Conditions: Hypotension Spinal Cord Injury
Keywords: Blood Pressure Cardiovascular Autonomic Control Nitric Oxide NOS Inhibitor Orthostatic Hypotension Spinal Cord Injury Tetraplegia
Allocation: NON_RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 16
Healthy volunteers: yes

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.

Arms:
arm 1: Placebo control (normal saline) is employed on a separate visit during procedure.

Interventions: intervention 1: N-Nitro L-arginine-methylester (L-NAME) intervention 2: Head-up Tilt maneuver
Intervention descriptions: intervention 1: A non-specific inhibitor of the nitric oxide synthase enzyme. intervention 2: 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.

Protocol document: