Br Heart J: first published as 10.1136/hrt.36.8.791 on 1 August 1974. Downloaded from

British Heart,Journal, I974, 36, 79I-797. Sinus 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 . 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 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. http://heart.bmj.com/

Although most patients presenting with sinus I967; Grodner et al., I970). The presence of the bradycardia are asymptomatic, some present with enzyme cholinesterase may be of importance in the syncope or dizzy spells. Physiological bradycardia is control of the since it is responsible for the usually of no clinical significance except when seen hydrolysis of acetylcholine and can be demonstrated in association with vasomotor syncope. When a in active form in the and atrium patient presents with Adams-Stokes syncope and (James and Spence, I966).

sinus bradycardia the problem is to differentiate Patients presenting with sinus bradycardia have on September 29, 2021 by guest. Protected copyright. the bradycardia of physiological origin from that been investigated by using various reflex tests and which may be associated with some atrial pathology. by infusion of drugs acting on the autonomic system The aim of the present work has been to investi- and atrial pacemaking sites. gate the autonomic influences acting in sinus brady- cardia and to develop routine tests useful in differ- Selection of subjects and methods entiating the physiological from the pathological Sixteen healthy adults volunteered as control subjects type of bradycardia caused by atrial disease. The after being fully informed about the nature of the in- tests described have developed from the need to vestigation. assess the clinical significance of sinus bradycardia Twenty-four patients with a persistent bradycardia in patients with syncopal attacks. at rest of less than 55 a minute were investigated The sinoatrial node and atrium are richly inner- after giving fully informed consent. No patient was ad- vated by both sympathetic and parasympathetic mitted to the investigation if the bradycardia could be et the related to drug therapy, untreated , nerve fibres (Grodner al., I970; James, I967), raised , recent cardiac infarction, or pacemaker cells being directly affected by the cerebrovascular accident. Some patients presented with release of the acetylcholine and catecholamines symptoms while others were found to have a persistent (James and Nadeau, I963; Hoffman and Cranefield, resting sinus bradycardia on routine electrocardio- I960; Toda and Shimamoto, I968; Toda and West, graphy. Patients with fixed rate pacemakers were ex- Received 5 March I974 cluded while some with demand pacemakers were Br Heart J: first published as 10.1136/hrt.36.8.791 on 1 August 1974. Downloaded from

