Atrial Fibrillation: Mechanisms and Management,
`2nd ed., edited by R. H. Falk and P J. Podrid.
`Lippincott—Raven Publishers, Philadelphia © 1997.
`
`6
`
`Role of the Atrioventricular Node
`in Atrial Fibrillation
`
`Frits L. Meijler and *Fred H. M. Wittkampf
`
`Professor of Cardiology, emeritus, The Interuniversity Cardiology Institute ofthe
`Netherlands, Utrecht, The Netherlands; and *Heart Lung Institute, University Hospital
`Utrecht, Utrecht, The Netherlands
`
`Atrial fibrillation (AF) is probably the most commoncardiac arrhythmia in humans, par-
`ticularly in the elderly (1-3). The irregularity and inequality of the heart beatfirst
`described by Hering in 1903 were, and continueto be, the landmark of the clinical diag-
`nosis ofAF (4,5). Sir Thomas Lewis (6) observedthe gross irregularity of the arrhythmia
`and stated “the pauses betwixt the heart beats bear no relationship to one another.”
`Thanks to work of Lewis (7), Mackenzie (8), Wenckebach (9), and others, the clinical
`syndrome of AF became well established, and gradually the pathophysiologic mecha-
`nisms involved were also recognized (10). In 1915 Einthoven and Korteweg (11) studied
`the effect of heart cycle duration on the size of the carotid pulse and concludedthat the
`strength of the heart beat was related to the duration of the preceding cycle. Later we
`repeated those observations by studying in a quantitative fashion the effects of randomly
`varying RR intervals on the contractions of isolated Langendorff perfusedrat hearts (12).
`Recently Hardmann confirmed the complicated relationship between the randomlyirreg-
`ular rhythm andleft ventricular function in patients with AF, confirming the involvement
`of postextrasystolic potentiation and restitution (13).
`Animals may also develop AF (14,15). Indeed, Lewis (7) observed the arrhythmia in an
`open-chest horse and used this observation to establish that the irregular pulse noticed in
`humans was dueto fibrillation of the atria. Until the 1950s, observations on AF were lim-
`ited to its etiologic, clinical, and surface ECG manifestations. The beginning of the com-
`puter era enabled several groups of investigators to analyze the ventricular rhythm during
`AF in a more quantitative fashion (16-18). The results of these studies were fascinating
`and allowed for the development of theories on the behaviorof the atrioventricular (AV)
`node during AF. Sophisticated computer techniques allowed Moe and Abildskov (19,20)
`to simulate atrial electrical activity during AF, and they formulated the so-called multiple
`wavelet theory, which was in 1985 supported by experimental evidence (21). Parallel to
`the growing insight into the electrical behavior of the atria during AF and into the corre-
`sponding ventricular rhythm, sophisticated experimental methods were designed to study
`AV nodal electrophysiology in a variety of circumstances, including induced AF (22,23).
`This chapter reexamines some of the established concepts of AV nodal function (24)
`because comparative physiology of the AV node and somespecific electrocardiographic
`observations in patients with AF have demonstrated inexplicable flawsin the current the-
`ories of AV nodal function. Alternate mechanisms, which till now have hardly been con-
`sidered as a basis for explaining AV nodal function during AF, will be discussed.
`
`109
`
`1
`
`APPLE 1022
`
`APPLE 1022
`
`1
`
`

