SIMULTANEOUS WIRELESS MEASUREMENT OF BLOOD

PRESSURE AND SYMPATHETIC NERVE ACTIVITY

A System for Investigating Neural Control Mechanisms in Long Term Blood

Pressure Regulation

Daniel McCormick

, Robert Kirton

, Alan Easteal

, Simon Malpas

1,3

, Carolyn J. Barret

Sarah Jane Guild

, Poul Nielson

, Augio Patrick Hu

, David Budgett

Auckland Bioengineering Institute,

Department of Chemistry

Department of Physiology

Department of Electrical and Computer Engineering, University of Auckland, Symonds Street, Auckland, New Zealand

Matthew Lim

Telemetry Research Ltd, PO Box 5504, Auckland, New Zealand

Bruce van Vliet

Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, Saint John's, Newfoundland

Keywords: Telemetry, Inductively Coupled Power Transfer, Sympathetic Nerve Activity, Blood Pressure, Bio-

potential.

Abstract: We report on the development of a combined sympathetic nerve activity and blood pressure telemeter for

long term implantation in freely moving small animals. The devices simultaneously records and transmits

blood pressure, temperature and sympathetic nerve data on the 2.4 GHz ISM band with a range of 5 m.

Blood pressure is measured with a 400 Hz bandwidth, fluid filled catheter at a resolution of 0.1 mmHg.

Sympathetic nerve activity is measured differentially using stainless steel electrodes attached to the renal

nerve. The telemeter measures 29x37x12mm (a volume of approximately 9.5 cm

) and weighs 17g, making

it suitable for use in rats with a weight greater than 170 g. Battery life is 12 h when used continuously,

however the device’s lifespan is effectively indefinite due to the use of in vivo inductively coupled battery

charging. Example data recorded in a conscious unconstrained rat is provided which verifies the telemeters

operation.

1 INTRODUCTION

Elevated blood pressure is a well established factor

in determining an individual’s risk of developing a

number of serious diseases, including heart failure,

renal failure and stroke (Whelton and Klag 1989;

MacMahon 2000). Although the short-term

regulation of blood pressure is well understood, not

much is known about the regulation of blood

pressure over the longer-term.

Recently, with the development of long life

implantable telemetry, researchers have been able to

investigate the role of the sympathetic nervous

system in regulating blood pressure over longer time

periods and under more natural unconstrained

conditions. It is clear that the sympathetic nervous

system is key to the short term regulation of blood

pressure. However, much less is known about its

role in regulating blood pressure over long time

periods (Mark 1996). One method of investigating

this relationship is to measure the sympathetic

nervous system’s output directly by exposing nerve

fibre bundles and recording action potentials

directly. The level of sympathetic nerve activity

204

McCormick D., Kirton R., Easteal A., Malpas S., J. Barret C., Jane Guild S., Nielson P., Patrick Hu A., Budgett D., Lim M. and van Vliet B. (2008).

SIMULTANEOUS WIRELESS MEASUREMENT OF BLOOD PRESSURE AND SYMPATHETIC NERVE ACTIVITY - A System for Investigating Neural

Control Mechanisms in Long Term Blood Pressure Regulation.

In Proceedings of the First International Conference on Biomedical Electronics and Devices, pages 204-209

DOI: 10.5220/0001050902040209

 SciTePress

Table 1: A Comparison between two existing commercial

telemeters which are capable of measuring both blood

pressure and bio-potential signals (Data Sciences

International C50-PXT and Konigsberg T31F) and the

new type.

C50-PXT T31F New

LxWxH 30x15

33x15x10 29x37x10

Volume 6 5 9.5

Weight 11 13 17

#Bio Channels 1 2 1

Bio Bandwidth 1-100Hz

0.1-250 Hz

1-4 kHz

Pk-Pk Range Unknown 1 mV

120 μV

BP Bandwidth <100Hz

>1KHz 120Hz

Stability 5 mmHg 3 mmHg

T.B.D.

