Significance of the Sinus-Node Recovery - …circ.ahajournals.org/content/circulationaha/45/1/140...Significance of the Sinus-Node Recovery Time By ONKAR S. NARULA, M.D., PHILIP SAMET,

Significance of the Sinus-Node Recovery TimeBy ONKAR S. NARULA, M.D., PHILIP SAMET, M.D., AND ROGER P. JAVIER, M.D.

SUMMARYThe phenomenon of postpacing depression of cardiac pacemakers was utilized to

evaluate the sinus-node function in 56 patients by analyzing the sinus-node recoverytime (SRT), that is, the interval between the last paced P wave and the followingsinus P wave. Corrected SRT (CSRT) is defined as the recovery interval in excess ofthe sinus cycle (SRT -sinus cycle length). The SRT was measured following sinus-node suppression by (1) isolated premature beats (PABs) and (2) atrial pacing(AP) at rates of 100 to 140/min for periods of 2 to 5 min at each level. Twenty-eight patients had normal heart rates (group A), and 28 patients had sinus bradyeardia(SB; group B). Ten of the 28 patients with SB were restudied after receiving atropine(2 mg intravenously). The CSRT with PABs was similar in both group A and groupB patients and remained essentially unchanged after atropine despite a decrease insinus cycle length. The phenomenon of interpolated PABs was demonstrated in sevenof the 56 patients. In 27 of the 28 patients with normal heart rates (group A), theCSRT with AP ranged from 110 to 525 msec and was essentially independent ofthe rate and duration of AP. In the remaining one patient of group A, despite anormal heart rate, the CSRT was prolonged (1810 msec) and directly dependenton the rate and duration of AP. In 12 of the 28 patients with SB, the CSRT was

comparable to that in group A (<525 msec). In the remaining 16 patients with SB(group B), the CSRT ranged from 560 to 3740 msec and was usually directly pro-

portional to the rate and duration of AP. After atropine in most of the patients witha prolonged CSRT, the CSRT remained abnormal whereas in others junctional escapebeats appeared first, followed eventually by normal sinus rhythm. In a single patientwith SB and an abnormal CSRT, restudy 7,i months later again showed a prolongedCSRT indicating the reproducibility of the measurement. The CSRT with AP providesa potentially useful clinical means of assessing the sinus-node function and therebyaids in the diagnosis of the "sick sinus syndrome." It is stressed that AP was foundto be more reliable than PABs in eliciting an abnormal response. Furthermore, a

normal sinus (atrial) rate does not necessarily provide assurance of a normal sinus-node response to AP, that is, normal sinus-node function.

Additional Indexing Words:Sinus-node function Atrial pacing

THE VARIOUS clinical and ECG mani-festations of disorders of sinus-node

function include sinoatrial block, sinus pauses.or sinus arrest, sinus bradyeardia, and thebrady-tachyarrhythmia syndrome. These con-

stitute the sick sinus syndrome.' This syn-

Sinus bradyeardia Atropine

drome has been known ever since theavailability of suitable recording instrumentspermitted differentiation from other forms ofbradyeardia. Although previously considered a

benign rhythm, it has gained clinical impor-tance due to several reports ascribing Stokes-Adams attacks to this syndrome.2 4 Interest in

From the Division of Cardiology, Department ofInternal Medicine, Mount Sinai Hospital of GreaterMiami, Miami Beach, Florida, and the University ofMiami School of Medicine, Miami, Florida.

Presented in part at the 55th Annual Meeting of theFederation of American Societies for ExperimentalBiology, Chicago, Illinois, April 12-17, 1971.

140

Address for reprints: Dr. Onkar S. Narula, Divisionof Cardiology, Department of Internal Medicine,Mount Sinai Hospital of Greater Miami, 4300 AltonRoad, Miami Beach, Florida 33140.

Received July 1, 1971; revision accepted forpublication September 14, 1971.

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SINUS-NODE RECOVERY TIME

patients with sinus bradyeardia or sick sinussyndrome has developed in view of availableeffective pacemaker therapy.;

Sinus bradyeardia (SB) may be a manifes-tation of one or more of the following threemechanisms : 7 8 ( 1) interactions of parasym-pathetic and sympathetic systems on the sinus-node automaticity; (2) poor function of thesinus node (SN) as an impulse generator; and(3) depressed conduction of the generatedimpulse from the sinus node to the atriumwith sinoatrial (SA) block.Thus far, the adequacy of sinus-node

function has been reflected primarily by theatrial rate during sinus rhythm. As yet, nomeans are available to record selectively and,if recorded, to validate the sinus-nodepotentials in man.The purpose of the present study is to

utilize the phenomenon of postpacing depres-sion of cardiac pacemakers to evaluate thesinus-node function by analyzing the sinus-node recovery time, that is, the intervalbetween the last paced P wave and thefollowing sinus P wave. The sinus-noderecovery time (SRT) was measured followingsinus-node suppression by (1) isolated prema-ture atrial beats (PABs) and (2) atrial pacing(AP), to provide quantitative measurementsin patients with normal and abnormal sinusnode. It should be stressed at the outset thatwve have used both AP and PABs to stress thesinus node and have found AP to be a morereliable means than PABs for use in thediagnosis of the sick sinus syndrome.

