Patterns of Atrioventricular Conduction in the Human Heart ANDREW L. WIT, MELVIN B. WEISS, WALTER D. BERKOWITZ, KENNETH M. ROSEN, CHARLES STEINER and Anthony N. Damato Circ. Res. 1970;27;345-359 Circulation Research is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX 72514 Copyright © 1970 American Heart Association. All rights reserved. Print ISSN: 0009-7330. Online ISSN: 1524-4571

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circres.ahajournals.org

Subscriptions: Information about subscribing to Circulation Research is online at http://circres.ahajournals.org/subscriptions/ Permissions: Permissions & Rights Desk, Lippincott Williams & Wilkins, a division of Wolters Kluwer Health, 351 West Camden Street, Baltimore, MD 21202-2436. Phone: 410-528-4050. Fax: 410-528-8550. E-mail: [email protected] Reprints: Information about reprints can be found online at http://www.lww.com/reprints

Downloaded from circres.ahajournals.org by on December 23, 2008

Patterns of Atrioventricular Conduction in the Human Heart By Andrew L. Wit, Ph.D., Melvin B. Weiss, M.D., Walter D. Berkowirz, M.D., Kenneth M. Rosen, M.D., Charles Steiner, M.D., and Anthony N. Damato, M.D. ABSTRACT Atrial, His bundle (H), and ventricular electrograms were recorded by an electrode catheter in unanesthetized man. Conduction time through the atrioventricular (A-V) conduction system was subdivided into A-V nodal (A-H interval) and ventricular specialized conduction system (H-V interval). The right atrium was driven at a constant rate and the pattern of A-V conduction of premature atrial test impulses was determined as they occurred progressively earlier in the cardiac cycle. In the type 1 response, conduction delay and block were limited to the A-V node only. The type 2 response was characterized by progressive conduction delay in both the A-V node and ventricular specialized conduction system with block occurring in several instances in the latter. In the type 3 response there was also a progressive delay in A-V nodal conduction time, and a sudden marked delay in conduction in the ventricular specialized conduction system. Conduction block occurred distal to the His bundle depolarization. The relevance of conduction delay and block in the different regions of the A-V conduction system to the full recovery time and the relative, functional, and effective refractory periods of A-V conduction are indicated. ADDITIONAL KEY WORDS premature atrial impulses functional refractory period effective refractory period

His bundle electrogram conduction block conduction delay full recovery time relative refractory period

• Conduction of impulses from the atria to the ventricles involves propagation through a series of elements known as the atrioventricular (A-V) conduction system. This system includes the A-V node and the ventricular specialized conduction system (VSCS), which includes the bundle of His, the bundle branches and peripheral Purkinje network (1). Previous investigations in dogs have shown some of the physiological properties of A-V conduction by studying the propagation of premature atrial impulses (2-5). The characteristic types of A-V delay differed in different From the Cardiopulmonary Laboratory, U. S. Public Health Service Hospital, Staten Island, New York 10304. This work was supported in part by the Federal Health Program Service, USPHS Project Py 70-1, National Institutes of Health Projects HE 11829 and HE 12536, and NASA Contract T 22416 (G). Received April 6, 1970. Accepted for publication July 14, 1970. Circul

ationResearch, Vol. XXVII,

September

animals, ranging from an increase in proportion to the prematurity of the propagated atrial response to an abrupt increase at a critical degree of prematurity (3, 4). A dual A-V nodal transmission system was originally postulated to explain the results (3). Experiments on the canine heart by Hoffman et al. have convincingly demonstrated by localized electrograms recorded from various regions of the A-V conduction system that both the A-V node and the VSCS can contribute to the delay in A-V conduction (4). Consequently, conduction delay in the VSCS could well account for several properties previously ascribed to the A-V node. Likewise, studies by Damato et al. in man have demonstrated that conduction delay of premature atrial impulses can also occur in the VSCS (6). The present study was undertaken to characterize the responses of the A-Vconduc tion system in man to premature atrial

1970

Downloaded from circres.ahajournals.org by on December 23, 2008

345

346

WIT, WEISS, BERKOWITZ, ROSEN, STEINER, DAMATO

Refractory Periods of the A-V Conduction System Diagnosis

FRT

AVCS FRP

ERP

A1-A2

V1-V2

A1-A2

B.C. F.C. J.W. H.M. J.V. A.M. R.F. R.P. J.B.

NHD ASHD NHD ASHD ASHD ASHD NHD NHD NHD

650 630 650 665 700 720 560 650 685

395 375 375 420 415 417 390 485 420

S.B. R.D. JQ. C.R. M.M. J.G. C.C.* K.C.*

NHD NHD ASHD ASHD NHD NHD AP ASHD

600 710 565 560 600 600 580 640

455 430 430 460 355 377 425 540

C.G. B.D. H.C.