`

`110
`
`ROLE OF THE ATRIOVENTRICULAR NODE
`
`In the first edition of this book (25) we postulated that the AV node,rather than acting
`as an intrinsic part of the cardiac conduction system,is primarily a pacemaker subject to
`electrotonic influences from other areas in the heart. However, as will be madeclear in
`this chapter, the pacemaker theory cannot explain all clinical phenomena inherent to AF.
`So a new model based on recently discovered cellular electrophysiologic principles
`(26,27) has been developed and will be presented.
`
`DEFINITION
`
`Atrial fibrillation has been defined by a WHO/ISFC Task Force (28) as “an irregular,
`disorganized, electrical activity of the atria. P waves are absent and the baseline consists
`of irregular wave forms which continuously change in shape, duration, amplitude, and
`direction. In the absence of advanced or complete AV block, the resulting ventricular
`responseis totally irregular (random).” This definition is applicable to routine medical
`practice, when we are usually satisfied that the atria are fibrillating if the ventricular
`arrhythmia fills the criterion ofbeingtotally irregular (random). This does not imply that
`during AF nonrandom ventricular rhythms cannot occur, but in case of a random ven-
`tricular ventricular rhythm anda typical aspect of the baseline of the ECG onecan becer-
`tain that the patient has true AF.
`Several investigators have studied the electrical activity of the atria during AF (29,30)
`and were able to demonstrate the chaotic character of the atrial electrical activity. Using
`signalanalysis of the atrial electrogram for the study of AF (31), we found a random pat-
`tern of the intervals between the zero crossings of the atrial deflections with a rate
`between 300 and 600/min. However, not only does the sequenceofthe recordedatrial sig-
`nals display a random pattern during AF, the form and strength of the recorded signals
`also fail to show any repetition. Thus, the AV node receivesor is surrounded by impulses
`that are random in time and almostcertainly also in form, strength and direction and this
`results in a random duration of the RR intervals (32,33).
`
`THE VENTRICULAR RHYTHM
`
`The (random) pattern of the ventricular rhythm during AF can be demonstrated by
`meansofa serial autocorrelogram (SAC), as illustrated on the right-handside ofFig.1.
`The SACis obtained by the measurementof the duration of the RR intervals. Each RR
`interval duration is correlated with itself, then with the duration of the next RR interval
`and subsequently with RR interval durations that are a given number of RR intervals
`ahead. Correlation coefficient number0is the result of correlating the duration of each
`RR interval with itself and consequently equals +1. Correlation coefficient | is the result
`of correlating the duration of each RR interval with the next and its value dependson the
`measure ofrelation between this two sets of RR interval durations. Similarly, correlation
`coefficient 10 represents the relation between the durationsof all RR intervals that are 10
`intervals apart, 20 represents all those that are 20 intervals apart, etc. In a random process
`all correlation coefficients greater than 0 have values that are statistically not signifi-
`cantly different from 0, and, consequently, if the values of successive correlation coeffi-
`cients of the RR intervals do not differ from 0, that rhythm may be called random. In Fig,
`1, derived from a patient with AF (32), it can be seen that before and after the adminis-
`tration of digitalis, the correlation coefficients do not differ from 0 and thus the ventric-
`ular rhythm under both circumstancesis, by definition, random. The histogram (left side
`
`2
`
`

`

`ROLE OF THE ATRIOVENTRICULAR NODE
`
`Ill
`
`
`
`
`
`
`
`
`PERIOD: REST
`TREATMENT: NONE
`
`coolficiont number
`
`fibrifation
`Atrial
`AHR = 108/min
`T
`2 557 mec
`$B = 126 mace
`
`500
`
`1000
`
`1500
`
`2000
`
`|
`
`i
`
`|i
`
`%
`ey
`
`.
`
`1S 4
`
`
`
`100
`
`50
`
`
`
`PERIOD: REST
`TREATMENT: DIGITALIS
`
`coofficiont number
`
`Atrial fibrillation
`ae 8 63/min
`!
`2 948 moc
`$0
`2233 moc
`
`500
`
`1000
`
`1500
`
`2000
`
`FIG. 1. Histogram and serial autocorrelogram (SAC) of a patient with atrialfibrillation without
`(A) and with (B) digitalis treatment. The SAC is unchanged,
`thus the ventricular rhythm
`remains random despite changein form and shift to the right of the histogram. For further
`details, see text. (From Bootsmaetal. ref. 32, with permission.)
`
`of Fig. 1) shows a decrease in ventricular rate produced by digitalis, but the degree of
`irregularity expressed as the dispersion of RR intervals (33) or coefficient of variation
`(CV) (34) remains constant. We will return to this later.
`The random ventricular rhythm in AF can also be described as a renewal process or as
`a “point process without memory.” A point process is a process in which the duration of
`the event—the R wave for instance—is short compared with the interval between events
`(the RR Interval). Well-known examples of point processes are the emissions from a
`radioactive source, the action potentials of a nerve fiber, coal mining disasters, and wars
`(35). In AF the duration of a forthcoming RR interval can neverbe predicted. After each
`event the processstarts anew,totally disregardingits past.
`Another way to display the ventricular rhythm during AF makes use of a so-called
`interval plot (Fig. 2). The duration of each RR interval is plotted against its sequential
`
`3
`
`

