Cardiovascular regulation post‐epidural stimulation in cervical spinal cord injury
Authors: Ditterline Bonnie Legg , Wang Siqi , Aslan Sevda , Harkema Susan 
Published: November 2023

BACKGROUNDPersons with spinal cord injury (SCI) often have poor blood pressure (BP) regulation, which decreases quality of life and increases morbidity and mortality when compared to non‐injured persons (NSCISC, 2015). Increased morbidity results, in part, from impairment to the sympathetic nervous system, resulting in poor reflex response, persistent hypotension and bradycardia, and bouts of orthostatic hypotension. We observed previously that spinal‐cord epidural stimulation (scES) for motor rehabilitation resulted in increased BP and heart rate (HR) during stimulation. The goal of this case study is to determine if scES, alone and with activity‐based interventions, can re‐engage spinal circuitry that would potentially regulate blood pressure, leading to increased resting cardiovascular (CV) outcomes.METHODSOur participant was a 24 year‐old male with a C5 AIS‐A injury; duration of injury at onset was 81 months. A 16‐electrode array (Specify 5‐6‐5, Medtronic) was implanted at T11‐L1 level with a stimulator unit (Harkema, 2011). Stimulation parameters, including current (0 – 10 V), frequency (5 to 40 Hz), and rostral/caudal configuration of the anodes and cathodes, were unique to each scES training protocol. Cardiovascular scES: Training parameters for targeting cardiovascular circuitry (CV‐scES; Image 1) were chosen based on the ability to sustain SBP between 110–120 mmHg for 15 minutes without recruitment of skeletal muscle. Voluntary Motor scES: Voluntary motor training with epidural stimulation (vol‐scES; Image 2) lasted 90 minutes, 3 times weekly, and was concurrent with CV‐scES for an additional 80 sessions. Vol‐scES training parameters were chosen to optimize initiation, termination, and control of trunk and lower extremity movements.RESULTSWe found improvements to his cardiovascular regulation following CV‐ES that were then sustained following the introduction of Vol‐ES: orthostatic hypotension that occurred during the pre‐intervention assessments (81 ± 6/48 ± 2 mmHg) was ameliorated (120 ± 2/72 ± 5 mmHg); there was increased sympathetic control over the heart (123±93 ms2 to 999±918 ms2) and more pronounced respiratory‐mediated oscillation of heart rate (56±52 ms2 to 778±755ms2) while seated; and an increased baroreceptor effectiveness (up‐up: 26 ± 19 % to 60 ± 18%) and baroreceptor sensitivity (up‐up: 3±1 to 19±10 ms/mmHg; down‐down: 3±1 to 20±12 ms/mmHg) while seated.CONCLUSIONSAfter 80 CV‐scES training sessions, this participant was able to prevent orthostatic hypotension while passively upright, possibly due to the greater sympathetic and parasympathetic control over the sinoatrial node during orthostatic stress and increased effectiveness and sensitivity of the baroreceptor reflex arc. These improvements to cardiovascular regulation persisted after 80 sessions of concurrent Vol‐scES and CV‐scES. scES could facilitate changes to the spinal network necessary for cardiovascular regulation that persist after stimulation has ceased, which may have led to the increased cardiovascular outcomes during stress.Support or Funding InformationThis work is funded by Craig H. Neilson Foundation, Christopher & Dana Reeve Foundation, US National Institutes of Health, and The Leona M. and Harry B. Helmsley Charitable Trust.