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Autonomic Influences on Sinus Bradycardia: A Study on Atrial Pacemaker Function, Exercises of Pathology

A study conducted by Dighton, from St. George's Hospital, London, investigating the autonomic influences on sinus bradycardia. The research involved 24 patients with sinus bradycardia and 16 control subjects, who were assessed using various autonomic reflex manoeuvres and drug response tests. The aim was to differentiate the physiological from the pathological type of bradycardia caused by atrial disease.

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British
Heart,Journal,
I974,
36,
79I-797.
Sinus
bradycardia
Autonomic
influences
and
clinical
assessment
David
H.
Dighton
From
the
Cardiac
Department,
St.
George's
Hospital,
London
Twenty-four
patients
with
sinus
bradycardia
and
i6
control
subjects
were
investigated
using
various
autonomic
reflex
manoeuvres
and
drug
response
tests.
Two
groups
of
patients
are
suggested
by
the
results:
i)
Bradycardia
due
to
atrial
disease
(sinoatrial
diseasel
sick
sinus)
-
poor
autonomic
reponses,
I6
patients.
Of
those
with
poor
autonomic
responses,
9
had
additional
AV
conduction
defects,
and
half
had
experienced
Adams-Stokes
syncope.
2)
Bradycardia
of
physiological
origin
-
normal
or
supernormal
autonomic
responses.
a)
Those
with
normal
autonomic
function,
7
cases.
The
dominant
atrial
pacemaker
in
this
group
is
possibly
set
at
a
lower
rate
than
normal.
Such
patients
were
not
found
to
be
liable
to
Adams-Stokes
syncope,
but
may
have
vasomotor
syncope.
b)
Vagotonia,
I
case.
On
the
basis
of
one
patient
it is
suspected
that
sinus
bradycardia
may
be
due
to
'vagotonia'
or
due
to
an
unusual
sensitivity
of
the
atrium
to
vagal
influence.
All
autonomic
responses
were
supernormal.
Such
patients,
though
probably
rare,
may
be
especially
liable
to
vasomotor
syncope.
It
is
suggested
that
the
investigations
presented
are
useful
in
the
routine
assessment
of
patients
presenting
with
syncope
and
sinus
bradycardia.
Those
patients
with
symptoms
and
poor
autonomic
responses
may
require
pacing
while
those
with
physiological
responses
may
need
no
treatment
or
may
be
helped
by
drugs.
Although
most
patients
presenting
with
sinus
bradycardia
are
asymptomatic,
some
present
with
syncope
or
dizzy
spells.
Physiological
bradycardia
is
usually
of
no
clinical
significance
except
when
seen
in
association
with
vasomotor
syncope.
When
a
patient
presents
with
Adams-Stokes
syncope
and
sinus
bradycardia
the
problem
is
to
differentiate
the
bradycardia
of
physiological
origin
from
that
which
may
be
associated
with
some
atrial
pathology.
The
aim
of
the
present
work
has
been
to
investi-
gate
the
autonomic
influences
acting
in
sinus
brady-
cardia
and
to
develop
routine
tests
useful
in
differ-
entiating
the
physiological
from
the
pathological
type
of
bradycardia
caused
by
atrial
disease.
The
tests
described
have
developed
from
the
need
to
assess
the
clinical
significance
of
sinus
bradycardia
in
patients
with
syncopal
attacks.
The
sinoatrial
node
and
atrium
are
richly
inner-
vated
by
both
sympathetic
and
parasympathetic
nerve
fibres
(Grodner
et
al.,
I970;
James,
I967),
the
pacemaker
cells
being
directly
affected
by
the
release
of
the
acetylcholine
and
catecholamines
(James
and
Nadeau,
I963;
Hoffman
and
Cranefield,
I960;
Toda
and
Shimamoto,
I968;
Toda
and
West,
Received
5
March
I974
I967;
Grodner
et
al.,
I970).
The
presence
of
the
enzyme
cholinesterase
may
be
of
importance
in
the
control
of
the
heart
rate
since
it
is
responsible
for
the
hydrolysis
of
acetylcholine
and
can
be
demonstrated
in
active
form
in
the
sinoatrial
node
and
atrium
(James
and
Spence,
I966).
Patients
presenting
with
sinus
bradycardia
have
been
investigated
by
using
various
reflex
tests
and
by
infusion
of
drugs
acting
on
the
autonomic
system
and
atrial
pacemaking
sites.
Selection
of
subjects
and
methods
Sixteen
healthy
adults
volunteered
as
control
subjects
after
being
fully
informed
about
the
nature
of
the
in-
vestigation.
Twenty-four
patients
with
a
persistent
bradycardia
at rest
of
less
than
55
a
minute
were
investigated
after
giving
fully
informed
consent.
No
patient
was
ad-
mitted
to
the
investigation
if
the
bradycardia
could
be
related
to
drug
therapy,
untreated
hypothyroidism,
raised
intracranial
pressure,
recent
cardiac
infarction,
or
cerebrovascular
accident.
Some
patients
presented
with
symptoms
while
others
were
found
to
have
a
persistent
resting
sinus
bradycardia
on
routine
electrocardio-
graphy.
Patients
with
fixed
rate
pacemakers
were
ex-
cluded
while
some
with
demand
pacemakers
were
pf3
pf4
pf5