792 David H. Dighton

included. This selection was necessary since only demand grams (5 to I0 second strips) were taken every 5 minutes pacemakers may be externally inhibited allowing the until 20 minutes after injection. At 20 minutes after atro- underlying spontaneous rhythm to manifest itself. pine the dose ofprostigmine was given. After the dose of All subjects were examined and weighed before in- prostigmine, io-second recordings were made every vestigation. Those with demand pacemakers had their minute for I0 minutes. units inhibited by an external pulse generator attached The electrocardiograms were analysed for atrial rate at least IS minutes before investigation. with a standard rate calculating ruler. The control rates were taken as an average offive measurements during the a) Reflex tests control period before each dose, only regular being acceptable during this period. In the With a continuous electrocardiographic recording (lead case of both atropine and isoprenaline the atrial rate was chosen to show largest P waves), all subjects performed analysed with one measurement at every 3-second inter- simple manoeuvres designed to stimulate the dominant val during the first minute. Further measurements were atrial pacemaker by autonomic reflexes. Recording made at is-second intervals for a further 2 minutes. started io to i5 seconds before the reflex test and was Thereafter, in the case ofatropine, measurements ofatrial continued throughout and for I0 seconds after each rate were made at 5-minute intervals until prostigmine manoeuvre. Recordings were made with quiet res- was given. During this analysis changes in rhythm or P piration, forced inspiration (with breath held in in- wave morphology were noted. During the prostigmine re- spiration for a minimum of I5 seconds), a Valsalva sponse an average of five measurements was made at one manoeuvre, using a sphygmanometer blown up to 40 minute intervals. mmHg, for a minimum of iS seconds and continued The results were plotted as atrial rate against time in for as long as possible; right and left carotid sinus each case. Atrial response was assessed in two ways: pressure continued until maximum response was ob- i) the maximum or minimum rate obtained above or tained (up to I0 seconds usually); and straight leg below the mean control rate, and ii) the maximum rate raising for 30 seconds. All the tests were performed in the of rise or fall in atrial rate during the response. This was sitting position on a couch or bed. The electrocardio- estimated from a gradient drawn through the steepest grams obtained were analysed for atrial rate using a four standard rate calculating ruler averaging two consecutive points on the response curve. PP intervals. The control rate was taken as the average ofthree measurements. Tne maximum or minimum rates Results during and after the manoeuvres were noted and ex- The ages, sex, mean resting heart rates, electro- pressed as the rate difference above or below the control cardiographic features, clinical features, and past rate. Any changes in P wave morphology or changes in history of both controls and those with sinus http://heart.bmj.com/ rhythm were noted. As far as possible recordings were made only during regular sinus rhythm. Recordings bradycardia are given in Table i. with nodal rhythm or some irregular rhythm were re- Seven patients presenting with sinus bradycardia jected and the manoeuvre repeated. were found to have P wave abnormalities; 4 having flat or bifid P waves (voltage less than Oi mV) with b) Drug tests 3 others having P waves of greater duration than normal (o-i6 A PR After the reflex tests, with the patient supine and at rest, sec). interval greater than 02 sec intravenous bolus injections of the following drugs were was seen in 8 patients, no higher degrees of AV made into a normal saline intravenous infusion. block being seen. A QRS duration greater than on September 29, 2021 by guest. Protected copyright. i) 5 ,Lg isoprenaline per 70 kg body weight (prepared in o0i sec was seen in 5 patients each with right bundle- 2 ml vials, 5 jig/ml containing sodium metabisulphate); branch block and . His bundle ii) 0-02 mg atropine sulphate per kg body weight; iii) electrograms showed normal His to ventricular o-8 mg prostigmine per 70 kg body weight given 20 activation times in these patients. minutes after the dose of atropine. The drugs were given in the order shown and flushed Reflex tests in with not more than 2 ml normal saline. A period of approximately I0 minutes elapsed between the doses of The changes in atrial rate with the various reflex isoprenaline and atropine while the heart rate returned manoeuvres are shown in Table 2. No significant to previous control level. Only one dose of each drug quantitative difference could be shown between the was given. control responses to quiet breathing, forced inspira- The doses given were chosen to give an easily measur- tion or straight leg raising, and those presenting with able response without resulting in undue side effects. sinus bradycardia. While the increase in rate during The dose of prostigmine was suggested by the work of a Valsalva manoeuvre was not significant, the total Fielder et al. (I969). drop in rate after the manoeuvre was significantly Electrocardiograms were made continuously, io seconds before and I minute after the dose of isoprena- less in the sinus bradycardia group. line. Only regular sinus rhythm was accepted as suitable Qualitative changes during the reflex responses during the control period. The same procedure was were not seen in the control group. In the sinus followed for the atropine dose but further electrocardio- bradycardia group various changes were seen. Br Heart J: first published as 10.1136/hrt.36.8.791 on 1 August 1974. Downloaded from

Sinus bradycardia 793

TABLE I Clinicalfeatures sinus bradycardia During forced inspiration atrioventricular nodal rhythm was seen in 4, while sinus arrest was seen in Controls Sinus bradycardia one. During right carotid sinus pressure atrio- ventricular nodal rhythm was seen in 3, with sinus Number of patients I6\8 female 24 I2 male arrest occurring in i patient. Similar responses were Age range I7-70 yr 29-77 yr observed with left carotid sinus pressure, atrio- mean 52 yr mean 6I yr ventricular nodal rhythm occurring in 2 and sinus Mean resting atrial rate 74 5/min 471i/min arrestvoccurring in 2 others. Number with past history of: Adams-Stokes syn- cope 0 I0 Drug tests (Table 2) Vasomotor syncope o 6 Cardiac pain o 5 I) Isoprenaline response Both the increase in Myocardial infarc- atrial rate and the maximum rate of change of atrial tion 0 3 rate were significantly lower in the sinus brady- 0 3 cardia group than in the control subjects (P < o Rheumatic fever 0 I oi) Epilepsy o I (Table 2). No P wave changes were seen in the con- Hypothyroidism trols during this response nor were any (treated) o I observed. The PR interval did not vary in any con- Electrocardiographic features trol subject. In one control subject the be- Atrial o I2 came flat. Atrioventricular conduction defect o I2 Of the 22 subjects with sinus bradycardia, I4 Ischaemia o 4 failed to achieve atrial rates within control range Cardiac infarction o 3 (Table 2) (Cases I, 3, 5, 6, 8, 9, 12, I3, I5, I7, i8, Number requiring pacemakers 20, 22, 24). One patient (Case io) spontaneously (permanent systems) o 9 reverted to atrial after the reflex tests and was therefore not tested further. In another TABLE 2 Results of reflex and pharmacological tests in sinus bradycardia

