Cardiac parasympathetic activity and ventricular diastolic interactions in individuals with spinal cord injury.

STUDY DESIGN: Cohort cross-sectional study. OBJECTIVE: To investigate the relationship between cardiac vagal activity and left ventricular filling at rest and during vagal stimulation, via the cold face test (CFT), in individuals with spinal cord injury (SCI). SETTING: University-based laboratory at Brock University, St. Catharines, ON, Canada. METHODS: A total of 12 able-bodied (age: 40 ± 8.5 years) and 13 SCI individuals (age: 41 ± 8.5 years; C4-T6; AIS: A-D) were recruited. Cardiac parasympathetic activity was assessed via heart rate variability (HRV) while LV filling was assessed by conventional echocardiography. All indices of HRV and diastolic function were obtained at rest and during cardiac vagal stimulation via the CFT. RESULTS: At baseline, the able-bodied group demonstrated strong positive correlations between HRV and early diastolic filling; however, such correlations were absent in the SCI group. The CFT resulted in elevated HRV with concomitant bradycardia in the able-bodied group, while the SCI group experienced no change in HRV or heart rate during the CFT. Able-bodied individuals showed a positive correlation between the change in HRV and the change in LV diastole during the CFT, which was attributed to increased cardiac vagal tone and not the change in heart rate, however, no relationships were observed in the SCI group. CONCLUSION: In able-bodied individuals, cardiac parasympathetic activity is associated with LV filling at rest and during elevated cardiac vagal tone. After SCI, there is a discord between vagal and LV diastolic activity, where changes in autonomic function do not influence LV filling, suggesting a disconnect between parasympathetic and cardiac function.

A call to reevaluate cardiac autonomic assessment after spinal cord injury.

This "Perspectives" article puts forward the notion that measuring heart rate variability, or other forms of cardiac autonomic regulation, after spinal cord injury must be performed during a test of autonomic stress. Resting values of heart rate variability are often similar to those obtained from able-bodied individuals, which may therefore be falsely interpreted as normal or healthy autonomic regulation. However, evidence shows that despite normal resting values, cardiac autonomic control is impaired when individual with spinal cord injury are subjected to a cold face test, head-up tilt, or recovery from exercise. Accordingly, examination of cardiac autonomic function must be performed during an autonomic challenge, as resting measures do not accurately reflect the state of cardiovascular regulation after spinal cord injury and can provide false information.

Effects of FES-Ambulation Training on Locomotor Function and Health-Related Quality of Life in Individuals With Spinal Cord Injury.

BACKGROUND: The combination of body weight-supported gait training with functional electrical stimulation (FES) may provide the optimal stimulus for improving overground walking after spinal cord injury (SCI). This potential benefit is likely due to the combination of specificity with the maximization of muscle contractions. OBJECTIVES: To investigate the effects of 12 weeks of FES-ambulation on overground walking and health-related quality of life (HRQOL) in individuals with SCI. METHODS: Six individuals (60.5 ± 13.2 years) with SCI (C4-L3; AIS D; 9.3 ± 12.0 years post injury), completed a thrice-weekly, 12-week FES-ambulation training program. Locomotor function was assessed via the Walking Index for Spinal Cord Injury II (WISCI II), the 6-minute walk test (6MWT), the 10-meter walk test (10MWT), and the body-weight support required during training. HRQOL was assessed via the Short Form-36, the Perceived Stress Scale, and the Center of Epidemiological Studies for Depression scale. RESULTS: Participants showed significant improvements in the 6MWT (223.6 ± 141.5 m to 297.3 ± 164.5 m; P = .03), the required body weight support (55.3% ± 12.6% to 14.7% ± 23.2%; P = .03), and a nonsignificant trend toward an increase in walking speed during the 10MWT (0.69 ± 0.4 m/s to 0.9 ± 0.5 m/s; P = .08) following the training program. Four participants showed improvements on the WISCI II (1-4 points). Participants also showed a decrease in the Short Form-36 pain score (6.5 ± 1.2 to 5.0 ± 1.7; P = .04) and an increase in the overall mental health score (47.8 ± 12.6 to 54.2 ± 6.7; P = .04). CONCLUSION: FES-ambulation was associated with enhanced overground walking in individuals with AIS D SCI, reduced pain, and improved mental health.

