Application of radio telemetry to cardiovascular monitoring in unrestrained animals

BRIEF COMMUNICATION

Application of Radio Telemetry in Unrestrained Animals

P. M.

MELLOR

Key Words:

AND

Radio

to Cardiovascular

Monitoring

S. J. Pettinger

telemetry;

Long-term

monitoring;

Unrestrained

monitoring

INTRODUCTION Radio telemetry of biological parameters has been used for over 25 years, and many designs, both simple and complex, have been published in journals and books (Jeutter, 1983; Mackay and Jacobson, 1957; Mackay, 1970; Matsumoto and Kimmich, 1980). Fields as diverse as wildlife tracking, using simple transistor oscillators, and multichannel physiological measurement implants employing thick film microcircuits have been covered. Companies specializing in making this type of equipment have risen and fallen. Despite this, the routine use of this medium as a research tool is still not as widespread as one might imagine. The small number of companies currently marketing suitable equipment is witness to this fact. As a result of this, we set out to design a relatively simple, reproducible, and inexpensive equipment to monitor systemic blood pressure in unrestrained conscious dogs, continuously over 24 hr or more. Continuous recording of this duration generates so much information that it is impractical to analyze the data manually. To measure both systolic and diastolic blood pressure, and to measure details of the electrocardiogram timings, would take many times the length of the actual experiments. A real time computer-based data reduction system was therefore designed to complement the radiotelemetry. METHODS Electronics The radio telemetry system chosen to telemeter initially one channel of information was of the FM-FM type. The design employs currently available high-performance integrated circuits to perform signal conditioning and frequency modu-

From the Biological Electronics Unit (P.M.M.) and the Bioscience Department II (S.J.P.), ICI Pharmaceuticals Division, Mereside, Alderley Park, Macclesfield, Cheshire, United Kingdom. Address reprint requests tot Dr. P.M. Mellor, Biological Electronics Unit, ICI Pharmaceutical Division, Mereside, Alderly Park, Macclesfield, Cheshire SKI0 4TC, UK. Received June, 1985; revised and accepted October, 1985. 181 journal of

Pharmacological

Methods

16, 181-184

(1986)

0160-5402/86/$03.50

182

P. M. Mellor and S. J. Pettinger lation.

This

modulates of 104.6

produces

to 105 MHz.

as the receiver, original

a varying

a low-power

audio

frequency

radio transmitter An unmodified

The

development

which

in the U.K.

domestic-type

a separate audio frequency

waveform.

tone,

operating

in turn

frequency

medical waveband

FM tuner-amplifier

demodulator

was used

being built to recover the

of the radiotransmitter

section

of the system

is covered by a Department of Trade and Industry development license. The transmitting equipment described is built into a small plastic box 72 x 50 x 25 mm3 and attached to a very low-speed with

heparinized

saline,

which

fluid

pump (Oxford

is used to keep an implanted

duration

of the experiment.

Medical)

is clipped to the transmitter

A miniature

blood pressure box. This

Perfuser catheter

transducer

complete

Mk III) filled patent for the

(Type P50, Gould

assembly

is carried

in one

side pocket of a standard dog jacket (Alice King Medical Arts, U.S.A.). The opposite pocket of the jacket carries the battery, which supplies power to the equipment and also acts as a counterbalance The wire

transmitter

antenna wrapped

quate for

most

mental animals

for the weight of the transmitter-pump

radio frequency around

work,

more

normally

of about I-mW

the pump assembly.

efficient

residing

initially appear that signal dipole type of “standard”

output,

radiators

in standard

power,

Whereas

are under

this

assembly.

is fed to a short has proved

evaluation.

With

ade-

experi-

pens of about 2 x 2 x 3 m’, it would

loss would be unlikely. However, the use of a half wave receiving antenna mounted on the ceiling above the pen

allowed occasional signal dropouts. The animal would sometimes find a position in which to sleep which has in a “null” of the radiation pattern, resulting in lasting signal dropout. which

A new receiving

is supported

antenna was developed

so as to receive both vertically

A matching circuit was added to transform for the receiver input circuit. The received signal tone, original

which

is then

is present

blood pressure

low speed and also on a storage check on the animal’s

to provide

waveform.

This

The computer ceiver,

examines

digitized

condition.

selecting

the digitized

electrocardiogram the systolic

as a varying

an analogue These

via a scaling amplifier, to an analogue-to-digital dore microcomputer for signal analysis. similarly

output

is recorded

oscilloscope.

past and present

crossed

dipoles,

polarized

signals.

the antenna impedance to a value suitable

at the receiver

demodulated

employing

and horizontally

on a chart recorder are purely

A further converter,

blood pressure

obtained

and diastolic

ogram P and R peaks. From this information,

from

audio frequency

representation

both minute

at

to provide

a visual

parallel output

is taken

and then to a Commo-

waveform,

together

a separate transmitter

blood pressure

of the

running

values

with

a

and re-

and electrocardi-

mean systolic

and diastolic

blood pressure are calculated and stored. Heart rate is calculated by counting blood pressure waveforms per minute, the electrocardiogram’s P-R interval is measured automatically, and the mean values are stored. As an indication

of cardiac contractility,

the interval

between

the electrocardi-

ogram’s R wave and the point of end diastole on the blood pressure curve is measured. This is taken to be a close approximation to the Q-A interval, which is often quoted (Alabaster and Henderson, 1982). Mean values are stored. These mean results are listed on a computer printout once a minute. All the stored minute means

Cardiovascular Radio Telemetry are available at the end of the experimental are contained

in separate

period

for graph plotting

routines,

which

software.