Batt Life 2 month 6 month 12 hour

#Trans Ch. 1 20 12

Trans. Type AM FM 2.4GHz

1. Cylinder (Length x Diameter).

2. Best estimate based on other devices made by the

manufacturer.

3. Smallest available input range.

4. Measured using frequency response rig.

5. Between charging.

(SNA) can then be compared with simultaineoulsy

aquired blood pressure measurements; allowing

researchers to experimentally investigate their

interaction.

Previously, researchers have had to implant two

seperate devices in order to record blood pressure

(Data Sciences International,St Paul, Minnisota) and

SNA (Telemetry Research, Auckland, New Zealand)

simutaineously over long periods of time (Barrett,

Ramchandra et al. 2003). This has meant that

research has typically been constrained to larger

animals such as rabbits. In this paper we present a

combined SNA and blood presssure telemeter that

can be implanted in animals as small as rats.

Figure 1: The SNA and BP telemeter.

Figure 2: Wireless charger (right rear) and charging pad

(foreground), implantable telemeter (on charger pad), and

analogue reconstruction units for pressure and SNA (left

rear).

Figure 1 shows the new experimental telemeter.

The leftmost leads are the nerve electrodes. At the

right is the fluid filled catheter for BP

measurements. Visible on top is the rechargable

lithium ion coin cell which provides power to the

telemeter between chargings. Inductive power

transfer is used to recharge the battery anytime while

still implanted. The electronics and electrodes are

incapsulated in medical grade silicon elastomer. The

telemeter measures 25x37x12mm (W x L x H,

excluding electrodes and catheter), occupies a

volume of approximately 9.5 cm

and weighs 17g,

making it suitable for use in rats with a weight

greater than 170 g (Moran, Roy et al. 1998).

Table 1 presents a summary of the specifications

of the new telemeter and its nearest comercially

available equivalents. These comparison devices

were chosen based on their size (small enough to be

used in a rat) and ability to measure both biopoential

signals and blood pressure. The major areas where

the new device differs from its equivelents are the

higher bandwith and sensitivity of the biopotential

ampifier, the abiltiy to recharge the new divice in

vivo and the use of a digital transmision system.

2 METHODS

2.1 System Architecture

The heart of the system is an 8051 microcontroller

which acts as an interface between the various

systems. An 8 channel (multiplexed) 12 bit A/D

converter is used to digitise recorded data. A bi-

directional transceiver operating on the 2.4 GHz

ISM band is used for communication, including data

transmission. This has a number of advantages

including the ability to wirelessly schedule

SIMULTANEOUS WIRELESS MEASUREMENT OF BLOOD PRESSURE AND SYMPATHETIC NERVE ACTIVITY

- A System for Investigating Neural Control Mechanisms in Long Term Blood Pressure Regulation

205

measurements in vitro. Additionally, 12 channels are

available for communication, allowing multiple

instrumented animals to be housed in close

proximity.

Power is provided wirelessly to the implant using

inductively coupled power transfer (Budgett, Hu et

al. 2007). This has allowed high power devices

(relatively speaking) such as A/D converters,

microcontrollers and digital transmission systems to

be used. During use, the implant can be charged by

placing a coil under the animal’s home cage through

which high frequency AC current is passed. Power is

received at the implant by a ferrite pickup which is

magnetically coupled to the charging coil.

Information about the charge state of the battery and

power received are embedded in the BP/SNA data

packets and transmitted to the wireless power

supply. The magnetic field can then be controlled

such that only the required amount of power is

delivered to the implant. This reduces the

temperature rise during charging to approximately

5°C.

Figure 3: Block diagram of the telemeter.

