Hart, E. C., Head, G. A., Carter, J. R., Wallin, B. G., May, C. N.,
Hamza, S. M., Hall, J. E., Charkoudian, N., & Osborn, J. W. (2017).
Recording sympathetic nerve activity in conscious humans and other
mammals: guidelines and the road to standardization.
AJP - Heart and
Circulatory Physiology
,
312
(5), H1031-H1051.
https://doi.org/10.1152/ajpheart.00703.2016
Peer reviewed version
License (if available):
Unspecified
Link to published version (if available):
10.1152/ajpheart.00703.2016
Link to publication record in Explore Bristol Research
PDF-document
This is the author accepted manuscript (AAM). The final published version (version of record) is available online
via APS at https://www.physiology.org/doi/10.1152/ajpheart.00703.2016. Please refer to any applicable terms of
use of the publisher.
University of Bristol - Explore Bristol Research
General rights
This document is made available in accordance with publisher policies. Please cite only the
published version using the reference above. Full terms of use are available:
http://www.bristol.ac.uk/red/research-policy/pure/user-guides/ebr-terms/
H-00703-2016 R2
1
Recording sympathetic nerve activity in conscious humans and other mammals:
guidelines and the road to standardization
Emma C. Hart
1
, Geoffrey A. Head
2
, Jason R. Carter
3
, B. Gunnar Wallin
4
, Clive N.
May
5
, Shereen M. Hamza
6
, John E. Hall
7
, Nisha Charkoudian
8
and John W. Osborn
9
Running title: Guidelines for measuring sympathetic nerve activity
1
University of Bristol, School of Physiology, Pharmacology and Neuroscience, Bristol,
United Kingdom
2
Baker IDI Heart and Diabetes Institute, Melbourne, Australia
3
Michigan Technological University, Houghton, MI, USA
4
University of Gothenburg, Gothenburg, Sweden
5
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville,
Victoria, Australia
6
University of Alberta, Canada
7
Department of Physiology and Biophysics, Mississippi Center for Obesity Research,
University of Mississippi Medical Center, Jackson, MS, USA
8
US Army Research Institute of Environmental Medicine, Natick, MA, USA
9
University of Minnesota, Department of Integrative Biology and Physiology, Medical
School, Minneapolis, MN, USA
Corresponding author: Dr. Emma C. Hart
School of Physiology Pharmacology and Neurosciences, Biomedical Sciences Building,
University of Bristol, BS8 1TD, UK. Email: emma.hart@bristol.ac.uk
Running title: Measuring and interpreting SNA in mammals
H-00703-2016 R2
2
Contents outline
1. Abstract
2. Introduction to the measurement of sympathetic nerve activity
3. Recording SNA in humans: microneurography
3.1. Multi-unit recordings of SNA
3.2. Single unit recordings
4. Recording SNA in conscious animals
4.1. Multi-unit recordings of SNA in conscious rabbits
4.2 Multi-unit recordings of SNA in conscious sheep
4.3. Recording SNA in conscious rats
4.4 Recording RSNA in conscious mice
4.5. Single unit recordings in animals
5. Similarities and differences between human and animal recordings of SNA
6. Criteria for validating sympathetic nerve activity
7. Overall summary and directions for future work
H-00703-2016 R2
3
1. Abstract
Over the past several decades, studies of the sympathetic nervous system in humans,
sheep, rabbits, rats and mice have substantially increased mechanistic understanding of
cardiovascular function and dysfunction. Recently, interest in sympathetic neural
mechanisms contributing to blood pressure control has grown, due in part to the
development of devices or surgical procedures, which treat hypertension by
manipulating sympathetic outflow. Studies in animal models have provided important
insights into physiological and pathophysiological mechanisms, which are not accessible
in human studies. Across species and among laboratories, various approaches have
been developed to record, quantify, analyze and interpret sympathetic nerve activity
(SNA). In general, SNA demonstrates “bursting” behavior, where groups of action
potentials are synchronized and linked to the cardiac cycle via the arterial baroreflex. In
humans, it is common to quantify SNA as bursts/minute or bursts/100 heartbeats. This
type of quantification can be done in other species, but is only commonly reported in
sheep, which have heart rates similar to humans. In rabbits, rats and mice, SNA is often
recorded relative to a maximal level elicited in the laboratory to control for differences in
electrode position among animals or on different study days. SNA in humans can also
be presented as total activity, where normalization to the largest burst is a common
approach. The goal of the present paper is to put together a summary of “best
practices” in several of the most common experimental models, and to discuss
opportunities and challenges relative to the optimal measurement of SNA across
species.
Keywords: blood pressure, autonomic nervous system, nerve recording, rat, rabbit,
sheep, mouse, human
H-00703-2016 R2
4
2. Introduction
Over the past several decades, the importance of sympathetic nerve activity (SNA) in
the control of human cardiovascular function has become increasingly clear. Elevations
in SNA have important roles in the pathophysiology of essential and renovascular
hypertension, as well as chronic kidney disease and congestive heart failure. From a
physiological perspective, the sympathetic nervous system is of considerable interest, as
it transmits patterns of information embedded in frequencies of nerve firing that provide
fine regulation of blood flow, perfusion pressure, cardiac output, and release of
hormones such as renin.
From the earliest recordings of postganglionic sympathetic nerves in anesthetized
rabbits and decerebrate cats by Adrian, Bronk and Phillips in the 1930’s, the distinctive
patterns of respiratory and cardiac coupling revealed that adaptation of brain centers
controlling SNA occurred at a rapid rate and that SNA was never really “steady” (1).
Importantly, different vascular beds receive levels of activity influenced by different
afferent and central signals. Thermoregulatory information controls SNA to skin as does
the level of oxygen, whereas baroreceptor input appears to have less influence (103). By
contrast, muscle, renal, splanchnic and cardiac SNA are strongly influenced by
baroreceptors and chemoreceptors (56). Thus recordings of sympathetic nerves were
recognized to reveal a dynamic window into the workings of the cardiovascular and
thermoregulatory systems.
While many studies extended these findings to other species, including rats and mice,
the impact of anesthesia on cardiovascular and autonomic function has limited the
usefulness of the technique. Kirchner described the first recordings from an
unanesthetized cat by means of chronically implanted electrodes embedded into a