Targeting inflammation to influence cognitive function following spinal cord injury: a randomized clinical trial.

STUDY DESIGN: This study was a randomized, parallel-group, controlled clinical trial. OBJECTIVES: The purpose of this study was to examine the efficacy of targeting inflammation as a means of improving cognitive function in individuals with spinal cord injury. SETTING: Participants were recruited from the Niagara region of Ontario Canada and all testing occurred on-site at Brock University. METHODS: Indices of memory and verbal learning were assessed by means of the California Verbal Learning Test (CVLT). Inflammation and concentrations of neuroactive compounds related to the kynurenine pathway were assessed via a number of pro- and anti-inflammatory cytokines, as well as tryptophan, kynurenine and several large neutral amino acids. All assessments were performed at baseline as well as at 1 month and 3 months during a 3-month intervention by means of an anti-inflammatory diet. RESULTS: Despite a reduction in inflammation, all measures of the CVLT, including list A, trial 1 (P=0.48), learning slope (P=0.46), long delay free recall (P=0.83), intrusions (P=0.61) and repetitions (P=0.07), showed no significant group × time interaction. CONCLUSION: It may be possible that the reduction in inflammation achieved in the current study was insufficient to induce substantial changes in indices of verbal learning and memory. Alternatively, as these participants likely underwent years of previous chronic inflammation, the underlying hippocampal damage may have negated potential improvements induced by acute reductions in inflammation.

Non-invasive electrocardiographic assessments of cardiac autonomic modulation in individuals with spinal cord injury.

STUDY DESIGN: Review. OBJECTIVES: The purpose of this review is to discuss the utility of linear and non-linear heart rate variability (HRV) as well as the QT-variability index (QTVI) as indices of cardiac autonomic control in individuals with spinal cord injury (SCI). SETTING: Brock University, Department of Kinesiology, St Catharines, Ontario, Canada. Brock-Niagara Centre for Health and Well-being, St Catharines, Ontario, Canada. METHODS: Literature review. CONCLUSION: Non-invasive markers determined from the electrocardiogram, such as linear and non-linear HRV, and, more recently, the QTVI have all shown some promise as indices of cardiac autonomic regulation in the SCI population. However, there are inconsistencies in the literature that call to question their true validity in this regard. Studies using pharmacological blockade, sympathetic manoeuvres and exercise suggest that both linear and non-linear HRV reflect cardiac parasympathetic activity, whereas their ability to quantify cardiac sympathetic outflow remains uncertain. The QTVI, although a novel method, correlates with both limbs of the autonomic nervous system and therefore may hold value as a measure of both cardiac sympathetic and parasympathetic activity in individuals with SCI; however, more research is required to confirm its utility.

Impact of shear rate pattern on upper and lower limb conduit artery endothelial function in both spinal cord-injured and able-bodied men.

NEW FINDINGS: What is the central question of this study? This study addresses the following two central questions. (i) What is the impact of vascular deconditioning after spinal cord injury (SCI) on shear rate patterns and endothelial function? (ii) What is the impact of acutely altered shear rate on endothelial function in both SCI and able-bodied control subjects? What is the main finding and its importance? Two main findings in the present study were as follows: (i) reduced superficial femoral artery endothelial function in the SCI group; and (ii) acutely altered shear rate decreased endothelial function in both SCI and able-bodied control subjects. These findings may shed some light on future interventions taking into account these regulatory mechanisms. Spinal cord injury (SCI) induces vascular deconditioning below the level of the lesion and disrupts sympathetic innervation of blood vessels. It is unclear how these changes affect shear rate (SR) profiles and endothelial function when compared with able-bodied (AB) persons. Recent evidence suggests that periods of increased retrograde SR are associated with acute decreases in endothelial function, but is unknown how modified SR patterns influence sublesional vasculature in SCI. The present study examined the acute and chronic effects of altered SR patterns and oscillatory shear index on endothelial function via relative flow-mediated dilatation (FMD%) in both the brachial and superficial femoral arteries (BA and SFA, respectively) of eight individuals with SCI and eight matched AB control subjects. Baseline BA SR patterns and FMD% were similar between groups, while SFA anterograde SR was higher (P < 0.01) and FMD% lower (P = 0.04) in SCI versus AB subjects. Shear rate patterns were then acutely altered through the BA and SFA using a subsystolic cuff-inflation model. Bilateral FMD assessments were conducted before and after 30 min of unilateral inflation of a forearm or thigh blood pressure cuff to 75 mmHg. Cuff inflation resulted in concomitant increases in both anterograde (P < 0.05) and retrograde SR (P < 0.05), as well as acute decreases in FMD% (P < 0.05) in the BA and SFA in both groups. These results highlight that brief manipulation of SR patterns can acutely impair FMD% in conditions of both normal and altered sympathetic innervation and arterial remodelling. This information is crucial when designing strategies to combat impaired vascular function in both healthy and clinical populations.

