1614

Effect of Continuous Enhanced Vagal Tone on

Atrioventricular Nodal and SinoatrialNodal Function in Humans

Richard L. Page, Anthony S. L. Tang, and Eric N. Prystowsky

A constant intravenous infusion of phenylephrine (0.74±0.41 ,ug/kg/min) was given to 10patients to cause a continuous augmentation in reflex vagal tone. After the infusion, thediastolic blood pressure increased from 76±7 to 89±11 mm Hg (p<0.01). The sinus cyclelength and atrial-His (AH) interval were measured, and incremental atrial pacing wasperformed before and during phenylephrine infusion until atrioventricular (AV) nodal blockwas achieved. For each patient, the AV nodal function curve (i.e., the AH interval plotted as a

function of the atrial pacing cycle length) was compared during both the control state andphenylephrine infusion; the AH intervals during each condition at chosen short (AHs) and long(AHL) cycle lengths were compared. The sinus cycle length increased during phenylephrineinfusion from 941±294 to 1,115±347 msec (p=0.013). The AH interval during sinus rhythmwas not significantly prolonged (77 versus 82 msec, p =NS). The shortest atrial pacing cyclelength yielding 1:1 AV nodal conduction increased during phenylephrine infusion from412±120 to 575+±211 msec (p<0.01). Of note, the degree of sinus cycle length prolongation didnot correlate with the degree of prolongation in the shortest atrial pacing cycle length yielding1:1 AV nodal conduction. The AV nodal function curve was shifted markedly to the right andonly slightly upward. Thus, even though there was a significant increase in both AHL (from84+±24 to 102+48 msec, p<0.05) and AHs (from 127 ±40 to 186±+66 msec, p<0.01), the meanincrease in AHs was substantially greater (59 versus 18 msec,p< 0.01). We conclude that duringbaroreflex-induced enhanced vagal tone there is a significant depression of AV nodalconduction, primarily related to the stressed portion of the AV nodal function curve. Althoughbaroreflex-induced changes in sinus automaticity and AV nodal conduction generally move inthe same direction, the degree of negative dromotropic effects on AV nodal conduction cannotbe predicted by the magnitude of change in sinus rate. (Circulation Research 1991;68:1614-1620)

P arasympathetic and sympathetic influences onatrioventricular (AV) nodal conduction at resthave been shown to be balanced in both human

and canine experiments.12 However, increased reflexvagal tone induced by several methods, including ca-rotid sinus massage or phenylephrine bolus infusion,may have markedly variable effects on AV nodal con-duction.3-5 For example, during supraventricular tachy-cardia when AV nodal conduction is stressed, en-hanced vagal tone often terminates tachycardia byblocking impulses in the AV node.4 In contrast, height-ened parasympathetic tone usually has minimal effect

From the Department of Medicine, Division of Cardiology,Duke University Medical Center, Durham, N.C.

Supported in part by National Research Service Award 5T32HL-07101 of the National Institutes of Health. R.L.P. was aStanley J. Sarnoff Scholar for Research in Cardiovascular Science,1987-1989, at the time this investigation was done.Address for correspondence: Richard L. Page, MD, Box 3152,

Duke University Medical Center, Durham, NC 27710.Received April 24, 1990; accepted February 12, 1991.

on AV nodal conduction during normal sinus rhythm.3,5Further, in some patients a discordance is noted duringperiods of expected increase in vagal tone, such assleep; for example, minimal PR prolongation mayoccur with substantial sinus slowing, or slight increasesin sinus rate may be accompanied by Mobitz type Isecond-degree AV block. The purpose of this investi-gation was to evaluate systematically the effects ofreflex-induced parasympathetic tone during steady-state conditions on the AV nodal function curve and tocorrelate changes in AV nodal conduction with sinusnode automaticity.

Materials and MethodsStudy PopulationThe study included 10 patients (80% men), 22-65

(mean, 47) years of age. In nine patients, electrophys-iological study was performed because of syncope orpresyncope; one patient (patient 1) was admitted foratypical chest pain and was studied because of a

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TABLE 1. Patient Population

Patient Age (yr) Gender History

1 36 Male Sinus arrest2 51 Male Syncope3 54 Male Bradycardia, presyncope4 31 Female Syncope5 61 Male Syncope6 64 Male Syncope7 65 Male Syncope8 37 Male Syncope9 52 Male Syncope

10 22 Female Syncope

15-second pause observed during sleep (see Table 1).No patient showed evidence of coronary artery dis-ease. All patients had normal intervals on the surfaceelectrocardiogram except for one (patient 3), whohad first-degree AV block. No patient was receiving acardioactive drug at the time of the study.