Investigation Change in atrial rate relative to control rate http://heart.bmj.com/ Controls Sinus bradycardia P Mean Range Mean Range t-test Respiratory arrhythmia 9gI7/min 3, i8/min 5-5/min 2, 20/min >O-I Forced inspiration - 4.75 +7,-26 - 2.67 +23,-26 <011 Valsalva on September 29, 2021 by guest. Protected copyright. (during) +23-64 +I0,+47 + I4-2 -2i,,+44 0 2 Isoprenalne (a) +30 5 +22,,+39 + 9-I +4,+40 <001I Isoprenaline r (b) + I*9 +0o9g+3 0 + I-07 +0-01,+3 0 < 0-02 (a) +34 75 +14,+53 +31.46 +I2,+70 >0 2 Atropine nodal (b) + I-97 +o-85,+2-8 + I199 +0o3,+8 7 >0-2 Prostigmine t (a) -25-6 -1_5,-46 - i6-8 -50,-57 > 0 2 f(b) - 3.9* -3,-5.7* - 2.9* - 028, -io* >0O2

(a) Increase in atrial rate (beats/minute). (*beats/mijn/min)(b) Rate of change of atrial rate (beats/min/sec) Br Heart J: first published as 10.1136/hrt.36.8.791 on 1 August 1974. Downloaded from