MethodsFifty-six patients (ranging in age from 16 to 90

years wvith mean age 61 vears) wvere studied.Group A included 28 patients with normal heartrates (table 1), and group B included 28patients with sinus bradyeardia (SB; table 2).Patients who showed a sinus rate of 55/mimi orless on more than one occasion were included inthe SB group. The electrocardiographic findingsand the cardiac medications are given in tables1 and 2.None of these patients had had a recent

myocardial infarction, that is, within 8 to 10weeks prior to the study, nor were anv in theimmediate postoperative period. All patients werestudied in the postabsorptive state and were

Circulation, Volumie XLV, January 1972

premedicated with 100 mg of pentobarbital(Nembutal), administered intramuscularly 30min prior to the study. One of these patients(case 38) was restudied 73 montlhs later.

Sinus recovery time (SRT) was measuredduring (1) premature atrial beats (PABs) and(2) after right atrial pacing (AP). Bipolarelectrograms (BE) were recorded from the highright atrium (RA) and the His bundle region(BH), simultaneous with three standard ECGleads (usually L-I, aVF, and V1). Right atrialstimulation was achieved from the high RAin the region of the sinus node. In the initial partof the study, pacing sites in the right atrium andstimulus strength were changed to assess theeffect of these factors, but no difference in theSRT was observed. Premature atrial stimuli, 2msec in duration and twice the diastolicthreshhold, were delivered after 12 to 14 sinuiscycles. The entire atrial cycle -,,as scanined bv theplacement of progressivelv more prematuire atrialbeats. All recordings were made at paper speedsof 100 to 200 mm/sec. After the entire atrialcycle had been explored by PABs, atrial pacing(AP) was performed at tvo or three differentheart rates, 100, 120, and 140/min for periods of2 and 5 min at each level. AP levels of over120/min were used only in selected patienits.Between each atrial pacing level a rest period of 2to 3 min vas given to alloxv the rhythm to returnto its basic levels. In our study, the sinus cveleusuallv returned to its control levels in less thani 1min. The blood pressure was monitored either viaan arterial needle or by a blood pressure cuffthroughout the studv.

In 10 of the 28 patients wvith sinus bradycardia,stuidies wvere performed after atropine (2 mg)wvas administer-ed intravenously. 'Measuremnentsxvere made 5 min after atropine administrationi toassess the effect of vagal tone and of alteringsinus rate on the SRT. After atropine, thestimulation sequence used xvith PABs durinlgcontrol study wvas repeated xvhereas atrial pacingwvas repeated only at a single level of 120/mim for2 or 5 min.

DefinitionsIn everv patient the intervals betwveen succes-

sive atrial depolarization were measured from thebipolar atrial electrograms. During each testcycle, the following intervals wvere measured: (1)A1A1 which is defined as the interval between thetxvo atrial electrograms of sinus origin; (2)average A1A1, xvhich is the average of 5 cycles(A1A1) measured preceding the PABs or AP; (3)A1A., the interval betxveen atrial electrograms ofsinus origin and the PAB; (4) A2A3, which is theinterval betwveen the PAB or the last atrial pacedP and the stucceedinig atrial electrogramii of sinus

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Case 24: Typical effect of prematurity (A1A.,) of PABson SRT (A.,A:) in group A patients. Initially there isa progressive increase in prematurity up to approxi-mately 75% of the sinuis cycle length. A further increasein prematurity is accompanied by little lengthening ofSRT and a plateau effect is seen. At RP = atrial abso-ltute refractory period.

origin and is defined as SRT; (5) the correctedSRT (CSRT) which is defined as the recoveryinterval in excess of the average sinus cycle length(SRT minus the average A1A1). In addition, thesinus cycle was measured for 5 or more cvelesfollowing the atrial stimulationi.

ResultsCorrected Sinus-Node Recovery Time (CSRT)After Isolated Premature Atrial Beats (PABs)Group A. In all 28 patients, the sinus cycle

length (A1A1) ranged from 600 to 920 msee(mean, 775). In all patients, as the A1A.,interval was shortened, the SRT (A,A.,) andthe CSRT (A2A3 - A1A1) were lengthenedprogressively to a point after which further

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decrease in the A1A2 interval resulted in noappreciable increase in CSRT but a plateaueffect was seen (fig. 1). This maximum effecton lengthening of CSRT was usually observedwhen A1A.2 ranged between 70 and 80% of thesinus cycle (range, 65 to 90%). The maximumCSRT following PABs was variable frompatient to patient and ranged from 100 to 370msec (mean, 197 ± 70) or 12 to 41% of thebasic sinus cycle (table 1). The CSRT wasreproducible in each patient during a givenprocedure.Group B. The CSRT in 24 patients was simi-

lar to those in group A and ranged from 100to 435 msec (mean, 226 ± 91) (table 2). Asingle other patient (case 42) showed amarkedly prolonged CSRT (900 msec or 75%of the sinus cycle). In the remaining threepatients (cases 36, 41, and 43), in contrast togroup A, the PABs were followed by a pause(AA,3) essentially equal to the sinus cyclelength or CSRT ranged from 0 to 40 msec (fig.2).