Immune dysfunction and chronic inflammation following spinal cord injury.

STUDY DESIGN: Review article. OBJECTIVES: The objective of this study is to provide an overview of the many factors that contribute to the chronic inflammatory state typically observed following spinal cord injury (SCI). METHODS: Literature review. RESULTS: Not applicable. CONCLUSION: SCI is typically characterized by a low-grade inflammatory state due to a number of factors. As bidirectional communication exists between the nervous, endocrine and immune systems, damage to the spinal cord may translate into both endocrinal and immune impairment. Damage to the autonomic nervous system may induce immune dysfunction directly, through the loss of neural innervation of lymphoid organs, or indirectly by inducing endocrinal impairment. In addition, damage to the somatic nervous system and the corresponding loss of motor and sensory function increases the likelihood of developing a number of secondary health complications and metabolic disorders associated with a state of inflammation. Lastly, numerous related disorders associated with a state of chronic inflammation have been found to be at a substantially higher prevalence following SCI. Together, such factors help explain the chronic inflammatory state and immune impairment typically observed following SCI. An understanding of the interactions between systems, both in health and disease, and the many causes of chronic inflammation may aid in the effective future treatment of immune dysfunction and related disorders following SCI.

Exercise equipment preferences among adults with spinal cord injury.

STUDY DESIGN: Cross-sectional. OBJECTIVES: To evaluate exercise equipment preferences and compare cardiometabolic demand for passive hybrid and arm-only exercise among adults with paraplegia (PP) and those with tetraplegia (TP). SETTING: Four community exercise programmes. METHODS: Thirty-six adults (mean age: 41.1±12.1 years) with chronic (11.4±10.7 years post injury) TP (C3-C8; n=17) or PP (T3-T12; n=19) were recruited. Participants completed 20 min of submaximal aerobic exercise at moderate to vigorous intensity on four types of aerobic exercise equipment: arm cycle ergometer (ACE), arm glider (AG), arm-leg recumbent stepper (ALRS), and arm-leg cycle ergometer (ALCE). Participants also completed 3 sets of 10 repetitions of resistance exercise using wall pulleys (WP) and weight stack (WS) equipment. A questionnaire was administered to evaluate equipment preference. Heart rate (HR) and oxygen uptake (VO2) were measured in a subset of participants (n=9) during submaximal aerobic exercise. RESULTS: Arm-only exercise modes were perceived as being safer than passive hybrid exercise modes. There were no differences in perceived enjoyment between equipment types and groups. There were significant group but not equipment differences in HR (TP: 101.4 bpm; PP: 124.9 bpm) and VO2 (TP: 6.5 ml•kg(-1)•min(-1); PP: 10.5 mL•kg(-1)•min(-1)) during submaximal aerobic exercise. CONCLUSION: In this cross-community assessment of exercise equipment preferences after spinal cord injury (SCI), arm-only exercise modes were perceived as safer than hybrid exercise modes and there were no differences between equipment types in physiological responses.

The effects of exercise training on physical capacity, strength, body composition and functional performance among adults with spinal cord injury: a systematic review.