Partial preview of the text

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British Heart,Journal, I974, 36, 79I-797.

Sinus bradycardia

Autonomic influences and clinical assessment

David H. Dighton

From the Cardiac Department, St. George's Hospital, London

Twenty-four patients with sinus bradycardia and i6^ control^ subjects were^ investigated using various^ autonomic

reflex manoeuvres and drug response tests.

Two groups ofpatients are suggested by the results: i) Bradycardia due to atrial disease (sinoatrial^ diseasel

sick sinus) -^ poor autonomic reponses, I6 patients. Of those with poor autonomic responses, 9 had additional

AV conduction defects, and half had experienced Adams-Stokes syncope. 2) Bradycardia of physiological

origin -^ normal or supernormal autonomic responses. a) Those with normal autonomic function, 7 cases. The

dominant atrial pacemaker in this group is possibly set at a lower rate than normal. Such patients were not

found to^ be^ liable to^ Adams-Stokes^ syncope,^ but^ may^ have^ vasomotor^ syncope.^ b) Vagotonia,^ I^ case.^ On^ the

basis of one patient it is suspected that^ sinus bradycardia may be^ due^ to^ 'vagotonia'^ or^ due^ to^ an^ unusual

sensitivity of the atrium to vagal influence. All autonomic responses were supernormal. Such patients, though

probably rare, may be especially liable to vasomotor syncope.

It is suggested that the investigations presented are useful in the routine assessment of patients presenting

with syncope and sinus bradycardia. Those patients with symptoms and poor autonomic responses may require

pacing while those^ with^ physiological^ responses^ may^ need^ no^ treatment^ or may^ be helped^ by^ drugs.

Although most patients presenting with sinus

bradycardia are^ asymptomatic,^ some^ present^ with syncope or^ dizzy spells. Physiological bradycardia is

usually of^ no^ clinical^ significance except when^ seen

in association with vasomotor syncope. When^ a

patient presents with Adams-Stokes syncope and

sinus bradycardia the problem is to differentiate

the bradycardia of physiological origin from that

which may be associated with some atrial pathology.

The aim of the (^) present work has been to investi-

gate the autonomic influences^ acting in sinus^ brady-

cardia and to^ develop routine^ tests^ useful^ in^ differ-

entiating the physiological from the^ pathological

type of bradycardia caused by atrial disease. The

tests described have developed from the need to

assess the clinical^ significance of^ sinus^ bradycardia

in patients with syncopal attacks.

The sinoatrial node and atrium are^ richly inner-

vated by both sympathetic and^ parasympathetic

nerve fibres (Grodner et^ al., I970; James, I967), the

pacemaker cells^ being directly affected^ by the

release of^ the^ acetylcholine and^ catecholamines

(James and^ Nadeau, I963; Hoffman^ and^ Cranefield,

I960; Toda^ and^ Shimamoto, I968;^ Toda^ and^ West,

Received 5 March (^) I

I967; Grodner et al., I970). The presence of the enzyme cholinesterase may be of importance in the control of the heart rate since it is responsible for the

hydrolysis of acetylcholine and can be demonstrated

in (^) active form in the (^) sinoatrial node and atrium

(James and Spence, I966).

Patients presenting with sinus bradycardia have

been investigated by using various reflex tests and

by infusion of drugs acting on the autonomic system

and atrial pacemaking sites.

