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Simultaneous noninvasive recording of electrocardiogram and skin sympathetic nerve activity (neuECG)

Nature Protocols volume 15, pages 1853–1877 (2020)Cite this article

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Abstract

neuECG, the simultaneous noninvasive recording of ECG and skin sympathetic nerve activity (SKNA), directly records sympathetic nerve activity over a long period of time. It can be used to measure sympathetic tone in healthy subjects and in subjects with non-cardiovascular diseases. The electrical activity that can be measured on the surface of the skin originates from the heart, the muscle or nerve structures. Because the frequency content of nerve activity falls in a higher frequency range than that of the ECG and myopotential, it is possible to use high-pass or band-pass filtering to specifically isolate the SKNA. neuECG is voltage calibrated and does not require invasive procedures to impale electrodes in nerves and thus has advantages over microneurography. Here, we present a protocol that takes <10 min to set up. The neuECG can be continuously recorded over a 24-h period or longer. We also describe methods to efficiently analyze neuECG from humans using commercially available hardware and software to facilitate adoption of this technology in clinical research.

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Fig. 1: Methods of SKNA recording and analyses.
Fig. 2: Effects of SGB on neuECG.
Fig. 3: SKNA and SSNA recordings during CPT, Valsalva maneuver, and handgrip.
Fig. 4: Effects of band-pass filter setting and electrode locations on the magnitudes of aSKNA.
Fig. 5: Stability of continuous neuECG recording over a 24-h period or longer.
Fig. 6: Schematic instruction of ADInstruments devices.
Fig. 7: ADInstruments devices setting (Part 1).
Fig. 8: ADInstruments devices setting (Part 2).
Fig. 9: ADInstruments devices setting (Part 3).
Fig. 10: Screenshots of aSKNA analysis using LabChart.
Fig. 11: Screenshots of SKNA burst analysis using JMP Pro software (Part 1).
Fig. 12: Screenshots of SKNA burst analysis using JMP Pro software (Part 2).
Fig. 13: Example of SKNA burst analyses.

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Data availability

All data described in the article will be made available upon reasonable request to the corresponding author.

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Acknowledgements

This study was supported in part by NIH Grants R01HL134864 (Y.-M.C.), R01AG049924 (D.R.W.), R42DA043391 (T.H.E.) and R56HL71140, TR002208-01, R01HL139829 and 1OT2OD028190 (P.-S.C.); a Charles Fisch Cardiovascular Research Award endowed by Dr. Suzanne B. Knoebel of the Krannert Institute of Cardiology (T.K. and T.H.E.); a Medtronic-Zipes Endowment and the Indiana University Health-Indiana University School of Medicine Strategic Research Initiative (P.-S.C.); and a Cardiovascular Prospective Award from Mayo Clinic (Y.-M.C.). We thank Matthew D. Podczerwinski of Rose Hulman Ventures for signals shown in Fig. 1a.

Author information

Author notes

  1. Deceased: Ronald G. Victor.

Authors and Affiliations

  1. Krannert Institute of Cardiology, Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    Takashi Kusayama, Johnson Wong, Xiao Liu, Wenbo He, Eric A. Robinson, David E. Adams, Thomas H. Everett IV & Peng-Sheng Chen

  2. Department of Cardiovascular Medicine, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan

    Takashi Kusayama

  3. Cardiovascular Research Institute and Department of Cardiology, Renmin Hospital of Wuhan University, and Hubei Key Laboratory of Cardiology, Wuhan, China

    Wenbo He & Ming-Yan Dai

  4. The Division of Cardiovascular Health and Disease, University of Cincinnati, Cincinnati, OH, USA

    Anisiia Doytchinova

  5. Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA

    Lan S. Chen

  6. Institute of Biomedical Engineering, National Chiao Tung University, Hsinchu, Taiwan

    Shien-Fong Lin

  7. Division of Nephrology, University of Massachusetts School of Medicine, Worcester, MA, USA

    Katherine Davoren

  8. Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Katherine Davoren & Ronald G. Victor

  9. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

    Cheng Cai & Minglong Chen

  10. Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA

    Cheng Cai, Ming-Yan Dai, Ying Tian, Pei Zhang, Dereen Ernst & Yong-Mei Cha

  11. Department of Cardiovascular Diseases, Beijing Chaoyang Hospital, Beijing, China

    Ying Tian

  12. Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    Pei Zhang

  13. Department of Anesthesiology and Pain Medicine, Mayo Clinic, Rochester, MN, USA

    Richard H. Rho

  14. Department of Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    David R. Walega

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Contributions

T.K., A.D., K.D. and D.R.W. performed the experiments. T.K., J.W., X.L., W.H. E.A.R., D.E.A., K.D., C.C., M.-Y.D., Y.T., P.Z., D.E., R.H.R., and M.C. analyzed the data. T.K., L.S.C., S.-F.L., R.G.V., Y.-M.C., D.R.W., T.H.E., and P.-S.C. designed the study. All authors participated in manuscript preparation and have read and approved the final manuscript for publication.

Corresponding author

Correspondence to Peng-Sheng Chen.

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Competing interests

Indiana University was awarded US patent no. 10,448,852 for inventing neuECG recording. The authors are willing to help and advise basic and clinical investigators who are interested in using these recording methods to study sympathetic tone.

Additional information

Peer review information Nature Protocols thanks John E. Madias, Stavros Stavrakis and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Related links

Key references using this protocol

Doytchinova, A. et al. Heart Rhythm 14, 25–33 (2017): https://doi.org/10.1016/j.hrthm.2016.09.019

Kusayama, T. et al. JCI Insight 4, e125853 (2019): https://doi.org/10.1172/jci.insight.125853

Liu, X. et al. Heart Rhythm 16, 1875–1882 (2019): https://doi.org/10.1016/j.hrthm.2019.06.017

Supplementary information

Supplementary Video 1

Actual data acquisition of neuECG. This video shows the actual neuECG recording in a subject with premature ventricular contractions. After baseline recording, the subject placed his right hand in a bucket of ice water for 2 min, which was associated with increases in aSKNA and HR. After CPT, aSKNA and HR decreased.

Reporting Summary

Supplementary Data 1

LabChart channel settings for single-channel recording using Lead 1. This file includes six channels for neuECG data acquisition and analyses using Lead 1. It was used to record Supplementary Video 1.

Supplementary Data 2

Original neuECG data recorded during Supplementary Video 1.

Supplementary Data 3

LabChart channel settings for Leads 1 and 2. This file includes 10 channel settings for neuECG data acquisition and analyses using Leads 1 and 2.

Supplementary Data 4

Original neuECG data from Leads 1 and 2. This file includes raw neuECG data using Leads 1 and 2 to demonstrate the LabChart data analyses.

Supplementary Data 5

LabChart data summary. This file includes the summary of LabChart analyses in Steps 25–31 using Supplementary Data 3 and 4.

Supplementary Data 6

SKNA burst analyses. This file includes the SKNA burst analyses using Excel software.

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Kusayama, T., Wong, J., Liu, X. et al. Simultaneous noninvasive recording of electrocardiogram and skin sympathetic nerve activity (neuECG). Nat Protoc 15, 1853–1877 (2020). https://doi.org/10.1038/s41596-020-0316-6

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