`

`112
`
`ROLE OF THE ATRIOVENTRICULAR NODE
`
`R-R ms
`2000
`
`1600
`
`1200
`
`
`
`FIG. 2. Interval plot of 500 RRinter-
`vals of a human patient with atrial fib-
`rillation. Each dot represents one RR
`interval. The
`arrow indicates
`the
`median RRinterval. For further details,
`0 500—see text. (From Meijler and Van der100 200 300 400
`
`
`Sequence Number
`Tweel, ref. 36, with permission.)
`
`
`
`
`
`
`
`number. The RR interval plot does not contain information that is not present in the his-
`togram and SAC,butit nicely illustrates the functional refractory period (FRP) of the AV
`junction as well as the maximal duration of the RR intervals of that particular patient at
`the time the recording was obtained (36).
`In 1970 we questioned (32) if the AV node hasa role to play in determining the degree
`of irregularity of the ventricular rhythm during AF since pharmacologic or physical inter-
`ventions that affect the ventricular rate during AF do not interfere with the random pat-
`tern of the ventricular rhythm. We concluded that the primary cause of the randomly
`irregular ventricular rhythm must reside in the fibrillating atria.
`
`DECREMENTAL CONDUCTION
`
`The slow ventricular response and its persistent randomness during AF have been
`explained by concealed conduction in, and the refractory periodof, the AV node. In 1948,
`Langendorf (37) introduced the term concealed conduction into clinical electrocardiog-
`raphy. The WHO/ISFC Task Force (28) defined concealed conduction as: “partial pene-
`tration of an impulse into the AV conduction system or a pacemaker-myocardialjunction,
`which exerts an influence on subsequent impulse formation or conduction or both.” The
`term has been redefined by Fisch (38) as “the presence of incomplete conduction cou-
`pled with an unexpected behavior of the subsequent impulse.” Concealed conductionis
`a concept, something that one cannot see but that has to be inferred from the aftereffect
`of a blocked impulse. Concealed conduction in the AV node during AF, amongothers,is
`assumed to result from decremental conduction (24,39). Hoffman and Cranefield (40)
`described decremental conduction as “a type of conduction in which the properties of the
`fiber change along its length in such a mannerthat the action potential becomes pro-
`
`4
`
`