Selection of subjects and methods Sixteen healthy adults volunteered as control subjects after being fully informed about the nature of the in- vestigation. Twenty-four patients with^ a^ persistent bradycardia at rest of less than 55 a minute were investigated after giving fully informed consent. No patient was ad- mitted to the investigation if the bradycardia could be related to drug therapy, untreated hypothyroidism, raised intracranial^ pressure, recent^ cardiac infarction, or cerebrovascular accident. Some patients presented with symptoms while others were found to have a persistent resting sinus bradycardia on routine electrocardio- graphy. Patients with fixed rate pacemakers were ex- cluded while some with demand pacemakers were

792 David H.^ Dighton

included. This selection was necessary since^ only demand pacemakers may be externally inhibited allowing the underlying spontaneous rhythm to manifest itself. All subjects were examined and weighed before in- vestigation. Those with demand pacemakers had their units inhibited by an external pulse generator attached at least IS minutes before investigation.

a) Reflex tests

With a continuous electrocardiographic recording (lead chosen to show largest P waves), all subjects performed simple manoeuvres designed to stimulate the dominant atrial pacemaker by autonomic reflexes. Recording started io to (^) i5 seconds before the reflex test and was continued throughout and for I0 seconds after each manoeuvre. Recordings were made with (^) quiet res- piration, forced inspiration (with breath held in in- spiration for a minimum of I5 seconds), a (^) Valsalva manoeuvre, using a^ sphygmanometer blown up to 40 mmHg, for a minimum of iS seconds and continued for as long as possible; right and left carotid sinus pressure continued until maximum response was ob- tained (up to I0 seconds usually); and (^) straight leg raising for 30 seconds. All the tests were (^) performed in the sitting position on a couch or (^) bed. The (^) electrocardio- grams obtained were (^) analysed for atrial rate using a standard rate (^) calculating ruler averaging two consecutive PP (^) intervals. The control rate was taken as the average ofthree measurements. Tne maximum or minimum rates during and after the manoeuvres were noted and ex- pressed as the rate difference above or below the control rate. Any changes in P wave morphology or changes in rhythm were noted. As far as possible recordings were made only during regular sinus (^) rhythm. Recordings with nodal (^) rhythm or some (^) irregular rhythm were re- jected and the^ manoeuvre^ repeated.

b) Drug tests

After the reflex tests, with the patient supine and at rest, intravenous bolus injections of the following (^) drugs were made into a normal saline intravenous infusion. i) (^) 5 ,Lg isoprenaline per 70 kg body weight (prepared in 2 ml (^) vials, (^5) jig/ml containing sodium metabisulphate); ii) 0-02 mg atropine sulphate per kg body weight; iii) o-8 mg prostigmine per 70 kg body weight given 20 minutes after the dose of atropine. The drugs were given in the order shown and flushed in with not more than 2 ml normal saline. A period of approximately I0 minutes elapsed between the doses of isoprenaline and atropine while the heart rate returned to previous control level. Only one dose of each (^) drug was given. The (^) doses given were chosen (^) to give an easily measur- able (^) response without (^) resulting in (^) undue side effects. The dose of (^) prostigmine was (^) suggested by the work of Fielder et al. (^) (I969).

Electrocardiograms were^ made^ continuously, io

seconds before and I minute after the dose of isoprena-

line. Only regular sinus (^) rhythm was (^) accepted as suitable during the control period. The same (^) procedure was followed for the atropine dose but further electrocardio-

grams (5 to I0 second strips) were taken every 5 minutes

until 20 minutes after injection. At 20 minutes after atro- pine the dose of prostigmine was given. After the dose of prostigmine, io-second recordings were made every minute for I0 minutes. The electrocardiograms were analysed for atrial rate with a standard rate (^) calculating ruler. The control (^) rates were taken as an average of five measurements (^) during the control period before each dose, only regular sinus rhythm being acceptable during this period. In the case of both atropine and isoprenaline the atrial rate was analysed with one measurement at every 3-second inter- val during the first minute. Further measurements were made at is-second intervals for a further (^2) minutes. Thereafter, in the case ofatropine, (^) measurements of atrial

rate were made at 5-minute intervals until prostigmine

was (^) given. During this analysis changes in rhythm or P wave morphology were noted. During the prostigmine re- sponse an average of five measurements was made at one minute intervals. The results were plotted as atrial rate against time in each case. Atrial response was assessed in two ways: i) the maximum or minimum (^) rate obtained above or below the mean control rate, and ii) the maximum rate of rise or fall in atrial rate during the response. This was estimated from a gradient drawn through the steepest four points on the response curve.

Results The ages, sex, mean resting heart rates, (^) electro-

cardiographic features, clinical features, and past

history of both controls (^) and those with sinus

bradycardia are given in Table i.

