Orthostatic responses to anticholinesterase inhibition in spinal cord injury.
BACKGROUND
Acetylcholine (Ach) is the pre-synaptic neurotransmitter of the sympathetic nervous system. Increased pre-synaptic Ach may augment post-synaptic release of norepinephrine, thereby increasing systemic blood pressure (BP).


OBJECTIVE
The primary objective of this investigation was to determine the hemodynamic effect of pyridostigmine bromide (PYRIDO: 60 mg), an Ach inhibitor (AchI), compared to no-drug (NO-D) during head-up tilt (HUT) in individuals with spinal cord injury (SCI). Secondarily, we aimed to determine the effects of PYRIDO compared to NO-D on symptoms of orthostatic intolerance (OI) and adverse event reporting (AE).


METHODS
Ten individuals with SCI (C4-C7) were studied on two occasions: visit (1) NO-D and visit (2) PYRIDO. On each visit subjects underwent a progressive HUT maneuver to 15°, 25°, 35° for 5 min at each angle and 45 min at 45°. Supine and orthostatic heart rate (HR), systolic and diastolic BP (SBP and DBP), as well as monitored and symptoms of OI and AE were monitored and recorded.


RESULTS
Supine hemodynamics did not differ between the trials. The significant fall in SBP during the NO-D trial was diminished with PYRIDO, and five subjects had an increased DBP during HUT with PYRIDO compared to the NO-D trial. Individuals that responded to PYRIDO with an increase in orthostatic BP had significantly lower resting HR than non-responders (p < 0.01), which suggests increased levels of pre-synaptic Ach. Subjective symptoms of OI and AE reporting did not differ between the two trials.


CONCLUSIONS
These preliminary data suggest that PYRIDO is safe and may be effective at ameliorating the orthostatic fall in BP in select individuals with SCI.
The National Center of Excellence, James J. Peters VAMC, Bronx, NY, USA, jm.wecht@va.gov.
Jill M
JM
Wecht
Christopher M
CM
Cirnigliaro
Frank
F
Azarelo
William A
WA
Bauman
Steven C
SC
Kirshblum
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D054971:Orthostatic Intolerance / Q000188:drug therapy / Q000209:etiology; D011729:Pyridostigmine Bromide / Q000009:adverse effects / Q000627:therapeutic use*; D011782:Quadriplegia / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D016683:Supine Position; D018667:Tilt-Table Test; D055815:Young Adult
D002800:Cholinesterase Inhibitors; D011729:Pyridostigmine Bromide