Orthostatic responses to anticholinesterase inhibition in spinal cord injury

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.

Figures

Figure 1

Depicts the study timeline.

Figure 2

Displays the change in supine hemodynamics during the NO-D (closed circles) and PYRIDO 60 mg (open squares) trials. Data reflect the change from pre- (BL time-points 0 and 25 minutes) to post- (BL time-point 55 minutes) for HR [A], SBP [B] and DBP [C]. There were no significant effects of PYRIDO compared to NO-D for supine hemodynamics.

Figure 3

Depicts the hemodynamic responses to the progressive HUT maneuver during the NO-D (closed circles) and PYRIDO 60 mg (open squares) trials. Data reflect the average HR [A], SBP [B] and DBP [C] during the supine observation and at each angle of HUT (i.e., 15°, 25°, 35°, 45°). The main effect for drug and the interaction effect were not significant; however, the main effect for tilt angle was significant for HR (p

Figure 4

Displays the change in hemodynamics from the BL to 45° HUT during the NO-D (closed circles) and PYRIDO 60 mg (open squares) trials. Data reflect the difference between the average HR [A], SBP [B] and DBP [C] at BL and 45°. The hemodynamic response to HUT was not different comparing the NO-D to the PYRIDO trial. * p

Figure 5

Displays the difference between the NO-D and PYRIDO trials for percent change in hemodynamics at 45° HUT for HR [closed circles], SBP [open squares] and DBP [closed triangles]. Dashed lines represent ±10% change in the hemodynamic parameters.