Spinal Cord Injury
Conditions
Keywords
Low oxygen therapy, Intermittent hypoxia, Blood pressure, Spinal cord injury, Cardiac function, Sympathetic nervous system
Brief summary
This study examines the effects of low oxygen therapy (LOT) on the stability of 24-hour blood pressure in persons with chronic cervical spinal cord injury. This study will examine if brief episodes of breathing lower oxygen, termed low oxygen therapy (LOT), which has been shown to enhance autonomic nervous system activity, can improve blood pressure stability in individuals with spinal cord injury. The research team will assess 24-hour blood pressure, as well as cardiac, vascular, and autonomic function before and after a 4-day LOT treatment intervention. This study will advance current understanding of treatments to mitigate cardiovascular disease risk in people with spinal cord injuries.
Detailed description
Spinal cord injury (SCI) interrupts signals travelling down from the brain to the rest of the body below the level of the injury. The loss of nerve connections involved in cardiovascular control results in blood pressure instability. This can lead to sudden drops in blood pressure, such as when shifting upright or during transfers, or sudden increases during autonomic dysreflexia. These swings in blood pressure are linked to a nearly 4-fold increase in the risk of cardiovascular disease in people with SCI. Repeated, brief exposure to breathing lower levels of oxygen, termed low oxygen therapy, has been shown to stimulate adaptation in the nervous system. This neuroplasticity increases the activity of cardiovascular control circuits, and has been shown to increase blood pressure in able-bodied individuals. Similar effects on respiratory and motor function in people with SCI, but the effects on the cardiovascular system have not been studied in this population. This study will test the effects of a 4-day low oxygen therapy intervention on 24-hour blood pressure stability in people with chronic cervical SCI. By assessing mechanisms of cardiac, vascular, and autonomic function, this study aims to improve current understanding of the therapeutic potential of low oxygen therapy to mitigate cardiovascular disease risk in SCI.
Interventions
DRUGLow oxygen therapy (LOT)
Participants will breathe variable concentrations of inspired oxygen, carbon dioxide, and nitrogen. The concentrations will be adjusted on a breath-by-breath basis to maintain end-tidal targets. Each daily session of the intervention will consist of forty 1-minute intervals. Each 1-minute interval will consist of 40 seconds of hypercapnic hypoxia, increasing the partial pressure of end-tidal carbon dioxide by +4 mmHg and decreasing the partial pressure of end-tidal oxygen to 45 mmHg, followed by 20 seconds in simulated room air to return to baseline carbon dioxide and oxygen levels.
Sponsors
Glen Foster
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Are between the ages of 19-65 * Living with a chronic cervical (at or above T1) spinal cord injury of at least one year * Are fluent in english
Exclusion criteria
* High-cervical injuries requiring ventilator assistance to breathe will be excluded on account of the necessity of the facemask for the delivery of hypoxia * Unhealed fracture, contracture, or pressure sore that might interfere with participants' ability to complete the protocol * Additional concurrent neurological conditions (e.g., multiple sclerosis, Parkinson disease, stroke or brain injury) * Uncontrolled cardiovascular or pulmonary disease * Severe neuropathic pain * Severe recurrent autonomic dysreflexia * History of seizure disorders * Known pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 24-hour blood pressure | Change from baseline of 24-hour mean arterial blood pressure at 1-day post-intervention | Mean arterial blood pressure (mmHg), averaged across 24 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in left-ventricular contractility | Change from baseline of left ventricular contractility indices immediately after the first intervention session, and at 1-day and 4-days post-intervention | Indices of load-independent pressure generation during systole: Estimated end-systolic elastance (mmHg/ml); end-systolic pressure-volume relationship slopes (mmHg/ml) |
| Change in baroreflex gain | Change from baseline of baroreflex gain indices immediately after first intervention session, and at 1-day and 4-days post-intervention | Indices of baroreflex sensitivity: Relationship of systolic blood pressure against subsequent R-R interval duration during Valsalva Maneuver phases II and IV (ms/mmHg); spectral power of low-frequency resting blood pressure variability |
| Change in circulating catecholamines | Change from baseline of circulating catecholamines immediately after first intervention session, and at 1-day and 4-days post-intervention | Venous plasma concentrations of norepinephrine and epinephrine (mmol/L) |
| Change in cerebral neurovascular coupling and autoregulation | Change from baseline of the responses of cerebral blood flow indices during a visual stimulus and head-up tilt immediately after first intervention session, and at 1-day and 4-days post-intervention | Middle and posterior cerebral artery blood flow velocity (cm/s) |
| Change in 24-hour blood pressure stability | Change from baseline of the standard deviation of 24-hour mean arterial blood pressure at 1-day post-intervention | Mean arterial blood pressure (mmHg), standard deviation across 24 hours |
| Change in flow-mediated dilation | Change from baseline in flow-mediated dilation immediately after first intervention session, and at 1-day and 4-days post-intervention | Brachial artery flow-mediated dilation following 5-minute forearm blood flow occlusion (mm) |
| Change in tonic peripheral chemoreflex activity | Change from baseline in the magnitude of ventilatory depression in hyperoxia immediately after first intervention session, and at 1-day and 4-days post-intervention | Magnitude of hyperoxic ventilatory depression (L/min) |
| Change in renal vascular function | Change in renal blood flow velocity from baseline during the first and final hypoxia cycles on the first session of the intervention | Renal artery blood flow velocity (cm/s) |
| Change in renal filtration function | Change from baseline in renal biomarkers and blood flow at rest immediately after first intervention session, and at 1-day and 4-days post-intervention | Humoral renal biomarkers (e.g., serum creatinine) |
Countries
Canada
Contacts
Primary ContactScott F Thrall, M.Sc.
Backup ContactGlen E Foster, Ph.D.
Outcome results
None listed