`

`ROLE OF THE ATRIOVENTRICULAR NODE
`
`113
`
`gressively less effective as a stimulus to the unexcited portion ofthe fiber aheadofit.” In
`a recent article Watanabe and Watanabe (24) strongly advocated the concept of decre-
`mental conduction but, as we will show, this concept is at odds with a number of ECG
`symptomsthat can be observed during AF.
`In 1965, Langendorfet al. (41) postulated that concealed conduction in the AV junc-
`tion could explain the characteristics of the ventricular rate and rhythm during AF. Sev-
`eral subsequentinvestigators used the concept of decremental conduction to explain con-
`cealed conduction within the AV node during experimentally induced AF (24,42,43). The
`effects of drugs such asdigitalis (44), quinidine (45), and beta-blockers (46) on the ven-
`tricular rate in AF were also explained by this theory, although the sometimes observed
`so-called regularizing effect of verapamil and other Ca** antagonists remained less well
`understood (47).
`
`ELECTROTONIC MODULATION OF AV NODE
`PACEMAKER ACTIVITY DURING ATRIAL FIBRILLATION
`
`The majority of clinical investigators seemssatisfied with the decremental conduction
`concept, although Grant (48) in 1956 and James and his group (49) in 1977 suggested
`alternate explanations based on the theory that atrial impulses may modify an intrinsic
`pacemaking function of the AV node rather than being directly, albeit more slowly, con-
`ducted throughit.
`The concept of the AV node as an unprotected pacemakeris not new. As early as 1925
`Lewis (50) postulated that AV nodal function could be interpreted in another fashion than
`as conduction: “Thestructure of the A-V node andits similarities to the Sino-Atrial (S-
`A) node has suggested the last as the ventricular pacemaker, and it has been thought that
`a new anddistinct wave maystart in this after each systole of the auricle.”In this state-
`ment, Lewis considered AV nodal function during sinus rhythm orat least during orga-
`nized “auricular” activity as a form of pacemakeractivity.
`In 1929, two Dutch physicists (51), Van der Pol and Van der Mark, proposed that the
`heart beat could be viewed as a relaxation oscillator. A relaxation oscillator is best
`described as a condenserthat is periodically discharged by the ignition of a neon tube.
`An important characteristic of an oscillator is that it can be synchronized by external
`electric forces.
`Van der Tweel etal. (52) showed that the sinus node as well as the AV nodeofan iso-
`lated rat heart can be synchronized in the same way as a relaxation oscillator. Many years
`later we demonstrated that the function of the canine AV nodecan be describedasa peri-
`odically perturbed biologic oscillator (53). Perturbation and/or synchronization of an
`oscillator can be electrophysiologically translated into entrainment of a pacemaker (54).
`Segers et al. (55) first referred to possible synchronization of the AV nodal pacemaker
`resulting in a fixed temporal relation between the atria and the ventricles to explain an
`isorhythmic dissociation during complete heart block in patients. Jalife and Michaels
`(56) defined entrainment as the coupling of a self-sustained oscillatory system (such as
`a pacemaker) to an external forcing oscillation with the result that either both oscillations
`have the same frequency, or both frequencies are related in a harmonic fashion. Winfree
`(57) defined entrainmentas “the locking of one rhythm to another, with N cycles of the
`one matching M cycles of the other.”
`A possible electrophysiologic mechanism responsible for entrainment or synchroniza-
`tion of pacemakercells is an alteration of the rate of their phase 4 depolarization. It might
`
`5
`
`

`

`114
`
`ROLE OF THE ATRIOVENTRICULAR NODE
`
`thus be considered plausible that during sinus rhythm, the AV node, like the SA node,
`behaves as an oscillator or pacemaker that
`is entrained by the atrial depolarization
`sparked by SAfiring (58,59).
`Cohenetal. (59) developed a quantitative model along these lines to also describe the
`ventricular response during AF. Electrotonic modulation of phase 4 depolarization of a
`pacemakercell equivalent, by randomly occurring atrial impulses of random strength and
`duration and coming from random directions, could thus explain both the random and the
`slower ventricular rhythm during AF.
`Vereckei and coworkers have challenged the AV nodal pacemaker hypothesis (58-60).
`Utilizing an open-chest dog model they examined the effect of ventricular pacing at dif-
`ferent cycle lengths during induced AF. They were unable to consistently reproduce
`observations seen in humans,that is, that anterograde conduction in AF can be blocked
`by venticular pacing with interstimulus intervals considerably longer than the shortest RR
`intervals during anterograde conduction. Although they concludedthattheir results failed
`to support the modulated pacemaker hypothesis, they did concedethattheir data did not
`totally refute this hypothesis. Indeed, their results show that overdrive supression resulted
`in a varying return cycle length which is in agreement with our observations in patients
`(61). Moreover they used open-chest dogs with inducedatrialfibrillation and flutter. Arti-
`ficial AF may or may not simulate true AF in dogs (62), let alone in patients.
`
`ELECTRONIC MODULATION OF AV NODAL PROPAGATION
`
`During AF the AV node need not be a pacemaker with spontaneous phase 4 depolar-
`ization to be electrotonically modulated by the atrial impulses. Antzelevitch and Moe
`(63) have shownthat in segments with stable resting membrane potentials, nonconducted
`impulses can exert an inhibitory effect on the electrotonically mediated transmission of
`subsequent impulses orfacilitate propagation when two subthreshold potentials occur in
`close succession. This form of electrotonic modulation may be responsible for the
`dynamic changes in AV nodal propagation that lead to the totally irregular ventricular
`rhythmsin AF.
`This idea has been tested using a computer model of the AV node, consisting ofa lin-
`ear array of nine cells (64). Two cells represented the atrium, five the AV node, and two
`the ventricles. The cells were connected by appropriate coupling resistances. During reg-
`ular atrial pacing, the model reproduced very closely the frequency dependence of AV
`node conduction and refractoriness. In addition extra atrial impulses concealed within the
`AV nodeled to electrotonic inhibition and blockade of immediately succeeding impulses.
`During simulated AF, the random variations in the atrial intervals yielded random varia-
`tions in the ventricular intervals but, as in the reallife situation, there was no scaling; that
`is, ventricular intervals were not multiples of the atrial intervals. As such the model sim-
`ulated the statistical behavior of the ventricles during AF, including (a) the ventricular
`
`a F
`
`IG. 3. Electrotonic modulation of the AV nodal propagation curve. a: The upper histogram
`represents the distribution of the random atrial rhythm (A-A) supplied to the system; the lower
`histogram represents the (also random) ventricular rhythm (V-V) obtained. b: Each dot repre-
`sents the conduction time (A-V) in msec of every succesfully conductedatrial impulse, plotted
`againstits A-A interval. ERP = effective refractory period. Note the smearing of the A-V inter-
`vals. For further details: see text. (From Meijler et al., ref. 64 with permission.)
`
`6
`
`

