percent shortening (0.256 %/month; P=.027). These associations were not differentially affected by exercise (Control vs AO vs FES, P>.05). CONCLUSIONS: These results indicate that within the subacute phase of recovery from SCI there is a linear loss of left ventricular cardiac structure and systolic function that is not attenuated by current rehabilitative aerobic exercise practices. Reductions in cardiac structure and function may increase the risk of cardiovascular disease in individuals with SCI and warrants further interventions to prevent cardiac decline.

Patient Perceptions and Clinical Assessments of Cardiometabolic Disease After Subacute Spinal Cord Injury.

OBJECTIVES: To investigate the effectiveness of health care team communication regarding cardiometabolic disease (CMD) risk factors with patients with subacute spinal cord injury (SCI). DESIGN: Multi-site prospective cross-sectional study. SETTING: Five National Institute on Disability, Independent Living, and Rehabilitation Research Model SCI Rehabilitation Centers. PARTICIPANTS: Ninety-six patients with subacute SCI, aged 18-70 years, with SCI (neurologic levels of injury C2-L2, American Spinal Injury Association Impairment Scale grades A-D), and enrolled within 2 months of initial rehabilitation discharge (N=96). INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Objective risk factors of CMD (body mass index, fasting glucose, insulin, high-density lipoprotein cholesterol, triglyceride levels, and resting blood pressure). Patient reported recall of these present risk factors being shared with them by their health care team. Medications prescribed to patients to address these present risk factors were checked against guideline- assessed risk factors. RESULTS: Objective evidence of 197 CMD risk factors was identified, with patients recalling less than 12% of these (P<.0001) being shared with them by their health care team. Thirty-one individuals (32%) met criteria for a diagnosis of CMD, with only 1 of these patients (3.2%) recalling that this was shared by their health care team (P<.0001). Pharmacologic management was prescribed to address these risk factors only 7.2% of the time. CONCLUSIONS: Despite high prevalence of CMD risk factors after acute SCI, patients routinely do not recall being told of their present risk factors. Multifaceted education and professionals' engagement efforts are needed to optimize treatment for these individuals.

Digital Interventions for Social Participation in Adults with Long-term Physical Conditions: A Systematic Review.

This review aims to identify and evaluate digital interventions for social participation in the growing population of adults with long-term physical conditions. Articles were sourced from MEDLINE, EMBASE, CINAHL and PsycINFO databases using subject headings and keywords related to "social participation" and "digital technology". Studies that adopted digital technology interventions to improve social participation in adults with long-term physical conditions were included. Data on study methodology, participant and digital intervention characteristics, and findings related to social participation were extracted. The search yielded a total of 4646 articles and 14 articles met criteria for final review with five randomized controlled trials, two non-randomized clinical trials and seven one-group pretest-posttest clinical trials. Studies were organized based on the digital intervention strategy implemented to improve social participation: group support (n = 4), individual skill training or counseling (n = 6), education and support (n = 3), and mixed intervention (n = 1). The group support interventions developed a social network among participants through videoconference, app, or virtual reality platform. Three studies reported positive improvements in different aspects of social participation. Individual skill training or counseling mainly utilized phone calls to help participants cope with activity participation and interpersonal relationship issues. Only two studies demonstrated benefits for social participation. The education and support intervention, which used messages and website information to increase participants' knowledge and provide support, showed positive findings in three studies. This review suggests digital interventions for improving social participation in adults with long-term physical conditions are feasible and the effectiveness of different strategies may vary.Registration: This review was prospectively registered on the International Prospective Register of Systematic Reviews (PROSPERO) (registry number: CRD42021254105).

Acute Spinal Cord Injury Is Associated With Prevalent Cardiometabolic Risk Factors.