After Atrial Pacing

Group A. In 27 of the 28 patients in groupA, the CSRT remained essentially unchangeddespite an increase in rate and duration of APfrom 100 to 140/min and from 2 to 5 min. Aslight fluctuation in CSRT in the range of + 20to ± 50 msec could be observed betweendifferent levels. A typical response to AP atthree different levels each for 2- and 5-minduration is shown in figure 3. The range ofCSRT in these 27 patients was 100 to 525 msec(mean, 260 + 98) or 15 to 59% of the sinuscycle (table 1).

In the remaining one patient (case 28) witha history of syncope and a normal heart rate,the CSRT was prolonged and directly propor-tional to the rate of AP. The CSRT progres-sively increased with increase in rate of APfrom 100 to 120 to 140/min for 2 min at eachlevel and ranged from 1810 to 3710 andbeyond . msec, respectively (fig. 4). How-ever, in this patient the CSRT with PABs was320 msec and was similar to that of the other27 patients in group A (fig. 5).Group B. Of the 28 patients in this group,

Cirt ulation, Volum-,Ae XLV, January 1972

12 had CSRT comparable to that in group A(<'525 msec) (fig. 6). In the remaining 16patients the maximum CSRT ranged from 560to 3740 msec (mean, 1880 + 1079; table 2).In the latter 16 patients the CSRT was usuallydirectly dependent on the rate and duration ofAP and progressively increased with increasein either of these two factors (fig. 7). In someof these 16 cases, after the termination of AP,the first sinus P was recorded without anappreciably prolonged CSRT but with amarkedly prolonged second sinus cycle. Insome of the patients with SB and prolongedCSRT, the postpacing depression persisted forseveral sinus cycles before returning to controllevels. Most patients with SB and prolongedCSRT were not receiving cardiac medications.In patients with prolonged CSRT, the devel-opment of symptoms was avoided by turningon the atrial pacemaker when the asystole,due to the sinus pause, exceeded 4 sec. Afterthe cessation of AP, no acceleration in sinusrate was observed for the following 15 sec.

After Atropine

WVith AP. Ten patients with SB (table 2)wvere restudied after atropine. In tvo of these10 patients (cases 50 and 56) with SB, thecontrol CSRT was not prolonged and re-mained unchanged after atropine. The othereight patients had a control prolonged CSRT.In four of the latter eight patients (cases 55,39, 36, and 34), the CSRT after atropine was1710, 620, 480, and 360 msec in contrast tocontrol levels of 1350, 2450, 1860, and 1420msec, respectively. In the remaining fourpatients (cases 30, 33, 37, and 38), junctionalescape beats at intervals of 1120, 2250, 1200,and 4260 msec were the first to appear,followed eventually by sinus rhvthm afterseveral cycles of junctional beats (fig. 8, lowerpanel).

AWith PAB.s. The duration of CSRT (A2A: -

A1A1) or the recovery interval in excess of thesinus cycle remained essentially unchangedafter atropine. The SRT (A.,Al) after PABsshortened because of a decrease in basic sinuscycle length (A1A1) and not because of anydecrease in the time required for the sinusnode to recover.

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U~~~~~~~~~~~~~~~~~~~~~~~~~-AP 100miA 770 70P-P 760 msec 78075

B 1 --7200, z,,, z~~~~~~~~~~~~~~~00' r-> t - - =~AP100mi i =770 P-P 780 msec 0

AP 1201 1min0/iC810 ( P-P 815 msec 810 810

D 780 P-P790Omsec \.775 J770

P, P 830 msec 820 P

830 P-P 850 msec 840

H. B, .,, 80069 312071 13

Figure 3

Case 5: Effect of iate ancd cluratio)i of atrial pacilg (AP) on1 SRT in paticltts tuiti normnal sinWisfunctiot. (A to F) Despite a progressiue it2crease in1 AP ate.s frotmi 1(0) to 120, arnd to 140 olinfor 2 atnd 5 mmir at each pacing rate, the CSRT (A)A -A A,) is essentially the same frompanels A (295 trisec) to F (310 misec). This indicates that CSRT is indep)endenit of rate andldurationt of AP, within limits, in patients with normal sinus function. After the cessation of AP,the depressant effect persists for a fetw beats as showsn by prolonged cycle lengths. PI = pacingimputlse. Time lines in this and suibsequent figtures are at 1-sec intervals.

Cuiiives are cotntint(otu.s from left hlalf to right half of that figuire.

After Spontaneotus Atrial TachycardiaIn one patient (case 18) with recurrent

spontaneous atrial tachycardia, CSRT wasmeasured during stable sinus rhythm by atrialpacing (fig. 9, upper panel). At the end of thestudy, the patient spontaneously developedatrial tachycardia with an atrial cycle lengthof 215 msec (fig. 8, lower panel). After atrialtachycardia had persisted for 5 min, it wasterminated by rapid atrial stimulation(400/min). The CSRT measured at thetermination of the tachycardia was essentiallythe same as that after atrial pacing (100/minfor 2 min), despite its spontaneous origin anda faster rate than AP (fig. 9).

