Hypotension, Spinal Cord Injury
Conditions
Keywords
Blood Pressure, Cardiovascular Autonomic Control, Nitric Oxide, NOS Inhibitor, Orthostatic Hypotension, Spinal Cord Injury, Tetraplegia
Brief summary
The aim of this investigation is to determine the blood pressure response to NOS inhibition, with L-NAME, in persons with tetraplegia compared to non-SCI control subjects and to establish if blood pressure can be increased while upright in those with tetraplegia. If blood pressure is increased with NOS inhibition in persons with tetraplegia, this would improve our treatment of the condition of low blood pressure during seated postures in individuals with tetraplegia.
Detailed description
Despite disruption of central command of the vasculature during orthostatic maneuvers, individuals with tetraplegia are generally able to be seated in an upright position for long periods of time without developing symptoms of orthostatic intolerance. It must be appreciated however, that orthostatic hypotension may occur unpredictably in persons with chronic tetraplegia. This may result in a range of symptoms due to cerebral hypoperfusion from mild reduction in mental acuity to loss of consciousness. Nitric oxide (NO) is the most potent endogenous vasodilator which is synthesized by the enzyme NO synthase (NOS) and may be largely responsible for orthostatic hypotension in individuals with immobilizing conditions. Recent evidence suggests an up-regulation of inducible nitric oxide synthases (NOS) activity with prolonged exposure to hind limb suspension. The effects of NOS inhibition during orthostasis on blood pressure regulation in those with chronic tetraplegia may provide insight into effective pharmacological therapy to reduce or prevent pathologic orthostatic changes. Treatment with a NOS inhibitor may facilitate the process of mobilization in those with acute higher cord lesions.
Interventions
A non-specific inhibitor of the nitric oxide synthase enzyme.
PROCEDUREHead-up Tilt maneuver
Participant will be placed onto tilt table and brought to 15 degrees of head up tilt for 60 minutes (intravenous infusion time). After this time, a progressive increase to 45 degrees will be completed with a 10 degree increase every 5 minutes. Participant will remain at 45 degrees for 45 minutes or until symptom onset.
Sponsors
US Department of Veterans Affairs
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* 18 to 65 year olds. * Non-ambulatory Chronic tetraplegia (1 year after acute SCI).
Exclusion criteria
* central nervous system disease (other than SCI) e.g., multiple sclerosis, amyotrophic lateral sclerosis, syringomyelia, tabes dorsalis; * peripheral neuropathies; * surgical sympathectomy; * coronary heart and/or artery disease; * anemia; * hypertension; * renal function abnormalities; * diabetes mellitus; * pituitary insufficiency; * adrenal insufficiency; * hypothyroidism; and * medications known to affect the cardiovascular system.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Systolic Blood Pressure During Head-up Tilt | Average systolic blood pressure during head-up tilt (45 degrees) comparing active drug (L-NAME: 1.0 and 2.0 mg/kg) to placebo. | Average systolic blood pressure over 45 minutes at 45 degrees of head-up tilt. |
Countries
United States
Participant flow
Recruitment details
Recruitment occured from January 2006 through May 2009; participants were recruited from the James J Peters VA Medical Center and the surrounding community.
Pre-assignment details
No subject was excluded after enrollment prior to participation.
Participants by arm
| Arm | Count |
|---|---|
| Individuals With Tetraplegia Systolic blood pressure responses to head-up tilt were determined after placebo, L-NAME (1.0 mg/kg) and L-NAME administration (2.0 mg/kg) administration. | 9 |
| Able-bodied Controls Systolic blood pressure responses to head-up tilt were determined in able-bodied controls following placebo administration | 7 |
| Total | 16 |
Baseline characteristics
| Characteristic | Able-bodied Controls | Individuals With Tetraplegia | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 9 Participants | 16 Participants |
| Age, Continuous | 33 years STANDARD_DEVIATION 9 | 40 years STANDARD_DEVIATION 10 | 38 years STANDARD_DEVIATION 12 |
| Region of Enrollment United States | 7 participants | 9 participants | 16 participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 4 Participants | 8 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 9 | 0 / 7 | 0 / 9 | 0 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 7 | 0 / 9 | 0 / 9 |
Outcome results
Primary
Systolic Blood Pressure During Head-up Tilt
Average systolic blood pressure over 45 minutes at 45 degrees of head-up tilt.
Time frame: Average systolic blood pressure during head-up tilt (45 degrees) comparing active drug (L-NAME: 1.0 and 2.0 mg/kg) to placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tetraplegic Systolic Blood Pressure Responses to Placebo | Systolic Blood Pressure During Head-up Tilt | 91.80 mmHg | Standard Deviation 20.96 |
| Control Systolic Blood Pressure Responses to Placebo | Systolic Blood Pressure During Head-up Tilt | 108.10 mmHg | Standard Deviation 12.18 |
| Tetraplegic Systolic Blood Pressure Responses to L-NAME 1.0 mg | Systolic Blood Pressure During Head-up Tilt | 112.04 mmHg | Standard Deviation 28.01 |
| Tetraplegic Systolic Blood Pressure Responses to L-NAME 2.0 mg | Systolic Blood Pressure During Head-up Tilt | 129.94 mmHg | Standard Deviation 26.43 |