Electrophysiological StudyThis protocol was approved by the Institutional

Review Board, and informed written consent wasobtained in each case. Patients were studied in thepostabsorptive state, typically with mild diazepamsedation (5.25 +5.7 mg i.v.). Activity within the labo-ratory was minimized during the study. Three multi-polar catheters were introduced percutaneously fromthe femoral vein and advanced under fluoroscopicguidance to the high right atrium, across the tricuspidanulus (His bundle electrogram), and to the rightventricular apex. The catheter positions were stablethroughout the study. Intracardiac bipolar electro-grams (filtered at 50-500 Hz) and standard electro-cardiographic leads I, II, III, V1, and V6 were dis-played simultaneously on a multichannel oscilloscopeand recorded at paper speeds of 100 mm/sec. Elec-trical stimulation was performed using a programma-ble stimulator delivering 2.0-msec constant-currentpulses at twice late-diastolic threshold. The atrialpacing protocol involved pacing at a cycle length justless than that of sinus rhythm and incremental short-ening of the pacing cycle length until AV nodal blockwas observed. No arrhythmia was induced.

Electrophysiological MeasurementsThe atrial-His (AH) interval was measured to the

nearest 5 msec on the His bundle electrogram fromthe first rapid atrial deflection crossing the baselineto the onset of the His bundle depolarization. TheAH interval was measured for. each pacing cyclelength after steady state was achieved by allowingseveral beats to elapse at that cycle length. Intervalsduring sinus rhythm were measured and were typi-cally averaged over six or more beats.

Phenylephrine InfusionA constant infusion of phenylephrine was used.6

Phenylephrine (100 gtg/ml) was administered via a

side-armed sheath located in the femoral vein start-ing with a dose of 0.2 ,ug/kg/min for 10 minutes; thedose was then doubled every 5-10 minutes until adiastolic blood pressure increase of 10-15 mm Hgwas observed or until a maximum dose of 1.6 ,ug/kg/min was administered. After the initial 10-15 mm Hgblood pressure increase was achieved, incrementalatrial pacing was performed. The primary purpose ofthis study was to evaluate the effects of phenyleph-rine on AV nodal conduction; thus, if no change in1:1 AV nodal conduction was observed, the nexthigher dose of phenylephrine was given. The dosewas increased in stages until 1) the highest level wasachieved, 2) some negative dromotropic effect on AVnodal conduction occurred, or 3) a 30 mm Hg rise indiastolic blood pressure was achieved. When AVblock was observed to occur during very long pacingcycle lengths or spontaneously during sinus rhythm,the infusion rate was reduced to allow the measure-ment of the AH interval at several pacing cyclelengths. Doses of phenylephrine were not altered onthe basis of change in the sinus cycle length. Bloodpressure was measured every minute during theinfusion by an automatic blood pressure recordingdevice (Infrasonde model D4000, Puritan-BennettCorp., Wilmington, Mass.).

AH Intervals at Short and Long Cycle LengthsAHS refers to the AH interval at the shortest A,-A,

pacing cycle length where consistent AV nodal con-duction was seen during both control and phenyleph-rine infusion. The A,-A1 pacing interval at which AH,was measured was the same for both conditions ineach patient, but the A,-A1 pacing interval used foreach case depended on the individual AV nodalfunction curve.AHL refers to the AH interval at the longest A,-A1

pacing cycle length where there were data availablefor both control and phenylephrine infusion. Again,data were obtained at the same cycle length in eachpatient, but a unique pacing cycle length was used ineach patient, depending on the sinus cycle length.

Statistical AnalysisStatistical evaluation was performed using the

Wilcoxon signed rank test for paired data; significancewas determined at p<0.05. Spearman's rank correla-tion coefficient was calculated where appropriate.

All data are expressed as mean± SD.

ResultsPhenylephrine InfusionThe infusion rate used in these patients was

0.74+0.40 ,ug/kg/min, yielding an increase in dia-stolic blood pressure of 13.0+6.2 mm Hg. There wereno side effects of the infusion.