Follow-uipIn one patient (ease 38) with a hiistory of

syncope, the CSRT was studied before andafter 712 months of a permanent pacemakelimplantation. The CSRT was markedly pro-

longed when first studiedabnormal during the secondeven at a slower AP rate.

and remainedstudy (fig. 8)

Interpolated Premature Atrial Beats

In seven of the 56 patients, pacer-inducedinterpolated PABs wvere observed. As thePABs were induced at progressively increasingprem-aturity, a level was reached at whichthe subsequent interval (A.,A:1) suddenlyshortened and exhibited no compensatorypause (A1A1 = A1A.. + A.,A:1) (fig. 10). Thisphenomenon could be reproduced in a givenpatient within a narrow range of the atrialcycle. A decrease in prematurity from thislevel resulted in sinus-node depression (in-crease in A2sA3) whereas an increase inprematurity exhibited relative or absoluterefractoriness of the atrium. During relativerefractoriness, the interval between the pac-ing impulse and the atrial depolarization

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SINUS-NODE RECOVERY TIME 149

AP = 1001min- 2 min- | !

Pi, <, ¢ q P-P 1065Smsec 835m 880 840

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jP/I PlP 1170 msec |900900 820

AP 120/min 5minq

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PI, l l PP 1150 msec 830 870 87

lengthened or a phenomenon of atrial reentryor repetitive atrial firing was exhibited for 2 to3 beats. In these patients, the couplinginterval, at which interpolated PABs wereproduced, ranged from 350 to 450 imsec andwas longer than the refractory period of theunderlying atrial myocardium.

DiscussionSinus-Node Recovery Time

The function of the sinus node is not only togenerate the normal heart beat but also torespond to physiologic influences. The presentstudy (by using atrial stimulation as aprovocative test) provides a potential clinical-ly useful parameter to assess sinus-nodefunction. The sinus-node response is character-ized by the duration of postpacing depressionor SRT. Gaskell9 first demonstrated thedepression of the intrinsic pacemaker activityby driving the heart at a rate faster than thedominant pacemaker. In a subsequent caninestudy, Lange10 found that the sinus node wasless readily depressed than other pacemakerswhen pacing was terminated. This phenome-non of overdrive suppression has been clinical-ly observed and utilized especially in terminat-ing supraventricular arrhythmias.11' 12

This study provides measurements of theCirculation, Volume XLV, January 1972

CSRT with PABs and AP in patients bothwith normal heart rate and with SB. Therange of CSRT with AP in all but one patient(case 28) with normal heart rates was narrow(110 to 525 msec), whereas in patients withSB it was very wide (140 to 3730 msec). Thedata show that patients with SB do notcomprise a homogeneous group (figs. 6 and 7)and may or may not show an abnormalresponse. The CSRT in the normal heart rategroup was usually independent of the dura-tion and rate of AP (up to 140/min) whereasin the majority of the patients with SB and anabnormal response it was directly proportion-al to the duration and rate of AP. In thepatients with normal heart rates the beatsfollowing AP showed a slight lengthening ofthe sinus cycle length which usually lasted fora short time with a progressive reversion tocontrol levels over 5 to 6 beats, whereas alonger period was required in patients withprolonged SRT. In an occasional case with SB,the maximum postpacing depression was notseen in the very first sinus P wave but in thesecond sinus P wave which appeared after amarked delay. Most of the patients with SBand prolonged SRT were receiving no cardiacmedication. This indicates that the abnormalSRT was not due to drugs. No overshoot or

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1.50 NARULA ET AL.

A L-1 ~ ~ 915~.~+ 795 915 890 9

AP 100/min 2 min VBH

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Figure 4

Case 28: A p)atienit uLvith histort of spiycope and no docneiented SB or A-V contdnictiont defectshowed a p)rolongedI SRT. (A) Conitiol rhtjthrii stril) (L-1) dnring niormial sinus rhythmn. (B toD) Sim7iiultanieo.us recordings of bip3olar electrogr,ani (BE) fronm tile area of the A-V jtictioni(BH) atid ECG lead L-1. SRT after AP is markedly prolonged and lengthened progressively(2710 to 4610 msec) weith p)rogre.ssite increase in AP tote from 100 to 140/mliuii.

acceleration of sinus rate sx as observed for a

period up to 15 see after the terimination ofAP. These findings are in contrast to a sttidyon dogs which showx ed that in presumabl-normal dogs the SRT was directly proportion-al to the rate and duration of AP.1'" Ananalysis of the data in the dog study1" showsthat the change in SRT with increase in rateand duration of AP was usuallv small and inthe range of about 50 msec. This increase isinsignificant in view of the normal fluctluationsin SRT (range, +50 msec) between differentlevels in our study. Recentlv reported x aluesof CSRT in patients with normal sinus rate are

comparable to that of onrs.l:3 However,because of a limited number of patients (threecases) with SB, that study did not showv that

patients with SB necessarily havre a proloigedCSRT.1'The temporary depression of pacemaker

automaticity subsequent to premature electri-cal stimulation has been demonstrated inseveral experimental and clinical studies.11 14-16Recently, Bonke and associates'1 studied thefactors determining the duration of the post-extrasystolic pause following induced PABsin the isolated right atrium of the rabbit. Theirstudy showed that the duration of the postex-trasystolic pause increased progressively witha progressive increase in prematurity of thePABs up to a level approximately equal to 70%cof the sinus cycle, beyond which a further in-crease in prematurity resulted in an essentiallyplateau effect. Our findings support these ob-