OBJECTIVES: To (1) describe the prevalence of cardiometabolic disease (CMD) at spinal cord injury (SCI) rehabilitation discharge; (2) compare this with controls without SCI; and (3) identify factors associated with increased CMD. DESIGN: Multicenter, prospective observational study. SETTING: Five National Institute on Disability, Independent Living, and Rehabilitation Research Model SCI Rehabilitation Centers. PARTICIPANTS: SCI (n=95): patients aged 18-70 years, with SCI (neurologic levels of injury C2-L2, American Spinal Injury Association Impairment Scale grades A-D), and enrolled within 2 months of initial rehabilitation discharge. Control group (n=1609): age/sex/body mass index-matched entries in the National Health and Nutrition Examination Education Survey (2016-2019) (N=1704). INTERVENTIONS: None MAIN OUTCOME MEASURES: Percentage of participants with SCI with CMD diagnosis, prevalence of CMD determinants within 2 months of rehabilitation discharge, and other significant early risk associations were analyzed using age, sex, body mass index, insulin resistance (IR) by fasting glucose and Homeostasis Model Assessment (v.2), fasting triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol, total cholesterol, and resting blood pressure (systolic and diastolic). RESULTS: Participants with SCI had significantly higher diastolic blood pressure and triglycerides than those without SCI, with lower fasting glucose and HDL-C. A total of 74.0% of participants with SCI vs 38.5% of those without SCI were obese when applying population-specific criteria (P<.05). Low HDL-C was measured in 54.2% of participants with SCI vs 15.4% of those without (P<.05). IR was not significantly different between groups. A total of 31.6% of participants with SCI had ≥3 CMD determinants, which was 40.7% higher than those without SCI (P<.05). Interplay of lipids and lipoproteins (ie, total cholesterol:HDL-C ratio and triglyceride:HDL-C ratio) were associated with elevated risk in participants with SCI for myocardial infarction and stroke. The only significant variable associated with CMD was age (P<.05). CONCLUSIONS: Individuals with SCI have an increased CMD risk compared with the general population; obesity, IR, and low HDL-C are the most common CMD risk determinants; age is significantly associated with early CMD.

The effect of heart rate variability on blood pressure is augmented in spinal cord injury and is unaltered by exercise training.

PURPOSE: To define differences in heart rate and blood pressure variability (HRV/BPV) after spinal cord injury (SCI) compared with uninjured controls, and to determine whether variabilities are impacted by whole-body exercise after SCI. METHODS: Individuals with SCI (n = 40), aged 18-40, and uninjured age/sex-matched controls (n = 22) had HRV and BPV determined during supine paced (0.25 Hz) breathing. Spectral and cross-spectral values were derived for fluctuations at low (LF 0.05-0.15 Hz) and high (HF 0.20-0.30 Hz) frequencies. Thirty-two individuals with SCI further underwent either 6 months of whole-body exercise training (n = 17) or a control intervention (n = 15). RESULTS: Individuals with SCI had injuries graded A-C in severity, neurological levels of injury C1-T10. LF and HF HRV and LF BPV were significantly lower in individuals with SCI (p = 0.008-0.002), though HF BPV was similar. The LF cross-spectrum demonstrated similar phase and gain relationships between groups. The HF phase relationship between pressure and heart rate differed markedly: individuals with SCI demonstrated a -11.7 ± 3.4° phase lag (241 ± 70 ms feedback mechanism of pressure into heart rate), whereas uninjured controls demonstrated a +21.5 ± 10.8° phase lead (443 ± 224 ms feedforward mechanism of heart rate into pressure, p = 0.007). Whole-body exercise increased mean VO2peak by 2.09 ml/kg, whereas HRV, BPV, and their cross-spectral relationships were not significantly altered relative to the control intervention after SCI. CONCLUSION: After SCI, marked frequency-specific differences exist in the relationship between heart rate and blood pressure variabilities. The high-frequency cross-spectral relationship indicates that a feedback mechanism of blood pressure into heart rate may predominate in this range.

Reductions in Cardiac Structure and Function 24 Months After Spinal Cord Injury: A Cross-Sectional Study.

OBJECTIVE: To determine the alterations in cardiac structure and function that occur in the months after spinal cord injury (SCI). STUDY DESIGN: Cross-sectional SETTING: Rehabilitation Hospital PARTICIPANTS: Volunteers (N=29; 4 women, 25 men) between 3 and 24 months after SCI. MAIN OUTCOME MEASURES: Transthoracic echocardiography was performed on each volunteer. The relationships between time since injury and neurologic and sensory levels of injury to cardiac structure and function were assessed via multiple linear regression. RESULTS: Time since injury was most strongly associated with reductions in left ventricular end diastolic volume (r2=0.156; P=.034), end systolic volume (r2=0.141; P=.045), and mass (r2=0.138; P=.047). These structural changes were paralleled by reduced stroke volume (r2=0.143; P=.043) and cardiac output (r2=0.317; P=<.001). The reductions in left ventricular structure and systolic function were not differentially affected by neurologic or sensory levels of injury (P=.084-.921). CONCLUSIONS: These results suggest progressive reductions in left ventricular structure and systolic function between 3 and 24 months after SCI that occur independent of neurologic and sensory levels of injury.