Effects of the Baroreflex During Sinus RhythmThe baseline (control) sinus cycle length was

941±294 msec; during steady-state phenylephrine

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TABLE 2. Summary of Experimental Data in 10 Patients

Baseline Phenylephrine

BP CL(S) AH(S) AHL AHs 1:1 Dose BP CL(S) AH(S) AHL AH5 1 :1Patient (mm Hg) (msec) (msec) (msec) (msec) (msec) (,ug/kg/min) (mm Hg) (msec) (msec) (msec) (msec) (msec)

1 124/80 895 86 100 210 490 0.60 148/90 976 97 110 280 5402 128/75 789 65 75 120 370 0.24 144/92 1,032 90 90 It60 4803 127/80 1,705 119 140 135 620 0.80 150/106 1,900 127 230 300 950)4 120/71 782 60 65 80 390 0.40 132/88 765 63 70 100 6705 128/73 895 80 75 115 290 0.40 144/80 893 79 90 180 4006 128/80 634 51 55 140 280 1.60 149/95 760 53 55 140 2807 97/67 1,005 92 100 140 580 1.20 123/74 1,430 86 85 220 7208 129/88 1,057 65 75 160 310 0.80 174/103 1,298 65 95 205 3309 132/66 850 75 80 90 450 0.60 144/73 1,000 82 90 135 600

10 148/80 795 78 75 80 340 0.80 148/89 1,098 82 105 135 780Mean 126/76 941 77 84 127 412 0.74 146/89 1,115 82 102 186 575SD 13/7 294 19 24 40 120 0.41 13/11 347 21 48 66 211

BP, blood pressure; CL(S), cycle length during sinus rhythm; AH(S), atrial-His interval during sinus rhythm; AHL and AHs, AH intervalsduring the longest and shortest, respectively, paced cycle lengths for which there were paired data available; 1 :1, the shortest atrial pacedcycle length at which there was 1:1 atrioventricular nodal conduction.

infusion, the sinus cycle length was significantly pro-longed to 1,115+347 msec (p=0.013). There was nocorrelation between the initial sinus cycle length andthe degree of sinus slowing with phenylephrine. Asseen in Table 2 and Figure 1, the degree of prolon-gation varied considerably.The AH interval during normal sinus rhythm was

insignificantly prolonged (from 77±+19 to 82±+21msec) in response to phenylephrine. The His-ven-tricular interval did not change, measuring 47+9msec during control and 47±8 msec during phenyl-ephrine infusion.

Effects of the Baroreflex on the AV NodalFunction CurveThe AV nodal curve generated in a typical experi-

ment (patient 2) is shown in Figure 2. Under baselineconditions (unfilled circles in Figure 2), the AH interval

1800

0 1200

CO

600 _

0

Baseline Phenylephrine

Sinus CLFIGURE 1. Plot showing sinus cycle length (CL) at baselineand during phenylephrine infusion for all 10 patients. Therewas a significant prolongation in CL (from 941+±294 to1,115+347 msec) during phenylephrine infusion.

is prolonged incrementally as the atrial pacing cyclelength shortens until AV nodal Wenckebach block isobserved, at a pacing cycle length 360 msec. Note thatduring incremental atrial pacing in the control state, atrelatively long paced cycle lengths, the Al interval isminimally prolonged; the major increase in the AHinterval occurs as the Wenckebach cycle length isapproached. Compared with the control state at similarlong pacing cycle lengths, the AH interval duringphenylephrine infusion (filled circles in Figure 2) is onlyslightly prolonged. However, as the paced cycle lengthis shortened progressively, the magnitude ofAH inter-val prolongation for the matched pacing cycle lengthsmarkedly increases until Wenckebach block occurs, at apacing cycle length 470 msec. The shortest pacing cyclelength that yielded consistent AV nodal conduction inthis patient (1:1) was 370 msec at baseline and 480msec during phenylephrine infusion.

25U

200

AH 150(msec)

100 H

50 K

300

O Baseline* Phenylephrine

0* Wenckebach Block

0

0

°00 * 000 0.

000°..O *

400 500 600 700 800 900

A1 A1 (msec)

FIGURE 2. Plot showing the atrial-His (AH) interval as a

function ofpacing cycle length (A7AI) at baseline and duringphenylephrine infusion forpatient 2. Control (baseline) valuesare represented by unfilled circles, and data obtained duringphenylephrine infusion are represented by filled circles. Thediamonds represent the point at which atrioventricular nodalWenckebach block was observed. Note the shift of the curve tothe right and slightly upward during phenylephrine infusion.

