# Toward Closed-Loop Control of Homeostatic Blood Pressure Following Spinal Cord Injury

> **NIH VA I21** · VETERANS HEALTH ADMINISTRATION · 2021 · —

## Abstract

Rationale: Approximately 42,000 Veterans have a spinal cord injury (SCI). For the 65% of these individuals with
an SCI above thoracic (T) spinal level 6, both hypo- and hypertension are common comorbidities. SCI above T6
increases the risk for autonomic dysreflexia (AD) because the central descending control over the greater
splanchnic nerves (GSNs) is lost, and with it the ability to control the abdominal splanchnic vasculature.
Uncontrolled hyperreflexia in the GSNs can evolve to AD-induced hypertension, which is a significant risk in this
population and increases the risk of stroke by up to 400%. Conversely, insufficient splanchnic tone leads to
hypotension and 57% of this population experience orthostatic hypotension (OH). OH is associated with up to a
65% reduction in cognitive function. An implantable system that delivers the appropriate electrical stimulation or
block to the splanchnic nerves could treat both conditions.
Objective: The greater splanchnic nerves are primary targets for restoring healthy arterial blood pressure (BPart).
Modulating activity in these nerves may provide a novel, immediate, and acute means to prevent both
hypotension (Aim 1) and hypertension (Aim 2). Our long-term goal is to develop a closed-loop, implantable
system that maintains BPart within a healthy range in individuals with SCI in which central control over the
abdominal vasculature has been compromised. To advance this goal, we require a clearer understanding of
splanchnic nerve control of the abdominal vasculature following loss of central control due to SCI.
Research Plan and Methodology: We will conduct pre-clinical trials in an established rodent T3 spinal
transection model that displays impaired regulation of BPart. In both aims, arterial blood pressure and abdominal
blood flow (BFabd) will be monitored. During Aim 1, splanchnic nerve stimulation (SpNS) will be applied whereas
during Aim 2, splanchnic nerve block (SpNB) will be applied. The effect of SpNS and SpNB on BPart and BFabd
over a broad range of frequencies will be determined. A dosage-response curve will be developed that expresses
the changes in BPart and BFabd as a function of SpNS and SpNB frequencies following SCI. This will be performed
for both unilateral and bilateral SpNS and SpNB. The relative contribution of each nerve to overall changes in
BPart and BFabd will be determined.
Expected Outcomes: This proof-of-concept study is an important first step in developing a new intervention and
preparing for the technical and regulatory activities necessary to move it into first-in-human trials and ultimately
pivotal clinical trials. This study will generate sufficient data to create a Merit Review that will develop the real-
time, closed-loop, and fully implantable system for controlling BPart during transient but large changes in BPart in
animals with a chronic SCI, including older animals that capture the full Veteran population. It is our long-term
goal to translate this system to Vetera...

## Key facts

- **NIH application ID:** 10124565
- **Project number:** 1I21RX003598-01
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** MATTHEW Anthony SCHIEFER
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10124565

## Citation

> US National Institutes of Health, RePORTER application 10124565, Toward Closed-Loop Control of Homeostatic Blood Pressure Following Spinal Cord Injury (1I21RX003598-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10124565. Licensed CC0.

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