Circolation. Voluniie XLV. Januar48}1972

BED (BH)

L-1

ll

! ~~~~I

.\y


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SINUS-NODE RECOVERY TIME 151v

A~~~~~~~~~~~~~~~~~H A

A (BH) K - - ', --- ,- _930 P8-A55

1020; 850 A-A 865 msec

[-1____________ Al 2 \~~~~PIA3

(BH). 1A A2

C 925Pl-A 75A-A 815 msec 325 1220 560

L-1 \ _ _

aVF n-- - -V, , _-J 5

C, Gol., #80603 2, 16/70.1148

Figure 5Case 28: Same patient as in Figure 4. Normal SRT with premature atrial beats (PABs). (A toC) With a decrease in cotnpling interval (A1A.) from panels A to C, the SRT (A. A:) rangedfrom 1105, to 1220, to 1220 mnsec, respectively, in contrast to the markedly long SRT afterAP (fig. 4 Ipanel D). This shows the inability of the PABs to differetntiate betwceeni a normaland abnormal sitntns-node functioni. PI-A = the interual bettwcen the PI and the prematuireatrial electrogranm (A.).

servations (fig. 1). With PABs, after atropineadministration, the absence of any change inCSRT despite an increase in sinus rate indi-cates that the CSRT is independent of thecycle length and vagal tone. Furthermore, itexplains the similar response to PABs in pa-tients with normal heart rates and SB.The mechanism of overdrive suppression

following AP is probably mediated in someway through humoral responses. 18-2' This in-ability to abolish completely the postpacingdepression after atropine in this and otherstudies"'. 13 suggests the role of factors otherthan acetylcholine. It has been suggested22. 23that driving stimuli. result in an increase inextracellular K+ which leads to the suppressionby two mechanisms (1) a decrease in phase 4depolarization and hence a decrease inautomaticity; (2) a decrease in the restingCirculation, Volume XLV, January 1972

potential and in the amplitude of the actionpotential which, in turn, may render itineffective as a stimulus for propagation.24 24However, as yet this issue is unsettled.2'

In most of the patients, SB was notsecondary to increased vagal tone as onlyminimal acceleration in sinus rate was exhibit-ed after atropine administration. In addition,a prolonged CSRT remained abnormal despitea decrease from the control levels and suggeststhat the prolongation was mainly due to apoor function of the sinus node itself, althoughvagal tone contributed to it.The important question is what parameter

of the sinus-node function is reflected by thisresponse (postpacing depression): (1) Is itdue to a delay or block in sinoatrial conduc-tion or (2) does the prolonged SRT indicate achange in automatic capacity of the sinus


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AP =75/min 2 min

(BEl (BH) ~~~~~A-A1350 msec 1310

A L-1-_ - _ _

.9W+,350g_>1 )G_jD ....l+i1260

AP 100/min 2 min A 3 ,

A. A,120i+A130 se

AP 120/min 2 min

AA1320 me

:I-,------1 ------1460

- 41220

...1l778265 3 6 '70 R

Figure 6

Case 43: A patient with SB and a normal CSRT which is independent of the rate of AP.(A to C) Simultaneous recordings of BE(BH) and ECG lead L-1. AP for 2 min at each levelwith a rate of 75, 100, and 120/min shows a normal CSRT (A2A5 - A1A1 - 140 msec)(panel C).

node as an impulse generator? The firstpossibility is unlikely for the following rea-

sons: (a) The presence of sinus rhythm (SR)is an indication of intact sinoatrial conductionwhereas the existence of a compensatorypause following the atrial stimulation (withPAB and AP) is suggestive of conductionfrom the atrium to the sinus node.17 (b) Atrialpacing at a rate faster than SR shoulddecrease the refractory period (RP) of theatrium, within limits, due to a decrease incycle length and thus facilitate conductionfrom SN to RA. (c) Concealed conductionfrom RA to SN with AP may delay SN to RAconduction for one subsequent sinus cycle, butlonger delays (SRT) cannot be attributed tothis property. (d) Experimental work showsthat following atrial stimulation a shift in

impulse origin may occur from true pace-

maker cells in the center of SN to latentpacemaker cells situated at the periphery ofthe SN.17 23 However, the conduction timefrom the latter pacemakers to RA should beshorter as opposed to that of the former.Therefore, the second possibility, that is, a

change in the automaticity of the sinuspacemaker cells (or decrease in the strengthof the sinus impulse) is the most likelyexplanation for postpacing depression. This isfurther supported by a recent editorial sug-

gesting that sinus impulses, if subthreshhold,may fail to excite the atrium and result in longpauses with atrial asystole.26 This decrease in

automaticity may be secondary to shift in

pacemaker site from true to latent pacemakercells or direct depression of automaticity


BEB (BH)

L-1

BEC (BH)