Seven patients presenting with sinus bradycardia were found to have P wave abnormalities; 4 having

flat or bifid P waves (voltage less than Oi mV) with

3 others having P waves of greater duration than

normal (o-i6 sec). A PR interval greater than 02 sec

was seen in 8 patients, no higher degrees of AV

block being seen. A QRS duration greater than

o0i sec was seen in 5 patients each with right bundle-

branch block and left axis deviation. His bundle

electrograms showed normal His to ventricular

activation times in these (^) patients.

Reflex tests

The changes in atrial rate with the various reflex

manoeuvres are shown in Table 2. No significant

quantitative difference could be shown between the

control responses to quiet breathing, forced inspira-

tion or straight leg raising, and those presenting with

sinus bradycardia. While the increase in rate during

a Valsalva manoeuvre was not significant, the total

drop in rate after the manoeuvre was significantly

less in the sinus bradycardia group.

Qualitative changes during the reflex responses

were not^ seen in the control group. In the sinus

bradycardia group various changes were seen.

794 David H. Dighton

patient (Case 14) the rate achieved was above control

range.

On the basis of decreased rate of change of atrial

rate II (^) patients had responses below normal range

(Cases I, 3, 5, 6, I2, I13, 15, i6, 17, I9, 23). One had

an above normal response (Case I4), the remaining

responses falling within control range.

In 2 patients frequent change in P wave shape

occurred (Cases I I, 23), with atrioventricular nodal

rhythm occurring at times in 5 (Cases 6, II, I2,

I3, i6). Supraventricular ectopics were frequently

observed in three (Cases I, 3, 6).

2) Atropine responses No significant difference

(P > o02) was found with either the increase in

atrial rate or in the maximum rate of change of

atrial rate between the control and sinus brady-

cardia groups. Only one patient had a response

below the normal range (Table 2) (Case I2) and

one had a response above normal range (Case 14).

With respect to the rate of change of atrial rate with

atropine, 5 patients had responses below the control

range (Table 2) (Cases I, I3, I5, 20, 24), 3 of whom

exhibited atrioventricular nodal takeover (Cases I,

I3, 20).

In the control group atrioventricular nodal take-

over occurred in one subject. In most subjects the

PR interval decreased by o0o4 sec. Nodal takeover

was observed in 8 patients (Cases I, 3, 6, I2, I4,

i6, I9, 20), with P wave variation occurring in one

case (Case 23).

3) Prostigmine responses Prostigmine was seen

to return the atrial rate to preatropine levels only.

When those with sinus bradycardia are compared

with controls, the differences between the drop in

atrial rate and the rate of change of atrial rate

fail to reach significant levels (P > o I).

In I3 of the sinus bradycardia group the decrease

in atrial rate observed was below the normal range

(Table 2, Cases 2, 3, (^) 5, 6, 7, 8, I2, I6, 17, 20, (^) 2I,

23, 24). One patient (Case 14) decreased his atrial

rate greater than any control subject.

Fourteen patients had a decrease in the rate of

change of atrial rate below the control range (Cases

I, 2, 3, 5, 6, 12, I3, i6, (^) 17, 20, 2I, 22, 23, 24). Four

patients had responses greater than the control

range in this respect (Cases 4, 9, 14, I9).

Results and clinical features

Of the io patients that had both reduced reflex and

drug responses (Cases 3, 6,8, (^) 13,i63, (^) I7, 20, 21, 23,

24), 5 had a history of Adams-Stokes attacks (Cases

3, 6, I3, I7, 20) and 2 a history of fainting attacks

(Cases 3, 8), with 5 requiring pacing (Cases 6, 13,

17, 20, 23). Two^ were^ satisfactorily controlled with long-acting (^) isoprenaline (Cases 3, i6). These patients all^ had^ below^ normal^ atrial^ responses and are (^) therefore (^) likely to have (^) sinoatrial disease or

'sick sinus syndrome'.

Of the I0 patients with both reduced reflex and

drug (^) responses, 5 had^ an^ abnormality of either P wave (^) voltage or (^) morphology (Cases 3, 8, I3, I7, (^) 23),

2 had evidence of sinoatrial block (Cases 6, i6), 2

of sinus arrest (Cases 8, 17), one of paroxysmal

atrial fibrillation (Case 13), and 4 had atrioven-

tricular nodal rhythm at times (Cases, i6, I7, 21,

23). Of^ the^ I0^ cases^ with^ reduced^ responses, 4 had evidence (^) of (^) right bundle-branch block (^) with left

axis deviation but no prolongation of His to ven-

tricular activation time. There was, therefore, no

electrophysiological evidence of trifascicular bundle-

branch disease in these cases. Since one patient also

had (^) first-degree atrioventricular (^) block with a PR

interval of 0-32 to 0'4 sec, 5 of the I0 patients with

reduced reflex and drug responses had evidence of

abnormal atrioventricular conduction.