1115 ±347941 9294--

P * 0.01

Q

n

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AHInterval

1 L (PE)

PhenylephrineControl

Short < LongA1-A1 Pacing CL

Phenylephrine shifted the AV nodal functioncurve in patient 2 to the right and minimally upward.This effect was noted in eight of the 10 patients andis schematically demonstrated in Figure 3. In two(patients 6 and 8), the AV nodal function curve wasminimally affected: the 1:1 cycle length was pro-longed by only 0-20 msec (see Figure 4 and Table 2).Of note, patients 6 and 8 demonstrated two of theshortest baseline 1:1 cycle lengths observed. In nocase did the curve shift downward or to the left. Forall 10 patients, the shortest atrial pacing cycle lengthwith 1:1 AV nodal conduction increased from412±+120 to 575±211 msec (p<0.01).

Figure 5 compares the effect of phenylephrine onAHs and AHL for the 10 patients. AHs, measured at amean pacing cycle length of 575 msec, was prolongedfrom 127±40 to 186±66 msec during phenylephrineinfusion (p<0.01). AHL, measured at a mean pacingcycle length of 845 msec, was also prolonged to asignificant degree, from 84±24 to 102±48 msec(p <0.05). However, the average magnitude of prolon-

1000

800 /

600 _ 5755211- 412t120

400

200 - P<0.01

0Baseline Phenylephrine

1: 1FIGURE 4. Plot showing shortest 1:1 pacing interval, atbaseline and during phenylephrine infusion, that yielded con-sistent atrioventricular nodal conduction. During phenyleph-rine infusion, there was a significant effect on atrioventricularnodal conduction as manifested by the shortest A,-A, interval,which increased from 412+120 to only 575±211 msec.

FIGURE 3. Schematic representation of the atrio-ventricular nodal function curve during control (C)and during phenylephrine infusion (PE). Thesecurves are drawn by hand, based on patient data.AHs, the atrial-His (AH) interval measurement atthe shortest A,-A, interval for which there werepaired data available; AHL, theAH interval for thelongest A1-A, interval for which there were paireddata available; CL, cycle length. Typical A,-A,intervals chosen for measurement ofAHL and AHsare indicated by broken lines (see text for furtherdetails). This curve is typicalfor eightpatients; in twopatients, the atrtioventricular nodal function curvewas shifted minimally or not at all. In no patient didphenylephrine cause a shift to the left.

gation ofAHs (59 msec) was substantially greater thanthat noted in AHL (18 msec) (p<0.01).

Comparison Between Sinus andAV Nodal Effects ofPhenylephrine InfusionAs seen in Figures 1 and 4, phenylephrine caused

a statistically significant increase in both sinus cyclelength and the shortest atrial pacing cycle length with1:1 AV nodal conduction, although certain patientsshowed relatively little change in sinus or AV nodalfunction. We evaluated whether the degree of sinusslowing during phenylephrine infusion could predictsimilar degrees of prolongation of the AV nodal 1:1paced cycle length. In Figure 6, we have plotted thevalue of sinus cycle length and the shortest 1:1pacing cycle length obtained during phenylephrineinfusion, normalized to the control data for eachpatient. Note the lack of a relation between thevariables, with r=0.11.

DiscussionIn this study, we present a new method for evaluating

changes in human AV nodal conduction due to reflexlyenhanced vagal tone. The method uses AV nodalfunction curves generated during incremental atrialpacing, which previously have been shown to have acharacteristic shape regardless of the paced Wencke-bach cycle length.7 Because of the universality of thesecurves, it is possible to investigate both the effect ofvarious induced perturbations onAV nodal conductionin patients with disparate AV nodal function at base-line and the relative magnitude of changes at differentphases of AV nodal conduction.

In the presence of augmented vagal tone, weobserved that the AV nodal function curve wasshifted to the right but minimally upward. Thus, themagnitude of response to the same vagal influencevaried; only minor prolongations of the AH intervalwere seen at the longer cycle lengths, whereas sub-stantial negative dromotropic effects were seen onlynear the steep portion of the curve at relativelyshorter pacing cycle lengths. A similar but oppositeeffect on human AV nodal function has been dem-

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280

240

200

AH 160Interval 120

80

40

0

r 186±66

(MSEC)127t40

Baseline* Phenylephrine

n = 10

84*24} L(MSEC)

FIGURE 5. Plot showing atrnal-His (AH) intervals at compara-ble long (AHL) and short (AHs)pacing cycle lengths at baselineand during phenylephrine infl-sion. Although both AHL andAHs were prolonged, there was agreater effect seen at the shorterpaced cycle length (p<0.01/).See text and Figure 3 for ftirtherdetails.