L-1

152

130- 1A J. fA1

i


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Control

A __ 1670 1680 P-P 1670 msec 1680

AP = 100/min 2 min

[~~~~~~~~~~~~~~~~~~~~~AI Li 1 lliJl!TllrT

~PP 3870 msecl 17i80

AP 120/min 2 min,

c P-P 1680 msecP

____________________T_

l--- P-P 5410 msecS~~~~~~_. w ~

110 3010

-T - r 1~~~~~-

L- r-0-

L1 260

..6-,S91696 3/16/71

Figure 7

Case 51: A patient with SB and an abnormal SRT. (A) Rhythm strip showing control sinuiscycle length (1670 msec). (B and C) An increase in AP rate from 100 to 120/min for 2 minat each level demonstrated a progressive increase in SRT from 3870 to 5410 msec. The severedepressent effect is demonstrated even in thesinnis cycle lengths.

mediated through humoral responses or al-terations in electrolytes. Accordingly, thequantitative data of SRT with AP in normalpatients probably provide a measure by whichthe function of the sinus node as an impulsegenerator can be assessed. The automatic ca-pacity of the sinus node may be reflected bythe duration of (1) the sinus-node recoverytime after the termination of atrial pacing andof (2) the depressant effect present in thesubsequent beats which show a longer sinuscycle length as compared to the control sinuscycles preceding AP.

It should be stressed that AP, rather thanPABs, is a more reliable method of differentiat-ing between a normal and an abnormal sinus-node response. The CSRT following PABs wasusually similar in all patients (normal or SB)and was in no way comparable to theprolonged CSRT seen with AP in patientswith sick sinus (tables 1 and 2). Case 28 (figs.4 and 5) is illustrative. This patient had a


subsequent beats with markedly prolonged

history of syncope and on admission showedheart rates within the normal range withoutany arrhythmias. The CSRT, although normalduring PABs, was grossly abnormal with AP.Following the cessation of AP, a period ofasystole more than 4.5 see in duration wasnoted. These findings are of clinical signifi-cance and suggest (1) that a normal sinus rateis no assurance of normal sinus-node functionand (2) that all patients with SB may not havea poor sinus node. They also may explain (3)why some patients with SB and comparablerates are stable and asymptomatic, whereasothers have syncopal or dizzy spells. The lattergroup probably represent patients with brady-tachy syndrome who manifest long periods ofasystole following supraventricular arrhyth-mias.The majority of the patients with SB and a

markedly prolonged CSRT did not demon-strate escape of lower pacemakers, that is, theA-V junctional or ventricular, during the

4- -1 -.sl

o.lLoomb,lm 33-- A --

153


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154 NARULA ET AL.

51370 AP =1201in 2 min

BE m-1i(BH)

A-A 1370 mse0

L-1 - xz .

-----4000 ----- ~1600 A1500

At,pine 2 mgAP = 80min 2 min

BE e ' -' -1 k . \ 'r

h ho TA {-v r

(BH) --46 148 13801 '

1080 AA 1080 10810 8- -

1/ 26/71 Control BV~

A A 1330 mon 5/ 15901300

APe APat10/min2omiina 00me.(B toie( g dinsee nrvnul

A BH V ~~ ~ ~ ~ ~~~~~~B1

waftgi en.TeSTdsptler APatt 120/mmn for 2 mmn was400me.(Bgtoiea2m)amiitrdintravkenouly

prolonged (3450 msec).



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periods of asystole. In no case was the escapeof an ectopic atrial pacemaker seen. Concern-ing man, no control data are available toindicate the normal escape interval of lower orsubsidiary pacemakers following suppressionby AP. Animal studies performed after crush-ing of the sinus node have suggested a greaterdepression or longer recovery time of the A-Vjunctional pacemakers than the sinus node.10These findings cannot necessarily be appliedto man. The long periods of asystole withoutthe escape of lower pacemakers leads us,however, to believe that the automatic capac-ity of these subsidiary pacemakers (especial-ly A-V junctional) is also compromised in thepatients with abnormal sinus response orprolonged SRT. In some of these cases whenSRT was reevaluated after atropine, junctionalpacemakers were the first to appear and werefollowed subsequently by sinus rhythm.

Patient 38 (fig. 8) with SB when initiallystudied showed markedly prolonged SRT. Be-cause of the history of syncope, a permanentpervenous demand pacemaker was implanted.Seven and a half months later, a follow-upstudy showed similarly prolonged SRT. An-other patient, case 18 (fig. 9), showedidentical SRT with AP (at 100/min for 2 min)and following termination of spontaneousatrial tachycardia (280/min for 5 min). Theabove findings demonstrate the reproducibili-ty of SRT and support the clinical use of APfor evaluation of sinus-node function. To testthe sinus-node function, we recommend thatthe AP be initially used only at one level(120/min for 2 min ). Demonstration of anormal SRT would eliminate the need for asecond level since the SRT in patients withnormal sinus node is independent of rate andduration of AP. However, if an abnormal SRTis recorded with a single level, a second higherlevel of AP showing further prolongation ofSRT may be employed as comfirmation.