`

`Yo
`
`%
`
`30
`
`20
`
`10
`
`0
`
`30
`
`20
`
`10
`
`0
`
`40
`
`200
`
`840 1000 1160
`520 680
`360
`A - A (msec)
`
`V - V (msec)
`
`A-V(msec) 3
`
`30 1200
`
`200
`
`400
`
`600
`B00
`A- A (msec)
`
`1000
`
`7
`
`

`

`116
`
`ROLE OF THE ATRIOVENTRICULAR NODE
`
`rhythm was random; and (b) the coefficient of variation (CV) of the ventricular rhythm
`was constant at any given ventricular rate. The random atrial intervals resulted in com-
`plex patterns of AV node concealment. Consequently the effects of electrotonic modula-
`tion were also random which resulted in a smearing of the AV node propagation curve,
`Fig. 3. During AF, electrotonic modulation acts in concert with the frequency-depen-
`dence of AV nodal conduction which results in the typical complex patterns of the ven-
`tricular intervals. Finally, similar to what has been shownin patients, regular pacing of
`the right ventricle at the appropriate frequency led to blockade of nearly all anterograde
`conduction. Electrotonic modulation of AV nodal propagation seemsto fulfill most if not
`all electrocardiographic requirements of AF (64).
`
`COMPARATIVE ASPECTS OF ATRIOVENTRICULAR NODAL FUNCTION
`
`Sinus Rhythm
`
`Waller in 1913 (65) studied comparative physiology and drew attention to the differ-
`ences in the “auriculo-ventricular” interval in dogs, humans, and horses. Clark (66) in
`1927 studied PR intervals in animals of different sizes and noted the small differences
`between PRintervals comparedto the differences in body size. A systematiclisting of PR
`intervals versus body size shows a comparatively short PR interval in hearts of large
`mammals and a long PRinterval in hearts of small mammals (42,67). Despite differences
`in detail, the overall architecture and microstructure of all mammalian hearts are essen-
`tially similar. Whether the source is the mouse or the whale, cardiac muscle is composed
`of individual cells that are relatively uniform in diameter, approximately 10 to 15 um
`(68). This similarity applies to the morphology of the mammalian AV node-His system
`as well. Both macroscopically and microscopically the structural arrangement of the
`mammalian AV conduction system tends to be similar, while the size of the heart varies
`greatly from species to species (69).
`Conduction velocity depends largely on cell (fiber) diameter (70,71). Assuming a
`more or less constant cell-to-cell resistance, it is unlikely that with increasing length or
`diameter of the His bundle and bundle branches the known conduction velocity of
`approximately 2.5 m/sec will increase significantly (72). However, Pressler (73) found a
`substantial difference of conduction velocity in Purkinje fibers in cats and sheep,
`although not enough to explain the small difference in PR interval between,for instance,
`a rat and an elephant(67).
`These observations suggest that in a large mammalian heart such as that of the ele-
`phant or whale the relative contribution to the AV conduction delay by the AV node or
`other components of the AV conduction system may be different from that of the heart in
`smaller mammals, for instance, the human, dog, or rabbit. For example, in the adult blue
`whale with a His bundle and branches that may be well over 1 m in length from theirori-
`gin at the distal end of the AV nodeto their terminal ventricular ramifications, approxi-
`mately 400 msec will be required for the impulse to cover that distance alone, assuming
`a conduction velocity of about 2.5 m/sec. Yet the PR interval in the elephant and hump-
`back whale does not exceed 400 msec (67,74—78).
`Therefore the AV node, although anatomically present in large mammals and physi-
`cally larger than in smaller mammals (69,79), would not be expected to create a substan-
`tial part of the delay of AV transmission during normalsinus rhythm, even if conduction
`velocity in the His bundles was greater than 2.5 m/sec. Figure 4 showsthat the PR inter-
`
`8
`
`

