POINT OF VIEWSection Editor: Yoram Rudy, Ph.D.

Anatomic and Functional Fast AtrioventricularConduction Pathway

EUGENE PATTERSON, PH.D., and BENJAMIN J. SCHERLAG, PH.D.

From the University of Oklahoma Health Sciences Center and Department of Veterans Affairs Medical Center,Oklahoma City, Oklahoma

Introduction

Dual AV nodal conduction pathways have long beenappreciated as an underlying electrophysiologic foundationnecessary, but not suf� cient, for the initiation and mainte-nance of sustained AV nodal reentrant tachycardia(AVNRT). Dual AV nodal electrophysiology consists oftwo different pathways for anterograde AV activation: onepathway with a short atrial–His-bundle activation (AH)interval and a prolonged refractory period (fast AV conduc-tion pathway) and a second pathway with a prolonged AHinterval and a shorter refractory period (slow AV conduc-tion pathway).1 ,2 When an atrial premature beat falls in theinterval between fast pathway and slow pathway refracto-riness, AV conduction abruptly switches from the fast con-duction pathway (shorter AH interval) to the slow conduc-tion pathway (longer AH interval).

Radiofrequency lesions producing a line of conductionblock from the coronary sinus os to the tricuspid annulus orslightly more anterior, from the tendon of Todaro to thetricuspid valve annulus, terminates AVNRT and eliminatesAV activation via the slow conduction pathway.3 ,4 Activa-tion over the fast AV conduction pathway remains relativelyunchanged, with little change in the AH interval or fastpathway refractory period. Transitional cells of the posteriorinput provide direct access to the anatomic compact AVnode (as described and de� ned by Tawara5) in a number ofdifferent mammalian species.5 In contrast, the anatomicpathways and the electrophysiologic roles for transitionalcells comprising other inputs to the compact AV node areless well de� ned. We propose the following four hypotheseswith regard to the nature of the fast AV conduction path-way.

Hypotheses

Hypothesis one: Transitional cells along the anteriorlimbus of the fossa ovalis are the normal input for theanterograde fast AV transmission pathway. In the rabbitand dog, transitional cells have a modest phase 2 plateauand prolonged refractoriness in contrast to atrial myocar-dium. A rapid phase 0 upstroke, rapid dV/dtmax, increasedaction potential amplitude, increased overshoot potential,

and decreased excitation threshold distinguish transitionalcells as distinct from the much less excitable N cells of thecompact AV node (Fig. 1 and Table 1).

Although transitional cells located along the anteriorlimbus of the fossa ovalis demonstrate only 2:1 block (asopposed to Wenckebach block) as the atrial heart rate in-creases, the selective destruction of these transitional cellsin the rabbit heart6 and the dog heart7 prolongs AH and PRintervals without altering the AH Wenckebach heart rate.The same lesion shifts the earliest site of retrograde atrialactivation posteriorly to the area of the coronary sinus os7 ,8

and prolongs the VA Wenckebach cycle length.7 Thus, inthe rabbit heart and the dog heart, selective ablation oftransitional cells located along the anterior limbus elimi-nates anterograde activation via the fast AV conductionpathway. Although these cells fail to determine AV Wenck-ebach block, transitional cells along the anterior limbusdetermine 2:1 AV conduction observed at atrial heart ratesfaster than the Wenckebach heart rate, underscoring part oftheir important role as an AV nodal input.6 ,7 ,9 ,10

Hypothesis two: AV Wenckebach can be observedduring fast pathway activation but is provided by an-other group of transitional cells (mid pathway) locatedimmediately superior to the compact AV node. Transi-tional cells located superior to the compact AV node pro-vide the site of AV Wenckebach block with pacing from theanterior limbus in rabbit and dog hearts. Microelectroderecordings obtained from the superfused rabbit AV junctionand perfused dog heart lead us to propose that transitionalcells located immediately adjacent to the compact AV nodeform an essential component of the fast AV conductionpathway. Although the same cells provide the site ofWenckebach block with pacing posterior to the fossa ovalis(mid pathway), the AH intervals and AV Wenckebach blockcycle lengths are markedly different for the two sites6 ,11

(Table 1).Pacing from the mid pathway provides for a prolonged

AV Wenckebach cycle length and a longer AH conductioninterval compared with pacing from the anterior limbus (fastpathway) (Table 1). After ablation of both the slow pathwayand fast pathway inputs, AH conduction is markedly pro-longed with mid pathway pacing. HA conduction uniformlyblocks between N cells and transitional cells of the midpathway. Thus, the transitional cells (mid pathway input)providing a third input to the compact AV node represent asecond “slow AV conduction pathway” rather than a “fastAV conduction pathway.”6 ,7 ,11

Hypothesis three: AV conduction via the fast path-

J Cardiovasc Electrophysiol, Vol. 13, pp. 945-949, September 2002.