794 David H. Dighton patient (Case 14) the rate achieved was above control 17, 20, 23). Two were satisfactorily controlled with range. long-acting isoprenaline (Cases 3, i6). These On the basis of decreased rate of change of atrial patients all had below normal atrial responses and rate II patients had responses below normal range are therefore likely to have sinoatrial disease or (Cases I, 3, 5, 6, I2, I13, 15, i6, 17, I9, 23). One had 'sick sinus syndrome'. an above normal response (Case I4), the remaining Of the I0 patients with both reduced reflex and responses falling within control range. drug responses, 5 had an abnormality of either P In 2 patients frequent change in P wave shape wave voltage or morphology (Cases 3, 8, I3, I7, 23), occurred (Cases I I, 23), with atrioventricular nodal 2 had evidence of (Cases 6, i6), 2 rhythm occurring at times in 5 (Cases 6, II, I2, of sinus arrest (Cases 8, 17), one of paroxysmal I3, i6). Supraventricular ectopics were frequently (Case 13), and 4 had atrioven- observed in three (Cases I, 3, 6). tricular nodal rhythm at times (Cases, i6, I7, 21, 23). Of the I0 cases with reduced responses, 4 had 2) Atropine responses No significant difference evidence of right bundle-branch block with left (P > o02) was found with either the increase in axis deviation but no prolongation of His to ven- atrial rate or in the maximum rate of change of tricular activation time. There was, therefore, no atrial rate between the control and sinus brady- electrophysiological evidence oftrifascicular bundle- cardia groups. Only one patient had a response branch disease in these cases. Since one patient also below the normal range (Table 2) (Case I2) and had first-degree with a PR one had a response above normal range (Case 14). interval of 0-32 to 0'4 sec, 5 of the I0 patients with With respect to the rate of change of atrial rate with reduced reflex and drug responses had evidence of atropine, 5 patients had responses below the control abnormal atrioventricular conduction. range (Table 2) (Cases I, I3, I5, 20, 24), 3 of whom There were 6 patients with reduced drug re- exhibited atrioventricular nodal takeover (Cases I, sponses but normal reflex tests (Cases I, 2, 5, I2, I3, 20). I5, 22). One of these had abnormal P waves with In the control group atrioventricular nodal take- intermittent sinus arrest (Case 5), 3 had nodal over occurred in one subject. In most subjects the rhythm at times (Cases I, I2, I5), 2 had right PR interval decreased by o0o4 sec. Nodal takeover bundle-branch block with left axis deviation (Cases was observed in 8 patients (Cases I, 3, 6, I2, I4, I, I5), and 2 had prolonged PR intervals (Cases 5, http://heart.bmj.com/ i6, I9, 20), with P wave variation occurring in one 22). None was seen to have either sinoatrial block or case (Case 23). atrial fibrillation. Of these 6, 5 had a history of Adams-Stokes attacks (Cases 2, 5, I2, I5, 22), with 3 3) Prostigmine responses Prostigmine was seen requiring pacing (Cases 5, I2, 22). This association to return the atrial rate to preatropine levels only. makes it likely that these patients have sinoatrial When those with sinus bradycardia are compared disease or 'sick sinus syndrome'. One was con- with controls, the differences between the drop in trolled with long-acting isoprenaline (Saventrine). atrial rate and the rate of change of atrial rate One only had a history of fainting episodes. on September 29, 2021 by guest. Protected copyright. fail to reach significant levels (P > o I). Eight patients (Cases 4, 7, 9, I0, II, I4, i8, I9) In I3 of the sinus bradycardia group the decrease were found to have no evidence of reduced atrial in atrial rate observed was below the normal range pacemaker function. Of these, 3 had syncope which (Table 2, Cases 2, 3, 5, 6, 7, 8, I2, I6, 17, 20, 2I, was thought to be vasomotor in type (Cases 4, II, 23, 24). One patient (Case 14) decreased his atrial 14) rather than Adams-Stokes syncope. Three had rate greater than any control subject. paroxysmal atrial fibrillation, one had occasional Fourteen patients had a decrease in the rate of atrioventricular nodal rhythm, and one other had change of atrial rate below the control range (Cases periods of sinus arrest (Case II). While 2 of these I, 2, 3, 5, 6, 12, I3, i6, 17, 20, 2I, 22, 23, 24). Four patients had first-degree atrioventricular block, none patients had responses greater than the control had evidence of bundle-branch block. These range in this respect (Cases 4, 9, 14, I9). patients have either physiological sinus bradycardia or undetectable sinoatrial disease. Results and clinical features Of the io patients that had both reduced reflex and Discussion drug responses (Cases 3, 6,8, 13,i63, I7, 20, 21, 23, Several workers have found that there may be re- 24), 5 had a history of Adams-Stokes attacks (Cases duced reflex and drug responses of heart rate in 3, 6, I3, I7, 20) and 2 a history of fainting attacks patients with slow atrial arrhythmias or sick sinus (Cases 3, 8), with 5 requiring pacing (Cases 6, 13, syndrome (Brasil, I955; Shaw and Eraut, I969; Br Heart J: first published as 10.1136/hrt.36.8.791 on 1 August 1974. Downloaded from

Sinus bradycardia 795

Eraut and Shaw, I97I; Easley and Goldstein, I97I; term ventricular pacing on atrial pacemaker func- Mandel et al., 1972). Whether the responses so tion is unknown. In short-term atrial pacing it is defined were reduced relative to normal is less characteristic for atrial rhythm to return within definite since no control group data have been pub- seconds after the cessation of pacing (Mandel et al., lished. Mandel et al. (I97I) did however use post- 197I). In this series those paced for syncope due to a pacing suppression to confirm subnormal atrial sinoatrial problem were the most likely to have an pacemaker function in their patients. After atrial abnormality. One paced patient was found to have pacing, good sinoatrial function is attended by early supernormal autonomic responses whereas others atrial takeover and poor function by delayed take- had only minor abnormalities of function. The find- over. ing of reduced responses in unpaced patients The results of the present work show that there shows that the phenomenon is not solely pacing in- are two groups of patients with sinus bradycardia, duced. In the absence of any known mechanism for those with normal reflex and drug responses and atrial pacemaker suppression by ventricular pacing those with reduced responses. When these tests are it must be assumed that reduced responses to used to differentiate two groups the inclusion of autonomic stimuli are most probably caused by a patients with probable physiological bradycardia has disturbance of atrial pacemaker cells themselves. perhaps tended to reduce the statistical significance Nine of the patients with defective sinoatrial of some results. pacemaker function were found to have an atrio- The results of this work suggest that those with ventricular conduction defect, suggesting that the presented evidence of reduced atrial pacemaker ' sinoatrial disease' is part of a widespread conduct- function are liable to Adams-Stokes attacks. In- ing tissue disease. As in complete idio- adequacy of lower pacemaking sites may be impor- pathic fibrosis may possibly be the commonest cause tant in the production of Adams-Stokes syncope of sinoatrial disease. in these patients. Those with normal atrial pace- The benefit of performing reflex tests lay in the maker responses may have been subject to syncope opportunity afforded to observe the occurrence of of vasomotor origin, but not to Adams-Stokes arrhythmias. During these tests, nodal escape, attacks. implying lesser automatic function in the atrial On the basis of drug responses alone, all patients pacemaking sites, sinus arrest, and supraventricular with Adams-Stokes attacks had evidence of reduced were occasionally seen, often with re-