NHD ASHD NHD

650 610 640

490 475 500

Patient

VSCS FRT ERP

AVN

FRT

A1-A2

Type 1 270 275 260 250 260 295 245 250 265 Type 2 280 330 315 255 275 280 365 505 Type 3 390 360 410

FRP

ERP

H1-H2 H1-H2

Hi-H 2

A1-A2

650 630 650 665 700 720 560 650 685

395 '375 375 420 415 417 390 485 420

270 275 260 250 260 295 245 250 265

600 710 565 560 600 600 580 640

385 405 395 375 345 365 365 490

280 330 315 255 275 280 275 400

450 430 405 450 350 382 420 525

400 530

650 610 640

420 410 365

335 330 285

495 485 435

430 420 400

All values are expressed in msec. AVCS = A-V conduction system; AVN = A-V node; VSCS = ventricular specialized conduction system; FRT = full recovery time; FRP = functional refractory period; ERP = effective refractory period; ASHD = arteriosclerotJc heart disease; AP = acute pericarditis; NHD = no heart disease. *Modified type 2 response.

stimulation. Since A-V conduction delay and block can be encountered in any of the structures in the A-V conduction system, localized His bundle electrograms were utilized to separate conduction time in the A-V node from that in the His-Purkinje system. Methods

Studies were performed on 20 subjects with normal A-V conduction as judged by electrocardiographic criteria; (normal sinus rhythm, normal P-R interval of 0.16 to 0.20 seconds, and normal ventricular depolarization). The presence or absence of heart disease was determined by clinical history, physical examination, resting and exercise electrocardiograms (ECG), and cardiac catheterization. The clinical status of these subjects is included in Table 1. All were advised of the nature of the study, and a signed consent was obtained. None of the subjects were on medication at the time of the study. Recording Techniques.—-The techniques for

recording His bundle electrograms in man and their validation have previously been described in detail (7). A right heart catheterization was performed on all subjects in the supine, postabsorptive, unsedated state. Using local anesthesia, a bipolar electrode catheter was introduced percutaneously into the right femoral vein and fluoroscopically positioned across the tricuspid valve. The terminals of the catheter1 were connected to a distribution switch box which allowed for bipolar recording between three pairs of electrodes (electrodes 1 and 2, 2 and 3, and 1 and 3). Each bipolar lead was connected to the A-C input of an ECG preamplifier. Frequencies below 40 and above 500 Hz were filtered out to provide greater baseline stability. The electrograms recorded by the catheter were displayed on a multichannel switched beam oscillographic recorder1 as the electrode catheter was then withdrawn slowly iElectronics for Medicine, White Plains, New York. Circulation Research, Vol. XXVII,

Downloaded from circres.ahajournals.org by on December 23, 2008

September 1970

347

PATTERNS OF ATRIOVENTRICULAR CONDUCTION

across the tricuspid valve. The appearance of a rapid deflection between the atrial and ventricular electrograms and within the P-R interval of a simultaneously recorded surface ECG signified electrical activity of the bundle of His (Fig. 3) (8). A second bipolar catheter was introduced percutaneously into an antecubital vein and fluoroscopically positioned against the lateral wall of the right atrium. This catheter was used to stimulate the right atrium. Records of the surface ECG and the local electrograms were recorded at a paper speed of 200 mm/sec. In addition, in some experiments standard electrocardiographic leads I, II, III, Vx and V6 were simultaneously recorded on a Sanborn 4560 series recorder. Experimental Procedure.—The experimental design was a replica of the procedure used by Moe et al. (3) in their studies on the canine heart, with the additional feature of delineating the various components of the A-V transmission system as described by Hoffman et al. (4). Basic drive and test stimuli delivered to the right atrium were provided by Tektronix 160 series waveform and pulse generators so arranged that the test stimuli could be introduced at any point in the cardiac cycle, at any multiple of the basic drive frequency. The right atrium was electrically driven at the lowest possible atrial rate that insured reliable "atrial capture" by the basic drive stimulus (SjJ. This stimulus consisted of a square-wave pulse of 2 msec at approximately twice diastolic threshold. A test stimulus (S2) w a s then introduced after every tenth driving stimulus through the same electrodes, and the S^S o interval was decreased in gradations of 5 msec or less until S9 was no longer conducted to the His bundle. S2 consisted of a square-wave pulse of 1 to 2 msec and three to four times diastolic threshold. Varied parameters of the test pulse did not influence the results and were chosen only to elicit a propagated atrial impulse which served as the stimulus for the A-V conduction system. Both driving and test stimuli were suitably isolated from ground (Bioelectric Instruments Type ISB). In 7 of the 20 studies, the basic drive stimulus following the test stimulus was omitted by means of a relay triggered by S2 to facilitate the observance of possible reciprocal excitation of the atria (atrial echoes). Subdivision of Total A-V Conduction.-Figure 3 shows an example of electrograms recorded from the region of the A-V conduction system by the electrode catheter. The His bundle electrogram recording consists of an atrial electrogram, a His deflection and a ventricular eTectrogram. The recordings are identical to those observed in the dog by using local electrode

plaques (4, 8). Conduction time through the components of the A-V conduction system were subdivided as follows. The time interval from the initial sharp deflection of the atrial electrogram to the Q wave of the ECG or to the beginning of the ventricular electrogram (A-Q or A-V intervals) was taken as a measurement of total A-V conduction time. Since the atrial electrogram is recorded in the vicinity of the tricuspid valve and A-V node, the error involving conduction from atrium to junctional tissue is minimal (4). The interval from the initial sharp deflection of the atrial electrogram to the His deflection (A-H interval) was taken as a measure of A-V nodal conduction time. This measurement almost totally excludes impulse transmission through the His bundle and remaining VSCS, which is represented by the interval from the His bundle deflection to the point of earliest ventricular muscle activation represented by the Q wave of the ECG or the ventricular electrogram (H-Q or H-V interval). In addition, conduction delay in the VSCS could usually be localized to one or both bundle branches by detecting bundle-branch block patterns on the standard ECG recordings. Definitions.—The following terms are used in this study to describe conduction properties of the elements constituting the A-V conduction system. Effective Refractory Period.—The effective refractory period of cardiac muscle begins when a propagated response cannot be evoked by an electrical stimulus (9). Accordingly, the effective refractory period of the A-V conduction system is the longest A,-A2 interval at which the atrial test response (A 2 ) fails to conduct to the ventricles. The effective refractory period of the A-V node refers to the latest atrial test response which fails to conduct to the His bundle. The effective refractory period of the VSCS is indicated by the latest test stimulus which depolarizes the bundle of His but fails to propagate to the ventricles (the interval between the basic and premature His bundle responses at which conduction block occurs in the VSCS). The H r H 2 in terval indicates the coupling interval between basic and premature stimuli arriving at the VSCS and takes into account the delay of the premature stimulus in the A-V node. Functional Refractory Period.—-The functional refractory period (10) of the A-V conduction system is the minimum interval between two successive ventricular responses, both propagated from the atrium (2, 5). By recording His bundle electrograms, the functional refractory period of the A-V node was also determined in this study (the minimum interval between two successive His bundle responses, both propagated from the atrium). Possible mechanisms involved are discussed by Rosenblueth (11). On the basis of