Address for correspondence: Eugene Patterson, Ph.D., Oklahoma HealthScience Center, 6E 103 Everett Tower-CARI, 1200 Everett Drive, Okla-homa City, OK 73104. Fax: 405-271-7455; E-mail: eugene-patterson@ouhsc.edu

945Reprinted with permission fromJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Volume 13, No. 9, September 2002

Copyright ©2002 by Futura Publishing Company, Inc., Armonk, NY 10504-0418

way in the normal heart and retrograde VA conductionduring slow-fast AVNRT can follow different anatomicpathways. Dual AV nodal conduction pathways and single-beat atrial echo beats are a common feature in the normalrabbit, dog, and human heart, as well as an obligate attributeof hearts demonstrating slow-fast sustained AVNRT.1 ,2 ,1 2 ,13

It has long been assumed that the reentrant pathways forsingle atrial echo beats and sustained AVNRT are identical,with identical anterograde fast conduction and retrogradeVA conduction pathways. Under this assumption, the site ofearliest atrial activation should be identical during ventric-ular pacing, atrial echo beats, and sustained slow-fastAVNRT. This contention has been challenged by clinicalelectrophysiologic studies.

Variation is present for the site of earliest retrogradeatrial activation during slow-fast sustained AVNRT. Thesite of earliest retrograde activation is not found consistently

at the same anterior site observed in normal hearts, but it canbe found posterior and inferior to the anterior limbus alongthe tendon of Todaro.14 ,1 5 In some patients with slow-fastsustained AVNRT, radiofrequency ablation on the atrialseptum eliminates VA conduction and the ability to sustainAVNRT. Dual AV node physiology without prolongationof the fast pathway AH interval and the ability to inducesingle echo beats persist in the absence of sustainedAVNRT,16 suggesting selective ablation of the retrogradelimb of AVNRT without ablation of the anterograde fastconduction pathway.

Anatomic and electrophysiologic variation exists for theretrograde conduction limb of the slow-fast AV nodal re-entry circuit. Earliest activation has been reported bothoutside and within the triangle of Koch, either superior orinferior to the tendon of Todaro. In many patients withsustained slow-fast AV nodal tachycardia, the retrograde

Figure 1. Intracellular recordings from the superfused rabbit AV junction. Intracellular microelectrode recordings are shown for three transitional cellpopulations (deep, super� cial, and posterior) constituting the mid pathway, fast pathway (FP), and slow pathway (SP) inputs to the compact AV node inthe superfused rabbit AV junction. Also shown are intracellular microelectrode recordings for the compact AV node (AVN) and His bundle (HB). The AVanatomy drawing has been modi� ed from Becker and Anderson.24 The electrophysiologic properties of the various cell populations are given in Tables 1and 2. CFB 5 central � brous body; RBB 5 right bundle branch.

TABLE 1Intracellular Recordings and Pacing Within the AV Junction

RMP(mV) APA (mV)

Vmax

(V/sec)APD90

(msec)Excitation

Threshold (nA)Local Conduction

Block (msec)AH Interval

(msec)

Atrial (N1 5 40; N2 5 34) 281 6 1‡ 108 6 2‡ 158 6 11‡ 114 6 5† 404 6 32 97 6 12 (2:1) 94 6 14Posterior input (SP) (N1 5 42; N2 5 17) 266 6 2‡* 70 6 2‡* 41 6 2‡ 125 6 3† 2186 6 173* 188 6 11 (WB) 93 6 19Mid pathway (MP) (N1 5 21; N2 5 9) 266 6 3‡* 70 6 2‡* 50 6 5‡ 121 6 5† 2345 6 198* 208 6 15** (WB) 108 6 14**Anterior input (FP) (N1 5 32; N2 5 30) 265 6 1* 71 6 2‡* 60 6 1‡ 120 6 5† 1284 6 202* 143 6 12†† (2:1) 88 6 18N cells–AV node (N1 5 22; N2 5 18) 258 6 3* 54 6 3* 18 6 6* 100 6 4† Inexcitable at

5,000 nA— —

NH cells–AV node (N1 5 20; N2 5 14) 262 6 1* 61 6 2* 29 6 6* 110 6 4† 1460 6 205* — —His bundle (N1 5 30; N2 5 15) 282 6 1‡ 111 6 1‡ 140 6 6‡ 177 6 4 402 6 19 — —

N1 5 number for ME recordings; N2 5 number for intracellular stimulation.RMP 5 resting membrane potential; APA 5 action potential amplitude; Vmax 5 dV/dt of phase 0 upstroke; APD90 5 action potential duration at 90% ofrepolarization; WB 5 Wenckebach.*P , 0.05 vs atrium and His bundle; †P , 0.05 vs His bundle; ‡P , 0.05 vs N cells–AV node and NH cells–AV node; **P , 0.01 vs atrium, posterior,and anterior input; ††P , 0.01 vs atrium, posterior, and mid pathway.

