Sympathetic Nerve Activity Clinical Trial
Official title:
STTR Phase II : Skin Sympathetic Nerve Activity and Cardiac Arrhythmias
Since the invention of electrocardiogram (ECG), ECG has been an important part of clinical
practice. A primary reason for the popularity of the ECG is that it is non-invasive and can
be performed in any patient by placing electrodes on the skin. The present methods of ECG
recording focus on detecting electrical signals from the heart. the investigators propose
that with high frequency sampling and high pass filtering, the investigators can also record
SNA from the skin. The somata of the subcutaneous sympathetic nerves on the skin are located
at the ipsilateral cervical and stellate ganglia. Because the left stellate ganglion nerve
activity (SGNA) is known to trigger cardiac arrhythmias, including AF, VF and VF, It is
possible that skin SNA can also be used for arrhythmia prediction. the investigators tested
that hypothesis in our preclinical studies (supported by R01 HL71140) using canine models.
The results showed that subcutaneous nerve activity (SCNA) recorded with implanted electrodes
can be used to estimate stellate ganglion nerve activity(SGNA) in normal dogs and in a canine
model of ventricular arrhythmia and sudden death. the investigators also showed that SCNA is
more accurate than heart rate variability in estimating cardiac sympathetic tone in
ambulatory dogs with myocardial infarction.Therefore, SKNA and SCNA may be useful in
estimating cardiac sympathetic tone. In addition to studying the autonomic mechanisms of
cardiac arrhythmia, these new methods may have broad application in studying both cardiac and
non-cardiac diseases. For example, sympathetic tone is important in the pathogenesis of heart
failure, atherosclerosis, peripheral neuropathies, epilepsy, vasovagal syncope, renal
failure, hypertension and many others diseases. Direct SKNA and SCNA recording may provide
new approaches to study the mechanisms of these common diseases. SKNA recording may also have
immediate clinical applications by assisting in the diagnosis and treatment of hyperhidrosis
(sweaty palms), paralysis, stroke, diabetes, and neuromuscular diseases. It may be used to
assist biofeedback monitoring performed by neurologists to control neuropsychiatric
disorders. Because of these potential clinical and commercial applications, the investigators
propose that this research project is significant.
b. Innovation
- Using conventional electrodes on the skin to record SNA. The neuECG utilizes the
conventional skin electrodes that are widely used in health care facilities. Skin SNA
had been recorded using microneurography techniques, and had been estimated using
cutaneous blood flow (vasodilator responses) skin temperature, skin conductance and
sweat release. However, microneurography cannot be used in ambulatory patients. The
other methods are not direct measurements of SNA. neuECG is the first method that can
directly and non-invasively measure the SNA from the skin.
- Automated real-time signal processing. the investigators will develop signal processing
software to automatically eliminate noise, such as that generated by muscle contraction,
electrical appliances, body motion, respiration, and radiofrequency signals. The
remaining signals are then processed to separately display in real time to provide
health care providers a new method to instantly estimate sympathetic tone. The ECG
signals are used for automated arrhythmia detection while the SNA signals are available
for risk stratification. This approach allows us to improve and broaden the clinical
application of Einthoven's original invention by simultaneous detecting ECG and SNA from
the skin.
- SKNA patterns as new biomarkers. the investigators have identified unique SKNA patterns
that precede the onset of human AF. If proven correct by Specific Aim 3, this new
biomarker can help physicians to estimate the arrhythmia risk and to predict the
efficacy of catheter ablation for AF.
Background Cardiac sympathetic innervation comes from the paravertebral cervical and thoracic
ganglia. Among them, the stellate (cervicothoracic) ganglion is a major source of sympathetic
innervation. It constantly connects with phrenic nerves and almost as often to the vagal
nerves.37 The paravertebral ganglia also directly connect with spinal nerves, which connect
with the intercostal nerves. These intercostal nerves split into ramus cutaneous lateralis
and a deep branch to the musculus rectus abdominis. Histological studies of human skin biopsy
confirmed the presence of abundant sympathetic nerves in arteriovenous anastomoses arrector
pilorum muscles, and arterioles. Using horseradish peroxidase as tracer, Baron et al and
Taniguchi et al found that all skin sensory and sympathetic neurons are located
ipsilaterally. The sympathetic somata are located in the middle cervical and stellate ganglia
as well as the thoracic ganglia. Because of the direct and extensive connections among
various nerve structures, it is possible for the sympathetic nerves in the various structures
to activate simultaneously. Therefore, the investigators hypothesized that SKNA recorded from
the upper thorax can be used to estimate the cardiac sympathetic tone.
Utilize the differential frequency contents of ECG and SNA to record neuECG To preserve the
signal and eliminate noise, the American Heart Association (AHA) standard recommendation for
low pass filtering of the ECG is 150 Hz for adolescents and adults, and 250 Hz for children.
Higher frequency signals, although known to be clinically important, are routinely eliminated
by this low pass filtering. Because there is no need to record high frequency signals, the
conventional ECG and Holter monitoring devices do not have a wide bandwidth and high sampling
rate. neuECG recording takes a different approach. the investigators use equipment with wide
bandwidth (2K Hz) and high sampling rate (4K/s-10K/s) to record the signals from the skin.
The signal is then band passed between 0.5 Hz and 150 Hz to display ECG signal. The same
signals are then high passed at > 150 Hz to reveal nerve activities. Figure 1 illustrates the
above concept. It shows Fast Fourier Transform (FFT) analyses of the signals recorded from
the skin. High pass filtering at 150 Hz eliminated the ECG signals. The remaining high
frequency signals may contain both muscle and nerve activities. McAuley et al reported that
the electromyography (EMG) usually has a frequency of <100 Hz. At most, small amounts of
muscle activities could reach 400 Hz. By high pass filtering at 500 Hz, the EMG is eliminated
but so are other signals with frequencies < 500 Hz. The standard high pass setting for
microneurography study is 700 Hz. High pass filtering at 500 or 700 Hz increased the
specificity but reduced the sensitivity of SKNA recording. The signal to noise ratio is
reduced. However, the basic patterns of nerve discharges remain.
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