Serotonin 1A agonist and cardiopulmonary improvements with whole-body exercise in acute, high-level spinal cord injury: a retrospective analysis.

PURPOSE: High-level spinal cord injury (SCI) can result in spinal and supraspinal respiratory control deficits leading to insufficient ventilatory responses to exercise and training-related adaptations. We hypothesized a serotonin agonist, known to improve respiratory function in animal models, would improve adaptations to whole-body functional electrical stimulation (FES) exercise training in patients with acute high-level SCI. METHODS: We identified 10 patients (< 2 years of injury with SCI from C4 to T3) in our program who had performed 6 months of FES-row training while on Buspirone (29 ± 17 mg/day) between 2012 and 2018. We also identified well-matched individuals who trained for six months but not on Buspirone (n = 11). A peak incremental FES-rowing exercise test and resting pulmonary function test had been performed before and after training. RESULTS: Those on Buspirone demonstrated greater increases in peak oxygen consumption (VO2peak: + 0.24 ± 0.23 vs. + 0.10 ± 0.13 L/min, p = 0.08) and peak ventilation (VEpeak: + 6.5 ± 8.1 vs. - 0.7 ± 6.9 L/min, p < 0.05) compared to control. In addition, changes in VO2peak and VEpeak were correlated across all patients (r = 0.63, p < 0.01), but most strongly in those on Buspirone (r = 0.85, p < 0.01). Furthermore, changes in respiratory function correlated with increased peak tidal volume in the Buspirone group (r > 0.66, p < 0.05). CONCLUSION: These results suggest Buspirone improves cardiorespiratory adaptations to FES-exercise training in individuals with acute, high-level SCI. The strong association between increases in ventilatory and aerobic capacities suggests improved respiratory function is a mechanism; however, controlled studies are needed to determine if this preliminary finding is reproducible.

Gains in aerobic capacity with whole-body functional electrical stimulation row training and generalization to arms-only exercise after spinal cord injury.

STUDY DESIGN: Longitudinal study in adults (n = 27; 19-40 years old) with tetraplegic or paraplegic spinal cord injury (SCI). OBJECTIVES: Determine physiological adaptations and generalizable fitness effects of 6 months of whole-body exercise training using volitional arm and functional electrical stimulation (FES) leg rowing. SETTING: Outpatient hospital-based exercise facility and laboratory. METHODS: Participants enrolled in hybrid FES-row training (FESRT) and performed peak exercise tests with arms-only (AO; baseline and 6 months) and FES rowing (baseline, 3, 6 months). RESULTS: Participants demonstrated increased aerobic capacity (VO2peak) after FESRT (p < 0.001, np2 = 0.56) that tended to be higher when assessed with FES than AO rowing tests (0.15 ± 0.20 vs. 0.04 ± 0.22 L/min; p = 0.10). Changes in FES and AO VO2peak were significantly correlated (r = 0.55; p < 0.01), and 11 individuals demonstrated improvements (>6%) on both test formats. Younger age was the only difference between those who showed generalization of training effects and those who did not (mean age 26.6 ± 5.6 vs. 32.0 ± 5.7 years; p < 0.05) but changes in FES VO2peak correlated to time since injury in individuals <2 years post-SCI (r = -0.51, p < 0.01, n = 24). Lastly, VO2peak improvements were greater during the first 3 months vs. months 4-6 (+7.0% vs. +3.9%; p < 0.01) which suggests early training adaptations during FESRT. CONCLUSIONS: Gains in aerobic capacity after whole-body FESRT are better reflected during FES-row testing format. They relate to high-intensity exercise and appear early during training, but they may not generalize to equivalent increases in AO exercise in all individuals with SCI.

Heart rate variability as a biomarker for anorexia nervosa: A review.

OBJECTIVE: Anorexia nervosa (AN) typically begins in early adolescence and other than weight status has few reliable biomarkers. Early diagnosis is a critical prognostic factor, but this can be clinically challenging. Heart rate variability (HRV), the beat-by-beat variance in heart rate (HR), may provide a unique assessment for the presence of AN because it has clinical utility as a biomarker of cardiac autonomic control in various populations (e.g., athletes, the aged, those with cardiovascular diseases, etc.). We present a review of the literature examining HRV in those with AN. METHOD: Relevant publications were selected from PubMed using the search terms 'anorexia nervosa AND (HR OR HRV)'. Twenty papers were selected and reviewed. RESULTS: The majority of studies suggest that those with AN have markedly and consistently elevated HRV compared to controls, even greater than among young athletes. However, no studies have explored HRV as a biomarker for AN. DISCUSSION: Future studies on HRV should elucidate its role as a diagnostic biomarker for AN as well as its responsiveness with serial measurement to track response rates and predict relapse.