Dual motor cortex and spinal cord neuromodulation improves rehabilitation efficacy and restores skilled locomotor function in a rat cervical contusion injury model.

Motor recovery after spinal cord injury is limited due to sparse descending pathway axons caudal to the injury. Rehabilitation is the primary treatment for paralysis in humans with SCI, but only produces modest functional recovery. Here, we determined if dual epidural motor cortex (M1) intermittent theta burst stimulation (iTBS) and cathodal transcutaneous spinal direct stimulation (tsDCS) enhances the efficacy of rehabilitation in improving motor function after cervical SCI. iTBS produces CST axon sprouting and tsDCS enhances M1-evoked spinal activity and muscle contractions after SCI. Rats were trained to perform the horizontal ladder task. Animals received a moderate midline C4 contusion, producing bilateral forelimb impairments. After 2 weeks, animals either received 10 days of iTBS+tsDCS or no stimulation; subsequently, all animals received 6 weeks of daily rehabilitation on the horizontal ladder task. Lesion size was not different in the two animal groups. Rehabilitation alone improved performance by a 22% reduction in skilled locomotion error rate, whereas stimulation+rehabilitation was markedly more effective (52%), and restored error rate to pre-injury levels. Stimulation+rehabilitation significantly increased CST axon length caudal to the injury and the amount of ventral horn label was positively correlated with functional improvement. The stimulation+rehabilitation group had significantly less proprioceptive afferent terminal labelling in the intermediate zone and fewer synapses on motoneurons . Afferent fiber terminal labeling was negatively correlated with motor recovery. Thus, the dual neuromodulation protocol promotes adaptive plasticity in corticospinal and proprioceptive afferents networks after contusion SCI, leading to enhanced rehabilitation efficacy and recovery of skilled locomotion.

Layer-specific systolic and diastolic strain in hypertensive patients with and without mild diastolic dysfunction.

This study sought to examine layer-specific longitudinal and circumferential systolic and diastolic strain, strain rate (SR) and diastolic time intervals in hypertensive patients with and without diastolic dysfunction. Fifty-eight treated hypertensive patients were assigned to normal diastolic function (NDF, N = 39) or mild diastolic dysfunction (DD, N = 19) group. Layer-specific systolic and diastolic longitudinal and circumferential strains and SR were assessed. Results showed no between-group difference in left ventricular mass index (DD: 92.1 ± 18.1 vs NDF: 88.4 ± 16.3; P = 0.44). Patients with DD had a proportional reduction in longitudinal strain across the myocardium (endocardial for DD -13 ± 4%; vs NDF -17 ± 3, P < 0.01; epicardial for DD -10 ± 3% vs NDF -13 ± 3%, P < 0.01; global for DD: -12 ± 3% vs NDF: -15 ± 3, P = 0.01), and longitudinal mechanical diastolic impairments as evidenced by reduced longitudinal strain rate of early diastole (DD 0.7 ± 0.2 L/s vs NDF 1.0 ± 0.3 L/s, P < 0.01) and absence of a transmural gradient in the duration of diastolic strain (DD endocardial: 547 ± 105 ms vs epicardial: 542 ± 113 ms, P = 0.24; NDF endocardial: 566 ± 86 ms vs epicardial: 553 ± 77 ms, P = 0.03). Patients with DD also demonstrate a longer duration of early circumferential diastolic strain (231 ± 71 ms vs 189 ± 58 ms, P = 0.02). In conclusion, hypertensive patients with mild DD demonstrate a proportional reduction in longitudinal strain across the myocardium, as well as longitudinal mechanical diastolic impairment, and prolonging duration of circumferential mechanical relaxation.

Autonomic dysreflexia: a cardiovascular disorder following spinal cord injury.