Between charging, a 70 mAH lithium ion coin

cell provides power. Consumption is 6 mA during

continuous operation which results in a battery life

of 12 h. In vivo charging takes between 2 and 4

hours and is dependent on how active the animal is

and how close the implant’s orientation is to the

optimum for charging. During charging SNA

recording is not possible as the nerve signal is

swamped by noise generated by the 200 kHz

charging field.

2.2 Blood Pressure Measurements

Blood pressure measurements are performed using a

10cm fluid filled polyurethane catheter, which acts

as an interface between the measurement site (for

instance the aorta) and the piezo resistive pressure

transducer in the telemeter. Pressure waveforms are

transmitted along the catheter using low viscosity

biocompatible fluid. No obvious reference pressure

is available internally to make measurements

against. Therefore, an absolute pressure sensor (one

with an internal vacuum reference) is used.

Physiologically, the pressure of interest is the

difference between the blood pressure and the

ambient or atmospheric pressure. This pressure is

derived by measuring the atmospheric pressure

using a second absolute transducer and subtracting it

from the internal pressure.

2.2.1 Frequency Response

Accurate measurements of systolic and diastolic

pressure require the use of a wide bandwidth

measurement system. One historical rule of thumb

is that the bandwidth should be greater than 10 times

the heart rate (Gabe 1972). For a rat, the maximum

heart rate that can be reasonably expected is 500

beats per minute. This requires a bandwidth of

greater than 80 Hz.

Figure 4: Frequency Response Measurement System.

In order to characterise the telemeters pressure

measurement bandwidth, the rig represented by

Figure 4 was constructed. A fluid filled chamber acts

as a pressure source for frequency response

measurements. Pressure waveforms are generated by

a voice coil actuator which exerts force on the fluid

through a thin brass diaphragm. The catheter of the

device under test (DUT) is inserted into the chamber

using a luer lock adaptor. A second high bandwidth

transducer provides a reference pressure for

calculations. Provided compliance of the chamber is

minimized, the system’s measurement bandwidth

can be high. Bandwidths of 5 kHz (-3 dB) have been

attained with usable signals present until approx

15 kHz.

Tests are preformed using the swept sine

technique where sinusoidal perturbations are applied

to the DUT. The LabVIEW Sound and Vibration

Analysis Toolbox (www.labview.com)

automatically calculates the magnitude transfer

function from reference pressure (P

ref

) to telemeter

output (P

) as defined by equation 1.

BIODEVICES 2008 - International Conference on Biomedical Electronics and Devices

206

A typical transfer function is presented in Figure

5. The bandwidth (-3 dB point) of the

catheter/amplifier combination (blue) is 400 Hz.

This is more that four times greater than the required

bandwidth of 80 Hz as described above. Gain

peaking is evident at around 100 Hz, but its

magnitude is exaggerated by the small vertical scale

and only amounts to a 15% increase in gain. The

small dip in magnitude at 50 Hz is due to power line

interference (in the test rig).After sampling at 500

Hz, transmission, reconstruction and filtering the

-3 dB frequency is reduced to 120Hz.

)(

20)(

LogjM

ref

(1)

-50

-40

-30

-20

-10

Frequency (Hz)

Magnitude (dB)

Raw Amplifier Output

Reconstructed

Figure 5: Frequency Response of the blood pressure

measurement system. Amplified pressure sensor output

(blue) and reconstructed response after transmission (red).

2.3 SNA

2.3.1 The Nature of SNA

Postganglionic sympathetic nerves are composed of

multitudes of unmyelinated fibres. The action

potentials generated by individual fibres are small

and difficult to measure. Because of this, the entire

nerve bundle is usually used when recording SNA.

Typically two electrodes placed on the nerve and a

differential measurement is made. Measurable

voltages result as large numbers of fibres fire almost

simultaneously whose contributions are additive in

nature. Even so, the potentials generated by a whole

bundle are still only in the μV range. This, combined

with the relatively high frequency content of the

signals (into the kHz range (Malpas 1998)) make

instrumentation troublesome, and especially so in a

micro power telemetry system.