946 Journal of Cardiovascular Electrophysiology Vol. 13, No. 9, September 2002

HA interval during ventricular pacing and sustained tachy-cardia, as well as the retrograde VA Wenckebach cyclelength during ventricular pacing, are dramatically reducedwith little or no HA decrement as the ventricular cyclelength is reduced.1 7 The incidence of rapid retrograde VAconduction in patients with sustained slow-fast AVNRTrepresents an approximate fourfold increase over the inci-dence of rapid retrograde conduction in the overall popula-tion of patients undergoing clinical electrophysiologic stud-ies.1 8 Rapid, nondecrementing retrograde conduction in therabbit is mediated by a unidirectional (retrograde conduct-ing only) bypass tract comprised of transitional cells con-necting the His bundle and the anterior limbus. Althoughsuch bypass tracts have been described in human hearts atautopsy, the incidence (2/687 hearts)1 9 differs from thehigher incidence in the rabbit heart (13/102 hearts) associ-ated with rapid nondecremental retrograde HA conductionin the rabbit heart, in the dog,2 0 and in man.1 8

Multiple reentrant pathways provide for slow-fast atrialecho beats in the superfused rabbit AV junction. Singleatrial reentrant beats can be observed following conductionblock in the fast conduction pathway, with anterogradeactivation proceeding along the posterior AV nodal input(Fig. 2). Only rarely are multiple atrial echoes observedusing this anatomic pathway.2 1 Surgical transection of thefast pathway prevents atrial echo beat formation (Fig. 2). A

more common reentrant mechanism for atrial echo beatsand sustained AVNRT also is present in the superfusedrabbit AV junction. Both the anterograde (inferior) andretrograde (superior) limbs of the reentrant pathway arecontained entirely within the triangle of Koch, with earlyatrial activation during a sustained slow-fast tachycardiaoccurring along the anterior limbus of the fossa ovalis (Fig.3). Longitudinal dissociation within the transitional cellpopulation comprising the posterior AV nodal input, andextending into the compact AV node, provides the reentrantpathway. Early fast pathway activation during slow-fastAVNRT occurs as a spur to the reentrant pathway. Singleand multiple echo beats and sustained AVNRT are providedby this mechanism. The sustained tachycardia can be resetby a single premature beat introduced below the coronarysinus os.

As suggested by Otomo et al.,2 2 any model for sustainedslow-fast AVNRT in humans must be consistent with thefollowing observations: (1) an ability to reset the tachycar-dia with a late atrial extrastimulus delivered within thecoronary sinus; (2) the occasional ablation of the slowpathway from within the proximal coronary sinus; and (3) arelatively late activation of the posteroseptal right atriumwithin the triangle of Koch (between the tricuspid annulusand the coronary sinus ostium), after the timing of activationwithin the coronary sinus. These criteria would be dif� cult

Figure 2. Localized reentry within the superfused rabbit AV junction. In the upper left panel (panel A), during pacing from the high right atrium at a cyclelength of 400 msec, a premature stimulus is introduced at a coupling interval of 240 msec, activating both the slow and fast pathway inputs. With ashortening of the coupling interval to 200 msec (panel B), conduction block is observed in the fast pathway (FP), distal to the FP microelectrode and bipolarrecordings. Slow pathway (SP) conduction is maintained with a prolonged AH interval in the His-bundle (HB) recording, with retrograde conduction intothe fast pathway and atrium (Ae). With a further shortening of the premature stimulus to 180 msec (panel C), block is observed in both the slow pathwayand fast pathway inputs despite high right atrial activation. After a transection performed immediately superior to the compact AV node (panel D), thepremature atrial stimulus producing an echo beat before transection in panel B now fails to produce an echo beat, despite maintaining slow conductionwithin the slow AV conduction pathway and producing delayed His-bundle activation.

Patterson and Scherlag Point of View 947

to satisfy without proposing a model wherein both theanterograde and retrograde conduction limbs of the tachy-cardia are contained within the triangle of Koch and/or atrialseptum. The data also could be consistent with an intranodallocation for the sustained tachycardia,2 3 with only localstimulation within the triangle of Koch capable of entrain-ing and terminating sustained reentry. Such an intranodallocation would require a substantially larger functional AVnode than the anatomic node described by Tawara5 andwould require the inclusion of transitional cells functioningas AN cells as components of the AV node.