`

`ROLE OF THEATRIOVENTRICULAR NODE
`
`117
`
`Horse
`
`@
`
`@
`
`Beluga
`Whale
`
`Killer
`Whale Elephant
`
`=e
`
`Humpback
`oe
`
`PRinterval | ms]
`
`500
`
`400
`
`300
`
`200
`
`Man
`
`3 V
`
`V Heart weight|g]
`
`Dog s
`Cat e
`
`
`
`100
`
`0
`
`0
`
`5
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`40
`
`45
`
`50
`
`55
`
`FIG. 4. S-shape relationship between PR interval and third root of heart weight. Values
`obtained from Altman and Dittmer (100). (From Meijler et al., ref. 78, with permission.)
`
`val in a variety of mammals follows an S-shaped relationship when plotted against the
`third root of heart weight (42,67,77,78). This in itself asks for an explanation (80). If
`indeed, as can be inferred from Fig. 4, in larger mammals the contribution of the AV
`nodal delay to the PR interval is proportionately less than in smaller animals,it is diffi-
`cult to explain the mismatch between the PR interval and heart weight from accepted the-
`ories of decremental conduction in the AV node (42,80). At the same time one should
`realize that nobody haseverreliably measured the conduction velocity in the His-Purkinje
`system in mammals larger than humans. Therefore any explanation of the fascinating dis-
`proportionality between heart size and PR interval in large mammals is based on specu-
`lation rather than facts (24,67).
`
`Atrial Fibrillation
`
`Veterinarians are well aware of the frequent occurrence of AF in large dogs (15) (usu-
`ally with mitral valve disease) and horses (16,81—83). Indeed, as mentioned earlier, the
`relationship betweenfibrillating atria andatotally irregular ventricular rhythm wasfirst
`demonstrated by Lewis (7) in 1912 in a horse. Moe’s (20) multiple wavelet theory states
`that AF is maintained by the presence of a numberof independent wavelets that wander
`randomly through the myocardium aroundislets or strands of refractory tissue. In order
`for AF to be maintained, Moe’s theory requires a critical mass ofatrial tissue. It is of
`interest that, in keeping with Moe’s hypothesis, spontaneous AFis hardly ever observed
`in smaller mammals (82). Figure 5 demonstrates a once-in-a-lifetime observation: the
`interval plot, SAC, and histogram of the ventricular rhythm of a kangaroo with AF. This
`observation lends further credence to the concept that AF may occurin the heart of any
`mammal if Moe’s conditions are fulfilled (20,21),
`i.e., a sufficient number of cells
`involved and/or a sufficient degree of electrical inhomogeneity.
`
`9
`
`

