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Orthostatic responses to anticholinesterase inhibition in spinal cord injury

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Abstract

Introduction

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).

Objectives

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.

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Acknowledgments

This research was supported by the Veterans Affairs Rehabilitation Research and Development Service (Grant # B9212C).

Conflict of interest

We certify that no party having a direct interest in the results of the research supporting this article has conferred or will confer a benefit on us or on any organization with which we are associated and, if applicable, we certify that all financial and material support for this research (e.g., NIH or NHS Grants) and work is clearly identified in the title page of the manuscript.

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Authors and Affiliations

  1. The National Center of Excellence, James J. Peters VAMC, Bronx, NY, USA

    Jill M. Wecht, Christopher M. Cirnigliaro, Frank Azarelo & William A. Bauman

  2. Medical Service, James J. Peters VAMC, Bronx, NY, USA

    William A. Bauman

  3. Department of Medicine, Icahn School of Medicine, Mount Sinai, New York, NY, USA

    Jill M. Wecht & William A. Bauman

  4. Department of Rehabilitation Medicine, Icahn School of Medicine, Mount Sinai, New York, NY, USA

    Jill M. Wecht & William A. Bauman

  5. Kessler Institute for Rehabilitation, West Orange, NJ, USA

    Steven C. Kirshblum

  6. Rutgers New Jersey Medical School, Newark, NJ, USA

    Steven C. Kirshblum

  7. Center of Excellence: Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Rm. 7A-13, 130 West Kingsbridge Rd., Bronx, NY, 10468, USA

    Jill M. Wecht

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  1. Jill M. Wecht
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  2. Christopher M. Cirnigliaro
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  5. Steven C. Kirshblum
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Correspondence to Jill M. Wecht.

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Wecht, J.M., Cirnigliaro, C.M., Azarelo, F. et al. Orthostatic responses to anticholinesterase inhibition in spinal cord injury. Clin Auton Res 25, 179–187 (2015). https://doi.org/10.1007/s10286-015-0272-3

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  • DOI: https://doi.org/10.1007/s10286-015-0272-3

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