Circulation Research, Vol. XXVII, September 1970

Downloaded from circres.ahajournals.org by on December 23, 2008

WIT, WEISS, BERKOWITZ, ROSEN, STEINER, DAMATO

348 our results, the term functional refractory period of the A-V conduction system does not contain as much physiological information as functional refractory period of A-V nodal conduction. Full Recovery Time.—The full recovery time of cardiac muscle occurs when the delay between the stimulus and the response becomes constant. It is indicated by normal conduction velocity or time (9, 12). The full recovery time of the A-V conduction system occurs at the minimum Aj-Ao interval at which conduction time of the premature atrial impulse to the ventricles equals that encountered with the basic response. Similarly, the full recovery time of the A-V node is the minimum A]-A2 interval at which conduction time of the premature atrial impulse to the His bundle equals that encountered with the basic response. The interval between the functional refractory period and the full recovery time is defined as the relative refractory period of the A-V conduction system and A-V node (3). The full recovery time of the VSCS begins at the minimum H,-!^ interval at which conduction time of a premature impulse throughout the HisPurkinje system equals conduction time of the basic impulse. The end of the full recovery time occurs at the H]-H2 interval at which conduction of the premature impulse in the VSCS is delayed relative to the basic response. The full recovery time does not correspond to the end of the relative refractory period of Purkinje tissue (9, 13,14).

studies and is illustrated in Figures 1A and 2A. It was characterized by an initial progressive decrease in the ventricular intervals as the premature atrial response occurred progressively earlier in the cardiac cycle. In the experiment shown in Figure 2A, the full 800 700600 500 400 -

700 600 500 400 -

Results

The intervals between the basic and the premature ventricular responses (Vi-V2) were plotted against the corresponding atrial intervals (Ai-A2) for each study. There were three distinct types of curves, indicating differences in the physiological characteristics of A-V conduction in man (Fig. 1). The curves can be readily compared with studies on the canine heart in which the data was presented in this manner (3-5). Similar plots of the intervals between the basic and premature bundle of His electrograms (Hi-H 2 ) enabled the site of conduction delay to be localized to either the A-V node or the VSCS, delineating the mechanism of these differences. This method of graphic presentation also demonstrates the relationship of the Hi-H2 intervals to conduction delay in the His-Purkinje system. Type 1 Response.—This characteristic type of A-V conduction was found in 9 of the 20

700 600 500 400-

4OO

6OO

8OO

A,-A_ msec FIGURE 1

Three types of curves when the intervals between ventricular depolarizations (V^Vg intervals on ordinate) were related to the intervals between atrial depolarizations (Aj-A^ intervals on abscissa). Each represents data acquired in a single patient which thereby shows the typical response representative of each group. The curve shown in A occurred in 9 studies, the one in B in 6 studies, and the one in C in 3 studies. Solid circles indicate A-V conduction with an aberrant QRS complex on the surface ECC. Circulation Research, Vol. XXVII, September

Downloaded from circres.ahajournals.org by on December 23, 2008

1970

PATTERNS OF ATRIOVENTRICULAR CONDUCTION A

349 B

7OO.

.400

O

H_-V o

msec

50O.

.200

O O O O O

A.-Ao

O

O

O O O O

msec

A: Type 1 curve relating V}-Vs and Hj-H2 intervals (ordinate) to Aj-As intervals (abscissa). Solid circles indicate A-V conduction with an aberrant QRS complex (see text for discussion). B: Relationship of AB-HZ and H2-Ve intervals (ordinate) to Ar'AB intervals (abscissa) for the same experiment as A.

recovery time of the A-V conduction system occurred at an Ai-A2 interval of 560 msec. At shorter Ai-A2 intervals, A-V conduction of the premature impulses (A2) were delayed relative to the basic drive impulse (Ai), as indicated by the deviation of the descending limb of the curve from the solid line (the theoretical line of no A-V conduction delay). The curve continued to descend during the relative refractory period of the A-V conduction system at a decreasing slope, indicating a progressive increase in A-V conduction time. At a critical Aa-A2 interval of 310 msec, Vi-V2 reached a minimum (390 msec) and then began to increase even though the atrial interval shortened further. The increase in ViV2 was progressive until complete block of conduction of the premature impulse occurred at an Ai-A2 interval of 245 msec. The shortest V1-V2 interval of 390 msec indicates the functional refractory period of the A-V conduction system, and the latest atrial test response which fails to conduct to the

ventricles (A!-A2 of 245 msec) indicates the effective refractory period. A similar plot of the intervals between His bundle responses (Hi-Ho intervals) and premature atrial stimulation (Ax-A2) for the same experiment is also shown in Figure 2A. The Hi-H 2 intervals can be seen to correspond exactly to the Vj-V2 values, indicating that the increase in A-V conduction time occurring with premature atrial stimulation was confined entirely to the region of the A-V node (between the atrial and His bundle electrogram). The site of A-V conduction delay in another type 1 experiment is demonstrated in Figure 3. When conduction delay occurred in the His-Purkinje system, the points on the curve representing the ventricular intervals differred from points representing the His bundle intervals in a positive direction (Fig. 4) (4). In Figure 2B (data from the same experiment as 2A), the A2-H2 intervals representing A-V nodal conduction time of the premature impulses are plotted