sinoatrial automaticity. Of the 8 patients found to production of the patients' symptoms. Some clue http://heart.bmj.com/ have Adams-Stokes attacks, 4 had no electro- as to the mechanism of the patients' dizzy spells, cardiographic evidence other than sinus brady- palpitations, or syncope was thus discovered. In cardia to suggest reduced atrial pacemaker function. some cases many hours of ward monitoring had One other had a P wave abnormality alone while 3 failed to reveal a significant arrhythmia. others had both P wave abnormalities and atrio- Isoprenaline infusion, as a bolus infusion, proved ventricular nodal rhythm at times. to be the most useful quantitative discriminating test P wave abnormalities, atrial fibrillation, sinoatrial of atrial pacemaker function. With the dose given

block, and sinus arrest have been found to occur occasional ectopics were seen and then only for a on September 29, 2021 by guest. Protected copyright. commonly in association with defective sinoatrial short period. The response lasted 2 tO 3 minutes and pacemaker function. The same abnormalities were at worst caused only brief palpitation. The present found, however, in some with normal atrial func- results do not support the results of Mandel et al. tion, suggesting either the physiological origin of (I972), i.e. that good responses are obtained in all these arrhythmias or defects not detected by the patients with sinoatrial disease or sick sinus syn- present investigations. drome. The doses of isoprenaline used in this study Since no pathological data are available at present, were much smaller however. Their method of con- it remains to be shown that reduced responses to tinuous drip infusion of isoprenaline was not em- autonomic stimuli are associated with recognizable ployed since it is difficult to standardize and is more atrial pathology. From the present work one may liable to cause prolonged symptoms and arrhythmia. deduce only that there is a disturbance of atrial The results of the present work agree with those of pacemaker function in some patients. The available Brasil (I955) and of Eraut and Shaw (I97I) in evidence suggests that sinus arrest, atrioventricular showing that patients with sick sinus syndrome have nodal rhythm, etc. (sick sinus syndrome) are asso- reduced responses to isoprenaline. ciated with atrial pathology (Brasil, I955; Rossi, The lack of control data in previous work may I969). have led to the conclusion that atrial responses to Some patients in this series were paced up to I5 atropine are reduced in 'sick sinus syndrome'. In minutes before investigation. The influence of long- the control subjects studied the range of normal Br Heart J: first published as 10.1136/hrt.36.8.791 on 1 August 1974. Downloaded from