Effects of hybrid-functional electrical stimulation (FES) rowing whole-body exercise on neurologic improvement in subacute spinal cord injury: secondary outcomes analysis of a randomized controlled trial.

STUDY DESIGN: Secondary outcome measures analysis of a randomized, controlled study. OBJECTIVE: To assess the effects of hybrid-functional electrical stimulation (FES) rowing on motor and sensory recovery in individuals with spinal cord injury (SCI) 6-18 months post injury. SETTING: Outpatient rehabilitation network. METHODS: 25 participants 6-12 months after SCI were randomly assigned to hybrid-FES rowing (n = 10) or standard of care (n = 15) groups. The hybrid-FES rowing group completed 6 months of rowing scheduled 3 times per week for 26 weeks at an exercise intensity of 70-85% of maximal heart rate. The standard of care group either participated in an arm ergometer exercise program (n = 6) or a waitlist without an explicit exercise program (n = 9). Changes in motor score and combined sensory score of the International Standards for Neurological Classification of SCI (ISNCSCI) were analyzed. RESULTS: Both groups demonstrated increases in motor and combined sensory scores, but no significant differences were noted between intervention groups (motor difference mean ↑1.3 (95% CI, -1.9 to 4.4), combined sensory difference mean ↓10 (-30 to 18)). There was an average of 63% adherence to the hybrid-FES rowing protocol, with no significant correlation in changes in motor or combined sensory score in the hybrid-FES rowing group with total distance or time rowed. CONCLUSIONS: No significant effects to neurologic improvement were found with hybrid-FES rowing when compared with standard of care interventions in individuals with SCI 6-18 months post injury.

A pilot randomized controlled trial of 6-week combined exercise program on fasting insulin and fitness levels in individuals with spinal cord injury.

PURPOSE: The aim of this randomized controlled trial study was to investigate the effect of combined exercise program on the fasting insulin and fitness levels of people with spinal cord injury (SCI). METHODS: A total of 19 individuals with SCI participated in a combined exercise program consisting of aerobic and resistance exercises for 60 min per day, 3 days per week for 6 weeks. Peak oxygen consumption, body mass index, percent body fat, waist circumference, shoulder abduction and adduction, shoulder flexion and extension, elbow flexion and extension, fasting insulin levels, and homeostasis model assessment of insulin resistance (HOMA-IR) levels were measured at baseline and after the intervention. RESULTS: The 6-week exercise program significantly decreased the average fasting insulin (baseline: 7.5 ± 4.7 µU/ml vs. post-intervention: 4.5 ± 2.2 µU/ml, p < 0.05) and HOMA-IR (baseline: 1.5 ± 1.0 vs. post-intervention: 0.9 ± 0.4, p < 0.05) in the exercise group, whereas there was no change in control group (between group difference, mean fasting insulin: - 3.2 µU/ml, p = 0.003; mean HOMA-IR: - 0.66, p = 0.001). In addition, muscle strength of the shoulder flexors, extensors, abductors, adductors, and elbow flexors was significantly improved in the exercise group compared to the controls. CONCLUSION: A combined exercise program is effective in decreasing fasting insulin and HOMA-IR levels while improving fitness in those with SCI. These slides can be retrieved under Electronic Supplementary Material.

Integrative physiological and computational approaches to understand autonomic control of cerebral autoregulation.

The brain requires steady delivery of oxygen and glucose, without which neurodegeneration occurs within minutes. Thus, the ability of the cerebral vasculature to maintain relatively steady blood flow in the face of changing systemic pressure, i.e. cerebral autoregulation, is critical to neurophysiological health. Although the study of autoregulation dates to the early 20th century, only the recent availability of cerebral blood flow measures with high temporal resolution has allowed rapid, beat-by-beat measurements to explore the characteristics and mechanisms of autoregulation. These explorations have been further enhanced by the ability to apply sophisticated computational approaches that exploit the large amounts of data that can be acquired. These advances have led to unique insights. For example, recent studies have revealed characteristic time scales wherein cerebral autoregulation is most active, as well as specific regions wherein autonomic mechanisms are prepotent. However, given that effective cerebral autoregulation against pressure fluctuations results in relatively unchanging flow despite changing pressure, estimating the pressure-flow relationship can be limited by the error inherent in computational models of autoregulatory function. This review focuses on the autonomic neural control of the cerebral vasculature in health and disease from an integrative physiological perspective. It also provides a critical overview of the current analytical approaches to understand cerebral autoregulation.