STUDY DESIGN: Systematic review. OBJECTIVES: To conduct a systematic review of evidence surrounding the effects of exercise on physical fitness in people with spinal cord injury (SCI). SETTING: Canada. METHODS: The review was limited to English-language studies (published prior to March 2010) of people with SCI that evaluated the effects of an exercise intervention on at least one of the four main components of physical fitness (physical capacity, muscular strength, body composition and functional performance). Studies reported at least one of the following outcomes: oxygen uptake/consumption, power output, peak work capacity, muscle strength, body composition, exercise performance or functional performance. A total of 166 studies were identified. After screening, 82 studies (69 chronic SCI; 13 acute SCI) were included in the review. The quality of evidence derived from each study was evaluated using established procedures. RESULTS: Most studies were of low quality; however, the evidence was consistent that exercise is effective in improving aspects of fitness. There is strong evidence that exercise, performed 2-3 times per week at moderate-to-vigorous intensity, increases physical capacity and muscular strength in the chronic SCI population; the evidence is not strong with respect to the effects of exercise on body composition or functional performance. There were insufficient high-quality studies in the acute SCI population to draw any conclusions. CONCLUSIONS: In the chronic SCI population, there is good evidence that exercise is effective in improving both physical capacity and muscular strength, but insufficient quality evidence to draw meaningful conclusions on its effect on body composition or functional capacity.

The development of evidence-informed physical activity guidelines for adults with spinal cord injury.

OBJECTIVES: To systematically develop evidence-informed physical activity guidelines to improve physical fitness in people with spinal cord injury (SCI). SETTING: This study was conducted in Canada. METHODS: The Appraisal of Guidelines, Research and Evaluation II guideline development protocol was used to develop exercise guidelines to improve physical capacity and muscular strength. The evidence base for the guideline development process consisted of a systematic review and quality appraisal of research examining the effects of exercise on physical fitness among people with SCI. A multidisciplinary expert panel deliberated the evidence and generated the guidelines. Pilot testing led to refinement of the wording and presentation of the guidelines. RESULTS: The expert panel generated the following guidelines: for important fitness benefits, adults with a SCI should engage in (a) at least 20 min of moderate to vigorous intensity aerobic activity two times per week and (b) strength training exercises two times per week, consisting of three sets of 8-10 repetitions of each exercise for each major muscle group. CONCLUSION: People with SCI, clinicians, researchers and fitness programmers are encouraged to adopt these rigorously developed guidelines.

The effects of body-weight supported treadmill training on cardiovascular regulation in individuals with motor-complete SCI.

STUDY DESIGN: Four-month longitudinal within-subject exercise training study. OBJECTIVE: Although body-weight supported treadmill training (BWSTT) has not shown promise as a means of improving ambulation in individuals with motor-complete spinal cord injury (SCI), it may still improve cardiovascular health and function in this population. The purpose of this study was to (i) investigate the effects of BWSTT on peripheral muscular and elastic artery dimension and function and measures of heart rate variability (HRV) and blood pressure variability (BPV) in individuals with motor-complete SCI, and (ii) to make a preliminary examination of what factors may predict favourable cardiovascular outcomes following BWSTT in this population. SETTING: Centre for Health Promotion and Rehabilitation, McMaster University, Hamilton, Ontario, Canada. METHODS: Six individuals (four male, two female; age 37.7+/-15.4 years) with chronic SCI (C4-T12; ASIA A-B; 7.6+/-9.4 years post-injury) were included in the present investigation. Doppler ultrasound was used to determine femoral (exercising; muscular), carotid (elastic) and brachial (non-exercising control; muscular) artery dimension and function before and after 4 months of BWSTT. Continuous heart rate and blood pressure were also recorded before and after 4-months of BWSTT to determine frequency domain measures of HRV and BPV; clinically valuable indices of neurocardiac and neurovascular control, respectively. RESULTS: Two-way ANOVA (vessel x time) revealed no exercise-induced change in femoral or carotid artery cross-sectional area, blood flow or resistance and no change in carotid artery compliance following the 4 months of BWSTT compared to the non-exercising control brachial artery. However, there was a significant exercise-induced increase in femoral artery compliance. There were no exercise-induced changes in HRV or BPV when all participants were considered together. However, the results suggest that the subgroup of individuals who had a substantial heart rate response to BWSTT (n=3), experienced exercise-training induced changes in HRV reflective of a relative shift toward cardiac vagal predominance and reductions in BPV. CONCLUSIONS: BWSTT may cause an increase in femoral artery compliance in individuals with motor-complete SCI and therefore, should be encouraged as a means of improving cardiovascular health in this population. BWSTT may also cause modest improvements in measures of HRV and BPV in a select subgroup of individuals who respond to ambulation with moderate to large increases in HR. In the present study, factors associated with a substantial HR response to BWSTT were a propensity to orthostatic intolerance and muscular spasticity.