Circulation Research, Vol. XXVII, September 1970

Downloaded from circres.ahajournals.org by on December 23, 2008

WIT, WEISS, BERKOWITZ, ROSEN, STEINER, DAMATO

350

ECG HBE

f i

N"—~—f~\|

! ;

200 msec

Type I response to premature atrial stimulation. Top trace of each panel = ECG lead V1; bottom trace = His bundle electrogram (HBE). Sj = basic drive stimulus artifact; At = atrial electrogram of basic response; Ht = His bundle electrogram; Vt = ventricular electrogram; Sj = premature test stimulus artifact; As = premature atrial electrogram; Hs = His bundle electrogram; Ve = ventricular electrogram. Basic drive cycle length zz 775 msec; basic A1-H1 = 90 msec; basic Hj-V^ = 40 msec. A: Aj-A2 = 405 msec; A2-Hs — 135 msec; Hs-Vs — 40 msec. B: ArAs = 360 msec; As-Hs = 180 msec; Hs-Vs = 40 msec. C: ArAs = 300 msec; As-Hs = 255 msec; Hs-Vs =40 msec. D: At-As = 270 -msec. Premature atrial impulse is blocked in the A-V node (His bundle is not depolarized). Note that A-V conduction delay of premature impulse in this experiment is localized to the A-H interval. Changes in amplitude or configuration of electrograms may be due to catheter movement with the pulsating heart.

against the atrial intervals. Also included is the relationship of the H2-V2 intervals (His-Purkinje conduction time) to the degree of prematurity of atrial stimulation. As Ai-A2 decreased, A-V nodal conduction time increased progressively. Block of the premature atrial impulse occurred in the A-V node at a coupling interval of 245 msec. No

changes in the H2-V2 intervals occurred. Thus in the type 1 response, the relative, functional, and effective refractory periods of the A-V conduction system are determined entirely by properties of the A-V node. The values for the refractory periods of the A-V conduction system and the A-V node for type 1 curves are summarized in Table 1. In Circulation Research, Vol. XXVH, September 1970

Downloaded from circres.ahajournals.org by on December 23, 2008

PATTERNS OF ATRIOVENTRICULAR CONDUCTION

*

351

H,-H,

- 300

• O

300

400

500

600

300

O

O

OO

OOOC

500

FIGURE 4

A: Type 2 curve relating V1-Vz and Hj-Hs intervals (ordinate) to At-Ae intervals (abscissa). Solid circles indicate A-V conduction with an aberrant QRS complex (see text for discussion). B: Relationship of A2-Hs and He-Ve intervals (ordinate) to A1-As intervals (abscissa) for same experiment as A.

this group, A-V nodal conduction time increased 2 to 3 times before the effective refractory period of the A-V node occurred. The premature atrial stimulus never reached the His bundle before the VSCS had recovered from the basic stimulus (the Hi-H2 interval did not attain a value less than the full recovery time of the VSCS). This was indicated by the constancy of the H2-V2 intervals. In three experiments, premature atrial stimulation resulted in a slightly aberrant QRS with normal H2-V2 intervals. Electrocardiographic analysis of the precordial leads indicated some minor intraventricular conduction delay. This finding may signify conduction delay at the most peripheral ramifications of the Purkinje network, resulting in a slightly altered sequence of ventricular activation. In addition, in two of the nine subjects in this group, reciprocal excitation of the atrium (atrial echoes) was observed when early premature atrial impulses were significantly delayed in the A-V node. The occurrence of Circulation Research, Vol. XXVII, September

echoes could not be predicted from values for refractory periods of the A-V node. Type 2 Response.—The second type of curve describing total A-V conduction of premature impulses is shown in Figure IB and Figure 4A. This type of response was encountered in 6 of 20 studies. The initial part of the curve occurring at large Ai-A2 intervals is similar to type 1. The full recovery time of AV conduction in the experiment shown in Figure 4 occurred at an A1-A2 interval of 560 msec. At an atrial interval of 425 msec, Vi-V2 began to assume a constant value, reaching a minimum of 460 msec at an atrial interval of 340 msec. Vi-V2 thereafter fluctuated slightly as A1-A2 was decreased further. The occurrence of the horizontal limb of this V1-V2 curve was accompanied by various degrees of aberration in the QRS of the ECG. Finally, when A2 occurred 255 msec after the basic atrial response, it was no longer conducted to the ventricles, indicating that the effective refractory period of A-V conduction was reached. Analysis of A-V nodal and His-

1970

Downloaded from circres.ahajournals.org by on December 23, 2008

WIT, WEISS, BERKOWITZ, ROSEN, STEINER, DAMATO

352

200 msec FIGURE 5

Type 2 response to premature atrial stimulation. Top trace in each panel = ECG lead 11. Abbreviations same as in Figure 3. Basic drive cycle length = 795 msec; basic A1-H1 = 85 msec; basic H1-V1 = 65 msec. A: A2-As = 400 msec; As-H2 = 225 msec; Hi-Ve •=. 80 msec. B: Aj-A2 = 345 msec; As-Hg = 145 msec; HJ-VJ = 110 msec. C: AX-AS = 315 msec; AJ-HJ = 175 msec; Hz-Vs = 140 msec. D: A3-Ae = 255 msec. Premature atrial impulse is blocked in the A-V node. Note that A-V conduction delay of the premature atrial impulse occurs in both the A-H and H-V interval.