There were 6 patients with reduced drug re-

sponses but^ normal^ reflex^ tests (Cases I, 2, 5, I2,

I5, 22). One^ of^ these had abnormal P waves with

intermittent sinus arrest (Case 5), 3 had nodal

rhythm at^ times (^) (Cases I, I2, I5), 2 had (^) right bundle-branch block with left axis deviation (^) (Cases

I, I5), and^2 had^ prolonged PR intervals (Cases 5,

22). None^ was^ seen to have either sinoatrial block or

atrial fibrillation. Of these 6, 5 had a history of

Adams-Stokes attacks (Cases 2, 5, I2, I5, 22), with 3

requiring pacing (Cases 5, I2, 22). This association

makes it likely that these patients have sinoatrial

disease or 'sick sinus syndrome'. One was con-

trolled with long-acting isoprenaline (Saventrine).

One only had a history of fainting episodes.

Eight patients (Cases 4, 7, 9, I0, II, I4, i8, I9)

were found to have no evidence of reduced atrial

pacemaker function. Of these, 3 had syncope which

was thought to be vasomotor in type (Cases 4, II,

14) rather than Adams-Stokes syncope. Three had

paroxysmal atrial^ fibrillation, one had occasional

atrioventricular nodal rhythm, and one other had

periods of^ sinus^ arrest^ (Case II). While 2 of these

patients had^ first-degree atrioventricular block, none

had evidence of bundle-branch block. These

patients have^ either^ physiological sinus bradycardia

or undetectable sinoatrial disease.

Discussion

Several workers have found that there may be re-

duced reflex and drug responses of heart rate in

patients with^ slow atrial arrhythmias or sick sinus

syndrome (Brasil, I955; Shaw and Eraut, I969;

Sinus bradycardia 795

Eraut and Shaw,^ I97I; Easley and Goldstein,^ I97I;

Mandel et al., 1972). Whether the responses so defined were reduced relative to normal is less definite since no control group data have been pub-

lished. Mandel et al. (I97I) did however use post-

pacing suppression to confirm subnormal atrial pacemaker function in their patients. After atrial pacing, good sinoatrial function is attended by early atrial takeover and poor function by delayed take- over. The results of the present work show that there are two groups of patients with sinus bradycardia, those with normal reflex and drug responses and those with (^) reduced responses. When these tests are used to differentiate two groups the inclusion of

patients with probable physiological bradycardia has

perhaps tended to reduce the statistical significance of some results. The results of this work suggest that those with the (^) presented evidence of reduced atrial pacemaker function are^ liable^ to^ Adams-Stokes^ attacks.^ In-

adequacy of lower pacemaking sites may be^ impor-

tant in the production of Adams-Stokes syncope in these patients. Those with normal atrial pace- maker responses may have been subject to syncope

of vasomotor origin, but not to Adams-Stokes

attacks.

On the basis of drug responses alone, all patients

with (^) Adams-Stokes attacks had evidence of reduced

sinoatrial automaticity. Of the^8 patients found^ to

have Adams-Stokes attacks, 4 had no^ electro-

cardiographic evidence other than sinus brady-

cardia to suggest reduced atrial pacemaker function.

One other had a P wave abnormality alone while 3

others had both P wave abnormalities and atrio-

ventricular nodal rhythm at^ times.

P wave abnormalities, atrial fibrillation, sinoatrial

block, and sinus arrest have been found^ to^ occur

commonly in association with defective sinoatrial

pacemaker function. The same abnormalities were

found, however, in some with normal atrial func-

tion, suggesting either the physiological origin of

these arrhythmias or defects not detected by the

present investigations.

Since no^ pathological data^ are^ available^ at^ present,

it remains to^ be^ shown^ that^ reduced^ responses to

autonomic stimuli are associated with recognizable

atrial pathology. From the present work^ one^ may

deduce only that there^ is^ a^ disturbance^ of atrial

pacemaker function^ in^ some^ patients. The^ available

evidence (^) suggests that sinus (^) arrest, atrioventricular

nodal rhythm, etc. (sick sinus syndrome) are asso-

ciated with atrial pathology (Brasil, I955; Rossi,

I969).

