Prevention of Low Blood Pressure in Persons With Tetraplegia

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.

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.

Blood Pressure, Cardiovascular Autonomic Control, Nitric Oxide, NOS Inhibitor, Orthostatic Hypotension, Spinal Cord Injury, Tetraplegia

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.

Average systolic blood pressure during head-up tilt (45 degrees) comparing active drug (L-NAME: 1.0 and 2.0 mg/kg) to placebo.

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.

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