Hybrid functional electrical stimulation exercise training alters the relationship between spinal cord injury level and aerobic capacity.

OBJECTIVE: To test the hypothesis that hybrid functional electrical stimulation (FES) row training would improve aerobic capacity but that it would remain strongly linked to level of spinal cord lesion because of limited maximal ventilation. DESIGN: Longitudinal before-after trial of 6 months of FES row training. SETTING: Exercise for persons with disabilities program in a hospitaL. PARTICIPANTS: Volunteers (N=14; age range, 21-63y) with complete spinal cord injury (SCI) (T3-11) who are >2 years postinjury. INTERVENTION: Six months of FES row training preceded by a variable period of FES strength training. MAIN OUTCOME MEASURES: Peak aerobic capacity and peak exercise ventilation before and after 6 months of FES row training. RESULTS: FES row training significantly increased peak aerobic capacity and peak minute ventilation (both P<.05). Prior to FES row training, there was a close relation between level of SCI and peak aerobic capacity (adjusted R(2)=.40, P=.009) that was markedly reduced after FES row training (adjusted R(2)=.15, P=.10). In contrast, the relation between level of injury and peak minute ventilation was comparable before and after FES row training (adjusted R(2)=.38 vs .32, both P<.05). CONCLUSIONS: The increased aerobic capacity reflects more than increased ventilation; FES row training effectively circumvents the effect of SCI on peak aerobic capacity by engaging more muscle mass for training, independent of the level of injury.

BP regulation VI: elevated sympathetic outflow with human aging: hypertensive or homeostatic?

Though conventional wisdom suggests that a rise in blood pressure is a reality of advancing age, in fact, it appears that progressive elevation in sympathetic activity, not necessarily accompanied by increased blood pressure, is intrinsic to cardiovascular aging in humans. The mechanism behind this elevation would seem to reside in homeostatic cardiovascular regulation; nonetheless, the balance of factors that result in elevated sympathetic outflow with age remains elusive. Age-related increases in sympathetic nervous outflow cannot be fully explained by increases in body mass, body adiposity, or other metabolic factors; interrelations among cardiac output, peripheral resistance, and blood pressure may not reflect a determinative hemodynamic interrelation but rather parallel phenomena; and there is no simple linear relationship between baroreflex control and resting levels of sympathetic activity. In contrast to systemic relationships, available data suggest that elevated sympathetic outflow may derive from the inter-relationship between centrally driven sympatho-excitation and a decline in the ability of sympathetic outflow to effect peripheral vascular responses. This review aims to integrate the current knowledge of mechanisms underlying elevated sympathetic outflow with age. It seeks to synthesize these data in the context of proposing that an age-related decline in the ability of sympathetic outflow to effect regional vascular responses incites a compensatory elevation in resting sympathetic activity to maintain homeostatic balance, presumably to maintain adequate control of blood pressure.

Characterizing preserved autonomic regulation following spinal cord injury: Methods of a novel concerted testing battery and illustrative examples of a new translationally focused data representation.

Autonomic dysfunction is common after spinal cord injury, though differing from motor and sensory function, there are currently no established batteries of tests to comprehensively characterize these deficits. Further, while individual established autonomic tests have a long history and sound scientific background, translating these autonomic testing results to inform clinical understanding is a major barrier. Herein, we outline a battery of six laboratory autonomic tests which were carefully curated to collectively describe the ability of individuals with spinal cord injury to inhibit and recruit sympathetic activity through the injured spinal cord. Presenting normative control data in 23 uninjured individuals completing this testing battery, we further demonstrate the utility of extracting three key testing metrics for each test, comparing these control results to 11 individuals with spinal cord injury. Results demonstrate strong normality of data with testing psychometrics suggesting reliable reproducibility on repeat testing. Further, even in this preliminary sample of individuals with spinal cord injuries, clear differences begin to emerge. This illustrates the ability of this collective testing battery to characterize autonomic regulation after spinal cord injury. To aid in clinical translation, we further present a graphical representation, an autonomic phenotype, which serves as a snapshot of how normal or abnormal sympathetic inhibition and recruitment of activation may be after spinal cord injury. Utilizing these autonomic phenotypes, three example cases of individuals with spinal cord injury highlight evidence of varied degrees of autonomically complete spinal cord injury. Together, this represents a key advancement in our understanding of autonomic function after spinal cord injury.