Orthostatic responses to anticholinesterase inhibition in spinal cord injury

Abstract

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). 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). Ten individuals with SCI (C4-C7) were studied on 2 occasions: visit 1) NO-D and visit 2) PYRIDO. On each visit subjects underwent a progressive HUT maneuver to 15°, 25°, 35° for 5 minutes at each angle and 45 minutes at 45°. Supine and orthostatic heart rate (HR), systolic and diastolic BP (SBP & DBP) were monitored and symptoms of OI and AE recorded. 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. These preliminary data suggest that PYRIDO is safe and may be effective at ameliorating the orthostatic fall in BP in select individuals with SCI.

Symptomatic Treatment of Myelopathy

“…40 For pharmacologic treatment, midodrine, fludrocortisone, droxidopa, pyridostigmine, and ergotamine have been used, with midodrine being the most studied. 41,42 The main side effect of these medications is supine hypertension, so administration of these medications should be monitored closely with frequent blood pressure measurements.…”

“…Exercise and functional electrical stimulation may be beneficial in delaying orthostatic hypotension through muscular contraction–induced venous return, 37-39 although data are limited in nonpharmacologic treatment modalities 40 . For pharmacologic treatment, midodrine, fludrocortisone, droxidopa, pyridostigmine, and ergotamine have been used, with midodrine being the most studied 41,42 . The main side effect of these medications is supine hypertension, so administration of these medications should be monitored closely with frequent blood pressure measurements.…”

Acetylcholinesterase Inhibitor Pyridostigmine Bromide Attenuates Gut Pathology and Bacterial Dysbiosis in a Murine Model of Ulcerative Colitis

“…PB restored cardiac autonomic balance in mice and rats after experimental myocardial infarction [9,70,71], and heart-specific overexpression of the ACh-synthesizing enzyme choline acetyltransferase was found to protect the myocardium against ischemia-induced injury in mice [72]. PB has also been shown to help some patients with spinal cord injuries [73] and diabetic patients with gastrointestinal disorders [74]. Moreover, release of ACh through electrical stimulation of the vagus nerve ameliorates gut inflammation through nAChRs [75].…”