Hypothesis four: The anterograde fast conduction

pathway and the retrograde VA conduction pathwaycan be different pathways in the absence of AVNRT.With pacing from the anterior limbus in the rabbit, thepredominate anterograde AV conduction sequence proceedsas follows: transitional � bers of the anterior (fast pathway)input–transitional cells superior to the compact AV node(mid pathway) (site of Wenckebach block)–N cells of thecompact AV node–NH cells of the compact AV node–Hisbundle. Evidence for a direct connection between anteriortransitional cells and the compact AV node is lacking.During His-bundle pacing in the same hearts, the earliestsite of retrograde atrial activation is observed along theanterior limbus of the fossa ovalis. The most commonretrograde VA conduction sequence proceeds as follows:His bundle–NH cells of the compact AV node–N cells ofthe compact AV node (site of retrograde Wenckebachblock)–transitional cells superior to the compact AV node–transitional � bers of the anterior input, a reversal of theanterograde conduction sequence. In approximately 1 of 3rabbit hearts, however, the His-bundle–fast pathway activa-tion time is signi� cantly reduced. Transitional cells of thefast pathway are activated before N cells in the compact AVnode, suggesting a direct connection between transitionalcells and the distal AV node during retrograde VA activa-tion. The incidence of partial AV nodal bypass (bypass ofthe N cell region) is increased for both anterograde AH andretrograde HA conduction with transection between thecompact AV node and transitional cells posterior to theanterior limbus. The anterograde AH or retrograde HAinterval is reduced and the site of AH or HA Wenckebachblock shifts to the NH region of the compact AV node. Thepresence of a partial AV nodal bypass tract may be asym-metric, with different activation sequences for anterogradeand retrograde activation.

Conclusion

We propose the following four hypotheses:

1. The fast pathway input to the AV node and earliestretrograde atrial activation site in the normal rabbit, dog,and human heart lie along the anterior limbus of the fossaovalis. The site is the typical His-bundle recording atwhich earliest atrial activation is seen during retrogradeconduction.

2. Anterograde AV Wenckebach with pacing from the fastpathway input (anterior limbus) is mediated by transi-tional cells located superior to the compact AV node.

3. The anatomic and electrophysiologic bases are differentfor anterograde fast pathway AV conduction in the nor-mal heart and retrograde VA conduction during slow-fast AVNRT.

4. Anterograde fast pathway and retrograde VA conductionmay be observed to bypass the N cell region of the AVnode. The incidence of partial AV nodal bypass is facil-itated by reduced input from the posterior and/or midpathways and results in asymmetric anterograde AH andretrograde HA conduction pathways.

The four hypotheses help to explain some of the newerexperimental and clinical � ndings concerning the normalfast AV conduction pathway as well as those related tosustained slow-fast AV nodal tachycardias in rabbit, dog,and human hearts.

Figure 3. Localized reentry within the triangle of Koch: a mechanism foratrial echo beats and sustained AV nodal reentrant tachycardia. Intracel-lular microelectrode recordings (upper three panels) are shown for twosites within the posterior AV nodal input and for NH cells of the compactAV node during pacing from the high right atrium at a basic cycle lengthof 230 msec and for the introduction of a premature stimulus with acoupling interval of 200 msec. Bipolar electrode recordings are shown forthe fast pathway (FP), slow pathway (SP), and His bundle (HB) (lowerthree panels). Locations for the recording sites are shown in the schematicin the lower left-hand panel. The st-His interval is shown for prematurestimuli introduced at intervals of 180 to 230 msec (lower right panel).Longitudinal dissociation extended into the compact AV node (N cellregion). Introduction of a premature stimulus at an interval of 200 msecblocks at SP-1 immediately inferior to the tendon of Todaro while con-ducting with a prolonged AH interval near the tricuspid valve. A sponta-neous beat is observed at SP-1, followed by reexcitation at SP-5 and blockagain at SP-1.

948 Journal of Cardiovascular Electrophysiology Vol. 13, No. 9, September 2002

Glossary of Terms for the Present Discussion

AH interval: Interval between atrial and His-bundle ac-tivation measured at the AV junction

Anterior AV nodal input: Transitional cells of the super-� cial AV nodal input located along the anterior limbus ofthe fossa ovalis

AV node: Compact AV node as described by Tawara,5consisting of N cells (long latency .20 msec with atrial andHis-bundle pacing) and NH cells (,20 msec latency withHis-bundle pacing and .20 msec latency with atrial pacing)

Fast AV conduction pathway: AV conduction pathwaywith a short AH interval and a prolonged refractory period

HA interval: Interval between His-bundle and atrial ac-tivation during ventricular pacing measured at the AV junc-tion

Mid pathway input: Transitional cells of the deep AVnodal input

Posterior AV nodal input: Transitional cells located pos-terior to the compact AV node extending toward the coro-nary sinus os

Slow AV conduction pathway: AV conduction pathwaywith a prolonged AH interval and a short refractory period

Wenckebach block cycle length: Cycle length producing3:2 HA or AH conduction block

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