A1-A1= 575±209 A1-A1l 845+132

onstrated in the setting of constant isoproterenolinfusion, where the curve was shifted to the left (E.N.Prystowsky, unpublished data). The more pro-nounced effect of isoproterenol on the steep portionof the AV nodal function curve may well be second-ary to the decrease in time-dependent refractorinessproduced by isoproterenol in slow channel tissue.8As expected, during sinus rhythm, augmentation of

vagal tone slowed the sinus rate and caused nosignificant change in AV nodal conduction, a findingpreviously reported by Mancia et a13 in humans andMartin9 in dogs. In contrast, Warner and Loeb10showed significant prolongation in both the caninesinus cycle length and AH interval in sinus rhythmafter a bolus injection of phenylephrine. Minimaleffects on AV nodal conduction occur in sinusrhythm during augmentation of vagal tone because ofthe resultant long atrial cycle lengths that are on theflat portion of the AV nodal curve where vagalinfluence is slight. Even if the sinus rate did not slow,there might be little increase in the AH interval

2.2 * r 0.11

1.8.

1:1 CL1.4

1.0

0

0

0 .0

e

1.0 1.2 1.4 1.6 1.8

Sinus CLFIGURE 6. Plot showing sinus cycle length (CL) versus

shortest atrial pacing cycle length with 1 :1 atrioventricularnodal conduction during phenylephrine infusion (normalizedto baseline measurements). Note the lack ofa relation betweenthe degree of prolongation of the sinus cycle length and thechange in atrioventricular nodal conduction. The correlationcoefficient observed was 0.11.

unless, as noted below, there was an exceptionallymarked effect on AV nodal conduction that shiftedthe curve far to the right with the steep part close tothe sinus cycle length.

Since the AV nodal action potential duration is notprolonged under vagal influence,11,12 we propose thatthe observed effects of enhanced vagal tone on AVnodal function are due to changes in time-dependentrefractoriness, a property that is characteristic ofAVnodal tissue.13 The slow conduction occurring on thesteep portion of the AV nodal function curve prob-ably is due, in part, to an excitation wave front thatencroaches on the time-dependent refractory periodof the AV node. Shortening of the time-dependentrefractoriness in slow channel action potentials hasbeen demonstrated with isoproterenol, and the effectof isoproterenol is seen primarily on the steep part ofthe function curve.'4 It is reasonable to postulate thatincreased vagal tone also will exert its major influenceduring time-dependent refractoriness, only in an op-posite direction. In addition, this may be a moreuniversal response of AV nodal tissue, since otheragents such as verapamil and ,B-adrenoreceptor block-ers also primarily affect stressed AV nodal conductionwhile minimally affecting baseline conduction. 516

It is interesting to note that two of the threepatients with the most enhanced baseline AV nodalconduction demonstrated minimal change with phen-ylephrine in the cycle length that yielded 1:1 AVnodal conduction. Although the existence of a dis-tinct syndrome of "enhanced AV nodal conduction"has been questioned,7 it has been observed thatpatients with relatively enhanced AV nodal conduc-tion may demonstrate a lessened response to avariety of agents that have negative dromotropiceffects on AV nodal conduction.17-20 The reason forthe minimal shift in AV nodal conduction in thesepatients is unknown but could relate to anatomicvariations such as a decrease in the N region, wherepredominant slowing of conduction occurs, or partialbypass of normal AV nodal tissue. Alternately, there

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also may be functional abnormalities (e.g., a decreasein time-dependent refractoriness in an AV nodewithout associated morphological abnormalities).

Compartison of Sinus Automaticity andAVNodal ConductionWe found no relation between sinus and AV nodes

in their response to enhanced vagal tone, and thedegree of change in sinus rate did not predict thenegative dromotropic alteration ofAV nodal conduc-tion, as measured by the atrial-paced Wenckebachcycle length. In general, directional changes weresimilar; that is, increased vagal tone slowed the sinusrate and prolonged the Wenckebach cycle length.However, it was common to observe minimal changesin sinus rate associated with rather pronouncedincreases in the Wenckebach cycle length. Alter-nately, substantial slowing of the sinus rate could beassociated with small changes in AV nodal conduc-tion. Clearly, one cannot judge the effect of height-ened vagal tone on overall AV nodal conduction byobserved changes in sinus automaticity.