Interpolated BeatsThe phenomenon of interpolated beats has

been reported clinically.27 This was observedin seven patients during our study (fig. 10).The interpolated beats indicate the inabilityof the PABs at that level of prematurity to


depolarize the sinus pacemaker. The absenceof sinus-node depression may be the result of(1) unidirectional conduction block from theRA to SN because of the refractoriness of thetissue at the periphery of the sinus node28 or(2) the penetration of the premature impulseinto the sinus node during the absolutelyrefractory period of the sinus pacemaker cells.In these patients, atrial depolarization with afurther increase in prematurity of the PABs,beyond that for interpolated PABs, indicates ashorter refractory period for the right atrialmuscle than the sinus node or perinodal sinustissue.28 Previous studies from this laboratoryhave demonstrated the presence of indepen-dent unidirectional blocks in conductingtissues, that is, A-V node or His-Purkinjesystem.29 30 Therefore, the demonstration ofinterpolated beats and the presence of uni-directional block during conduction from RAto SN does not permit the prediction of theconduction capabilities from SN to RA, that is,sinoatrial block. In addition, many patientswhose ECG pictures were compatible withthe diagnosis of sinus arrest or SA block didnot demonstrate this phenomenon of interpo-lated PABs. All the seven patients whomanifested interpolated PABs had normalheart rates and a normal SRT during AP.

References1. FERRER MI: Sick sinus syndrome in atrial disease.

JAMA 206: 645, 19682. BIRCHFIELD RI, MENEFEE EE, BRYANT GDM:

Disease of the sinoatrial node associated withbradyeardia, asystole, syncope and with parox-ysmal atrial fibrillation. Circulation 16: 20,1957

3. FowLE NO, FENTON JC, CONWAY GF: Syncopeand cerebral dysfunction caused by bradyear-dia without atrioventricular block. Amer HeartJ 80: 303, 1970

4. RAMUSSEN K: Chronic sino-atrial heart block.Amer Heart J 81: 38, 1971

5. SILVERMAN LF, MANKIN HT, MCGOON DC:Surgical treatment of an inadequate sinusmechanism by implantation of a right atrialpacemaker electrode. J Thorac CardiovascSurg 55: 264, 1968

6. CLARKE M, EVANS DW, MILSTEIN BB: Sinusbradyeardia treated by long term atrial pacing.Brit Heart J 32: 458, 1970

7. EYSTER JAE, MEEK WJ: Cardiac irregularities in

155


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156 NARULA ET AL.

A A A _ A Pacing 100/=3in~~~~~~~~~A

A (RA) r 820 AA 820 msec 805

BE -

(RA)~~~~~~~~~~~~~~~~~~~~~~~~~

[-1 X: ;/7, A ,<,

(RA) _ -rrrrrrrr r r,

MElk, 686165 3/2/71 3

8/25/70

3/2/71'I ilk;igi !+ 1X + >! W' ts,-i1A/A' A' A1

BE 1 I ~(RA)