Purkinje conduction times in this study indicates that the delay in A-V conduction of the premature atrial impulse is not entirely confined to the A-V node. As shown in Figure 4A, as Ai-A2 decreased, F^-Ho also decreased. Delay in A-V nodal conduction was responsible for the initial A-V conduction delay occurring at Aj-A2 intervals less than the full recovery time, since the ventricular and His

bundle intervals still coincided at this point. When Ai-A2 reached 400 msec, a gradual conduction delay of the premature impulse also began to occur in the His-Purkinje system. This is indicated by the differences in the Vj-V2 intervals from the H1-H0 intervals at Ai-A2 values from 400 to 255 msec. The minimum ventricular interval of 460 msec, defined as the functional refractory period of Circulation Research, Vol. XXVll, September 1970

Downloaded from circres.ahajournals.org by on December 23, 2008

353

PATTERNS OF ATRIOVENTRICULAR CONDUCTION

O V,-V2 msec

a A2-H2 msec O Hg-V2 msec

- 200

• * ^ A

40O -

• 0 0 0 0 0 0 0 0 0 0 o ooc .

A: Modified type 2 curve relating Vx-Ve and H1-Hi intervals (ordinate) to At-A2 intervals (abscissa). Solid circles indicate A-V conduction with an aberrant QRS complex (see text for discussion). B: Relationship of As-H2 and Hs-Ve intervals (ordinate) to At-At intervals (abscissa).

A-V conduction, occurred during conduction delay in the His-Purkinje system. The functional refractory period of the A-V node (minimum H1-Ha interval) was not reached until Ai-A2 was decreased to 275 msec. Conduction delay began in the VSCS at HiH2 coupling intervals less than 450 msec. This value therefore signifies the full recovery time of the His-Purkinje system. As Ai-A2 decreased from 400 to 255 msec, both A-V nodal and His-Purkinje conduction times were progressively prolonged (Fig. 4B). At an Ai-A2 interval of 255 msec the premature impulse was blocked in the A-V node (before His bundle depolarization), which therefore determined the effective refractory period of the A-V conduction system. The prolongation of A-V nodal and His-Purkinje conduction is also demonstrated in Figure 5. In two other experiments, a modified type 2 curve was found (Fig. 6). The horizontal limb of the V1-V2 curve was markedly shortened. In

these cases, as the Ai-A2 interval was shortened by 15 to 20 msec after the Vi-V2 intervals began to assume a constant value, the effective refractory period of the VSCS occurred and the premature impulse was blocked after traversing the His bundle, before ventricular activation occurred (Fig. 7). A-V nodal conduction properties determined after A-V block had occurred were similar to that described for other type 2 experiments (Fig. 6). Since the effective refractory period of the VSCS was reached before that of the A-V node, in these instances the His-Purkinje system determined the effective refractory period of the A-V conduction system. In the experiment shown in Figure 6, the effective refractory period of the VSCS was 400 msec (Hi-H 2 interval at which conduction block in the VSCS occurred) and that of the A-V node was 275 msec (Ai-A2 interval at which conduction block in the node occurred).

Circulation Research, Vol. XXVII, September 1970

Downloaded from circres.ahajournals.org by on December 23, 2008

354

WIT, WEISS, BERKOWITZ, ROSEN, STEINER, DAMATO

ECG

200 msec

Modified type 2 response to premature atrial stimulation. Top trace in each panel = ECG lead H. Abbreviations same as in Figure 3. H electrogram is characterized by an initial positive followed by a negative deflection. The latter may indicate right bundle-branch activity (25). Basic drive cycle length = 980 msec; basic A1-H1 = 105 msec; basic H1-V1 = 45 msec. A: ArA2 = 545 msec; Ae-Hs — 130 msec; Hs-Vs = 45 msec. B: ArAs — 525 msec; As-H2 — 180 msec; HJ-VJ = 45 msec. C: A±-A2 = 400 msec; A2-ff2 = 195 msec. Premature atrial impulse is blocked in the VSCS after depolarizing the His bundle.

A summary of the values of the refractory periods of the A-V conduction system and its components for type 2 curves are presented in Table 1. Conduction delays of premature atrial impulses in the A-V node was not as marked as that seen in type 1, increasing less than 2 times before the effective refractory period of the A-V node was reached. There was no ascending limb on the H1-H2 curve. No atrial echoes were observed in this group. In six of the previously described experiments, the precordial limb leads reflected the conduction delay in the VSCS. In five, QRS morphologies indicative of incomplete right bundle-branch block were found. The remaining experiment showed a combination of

incomplete right and left bundle-branch block patterns. Type 3 Response.—In three experiments, a plot of the transmission of premature atrial activity to the ventricles gave the type of curve illustrated in Figures 1C and 8A. This curve is characterized by decreasing ventricular intervals similar to that previously described, followed by a sudden marked prolongation when the atrial test response became sufficiently premature. This prolongation was accompanied by an aberrant QRS complex on the ECG. The ventricular intervals then fluctuated with decreasing atrial intervals until A2 was no longer conducted to the ventricles. The intervals between driven (Hi) and premature (H 2 ) His bundle responses for a Circulation Research, Vol. XXVII, September 1970