It is possible that the disparity between the re-sponse of the sinus and AV nodes to phenylephrine-induced enhanced vagal tone is due to differentialefferent nerve traffic to these structures. Randall andArmour21 demonstrated a variable and selective in-put of autonomic stimuli to the sinus and AV nodes.Discordant effects of autonomic influence on thesestructures also have been reported by others,1"2,22 andpreliminary data in humans have demonstrated se-lective vagal effects on the sinus and AV nodes withlocal discrete parasympathetic nerve stimulation.23,24Alternatively, there may be similar degrees of ef-ferent nerve impulses to both nodes but a greatersensitivity of the AV or sinus node to enhancedparasympathetic tone in a given patient.

Clinical CorrelationsThere are several clinical implications of the find-

ings in this study. Termination of paroxysmal su-praventricular tachycardia with carotid sinus massagetypically involves anterograde block of the impulse inthe AV node; in sinus rhythm, however, block in theAV node is markedly unusual. We have observedthat the cycle length during paroxysmal supraventric-ular tachycardia is most commonly within 30-40msec of the Wenckebach cycle length, with AV nodalconduction near the steep part of the function curve;this is where one would expect enhanced vagal toneto exert a prominent effect. The cycle length of sinusrhythm is on the flat part of the curve, and changes invagal tone typically alter AV nodal conduction onlyminimally. Another clinical correlation is observedduring sleep, a period associated with an increase invagal tone. Sinus slowing without AV nodal block isusual, but when the sinus rate is not significantlychanged, transient type I second-degree AV nodalblock may occur, presumably due to a significantdivergence of the vagal effect on the two nodes. Onthe other hand, abrupt AV nodal block accompanied

by sinus slowing can occur in patients with normalAV nodal function in response to a vagal surge,25demonstrating that large increases in parasympa-thetic activity can shift the AV nodal function curvesubstantially to the right, causing block even atslower sinus rates.

LimitationsWe assume that the effects noted during phenyl-

ephrine infusion are due to reflex vagal tone, al-though a direct effect of phenylephrine should beconsidered. In isolated canine Purkinje fibers, phen-ylephrine can decrease (low concentrations) or in-crease (high concentrations) automaticity.26 How-ever, direct canine sinus nodal artery infusion ofphenylephrine, at concentrations higher than thoseused in this study, caused acceleration of the sinusrate.27 Sympathectomy and vagotomy abolished thereflex sinus and AV nodal slowing in dogs in spite ofa continued pressor effect of phenylephrine.'0 Also,the canine bradycardiac response to phenylephrine isblunted when the hypertensive effect is mechanicallybuffered.28 Detailed electrophysiological evaluationof the effects of phenylephrine in vagotomized dogs,in the presence of atropine and nadolol, demon-strated that AV nodal function was unchanged andthat the sinus rate was accelerated slightly; this sinusnode effect persisted after blood pressure normaliza-tion with nitroprusside but was abolished by pra-zosin, suggesting that it was due to a direct effect ofphenylephrine.29 In humans, the reflex bradycardiaobserved with phenylephrine infusion has beenshown to be abolished by atropine22 and is notpresent in the denervated heart status after cardiactransplantation.30 On the basis of these data, weconsider it highly unlikely that phenylephrine in thedoses used exerted a significant direct effect on eitherthe sinus or AV nodes.

Increases in blood pressure induced by phenyleph-rine may diminish sympathetic tone, which couldaffect sinus and AV nodal function. Warner andLoeb'0 observed a markedly reduced slowing of thesinus rate and AV conduction in dogs with phenyl-ephrine after vagotomy. Further, Mancia et al3 notedthat the reflex effect of phenylephrine on the humansinus and AV nodes was abolished by atropine. Thus,with the doses of phenylephrine used in this study,the major effect appears to be secondary to enhancedparasympathetic tone, although there may be a minorcontribution due to sympathetic withdrawal.

AcknowledgmentsWe are grateful to Jackie H. Kasell for his engi-

neering support and to M. Laura Cook and thenursing staff of the Electrophysiology Laboratory.

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KEY WORDS * atrioventricular node * sinus node * vagus nerve* electrophysiology

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R L Page, A S Tang and E N Prystowskyfunction in humans.

Effect of continuous enhanced vagal tone on atrioventricular nodal and sinoatrial nodal

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