Some patients in this series were paced up to I

minutes before investigation. The^ influence of^ long-

term ventricular pacing on atrial pacemaker func-

tion is unknown. In short-term atrial pacing it is characteristic for atrial rhythm to return within

seconds after^ the^ cessation of^ pacing^ (Mandel^ et^ al.,

197I). In this series those paced for syncope due to a sinoatrial problem were the most likely to have an abnormality. One paced patient was^ found^ to^ have

supernormal autonomic^ responses^ whereas^ others

had only minor^ abnormalities of^ function.^ The find- ing of reduced responses in unpaced patients shows that the phenomenon is not solely pacing in- duced. In the absence of any known mechanism for

atrial pacemaker suppression by ventricular pacing

it must be assumed that reduced responses to

autonomic stimuli are^ most^ probably caused^ by^ a

disturbance of atrial pacemaker cells themselves. Nine of the patients with defective sinoatrial pacemaker function were found to have an atrio-

ventricular conduction defect, suggesting that

' sinoatrial disease' is part of a widespread conduct- ing tissue disease. As in complete heart block idio-

pathic fibrosis may possibly be the commonest cause

of sinoatrial disease.

The benefit of^ performing reflex^ tests^ lay in the

opportunity afforded to^ observe^ the^ occurrence of

arrhythmias. During these tests, nodal escape,

implying lesser automatic function in the atrial

pacemaking sites, sinus arrest, and supraventricular

tachycardias were occasionally seen, often with re-

production of the patients' symptoms. Some clue

as to the mechanism of the patients' dizzy spells,

palpitations, or^ syncope was^ thus^ discovered.^ In

some cases many hours^ of^ ward^ monitoring had

failed to reveal a significant arrhythmia.

Isoprenaline infusion, as a bolus infusion, proved

to be the most useful quantitative discriminating test

of atrial pacemaker function. With the dose given

occasional ectopics were seen and then only for a

short period. The response lasted 2 tO 3 minutes and

at worst caused only brief palpitation. The present

results do not support the results of Mandel et al.

(I972), i.e. that^ good responses^ are^ obtained^ in all

patients with^ sinoatrial disease^ or^ sick^ sinus^ syn-

drome. The doses of^ isoprenaline used in this study

were much smaller however. Their^ method of con-

tinuous drip infusion of isoprenaline was not em-

ployed since it is difficult to standardize and is more

liable to cause prolonged symptoms and^ arrhythmia. The results of the^ present work^ agree with those of

Brasil (I955) and of Eraut and Shaw (I97I) in

showing that^ patients with sick sinus^ syndrome^ have

reduced responses to isoprenaline.

The lack of control data in previous work may

have led to the conclusion that^ atrial^ responses to

atropine are reduced in^ 'sick^ sinus^ syndrome'. In

the control subjects studied^ the range of^ normal

Sinus bradycardia 797

autonomic influence. This group might, therefore, be regarded as having a physiological bradycardia and probably form the commonest naturally occur- ring group. As with other normal persons, they may be subject to vasomotor syncope, but not to Adams- Stokes syncope. The atrioventricular nodal rhythm and sinus arrest in these cases may be physiological in origin and caused by a spontaneous mechanism involving vagal stimulation (Hoffnan and^ Crane- field, i960). Some patients in this group may have sinoatrial disease, but with normal function in the dominant atrial pacemaker. Long-term follow-up may answer this question. Widespread atrial damage is probably necessary to produce an abnormality in the results of the tests described.

b) Vagotonia: one case (Case 14) One patient was seen to^ have^ 'supernormal' reflex^ and^ drug^ re- sponses. Since the^ vagal tone^ usually predominates at rest, this patient may have^ truly increased^ vagal tone accounting for his bradycardia. This^ type is probably rare.

It is suggested that the evaluation of^ atrial^ pace- maker function is of clinical value in^ patients pre- senting with bradycardia and syncope. The tests presented are at present in routine use for both^ inpatients and^ outpatients of^ this^ depart- ment.

The author is indebted'^ to^ Dr.^ Aubrey Leatham^ for^ his help, criticism, and^ advice; to^ Dr.^ Brian^ Robinson for his help during the planning stage of this^ work; and^ to^ Dr. Alan Harris and Mr. H.^ Siddons^ for^ their^ advice^ and comments.

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