A-A 215msec

J-RAS 400/min

BE k.~ 'lA y \A(RA) 1 A;-/ RJ^;v- ~ys U; 2^-A 215 msec

LA~~~~~~~~~~~~~~~~~~~~~~P10 sec

~~~1iA~~~~ Al~ABE

C 250 190 190 215 :340 A-A 1220 msec 1040 1010

M, Elk., #86165 312/71 1136

Figure 9

(Upper panel A to C) Case 18: Patient with paroxysmal supraventricular tachycardias anda permanent ventricular demand pacemaker (QRS blocking). Simultaneous recordings of BEfrom the right atrium (RA) and ECG lead L-1 during NSR show SRT of 1170 msec (C)after AP at 100/min for 2 fin. Chest wall stimuli (CWS) are applied at the cessation of APto block the escape of the demand ventricular pacemaker.

(Lower panel) Rhythm strip (L-1) recorded from the same patient (case 18) prior to theimplantation of the permanent pacemaker (8/25/70) shows spontaneous onset and cessation of



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SINUS-NODE RECOVERY TIME 157

Al Al A2A3

BE K 820 J A-A 810 ms ! 30 P 1090 A 820iRAi A

I I BH V

B>E

Aw~~ClV F

v

0l -'----v I_ _ _ _ _ _ __ _ _ _ _ _

Al jAl A2 jA3 AI 820 1

825 A-A 830 ms 430 PI 390 800 820

B E- 'fI_(RA)

(BH) I

L1 n ,_ r w

OVF~~~ v W waV1------__ ___-~~~~~~~~~'

H G- 133982 12 29 70 1153

Figure 10

Case 16: Interpolated premature atrial beat. (A) Simultaneous recordings of BE(RA), BE(BH),and three ECG leads (L-1, aVF, and V1). The premature atrial beat is followed by an expectedpartially compensatory pause (A2A3) of 1090 msec. (B) The induced (PI) PAB is interpolatedand is not followed by any compensatory pause. The sum of A1A2 (430 msec) and A2A3 (390msec) intervals is equal to the sinus cycle length (820 msec). The atrial beat following thePAB is sinus in origin as indicated by the normal sequence of atrial activation from highright atrium [BE(RA)] to the region of the A-V junction [BE(BH)] and the shape of the Pwaves. At this coupling interval some beats were interpolated and some followed by a com-pensatory pause as in panel A.

morphine poisoning in the dog. Heart 4: 59, 10. LANGE G: Action of driving stimuli from intrinsic1912 and extrinsic sources or in situ cardiac

8. CUSHNEY AR: The irregularity of the mammalian pacemaker tissues. Circ Res 17: 449, 1965heart observed under aconite and an electrical 11. PICK A, LANGENDoRF R, KATz LN: Depression ofstimulation. Heart 1: 1-22, 1910

cardiac pacemakers by premature impulses.9. GASKELL WH: On the innervation of the heartwith special reference to the heart of tortoise: j Amer Heart J 41: 49, 1951Physiol 4: 43, 1884 12. LISTER JW, COHEN LS, BERNSTEIN WH, SAMET

SVT. (A) Again on 3/2/71 during the same study as in upper panel the patient spontaneouslydeveloped atrial tachycardia (AT) with a cycle length (A-A) of 215 msec. (B and C) Fiveminutes after the onset of AT, rapid atrial stimulation (RAS) was instituted at a rate of 400/minfor 10 sec. The cessation of RAS is followed by a normal sinus P wave with an SRT of1220 msec which is essentially similar to that in the upper panel despite the spontaneousorigin of atrial tachycardia at a rapid rate (approximately 280/min) for longer duration asopposed to AP at 100/min for 2 min only. At the cessation of AT, the demand ventricularpacemaker escapes (VPI) simultaneously with the sinus P shown in BE(RA). This P and thesubsequent two P waves are not conducted because of a rate similar to that of the pacemakerescape interval.



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P: Treatment of supraventricular tachycardiasby rapid atrial stimulation. Circulation 38:1044, 1968

13. MIANDEL W, HAYAKAWA H, DANZIG R, 'MARCUSHS: Evaluation of sino-atrial node function inman by overdrive suppression. Circullation 44:59, 1971

14. CUSHNEY AR: Stimulation of the isolatedventricle, with special reference to the devel-opment of spontaneous rhythm. Heart 3: 257,1911-1912

15. EcciiFs JC, HOFF HE: Rhythm of the heart beat;2. Disturbance of rhythm produced by latepremature beats. Proc Roy Soc 115: 327,1934

16. EYSTER JAE, MEEK WJ: Experiments on theorigin and conduction of the cardiac impulse.Arch Intern Med (Chicago) 18: 775, 1916

17. BONKE FIM, BOU.MAN LN, VAN RIJN HE:Change of cardiac rhythm in the rabbit afteran atrial premature beat. Circ Res 24: 533,1969

18. HUTTER OF, TRAUT-WEIN W: Vagal and sympa-thetic effects on the pacemaker fibers of thesinus venosus of the heart. J Gen Physiol 39:715, 1956

19. WEST TC: Effects of chronotropic influences onsubthreshold oscillations in the sino-atrial node.In Specialized Tissues of the Heart, edited byA Paes de Carvalho, WC de Mello, BFHoffman. New York, Elsevier Publishing,1961

20. VINCENzI FF, WEST C: Release of autonomicmediators in cardiac tissue by direct subthresh-

old electrical stimulation. J Pharmacol ExpTher 141: 185, 1963

21. GRODNER AS, LAHRTZ HG, POOL PE, BRAUNWALDE: Neurotransmitter control of sino-atrialpacemaker frequency in isolated rat atria andin intact rabbits. Circ Res 27: 867, 1970

22. SCHER AM, RODRICUES MI, LUKANE J, YOUNGAC: The mechanism of atrioventricular con-duction. Circ Res 7: 54, 1959

23. Lu HH, LANGE G, BROOKES C McC: Factorscontrolling pacemaker action in cells of thesino-atrial node. Circ Res 17: 460, 1965

24. HOFF.MAN BF, CRANEFIELD PF: The physiologi-cal basis of cardiac arrhythmias. Amer J Med37: 670, 1964

25. HASHI'NOTO H, SUZUKI Y, CHIBA S: Effect ofpotassium excess in pacemaker activity ofcanine sino-atrial node in vivo. Amer J Physiol218: 83, 1970

26. SCHERF D: The mechanism of sino-atrial block.Amer J Cardiol 23: 769, 1969

27. SCHAMROTH L: Sinus parasystole. Amer J Cardiol20: 434, 1967

28. STRAUSS HC, BIGGER JT: The physiological roleof the perinodal fiber. (Abstr) Circulation 42(suppl III): 111-68, 1970

29. CASTILLO C, SAMET P: Retrograde conduction incomplete heart block. Brit Heart J 29: 553,1967

30. NARULA OS, SAMET P: Study of ventriculo-atrialconduction by His bundle recordings in man.(Abstr) Circulation 42 (suppl III): 111-47,1970

Circulation, Volunze XLV, January 1972

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ONKAR S. NARULA, PHILIP SAMET and ROGER P. JAVIERSignificance of the Sinus-Node Recovery Time

Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 1972 American Heart Association, Inc. All rights reserved.

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Significance of the Sinus-Node Recovery - …circ.ahajournals.org/content/circulationaha/45/1/140...Significance of the Sinus-Node Recovery Time By ONKAR S. NARULA, M.D., PHILIP SAMET,