Acetylcholinesterase Inhibition and Orthostatic Hypotension in SCI
Status:
Completed
Trial end date:
2015-03-01
Target enrollment:
Participant gender:
Summary
Due to de-centralized cardiovascular control, persons with spinal cord injury (SCI)
experience blood pressure (BP) dysregulation which manifests in chronic hypotension with
exacerbation during orthostatic positioning. Although many individuals with SCI remain
asymptomatic to hypotension and orthostatic hypotension (OH), we recently reported reduced
memory and marginally reduced attention and processing speed in hypotensive individuals with
SCI compared to a normotensive cohort. Thus, we believe that treatment of overtly
asymptomatic hypotension and OH in the SCI population is clinically warranted. Currently the
FDA has approved only midodrine hydrochloride for the treatment of dizziness associated with
OH and proof of efficacy is limited. Acetylcholinesterase inhibition for treatment of OH is a
novel concept and has gained recent recognition in models of neurogenic OH (multiple system
atrophy; pure autonomic failure, diabetic neuropathy). The physiological rationale of this
concept is unique: acetylcholine (AcH) is the pre-ganglionic neurotransmitter of the
sympathetic nervous system. Inhibition of acetylcholinesterase will limit the breakdown of
AcH thereby facilitating vascular adrenergic tone and peripheral vasoconstriction.
Acetylcholinesterase inhibition has been reported to be efficacious in models of both
pre-ganglionic (multiple system atrophy) and post-ganglionic (pure autonomic failure,
diabetic neuropathy) origin and persons with SCI reflect a model of a preganglionic disorder.
In theory, if an individual has a complete autonomic lesion, acetylcholinesterase inhibition
would not be expected to improve orthostatic BP because little/no neural traffic would be
transmitted to the pre-synapse. However, individuals with an incomplete autonomic lesion may
benefit from this class of agent. Researchers are currently investigating the orthostatic BP
effects of acetylcholinesterase inhibition with pyridostigmine bromide (60 mg) in 10
individuals with SCI.