Downloaded from circres.ahajournals.org by on December 23, 2008

PATTERNS OF ATRIOVENTRICULAR

355

CONDUCTION

O V - V_ msec

^ A . - Hp msec

a H , - H. msec

OH.-V,

msec

OO O O O O O O

300

400

500

600 A. - A g

300

400

500

O

600

msec

FIGURE 8

A: Type 3 curve relating Vj-Vs and H1-He intervals (ordinate) to ArA& intervals (abscissa). Solid circles indicate A-V conduction with an aberrant QRS complex (see text for discussion). B: Relationship of As-H2 and H^-Vg intervals (ordinate) to Ax-A2 intervals (abscissa) for same experiment as in A.

representative experiment are also shown in Figure 8A, and a separate plot is included of A-V nodal and His-Purkinje conduction times (Fig. 8B). The full recovery time of the A-V conduction system (A1-A2 = 610 msec in Fig. 8A) ended when conduction delay of the premature impulse occurred in the A-V node. The point on the curve defined as the functional refractory period of the A-V conduction system (the minimum ventricular interval) occurred just before a marked conduction delay between His bundle depolarization and ventricular activation. The precordial limb leads demonstrated the pattern of complete right bundle-branch block at this H1-H2 of 485 msec. The functional refractory period of the A-V node was not reached until an atrial interval of 340 msec and could be determined only because a His bundle electrogram was recorded. At an interval of 360 msec between the driven and premature atrial response, the effective refractory period ofthe A-V conduction system was reached. However, A2 was blocked at this

point after traversing the A-V node and depolarizing the His bundle (Fig. 9). The effective refractory period of A-V conduction was thus determined by the His-Purkinje system in this and other type 3 curves. The effective refractory period of the VSCS in this study was 420 msec (H1-H2 interval at which conduction block occurred). Further shortening of the atrial interval to 330 msec finally resulted in block of A2 in the A-V node (Fig. 8). A summary of the values for the refractory periods of the A-V conduction system and its components for type 3 are presented in Table 1. The magnitude of conduction delay of the premature impulse in the A-V node was similar to type 2, rarely increasing twofold. There was no ascending limb on the Hi-H 2 curve. No atrial echoes were observed in this group. Atrium as an Additional Factor in Limiting A-V Conduction—-In three additional experiments, the premature impulse was blocked in the atrium before the effective refractory

Circulation Research, Vol. XXVII, September 1970

Downloaded from circres.ahajournals.org by on December 23, 2008

356

WIT, WEISS, BERKOWITZ, ROSEN, STEINER, DAMATO A

•:

ECG 1

I

:V,|

S2/

A 2 .H

^

HBE

FIGURE 9

Type 3 response to premature atrial stimulation. Top trace in each panel = ECG lead II. Abbreviations same as in Figure 3. Basic drive cycle length = 1000 msec; basic AJ-H1 = 85 msec; basic H1-V1^50 msec. A: A1-A2=480 msec; A2-H2=z 115 msec; HS-Vg = 50 msec. B: ArAs — 410 msec; A s -H s = 125 msec; Hs-Vs = 180 msec. C: ArAs = 390 msec; A2-He = 135 msec. Premature atrial impulse is blocked in VSCS after depolarizing His bundle.

period of the A-V node or His-Purkinje system was reached. As At-A2 was shortened, a progressive increase in the interval from the premature stimulus artifact to the A2 response was noted in addition to the increase in A-V conduction time, until S2 was not followed by an atrial electrogram. This increase in the S2A2 interval may be due to an increase in latency time of the stimulus response or to slow conduction in the atria. The lack of an atrial response to S2 does not seem to be due to poor electrode contact with the atrium wall, since Si repeatedly elicited an atrial response through the same electrodes. Also, the S!-S2 interval which failed to elicit an atrial response was remarkably constant throughout many determinations. When the voltage of S2 was increased to as much as 8 times threshold, an atrial response still could not be elicited. Discussion

The present study demonstrates three char-

acteristic types of A-V conduction of premature atrial impulses in man. By recording His bundle activity it was demonstrated that the differences in the types of responses could be related to the site or sites of conduction delay of the premature impulse. A dual transmission system in the A-V node need not be evoked to explain the results. However, this study does not eliminate the possible existence of a dual A-V nodal conduction system in the human heart. Moe et al. (3) in their studies on the canine heart demonstrated the frequent occurrence of atrial echoes after premature atrial impulses which showed a marked delay in AV conduction time. These findings suggested the presence of dual conducting pathways through the A-V node providing the reentrant circuit for the reciprocal beat. Atrial echoes were noted in two instances during the course of our studies, and their occurrence has also been described previously in the human heart during premature atrial stimulation (15). Circulation Research, Vol. XXVII, September