`

`118s
`
`ROLE OF THE ATRIOVENTRICULAR NODE
`
`R-R ms
`
`=
`
`2000
`
`SAC
`
`LAG KANGAROO
`1.0
`
`750-750
`
`2750
`~=«—*1250«1750=«2250
`R-R (ms)
`
`«Sg 5
`
`10
`
`15
`
`20
`
`0
`
`100
`
`200
`
`400
`300
`Sequence Number
`
`500
`
`treatment : none
`median RR interval
`
`: 532 ms
`
`Interval plot, SAC, and histogram of a kangaroo with AF. FAP, functional refractory
`FIG. 5.
`period. The arrow indicates the median RRinterval. For further details, see text. (From Meijler
`et al., ref. 36, with permission.)
`
`Figure 6 shows median RR interval duration versus log body mass in kilograms in
`dogs, humans, and horses with spontaneous AF. The differences in ventricular rates
`between the three species as compared with the differences in body weightare small (34).
`The dog, human, and horse with AF may have almost equal ventricular cycles despite the
`fact that a horse’s heart is 50 to 100 times as heavy as that of a dog. In dogs, as in humans,
`the ventricular rhythm is random.In horses, depending on the ventricular rate, a certain
`degree of periodicity may occasionally be present. This could be caused by autonomic
`nerve interference with AV junctional electrophysiologic properties elicited by the very
`long RR intervals that often occur (4 sec and longer) and are associated with a concomi-
`tant drop in blood pressure (83).
`
`1500
`
`1000
`
`un > o
`
`MedianR-Rintervalinms FIG. 6. Median RRintervals of dogs, humans,
`
`“4
`
`0
`
`1
`
`4
`3
`2
`Log (body massin kg)
`
`5
`
`fibrillation versus log
`and horses with atrial
`body weight. For further details, see text. (From
`Meijler et al., ref. 34, with permission.)
`
`10
`
`10
`
`

`

`ROLE OF THE ATRIOVENTRICULAR NODE
`
`119
`
`THE ATRIOVENTRICULAR NODE
`AS A GATEKEEPER IN ATRIAL FIBRILLATION
`
`Patients with AF and a bypass of their AV node may experience very high ventricular
`rates and often ventricular fibrillation. It is fair to say that the ventricles are protected
`against high atrial rates like AF by the AV node (84-87). Thus the AV node may be con-
`sidered as a guard or a gatekeeper, allowing someatrial impulses to pass while prevent-
`ing many others from entering the gate.
`Theclassical theory that during AF the AV node behavesas a gatekeeper by means of
`decremental conduction (24,40), enabling someatrial impulses to be propagated to the
`ventricles, while others are prevented from propagation, has been challenged by several
`investigators (48,49,58,61,64,88-90). Howeverin itself, the metaphor of the AV node as
`gatekeeper is useful, depending on how the function of the gatekeeper is prescribed. A
`gatekeeper may considerall subjects that want to pass the gate and then select, for what-
`ever reason, one or more that will be admitted. He may also guard his gate by only let-
`ting pass subjects with certain properties, while others not having such a property are
`not even considered. Moreover, the gatekeeper can also set a fixed or variable time (a
`refractory period) within which no subject, not even one with a valid passport,
`is
`allowed to pass the gate. One may also assume that the guard changes its behavior
`depending on the number and quality of the impulses and the direction they come from.
`As we will show, the latter form of AV node behavior seems a fair description of what
`actually goes on.
`
`THE COMPENSATORYPAUSE IN ATRIAL FIBRILLATION
`
`A compensatory pause following a premature ventricular depolarization during sinus
`rhythm is a well-recognized electrocardiographic phenomenon. Langendorf(91), Pritch-
`ett et al. (92), and others (93) have demonstrated that the ventricular cycle is lengthened
`after a ventricular extrasystole even in the presence of AF. Langendorf (91) termed this
`phenomenon the “compensatory pause in atrial fibrillation” and believed that it was
`caused by lengthening of the AV nodal refractory period due to retrograde concealed con-
`duction into the AV node of the spontaneousorartificially induced ventricular extrasys-
`tole. However, both Moore and Spear (94) and Akhtar and coworkers (95) have subse-
`quently shownthat properly timed retrograde concealed conduction into the AV node
`facilitates rather than slows AV anterograde conduction. A substantial numberofatrial
`impulses normally delayed and blocked within the AV node would be potential candi-
`dates for facilitated propagation following concealed retrograde penetration of a ventric-
`ular extrasystole into the AV node. Facilitation of anterograde transmissionhasto the best
`of our knowledge never been observed after ventricular extrasystoles in the presence of
`AF, nevertheless lengthening of the refractory period of the AV node by the ventricular
`extrasystole is not likely to explain the compensatory pause in AF.
`In 1990 wepostulated that the duration of the (compensatory) pause after single ven-
`tricular extrasystoles may be caused by two different mechanisms, depending on the time
`of the extrasystole relative to the preceding “normally propagated” QRS complex (96).
`
`1. Relatively early, retrogradely conducted ventricular extrasystoles [interval between R
`wave and extrastimulus (RS in Fig. 7)] cause the histogram of the postextrasystolic
`RR intervals (SR in Fig. 7) to shift to the right without a change in shape when com-
`pared with the histogram of the “normal” RR intervals. Thus, a ventricular extrasys-
`
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`