796 David H. Dighton responses to atropine was large, thus diminishing 8 had clinical evidence of probably significant the usefulness of atropine infusion as a clinical test aetiological factors. Two had resting electrocardio- of atrial pacemaker function. Since atropine com- graphic evidence ofischaemic heart disease (Cases 2, petitively inhibits acetylcholine it may be that there 23), 2 had previous inferior cardiac infarction is no atrial abnormality in atrial acetylcholine in (Cases 2, 5), 3 had diphtheria as children (Cases 3, sinoatrial disease - that is if the heart rate response 10, 24), one (Case 2), one was pre- to atropine is directly related to the amount oftrans- sumed to have influenza requiring admittance to mitter present. hospital (Case 4), while one other had treated It is possible that atrial cholinesterase activity is myxoedema (Case 20). Of the 3 patients with reduced in sinoatrial disease, thus leading to a build- ischaemic heart disease, one had first-degree atrio- up of acetylcholine in atrial tissues. This would ventricular block (Case 5). Since pathological data cause bradycardia and perhaps result in a change of are not available, the presence, nature, and aetiology the dominant atrial pacemaker site. In the pre- of any atrial disease entity has yet to be established. sence of a local build-up of acetylcholine, atropine As a result of this investigation, one might postu- might increase the atrial rate more than anticipated late three states of atrial pacemaker function result- even in the presence of less automatic pacemaker ing in chronic resting sinus bradycardia (unrelated cells. This consideration makes speculation about to drug therapy, cardiac infarction, etc.). the role of acetylcholine in sinus bradycardia all the more difficult. Prostigmine lowers the atrial rate by inhibition I) Sinoatrial disease (sick sinus syndrome) of cholinesterase, thereby increasing the avail- Sixteen cases (Cases I, 2, 3, 5, 6, 8, I2, 1533, , i6, ability of acetylcholine. The response is thus deter- I7, 20, 2I, 22, 23, 24) had sinoatrial disease. mined by the activity of the local enzyme to- Sinus bradycardia may be due to reduced atrial gether with the availability and atrial sensitivity pacemaker function, the best of the pacemaker sites to acetylcholine. As there is demonstrable activity in the atrium being unable to respond normally of cholinesterase in the atrium of animals and either to direct drug or to reflex stimulation. Be- humans (Csapo, I970; James and Spence, I966), cause of the reduced response to some reflexes in normal responses to atropine, associated with de- this group, one cannot exclude additional primary creased responses to prostigmine in some patients, disease of the autonomic atrial nerve supply. Histo- may indicate reduced activity of atrial cholinesterase logical evidence for atrial autonomic nerve damage http://heart.bmj.com/ in sinoatrial disease. It is possible that reduced has been obtained by Rossi (1969). Reduction in activity of atrial cholinesterase alone could account atrial cholinesterase may be important and explain for some forms of sinus bradycardia. Diphtheria the decreased responses to prostigmine, the often , previously a cause of sinus bradycardia normal response to atropine, and the occasional in man has been shown to be associated with in- paradoxical finding of sinus arrest with carotid sinus active atrial cholinesterase in rabbits (Maliovanova, pressure in patients with otherwise reduced reflex I968). responses. Patients with reduced pacemaker func- Whereas, with carotid sinus pressure, sinus arrest tion may have Adams-Stokes attacks, and have an on September 29, 2021 by guest. Protected copyright. might be caused by abnormal carotid sinus sensi- associated atrioventricular conduction disorder. A tivity, it might possibly be caused by either abnormal phase of increased excitability of damaged pace- atrial sensitivity to acetylcholine or by excess local maker cells may account for associated fast rhythms build-up of acetylcholine resultant on the inactiva- in some patients. tion of atrial cholinesterase. The finding of reduced responses to prostigmine in 3 ofthe 4 patients found to have sinus arrest on carotid sinus pressure sup- 2) Physiological bradycardia ports the latter theory. Seven cases (Cases 4, 7, 9, I0, II, i8, I9) had One patient having sinus arrest with carotid sinus physiological bradycardia. pressure had supersensitive responses to all re- flexes and to atropine, isoprenaline, and prostigmine. a) Low rate setting: normal pacemaker func- This supports the possibility of increased sensi- tion Atrial pacemaker function may be normal, tivity to both sympathetic and vagal neurotrans- with no evidence of either an increased response to mitters in this case. Sinus bradycardia might, atropine or vagal withdrawal to suggest 'vagotonia', therefore, be caused by vagal supersensitivity in or a lack of sympathetic drive as a cause of brady- some cases. cardia. It is possible that these patients may have Of the I6 patients found to have reduced atrial atrial pacemaker rates set at a lower rate than nor- pacemaker function on the basis of drug responses, mal while retaining normal pacemaker function and Br Heart J: first published as 10.1136/hrt.36.8.791 on 1 August 1974. Downloaded from