Downloaded from circres.ahajournals.org by on December 23, 2008

1970

357

PATTERNS OF ATRIOVENTRICULAR CONDUCTION

Curves relating ventricular intervals to the intervals between basic and premature atrial responses have been used as an index to determine the refractory periods of the A-V conduction system in both the canine and human hearts (2, 3, 5, 11, 16-19). Since conduction delay and block of premature atrial impulses can occur in the VSCS, the recording of His bundle activity enables values for the refractory periods of the A-V node to be distinguished from His-Purkinje conduction delay and block. The three basic response curves for A-V conduction obtained in this study are similar to the curves previously described for the canine heart (3, 4). The type 1 curve was found in 45% of the patients studied. In this group, conduction delay of the premature impulse was confined to the A-V nodal region. The values for the full recovery time and the functional and effective refractory periods of the A-V conduction system were those of the A-V node. The site of block of the premature atrial impulse during the effective refractory period of A-V conduction was in the A-V node. This characteristic type of A-V conduction was observed in most of the chronic studies on the canine heart by Hoffman et al. (4) and in 30% of acute studies in the series of Moeetal(3). The type 2 response curve as here reported is also similar to responses previously described for the canine heart (3, 4). However, whereas in the canine heart this curve was also indicative of only A-V nodal delay (4), in our studies it indicated conduction delay in both the A-V node and VSCS. Initial conduction delay of A2 was confined to the A-V node, but as A2 occurred earlier in the cardiac cycle, a progressive delay in conduction also began to occur in the His-Purkinje system. An altered sequence of ventricular depolarization was indicated when aberrant QRS complexes occurred. The functional refractory period of the A-V conduction system in this type of response does not indicate the physiological state of the A-V -node.—The minimum Vj-Vz interval was a function of conduction delay in both the A-V Circulation Research, Vol. XXVII, September

node and His-Purkinje system and probably occurred during the relative refractory periods of both these structures. The functional refractory period of the A-V node (minimum H1-H2 interval) occurred at a shorter Ai-A2 interval. In most experiments in this group, the effective refractory period of the A-V node was the limiting factor for conduction of the premature impulse. In the two experiments showing modified type 2 curves, the effective refractory period of the VSCS was reached before A-V nodal block and thus determined the effective refractory period of the A-V conduction system. This phenomenon was not observed under normal physiological circumstances in a previously reported study on the canine heart (4). Conduction block of premature atrial impulses distal to the bundle of His in the dog has been demonstrated during cardiopulmonary bypass (20) and infusion of relatively high concentrations of epinephrine to speed A-V nodal conduction (21). In addition, Preston et al. have demonstrated in young mammals that the functional refractory period of the A-V nodal region is shorter than the peripheral A-V transmission system of the ventricle (22). The type 3 curve which was found in 15% of our studies was never found in the chronic dog studies of Hoffman et al. during atrial stimulation (4), although Moe and his associates have reported this type of response in acute open-chested dogs after sinus crush, neural ablation, and in cross-perfused canine hearts (3, 5). In this group, the relative refractory period of A-V conduction was again due to conduction delay in the A-V node. As the atrial intervals were reduced further, there was a sudden marked increase in the ventricular intervals due to conduction delay distal to the A-V node. The minimum Va-V2 interval (functional refractory period of A-V conduction) occurred just before significant conduction delay in the His-Purkinje system (right bundle-branch block pattern). Agaim, the functional refractory period of A-V conduction did not indicate the physiological state of the A-V noder A2 was still entering the A-V node during its relative refractory period at

1970

Downloaded from circres.ahajournals.org by on December 23, 2008

358

WIT, WEISS, BERKOWITZ, ROSEN, STEINER, DAMATO

this time. The functional refractory period of the A-V node did not occur until the atrial coupling interval was decreased further. The effective refractory period of the A-V conduction system was due to block of the premature impulse in the VSCS and not in the A-V node. The difference in the functional characteristics of the A-V conduction system of the various types described in this study are due to the relationships of the refractory periods of the A-V node to those of the VSCS. For conduction delay or block to occur in the VSCS, the premature atrial impulse must be able to traverse the A-V node rapidly enough to encounter any part of the His-Purkinje system while it is incompletely repolarized (9, 13, 14, 20, 23). Action potential duration of Purkinje fibers increases progressively from His bundle to the distal specialized conducting system (4, 9, 20, 24). The recent work of Myerberg et al. (24) has also demonstrated a progressive increase in the local refractory periods of Purkinje fibers, reaching a maximum just before the junction of free-running fibers with the endocardium. This area of maximum duration of refractory period functions as the limiting segment or "gate" for propagation of premature impulses arising proximally (24). In our type 1 responses all premature impulses were sufficiently delayed in the A-V node to allow full recovery of the His-Purkinje system. The minimum interval between basic and premature stimuli arriving at the His bundle which occurs at the functional refractory period of the A-V node (minimum Hi-H 2 interval) must be greater than the longest full recovery time of the VSCS (the region of the gate). Conduction block always occurred in the A-V node, indicating that the functional refractory period of the node was longer than the effective refractory period of the distal HisPurkinje system. In response curves of types 2 and 3, premature atrial stimuli were able to cross the A-V node rapidly enough to encounter the VSCS before the full recovery time, and this resulted in conduction delay in this structure. In these groups, the functional

refractory period of the A-V node was less than the full recovery time of the VSCS, thus enabling the rapid conduction required by the premature impulse. In several instances, the A-V nodal functional refractory period was less than the effective refractory period of the VSCS, and this resulted in conduction block distal to the A-V node. The relationships of the refractory periods of the A-V node and the VSCS are shown in Table 1. Since the refractory period of the VSCS increases as the periphery is approached, the values reported here may be due to the region of the His-Purkinje system with the longest refractory period duration (the gate of Myerberg et al.) (24). These results therefore indicate that the A-V conduction system in the human heart has two gates, the A-V node and the distal VSCS, each of which may limit the propagation of premature atrial impulses. In conclusion, the present study demonstrates that the properties of the human A-V conduction system are similar to the previously reported studies in animals (mostly the dog). In man, conduction delay and block of premature atrial impulses is not confined to the A-V node but occurs quite readily in the His-Purkinje system. Since these studies were performed on subjects who were not sedated or anesthetized and since control heart rates were normal (60 to 80 beats/min), indicating no abnormal excess of neural discharge (either vagal or sympathetic), it can be concluded that these are real functional properties of the human A-V conduction system. References 1. HOFFMAN, B. F.: Physiology of atrioventricular transmission. Circulation 24: 506, 1961. 2. KRAYEH, O., MANDOKI, ]. J., AND MENDEZ,