2.3.2 Signal Acquisition

Figure 6 shows the approach taken, which is

similar in nature to many previously described AC

coupled bio-potential amplifiers (Prutchi and Norris

2005).

Figure 6: Nerve Electrode Amplifier.

With a system gain of 10000 and a 3V power

supply, the amplifier is susceptible to saturation due

to electrode polarization offsets. Capacitively

coupling the active electrodes reduces the likely

hood of this happening but requires the use of a third

reference electrode. A low noise Instrumentation

amplifier (IA) amplifies and level shifts the signal

for analogue to digital conversion. A servo

amplifier monitors the DC level of the nerve signal

and centres it in the A/D converter’s range. This is

effectively a second form of AC coupling but also

improves headroom by reducing the effects of input

offset voltage. With a gain of 10000, the typical

input offset voltage of an instrumentation amplifier

(50 - 500 μV) could easily cause saturation.

Digitization is performed using a 12 bit A/D running

at 8 kHz. Full scale input range is ±60 μV. Intrinsic

noise is 650 nV

RMS

over the devices Bandwidth of

1 Hz-4 kHz. This results in a signal to noise ratio of

37 dB for a full scale sinusoidal input.

3 EXPERIMENTAL RESULTS

3.1 Experimental Procedure

Experiments were conducted in Wistar rats with

initial minimum weight of 250g and were approved

by the University of Auckland Animal Ethics

Committee (approval R543). The rats were housed

individually in standard rat cages, with food and

water available ad libitum. The room was kept at a

constant temperature (18 °C) and dark-light cycle

(lights on from 0600 to 1800).

SIMULTANEOUS WIRELESS MEASUREMENT OF BLOOD PRESSURE AND SYMPATHETIC NERVE ACTIVITY

- A System for Investigating Neural Control Mechanisms in Long Term Blood Pressure Regulation

207

Prior to implantation the implant was sterilized

in an 8% gluteraldehyde solution overnight and then

rinsed in sterile saline. The surgery was performed

using sterile procedures on a heated surgical table.

Anesthesia was induced by placing the rat in a

chamber filled with isoflorane, then a nose cone

arrangement was used to maintain the isoflorane

anaesthesia at a surgical level. An abdominal

incision was made and the abdominal aorta cleared

just above the iliac bifurcation. Using silk sutures

the aorta was temporarily occluded and a 23 gauge

needle used to pierce the aorta. The cannula of the

transmitter was inserted into the aorta and advanced

approximately 4cm. The cannula was secured in

place using cyanoacryalate adhesive and blood flow

restored. The body of the transmitter was placed in

the abdominal cavity, with the nerve electrodes and

ground electrode exteriorized, and the muscle

incision closed. A left flank incision was then made

and the electrodes tunneled under the skin to this

incision. A retroperitoneal incision was made

through the muscle and gentle retraction used to

expose the kidney. The renal nerve was found near

the renal artery and dissected free of the surrounding

tissue using fine forceps and visualisation under a

surgical microscope. The Teflon coating was

removed from the last 3mm of the electrode leads

and the stainless steel fashioned into small

hooks.The electrode leads were will be sutured to

the wall of the artery and the intact nerve placed

over the hooks. The nerve/electrode assembly is

insulated from the surrounding tissue using silicone

elastomer (Kwik-sil, World Precision Instruments).

The muscle layer was then closed, with the earth

electrode placed subcutaneously. Then both skin

incisions were closed with staples. As soon as a rat

regained consciousness it was returned to its home

cage. A heating pad was placed under the cage for

24 h after the surgery. Rats received buprenorphine

(Temgesic 1 μg/100 g) as an analgesic.

