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Increasing Blood Pressure by Greater Splanchnic Nerve Stimulation: a Feasibility Study

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Abstract

The splanchnic vascular compartment is the major reservoir for intravascular blood volume, and dysregulation of the compartment was implicated in a series of cardiovascular conditions. We explored feasibility and effectiveness of an implantable cuff system on the greater splanchnic nerve (GSN) in healthy canines for short- and long-term neuromodulation to affect the circulation. Five mongrel hounds underwent minimally invasive right-sided unilateral GSN cuff placement. All animals underwent same day GSN stimulation and repeat stimulation at 9–30 days. Stimulation parameter optimization was conducted both acutely and chronically. Parameters ranged from 1–250 Hz, 0.25 mA–35 mA, 0.1–0.5 ms, and 30-s pulse duration. Two animals were survived for 9 days and 3 animals for 30 days. Stimulation of the right GSN increased mean arterial blood pressure by 36.9 mmHg ± 13.4 (p < 0.0001), central venous pressure by 6.9 mmHg ± 1.7 (p < 0.0001), and mean pulmonary arterial pressure by 6.3 mmHg ± 2.0 (p < 0.0001). Peak effects were observed within 30 s, and magnitude of effects was comparable between stimulation cycles (p = 0.4). Stimulation-induced changes in hemodynamics were independent of afferent nerve fibers (pain response) or the adrenal gland. Necropsy showed no evidence of nerve damage on histologic studies up to 30 days after implantation. GSN stimulation via an implanted nerve cuff provided a reproducible and rapid method to increase arterial, central venous, and pulmonary arterial pressures. The neuromodulation cuff was well tolerated and elicited a response up to 30 days after implantation. The clinical application of GSN stimulation as a tool to change central and peripheral cardiovascular hemodynamics needs to be explored.

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Funding

This research was funded by NIH Grant 1R44HL132656-01A1.

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Authors and Affiliations

  1. Coridea LLC., New York City, NY, USA

    Anisha Bapna & Zoar J. Engelman

  2. Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA

    Christopher Adin

  3. Duke Clinical Research Institute, Durham, NC, USA

    Marat Fudim

  4. Duke University Medical Center, 2301 Erwin Road, Durham, NC, 27715, USA

    Marat Fudim

Authors
  1. Anisha Bapna
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  2. Christopher Adin
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  3. Zoar J. Engelman
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  4. Marat Fudim
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Corresponding author

Correspondence to Marat Fudim.

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Conflict of Interest

AB is an employee at Coridea LLC, INC, serves as consultant to Axon Therapies and supported by R44-HL132656-02 grant.

ZE is an employee at Coridea LLC, INC, serves as consultant to Axon Therapies and supported by R44-HL132656-02 grant.

MF is supported by an American Heart Association Grant 17MCPRP33460225, and serves as a consultant to Coridea, Axon Therapies, Galvani and Daxor.

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Associate Editor Enrique Lara-Pezzi oversaw the review of this article

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Statement of Clinical Relevance

Splanchnic vascular compliance has been suggested to be central to the pathophysiology of heart failure. Splanchnic nerve stimulation via an implanted nerve cuff provided a reproducible and rapid method to increase arterial, central venous, and pulmonary arterial pressures. The present research opens up numerous avenues of splanchnic nerve modulation for the treatment of diseases such as neurally mediated syncope.

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Bapna, A., Adin, C., Engelman, Z.J. et al. Increasing Blood Pressure by Greater Splanchnic Nerve Stimulation: a Feasibility Study. J. of Cardiovasc. Trans. Res. 13, 509–518 (2020). https://doi.org/10.1007/s12265-019-09929-7

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  • DOI: https://doi.org/10.1007/s12265-019-09929-7

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