C:

Studies on veratrum alkaloids: XVI. Action of epinephrine and of veratramine on the functional refractory period of the auriculoventricular transmission in the heart-lung preparation of the dog. I Pharmacol Exp Ther 103: 412, 1951. 3. MOE, G. K., PBESION, J. B., AND BURIJNGTON,

H.: Physiologic evidence for a dual A-V transmission system. Circ Res 4: 357, 1956. 4. HOFFMAN, B. F., MOOBE, E. N., STUCKEY, J. H., Circulation Research, Vol. XXVll, September 1970

Downloaded from circres.ahajournals.org by on December 23, 2008

359

PATTERNS OF ATRIOVENTRICULAR CONDUCTION

10.

11.

13.

14.

AND CRANEFIELD, P. F.: Functional properties of the atrioventricular conduction system. Circ Res 13: 308,1963. MOE, G. K., MENDEZ, C, AND HAN, J.: Aberrant A-V impulse propagation in the dog heart: Study of functional bundle-branch block. Circ Res 16: 261, 1965. DAMATO, A. N., LAU, S. H., PATTON, R. D., STEINER, C, AND BERKOWITZ, W. D.: Study of atrioventricular conduction in man using premature atrial stimulation and His bundle recordings. Circulation 40: 61, 1969. SCHERLAG, B. J., LAU, S. H., HELFANT, R. H., BERKOWITZ, W. D., STEIN, E., AND DAMATO, A. N.: Catheter technique for recording His bundle activity in man. Circulation 39: 13, 1969. HOFFMAN, B. F., CRANEFIELD, P. F., STUCKEY, J. H., AND BAGDONAS, A. A.: Electrical activity during the P-R interval. Circ Res 8: 1200, 1960. HOFFMAN, B. F., AND CRANEFIELD, P. F.: Electrophysiology of the Heart. New York, McGraw-Hill Book Co., 1960. ROSENBLUETH, A., ALANIS, J., AND MANDOKI, J.: Functional refractory period of axons. J Cell Comp Physiol 33: 405, 1949. ROSENBLUETH, A.: Functional refractory period of cardiac tissues. Amer J Physiol 194: 171, 1958. DRURY, A. N.: Effective refractory period, full recovery time, and premature response interval of ventricular muscle in the intact unanesthetized cat and rabbit, Quart J Exp Physiol 26: 181, 1936. VAN D A M , R. T., MOORE, E. N., AND HOFFMAN, B. F.: Initiation and conduction of impulses in partially depolarized cardiac fibers. Amer J Physiol 204: 1133, 1963. VAN DAM, R. T., HOFFMAN, B. F., AND STUCKEY, J. H.: Recovery of excitability and of impulse propagation in the in situ canine conduction system. Amer J Cardiol 14: 184, 1964.

Circulation

15. SCHUILENBURG, R. M., AND DURRER, D.: Atrial echo beats in the human heart elicited by induced atrial premature beats. Circulation 37: 680, 1968. 16. MENDEZ, C, ACEVES, J., AND MENDEZ, R.: Antiadrenergic action of digitalis on the refractory period of the A-V transmission system. J Pharm E x p T h e r l 3 1 : 199, 1961. 17. MENDEZ, R., AND MENDEZ, C: Action of cardiac glycosides on the refractory period of heart tissues. J Pharmacol Exp Ther 107: 24, 1953. 18. COLDREYER, B. N., AND BlGGER, J. T.: Spontaneous and induced reentrant tachycardia. Ann Intern Med 70: 87, 1969. 19. MENDEZ, C, GRUHZIT, C. C, AND MOE, G. K.: Influence of cycle length upon refractory period of auricles, ventricles, and A-V node in the dog. Amer J Physiol 184: 287, 1956. 20. HOFFMAN, B. F., CRANEFIELD, P. F., STUCKEY, J. H.: Concealed conduction. Circ Res 9: 194, 1961. 21. MENDEZ, C, HAN, J., AND MOE, G. K.: Comparison of the effects of epinephrine and vagal stimulation upon the refractory periods of the A-V node and the bundle of His. Arch Exp Path Parmakol 248: 99, 1964. 22. PRESTON, J. B., MCFADDEN, S., AND MOE, G. K.: Atrioventricular transmission in young mammals. Amer J Physiol 197: 236, 1959. 23. MOORE, E. N.: Microelectrode studies on concealment of multiple premature atrial responses. Circ Res 18: 660, 1966. 24. MYERBERG, R. J., STEWART, J. W., AND HOFFMAN, B. F.: Electrophysiological properties of the canine peripheral A-V conducting system. Circ Res 26: 361, 1970. 25. DAMATO, A. N., LAU, S. H., BERKOWITZ, W. D., ROSEN, K. M., AND LBI, K. R.: Recording of specialized conducting fibers (A-V nodal, His bundle and right bundle-branch) in man using an electrode catheter technique. Circulation 34: 435, 1969.

cb, Vol. XXVII, September 1970

Downloaded from circres.ahajournals.org by on December 23, 2008