Surgery For blood pressure implanted

trical contacts skin

transducers

to the outside

and connecting

Gould with

measurement,

catheter-tip

P50). Method

an implanted

a $300

world;

Konigsberg

2) simple

conventional

1) is expensive,

requiring

for

invasive

P6.5) requiring

direct catheters,

to an external transducer

transducer

there are two possible (e.g.,

transmitting

multiway

system,

the

cost

the

transducer

that every likely test animal

I)

elec-

passing through

type of pressure

at a cost of over $1000 each. Method

each

approaches.

(e.g.,

be fitted

2) only requires

of

catheters

being

negligible. Up to the present time, direct catheters have been used exclusively on the radiotelemetry system, offering simplicity and reliability once the implantation technique

has been

use in “directly Two

different

implanted months, problems buildup, bination

mastered. wired” implant

correctly, whereas with

The

same catheterization

experiments sites

for several

are used:

the carotid

chronic

has been in routine

the carotid artery and the thoracic

catheters

thoracic aorta catheters indwelling

method

years.

should

last for approximately

catheters

aorta. If

stay patent for a minimum

are those

9 months.

of clot

of 3

The main

formation,

fibrin

and infections. These problems have been virtually eliminated by a comof materials used and surgical implant techniques. The catheter itself con-

sists of a vinyl core, supported at two points by polythene dumbbells and covered for most of its length by silastic tubing. Catheters implanted in the carotid are of a length that ensures are implanted

that the tip of the catheter is in the aortic arch. Thoracic

directly

into the aorta using

purse

string

sutures

catheters

to secure them

into

the vessel. Both types of catheter are routed (avoiding kinking) so as to exit through the skin as high up and as centrally as possible on the back of the neck. All catheters are sealed with without

a blunt

any attention

fore a blood

pressure

metal

spigot.

to the catheters recording

Prepared

dogs can be left for long periods

and only need heparinizing

immediately

be-

session.

RESULTS The radio telemetry of about 4000 hr. The

and computer system described has been in use for a total longest continuous sessions have been several of 6 days’ and

nights’ duration, the only breaks being for a few minutes and replenish catheter pump fluids. Resting levels of the measured parameters lower than those measured in directly wired dertaken smaller

in apparent/y changes

relaxed

conditions.

daily to change batteries

have been found to be substantially animal experiments, which were unAs a result

of this,

in drug effect can now be seen as a result

masking effect of falsely elevated basal data. Experience has also shown that true mean diastolic cannot be deduced from a compressed

slow-speed

it is probable

of the removal

or systolic

chart recording,

blood

that

of the

pressure

as high diastolic

183

184

P. M. Mellor and S. I. Pettinger and low systolic

values

are masked

analysis is, therefore, essential P-R and R-A intervals. Despite

the successful

employment

tems have been necessary may result casions,

in bleeding.

Because

The alarms

of these

of the catheter have been

or antenna

of this problem catheter

peaks and troughs.

readings

wiring

it is planned

as well

activated

on a small

as of

alarm

in case of fluid leakage,

damage

and the complication

patency,

The computer

parameters

system described,

to fulfill legal requirements

due to transducer

guarantee

by adjacent

for true

sys-

which

number

of oc-

on the dog jacket.

of requiring

to move

the fluid

to implanted

pump

pressure

to

trans-

ducers, which require only an electrical connection and no catheter, whenever a period of overnight recording is envisaged. Both the alarm system and the fluid pump

can then

The

electronic

band

be dispensed design

FM oscillator

with a narrow stability

band crystal controlled

lating circuits produced at present

improved

type of transmitter

and more

Recently,

with.

is being

economical

have been

design,

spectrum

improved

collaboration

continuously.

originally

making

and reduced

wide-

has now been

for much improved

use. The signal conditioning

with a company

a four-channel Pulse Coded undergoing trials. Complete

The free-running

employed

replaced frequency

and modu-

in size.

involved

in industrial

radio telemetry

has

Modulation (PCM) type of system, which is systems will be on the market by mid-1985.

DISCUSSION The implementation the throughput to chemotherapy now apparent,

of the system

of work,

as well

to be observed. as experiments

An extra advantage

is gained

of the data collection

described

as allowed

in this paper

more

Longer-lasting

can continue

effects

beyond

in manpower

normal

of some

the normal

utilization,

and the computerization

has greatly

physiologically

increased reactions

compounds

working

are

day.

due to the automatic

nature

of results.

CONCLUSION We believe that this paper demonstrates that radio telemetry techniques can be used routine/y as a laboratory tool to great advantage; that it is not restricted to special case applications and should not be regarded as a technological curiosity by the pharmaceutical

industry

in the 1980s.

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CT,

Henderson

CC

(1982) The

stimulant

effects of isoprenaline

dog. Br)

Pharmacol76:251P.

Jeutter

DC (1983) Telemetry

Med Viol March Mackay

Biological

imak

and Man.

New

of age. Eng

Information

Sensing from An-

John Wiley

& Sons,

B (1957) Endoradiosonde.

Na-

ture 179:1239-1240. Matsumoto

Telemetry:

York:

Inc. Mackay RS, Jacobson

is coming

1983:10-50.

RS (1970) Biomedical

and Transmitting

cardiac

in the conscious

Basel:

G, Kimmich

Karger.

HP (1980) Biotelemety

5.