`120
`
`ROLE OF THE ATRIOVENTRICULAR NODE
`
`
`
`500
`
`1000
`
`1500
`
`2000
`
`FIG. 7. Histograms of the spontaneous RR intervals (RA) and of the compensatory pauses
`(SR) after properly timed ventricular extrasystoles (RS) in a patient with atrial fibrillation. S
`standsfor the ventricular extrastimulus. The similarity of both histograms should be noted. For
`further details, see text.
`
`tole that reaches and depolarizes the AV node has the same effect on the timing of
`the next AV nodal discharge as an impulse that has depolarized the AV node from the
`atrial side and resets the refractory period of the AV nodalcells causing the AV nodal
`propagation curve to shift to the right.
`2. Retrograde conduction of extrasystoles occurring later in the ventricular cycle will
`simply intercept anterograde impulses below the AV node,resulting in a completely
`different postextrasystolic histogram (96) (not shownin Fig.7).
`
`THE EFFECT OF VENTRICULAR PACING IN ATRIAL FIBRILLATION
`
`If one properly timed ventricular extrasystole penetrates into the AV node andis able
`to reset the AV nodal propagation curve, it follows that repeated ventricular pacing at an
`appropriate rate will continuously activate and reset the AV node (88,89). In Fig. 8 the
`effect of right ventricular (RV) pacing with decreasing pacingintervals in a patient with
`AFis shown in an interval plot. It can be seen that, as expected, at a pacing interval of
`1,000 msecall RR intervals over 1,000 msec are abolished. However, at the same time
`the numberof short RR intervals diminishes. This becomes even more evident at a pac-
`ing interval of 850 msec, and at 700 msec all anterograde transmission is blocked
`despite the fact that the pacing intervals are almost twice as long as the shortest RR
`intervals before ventricular pacing. Only during AF and intact AV nodal conduction
`pathways is a ventricular rhythm capable of continuously blocking anterograde con-
`duction. In other words, during AF ventricular captures often observed during sinus
`rhythm and an accelerated ventricular rhythm or ventricular tachycardia should not
`occur. Single wide QRS complexes without a compensatory pause (91) must be due to
`aberrant anterograde conduction.
`This observation fits well with the theory that repetitive RV pacing (or an accelerated
`ventricular rhythm) may cause overdrive suppression of an AV nodal pacemaker or con-
`tinuously reset
`the AV nodal propagation curve, making it
`impenetrable for atrial
`impulses and resulting in total anterograde block. This observation can also be explained
`on the basis of overdrive suppression of conduction (97).
`
`12
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`12
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`

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`ROLE OF THE ATRIOVENTRICULAR NODE
`
`12]
`
`ms
`
`1500
`
`CO 58.67. 329
`
`
`
`N
`aaa14;SeaamIaGiainnaRIInAmIaaLT)KREERAREREEETREiEEaaa
`0
`500
`1000
`1500
`2000
`
`FIG. 8. Successive RR intervals in a patient with AF before (first 500 cycles) and during pac-
`ing on the right ventricle with a pacing interval of 1,000, 850, and 700 msec (cycles 50