Na+,K+-ATPase concentration and fiber type distribution after spinal cord injury.

Complete spinal cord injury (SCI) is characterized, in part, by reduced fatigue-resistance of the paralyzed skeletal muscle during stimulated contractions, but the underlying mechanisms are not fully understood. The effects of complete SCI on skeletal muscle Na(+),K(+)-adenosine triphosphatase (ATPase) concentration, and fiber type distribution were therefore investigated. Six individuals (aged 32.0 +/- 5.3 years) with complete paraplegia (T4-T10; 1-19 years since injury) participated. There was a significantly lower Na(+),K(+)-ATPase concentration in the paralyzed vastus lateralis (VL) when compared to either the subjects' own unaffected deltoid or literature values (from our laboratory, utilizing the same methodology) of VL Na(+),K(+)-ATPase concentration for the healthy able-bodied (141.6 +/- 50.0, 213.4 +/- 23.9, 339 +/- 16 pmol/g wet wt., respectively; P < 0.05). There was also a significant negative correlation between the Na(+),K(+)-ATPase concentration in the paralyzed VL and years since injury (r = -0.75, P < 0.05). These findings are clinically relevant as they suggest that reductions in Na(+),K(+)-ATPase contribute to the fatigability of paralyzed muscle after SCI. Unexpectedly, the VL muscles of our subjects had a higher proportion of their area represented by type I fibers compared to literature values for the VL of the healthy able-bodied (52.6 +/- 25.3% vs. 36 +/- 11.3%, respectively; P < 0.05). As all our subjects had upper motor neuron injuries and, therefore, experienced muscle spasticity, our findings warrant further investigation into the relationship between muscle spasticity and fiber type expression after SCI.

Maintenance of exercise participation in individuals with spinal cord injury: effects on quality of life, stress and pain.

STUDY DESIGN: Follow-up study of seven individuals with spinal cord injury (SCI) who completed a 9-month randomized control trial (RCT) of exercise training. OBJECTIVE: In a 9-month RCT conducted in our lab, individuals with SCI who participated in a twice-weekly supervised exercise training reported greater perceived quality of life (PQOL), and less stress and pain than a nonexercising control cohort. The present follow-up study examined the voluntary continuation of exercise training after the study ended and the persistence of the accrued psychosocial benefits. SETTING: Centre for Health Promotion and Rehabilitation, McMaster University, Hamilton, Ontario, Canada. METHODS: Five men and two women (age 42.3+/-3.6 years) with SCI (C5-T12; ASIA A-D 12.7+/-8.2 years postinjury) were invited to continue supervised exercise training twice weekly at the completion of the 9-month RCT. Exercise adherence, PQOL, stress and bodily pain were measured at a 3-month follow-up and were compared to values obtained at baseline, and at 3, 6 and 9 months during the intervention. RESULTS: There was a significant decrease in adherence at the 3-month follow-up compared to the overall 9-month adherence rate (42.7 versus 80.6%, respectively; P<0.01). There was also a significant decrease in PQOL (P<0.05) and a trend for increased pain (P=0.07) and stress (P=0.12), at follow-up compared to the end of the 9-month trial. Finally, there was a significant negative correlation between pain at the conclusion of the RCT and exercise adherence over the 3-month follow-up period (r=-0.91; P<0.01). CONCLUSIONS: These findings emphasize the importance of continued exercise adherence to the maintenance of exercise-related increases in psychological well-being among individuals with SCI.