Sinus bradycardia 797 autonomic influence. This group might, therefore, Easley, R. M., and Goldstein, S. (197I). Sino-atrial syncope as having a physiological bradycardia American Journal of Medicine, 50, I66. be regarded Eraut, D., and Shaw, D. B. (I97I). Sinus bradycardia. and probably form the commonest naturally occur- British Heart_Journal, 33, 742. ring group. As with other normal persons, they may Fielder, D. L., Nelson, D. C., Andersen, T. W., and Graven- be subject to vasomotor syncope, but not to Adams- stein, J. S. (i969). Cardiovascular effects of atropine and neostigmine in man. Anesthesiology, 30, 637. Stokes syncope. The atrioventricular nodal rhythm Grodner, A. S., Lahrtz, H.-G., Pool, P. E., and Braunwald, E. and sinus arrest in these cases may be physiological (I970). Neurotransmitter control of sino-atrial pacemaker in origin and caused by a spontaneous mechanism frequency in isolated rat atria and in intact rabbits. Circu- involving vagal stimulation (Hoffnan and Crane- lation Research, 27, 867. Hoffman, B. F., and Cranefield, P. (I960). Electrophysiology field, i960). of the Heart. McGraw-Hill, New York. Some patients in this group may have sinoatrial James, T. N. (I967). Cardiac innervation: anatomic and disease, but with normal function in the dominant pharmacologic relations. Bulletin of the New York Academy atrial pacemaker. Long-term follow-up may answer of Medicine, 43, I041. James, T. N., and Nadeau, R. A. (I963). Sinus bradycardia this question. Widespread atrial damage is probably during injections directly into the sinus node artery. necessary to produce an abnormality in the results of American Journal of Physiology, 204, 9. the tests described. James, T. N., and Spence, C. A. (I966). Distribution of cholinesterase within the sinus node and A-V node of the b) Vagotonia: one case (Case 14) One patient was human heart. Anatomical Record, ISS, I5I. Maliovanova, S. D. (I968). Cholinesterase activity of the ner- seen to have 'supernormal' reflex and drug re- vous apparatus and myocardium of the rabbits heart sponses. Since the vagal tone usually predominates during experimental diphtheritic myocarditis. Doklady at rest, this patient may have truly increased vagal Akademnit Nauk SSSR, 178, 2I3. tone accounting for his bradycardia. This type is Mandel, W. J., Hayakawa, H., Allen, H. N., Danzig, R., and Kermaier, A. I. (I972). The assessment of sinus node probably rare. function in patients with the sick sinus syndrome. Circu- lation, 46, 76I. It is suggested that the evaluation of atrial pace- Mandel, W., Hayakawa, H., Danzig, R., and Marcus, H. S. maker function is of clinical value in patients pre- (I97i). Evaluation of sino-atrial node function in man by senting with bradycardia and syncope. overdrive suppression. Circulation, 44, 59. are in use Rossi, L. (I969). Disturbances in impulse conduction, sino- The tests presented at present routine atrial arrest, sinu-atrial block, sinus arrest and atrial stand- for both inpatients and outpatients of this depart- still. In Histopathologic Features of Cardiac Arrhythmias,

ment. pp. 126-I3I. Casa Editrice Ambrosiana, Milan. http://heart.bmj.com/ Shaw, D. B., and Eraut, D. (I969). Atrial bradycardia or the The author is indebted' to Dr. Aubrey Leatham for his lazy sinus syndrome. Bristol Medico-Chirurgical J7ournal, and to Dr. Brian Robinson for his 84, 213. help, criticism, advice; Toda, N., and Shimamoto, K. (I968). The influence of help during the planning stage of this work; and to Dr. sympathetic stimulation on transmembrane potentials in Alan Harris and Mr. H. Siddons for their advice and the S-A node. Journal of Pharmacology and Experimental comments. Therapeutics, IS9, 298. Toda, N., and West, T. C. (I967). Interactions of K, Na, and References vagal stimulation in the S-A node of the rabbit. American

Journal of Physiology, 212, 416. on September 29, 2021 by guest. Protected copyright. Brasil, A. (I955). Autonomic sino-atrial block. A new dis- turbance of the heart mechanism. Arquivos Brasileiros de Cardiologia, 8, I59. Requests for reprints to Dr. D. H. Dighton, Depart- Csap6, G. (1970). Changes of myocardial enzyme activities in ment of , Charing Cross Hospital, Fulham atrial fibrillation. British Heart Journal, 32, 76I. Palace Road, London W6 8RF.