An Autonomic Neuroprosthesis: Noninvasive Electrical Spinal Cord Stimulation Restores Autonomic Cardiovascular Function in Individuals with Spinal Cord Injury

Aaron A Phillips, Jordan W Squair, Dimitry G Sayenko, V Reggie Edgerton, Yury Gerasimenko, Andrei V Krassioukov, Aaron A Phillips, Jordan W Squair, Dimitry G Sayenko, V Reggie Edgerton, Yury Gerasimenko, Andrei V Krassioukov

Abstract

Despite autonomic dysfunction after spinal cord injury (SCI) being the major cause of death and a top health priority, the clinical management options for these conditions are limited to drugs with delayed onset and nonpharmacological interventions with equivocal effectiveness. We tested the capacity of electrical stimulation, applied transcutaneously over the spinal cord, to manage autonomic dysfunction in the form of orthostatic hypotension after SCI. We assessed beat-by-beat blood pressure (BP), stroke volume, and cardiac contractility (dP/dt; Finometer), as well as cerebral blood flow (transcranial Doppler) in 5 individuals with motor-complete SCI (4 cervical, 1 thoracic) during an orthostatic challenge with and without transcutaneous electrical stimulation applied at the TVII level. During the orthostatic challenge, all individuals experienced hypotension characterized by a 37 ± 4 mm Hg decrease in systolic BP, a 52 ± 10% reduction in cardiac contractility, and a 23 ± 6% reduction in cerebral blood flow (all p < 0.05), along with severe self-reported symptoms. Electrical stimulation completely normalized BP, cardiac contractility, cerebral blood flow, and abrogated all symptoms. Noninvasive transcutaneous electrical spinal cord stimulation may be a viable therapy for restoring autonomic cardiovascular control after SCI.

Keywords: autonomic; cardiovascular; neurological injury; spinal cord; spinal cord injury; stimulation.

Conflict of interest statement

VRE and YPG are researchers on the study team who hold shareholder interest in NeuroRecovery Technologies and hold certain inventorship rights on intellectual property licensed by The Regents of the University of California to NeuroRecovery Technologies and its subsidiaries.

Figures

FIG. 1.
FIG. 1.
Vignette: Electrical spinal cord stimulation improved integrated cardiovascular responses to orthostatic challenge. Participant: female, 32 years of age, spinal cord injury at C6 (AIS-A), injured August 2009. Left blue inlet: Although experiencing severe orthostatic hypotension when assuming upright posture, electrical stimulation at the TVII level restored blood pressure, cerebral blood flow, cardiac function, and symptoms of orthostatic intolerance to supine levels. Note: Increasing current (20, 40, and 50 mA) resulted in step-wise increases in cardiovascular function. Right red inlet: electromyography recording of lower limbs shows that skeletal muscle contraction was not activating the skeletal muscle pump of the venous vasculature, indicating that excitation of sympathetic preganglionic neurons was responsible for the cardiovascular restoration. Note: Without stimulation, self-reported symptoms of pre-syncope were severe, being between 6 and 9, whereas with stimulation symptoms were completely abrogated. Participant reported that cognitive processing was so slow in the upright position that she was “not conversational” until the stimulation was turned on. AIS-A, American Spinal Injury Association Impairment Scale Grade A; BP, blood pressure; MCA, middle cerebral artery; PCA, posterior cerebral artery; vmean, mean flow velocity; PCAvmean, mean flow velocity; SV, stroke volume; dP/dt, delta pressure over delta time (cardiac contractility); SOL, soleus; TA, tibialis anterior; MH, medial hamstring; VL, vastus lateralis; SCG, superior cervical ganglia; SG, stellate ganglia; CG, celiac ganglia; SMG, superior mesenteric ganglia; IMG, inferior mesenteric ganglia. Color image is available online at www.liebertpub.com/neu
FIG. 2.
FIG. 2.
Cardiovascular, cardiac, and cerebrovascular responses to orthostatic challenge were normalized with transcutaneous electrical spinal cord stimulation. (A) Blood pressure responses were normalized with stimulation. (B) Cerebral blood flow was normalized with stimulation. (C) Although systolic function in terms of contractility (dP/dt) was normalized with stimulation, heart rate was still elevated and stroke volume was not restored. (D) Symptoms of orthostatic intolerance were almost completely abrogated with stimulation. Repeated-measures ANOVA with Bonferoni contrasts. #p = 0.07; *p < 0.05; **p < 0.01; ***p < 0.001. ANOVA, analysis of variance; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial blood pressure; MCA, middle cerebral artery; PCA, posterior cerebral artery; vmean, mean flow velocity; PCAvmean, mean flow velocity; SV, stroke volume; HR, heart rate; Q, cardiac output; TPR, total peripheral resistance. Color image is available online at www.liebertpub.com/neu
FIG. 3.
FIG. 3.
Theoretical framework. Thoracic level stimulation using transcutaneous electrical stimulation excites dorsal afferents that likely excited intersegmental and intrasegmental neurons, which directly and indirectly lead to depolarization of sympathetic pre-ganglionic neurons leading to increased vascular tone. RVLM, rostral ventrolateral medulla. Color image is available online at www.liebertpub.com/neu

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