3.2 Results

Figure 7 is an example of data recorded from a

conscious unconstrained rat. The recording shows

the hallmark traits of SNA, with bursts of activity

occurring synchronously with the cardiac cycle

(Malpas and Ninomiya 1992). Evident in this trace

are small expiration related decreases in blood

pressure with a corresponding increase in the bursts

of renal sympathetic nerve activity illustrating the

arterial baroreflex response and its dependence on

renal sympathetic nerve activity (Dorward, Riedel et

al. 1985). BP recordings show good fidelity with a

crisp reproduction of the diastolic inflection without

ringing or undershoot. However, pulse pressure is

considerably lower than expected with a peak to

peak value of approximately 5 mmHg. The cause of

this is unknown, but may be due to the positioning

of the catheter or surgery trauma. Further

verification of the coordination between blood

pressure and SNA are shown in Figure 8 where 500

Figure 7: Example from one rat showing raw renal sympathetic nerve activity (top panel), rectified and integrated nerve

activity (middle panel) and arterial blood pressure (bottom panel) recorded whilst conscious over a period of 5 s.

Integrated

Sympathetic

nerve act

(uV)

100

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5

time (s)

Arterial

Pressure

(mmHg)

-20

-10

Raw

Sympathetic

nerve act

(uV)

BIODEVICES 2008 - International Conference on Biomedical Electronics and Devices

208

ms intervals of blood pressure and SNA are

averaged using peak systolic pressure as a trigger

(similar to the triggering mechanism of an

oscilloscope). This figure illustrates that the renal

sympathetic nerve exhibited a clear cardiac related

rhythm.

4 CONCLUSIONS

An implantable telemeter which simultaneously

acquires blood pressure and microvolt level nerve

signals has been presented. The telemeter is of a

similar size to existing devices but posses many

advantages such as inductive charging, digital

transmission, and a high bandwidth microvolt input

range bio-potential amplifier. Future work will

concentrate on miniaturization and ascertaining the

long stability of the blood pressure measurement

system.

ACKNOWLEDGEMENTS

The authors wish to acknowledge the support of the

Circulatory Control Group, University of Auckland

and Telemetry Research Limited. Daniel

McCormick was supported by a New Zealand

Tertiary Education Commission Top Achiever

Doctoral scholarship.

REFERENCES

Barrett, C. J., R. Ramchandra, et al. (2003). "What Sets

the Long-Term Level of Renal Sympathetic Nerve

Activity: A Role for Angiotensin II and Baroreflexes?"

Circ Res 92(12): 1330-1336.

Budgett, D. M., A. P. Hu, et al. (2007). "Novel technology

for the provision of power to implantable

physiological devices." J Appl Physiol 102(4): 1658-

1663.

Dorward, P. K., W. Riedel, et al. (1985). "The renal

sympathetic baroreflex in the rabbit. Arterial and

cardiac baroreceptor influences, resetting, and effect of

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physiology Cardiovascular Fluid Dynamics. D.

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MacMahon, S. (2000). "Blood Pressure and the Risk of

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nerve activity." Progress in Neurobiology 56(1): 65-

96.

Malpas, S. C. and I. Ninomiya (1992). "A new approach to

analysis of synchronized sympathetic nerve activity."

Am J Physiol Heart Circ Physiol 263(4): H1311-1317.

Mark, A. L. (1996). "The sympathetic nervous system in

hypertension: a potential long-term regulator of

arterial pressure." J Hypertens Suppl 14(5): S159-65.

Moran, M. M., R. R. Roy, et al. (1998). "Size constraints

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Prutchi, D. and M. Norris (2005). Design and

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I19-27.

Figure 8: Example from one rat showing renal sympathetic

nerve activity (top panel) and arterial blood pressure

(bottom panel) averaged over 500 ms synchronized using

peak systolic blood pressure.

100

110

120

Renal

Sympathetic

nerve act

(uV)

100

0 100 200 300 400 500 600

time (ms)

Arterial

Pressure

(mmHg)

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- A System for Investigating Neural Control Mechanisms in Long Term Blood Pressure Regulation

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