Autonomic dysreflexia (AD) is a serious cardiovascular disorder in patients with spinal cord injury (SCI). The primary underlying cause of AD is loss of supraspinal control over sympathetic preganglionic neurons (SPNs) caudal to the injury, which renders the SPNs hyper-responsive to stimulation. Central maladaptive plasticity, including C-fiber sprouting and propriospinal fiber proliferation exaggerates noxious afferent transmission to the SPNs, causing them to release massive sympathetic discharges that result in severe hypertensive episodes. In parallel, upregulated peripheral vascular sensitivity following SCI exacerbates the hypertensive response by augmenting gastric and pelvic vasoconstriction. Currently, the majority of clinically employed treatments for AD involve anti-hypertensive medications and Botox injections to the bladder. Although these approaches mitigate the severity of AD, they only yield transient effects and target the effector organs, rather than addressing the primary issue of central sympathetic dysregulation. As such, strategies that aim to restore supraspinal reinnervation of SPNs to improve cardiovascular sympathetic regulation are likely more effective for AD. Recent pre-clinical investigations show that cell transplantation therapy is efficacious in reestablishing spinal sympathetic connections and improving hemodynamic performance, which holds promise as a potential therapeutic approach.

Reproducibility of the QT-variability index in individuals with spinal cord injury.

PURPOSE: To examine the day-to-day reproducibility of the QT-variability index (QTVI) and the QT-apex variability index (QTaVI) in individuals with spinal cord injury (SCI). METHODS: Ten individuals with SCI participated in the current study (C2-T10; AIS A-D; 8.6 ± 7.8 years post-injury). On two occasions, with a 10-day interval, a 10-minute resting electrocardiogram was obtained from each participant. The QTVI and QTaVI were analyzed from 256 electrocardiographic beats from all participants, and a separate analysis was performed on those with injuries above the 4th thoracic level. An intraclass correlation coefficient (ICC) test was performed to measure day-to-day reproducibility of these measures and a Bland-Altman test was performed on all participants in order to examine the skewness of the measures. RESULTS: The reproducibility values were found to be high for both the QTVI (all participants: R=0.892; above T4: R=0.893) and the QTaVI (all participants: R=0.908; above T4: R=0.915). In addition, the reproducibility of QTVI and QTaVI did not appear to be skewed as indicated by Bland-Altman plots. CONCLUSION: Both the QTVI and the QTaVI may be used as reproducible means of assessing cardiac autonomic function in individuals with SCI. Further, a reduction in cardiac sympathetic regulation after high thoracic and cervical level SCI does not appear to influence the day-to-day reproducibility of these measures.

The influence of cardiac autonomic activity on the QT-variability index in able-bodied and incomplete spinal cord injured individuals.

OBJECTIVES: To investigate, via autonomic blockade, if the QT-variability index (QTVI) is a measure of cardiac autonomic regulation in able-bodied (AB) and incomplete spinal cord injured (SCI) individuals. METHODS: Four SCI (41.6±13.4years; C4-C7, AIS B-D, 13.4±13.4years post injury) and 4 AB (33.0±7.8years) individuals were tested. QTVI was determined from electrocardiographic readings obtained during supine rest and cardiovascular (CV) stress, with and without autonomic blockade. CV stress was induced by 40° head-up tilt, the hand submerged in 10°C water and the jaw clenched. Autonomic blockade was achieved with metoprolol (ß-blockade) and atropine (cholinergic blockade). RESULTS: There was no group×condition interaction for QTVI, although there was a significant main effect for condition. After collapsing across groups, QTVI increased with CV stress (p=0.01) and decreased with subsequent ß-blockade (p=0.04), suggesting that during CV stress, QTVI is reflective of cardiac sympathetic activity. During supine rest, ß-blockade did not change QTVI (p=0.24), however, cholinergic blockade increased QTVI (p<0.001), suggesting that during rest, QTVI is inversely related to cardiac parasympathetic regulation. CONCLUSION: During times of CV stress, QTVI reflects cardiac sympathetic activity, while during resting conditions, QTVI is inversely related to cardiac parasympathetic activity. These relationships persist after autonomically incomplete SCI.