Long-term exercise training in persons with spinal cord injury: effects on strength, arm ergometry performance and psychological well-being.

STUDY DESIGN: Randomized controlled trial of exercise training in persons with spinal cord injury. OBJECTIVE: The purpose of this study was to examine the effects of 9 months of twice-weekly exercise training on strength, arm ergometry performance, and indices of psychological well-being and quality of life. SETTING: Centre for Health Promotion and Rehabilitation, McMaster University, Hamilton, Ontario, Canada. METHODS: Thirty-four men and women (aged 19-65 years) with traumatic spinal cord injury (C4-L1; ASIA A-D) of 1-24 years duration volunteered to participate, and were randomized into exercise (EX; n=21) and control (CON; n=13) groups. Twenty-three subjects (11 EX; 12 CON) successfully completed the 9-month study. Subjects were assessed for one repetition maximum (1RM) strength, arm ergometry performance, and several indices of quality of life and psychological well-being at baseline, 3, 6, and 9 months. RESULTS: At baseline, there were no significant differences between groups in age, submaximal arm ergometry performance, muscle strength, or psychological well-being. Following training, the EX group had significant increases in submaximal arm ergometry power output (81%; P<0.05), and significant increases in upper body muscle strength (19-34%; P<0.05); no significant changes occurred in CON. Participants in EX reported significantly less pain, stress and depression after training, and scored higher than CON in indices of satisfaction with physical function, level of perceived health and overall quality of life (P<0.05). Exercise adherence (per cent of prescribed sessions attended) in those subjects who completed the 9 months of training was 82.5%. CONCLUSIONS: These results demonstrate that long-term twice-weekly exercise training in this population is feasible, and results in significant gains in both physical and psychological well-being.

Sex differences in human skeletal muscle fatigue.

Research on muscle fatigue suggests that greater fatigue resistance may be evident in females compared with males. The possible mechanisms for this sex difference include factors related to muscle mass, substrate utilization, muscle morphology, and neuromuscular activation.

The effect of age and gender on the relative fatigability of the human adductor pollicis muscle.

The purpose of this study was to examine the relative influence of such factors as age, gender, and absolute force on the fatiguability of the human adductor pollicis muscle. 12 young males (YM, 25.3 +/- 2.1 y), 12 young females (YF. 23.5 +/- 2.1 y), 12 older males (OM, 71.7 +/- 5.6 y) and 12 older females (OF, 69.5 +/- 4.6 y) participated. Three minutes of intermittent (5 s contraction, 2 s rest) maximal voluntary contractions (MVC) were used to fatigue the adductor pollicis muscle; the ulnar nerve was also stimulated in each 2 s rest period to evoke a maximal twitch. Males were stronger than females in both voluntary and evoked force (PT) in the young age group (MVC: YM, 10.0 +/- 2.7 kg vs. YF, 6.6 +/- 1.1 kg, P < 0.05) (PT: YM, 0.99 +/- 0.21 kg vs. YF, 0.71 +/- 0.12 kg, P < 0.05). In the older adults, however, males were stronger only in the evoked twitch (OM, 0.73 +/- 0.24 kg vs. OF, 0.48 +/- 0.07 kg, P < 0.05). There was no significant effect of gender or absolute muscle force on relative fatigability; the only variable found to significantly affect fatigability was age. Older adults were significantly less fatigable than young adults as indicated by the voluntary fatigue index (FI) (percentage of force reduction from baseline; FI-young, 40.2 +/- 12.6% vs. FI-old, 25.2 +/- 12.3%). This age effect, however, was more prominent in males than females (FI-YM, 44.7 +/- 10.5% vs. FI-OM, 24.2 +/- 10.7%, P < 0.01; FI-YF, 37.8 +/- 14.1% vs. FI-OF, 26.3 +/- 14.5%, P = 0.13). In conclusion, age was found to be the strongest single predictor of fatigability during short duration, intermittent exercise in human adductor pollicis muscle.