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The Sequence of Retrograde Atrial Activation in the Canine Heart CORRELATION WITH POSITIVE AND NEGATIVE RETROGRADE P WAVES By Albert L. Waldo, Kari J. Vitikainen, and Brian F. Hoffman Downloaded from http://circres.ahajournals.org/ by guest on May 4, 2017 ABSTRACT The relationship of P-wave polarity and morphology in leads II, III, and aVF to the sequence of atrial activation was studied in the canine heart when the atria were paced from the region of the sinus node or the posterior-inferior left atrium and when retrograde activation of the atria occurred with right ventricular epicardial pacing. Deeply negative P waves in leads II, III, and aVF which occurred when the posterior-inferior left atrium was paced were associated with true retrograde activation of the atria. Positive P waves recorded in leads II, III, and aVF during retrograde atrial capture with right ventricular pacing were associated with rapid retrograde spread of the impulse in the interatrial septum to the region of Bachmann's bundle from which site the impulse spread to depolarize significant portions of both atria in a manner similar to that demonstrated during pacing from the region of the sinus node. When the atria were paced from a site just anterior to the coronary sinus ostium, positive P waves recorded in leads II, III, and aVF were associated with early activation in the vicinity of Bachmann's bundle and later activation of the posterior-inferior left atrium. When the atria were paced from a site just posterior to the coronary sinus ostium, negative P waves in leads II, III, and aVF were associated with early activation of the posterior-inferior left atrium and later activation in the vicinity of Bachmann's bundle. It was concluded that the time of arrival of the impulse at Bachmann's bundle relative to that at the posterior left atrium and the direction of spread of the impulse from and within Bachmann's bundle are critical in determining P-wave polarity and morphology. • Previous reports from this (1-4) and other (5-8) laboratories and scattered clinical reports (9-14) disagree with the classic concept that the "retrograde" P waves produced during ventricular, atrioventricular (AV) junctional, and low atrial rhythms are necessarily negative in electrocardiogram (ECG) leads II, III and aVF. One report (8) has correlated the sequence of activation of portions of the right atrial appendage, the left atrial appendage, and the free wall of the right atrium with P-wave polarity in standard ECG leads during the retrograde atrial capture which occurred with right ventricular epicardial pacing. With the exception of this paper, we are unaware of any previous studies which have correlated P-wave From the Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032. This investigation was supported in part by U. S. Public Health Service Grants HL12738 and HL11.310 from the National Heart and Lung Institute. Dr. Waldo is the Otto G. Storm Established Investigator of the American Heart Association. His present address is Department of Medicine, University of Alabama Medical Center, Birmingham, Alabama 35294. Please address reprint requests to Albert L. Waldo, M.D., UAB Medical Center—LHR 339, University Station, Birmingham, Alabama 35294. Received October 24, 1974. Accepted for publication April 29, 1975. 156 polarity and morphology in standard ECG leads during ectopic atrial rhythms with a map of the sequence of atrial activation. The present report describes a series of studies performed on the canine heart which correlate P-wave polarity and morphology with the origin and the time course of atrial epicardial and endocardial activation during ectopic atrial rhythms. Ectopic pacing sites were selected which produced either a negative retrograde P wave (3, 4) or a positive retrograde P wave (1, 8) in ECG leads II, III, and aVF. The sequences of atrial activation during rhythms produced when these ectopic sites were paced were then compared with each other as well as with that demonstrated when the atria were paced from a site close to the sinus node. Methods STUDIES OF P-WAVE POLARITY AND MORPHOLOGY Twenty-seven healthy adult mongrel dogs weighing 18-25 kg were studied. The dogs were anesthetized with sodium pentobarbital (30 mg/kg, iv) and ventilated with room air using a Harvard respirator. Each dog was placed on its left side, and a right thoracotomy through the fifth intercostal space was performed. A pericardiotomy was performed and a pericardial cradle created. Using previously described techniques (1, 4), electrodes were placed at selected sites which included (Fig. 1) the region of the sinus node (SN), the portion of Bachmann's Circulation Research, Vol. 37, August 1975 157 SEQUENCE OF ATRIAL ACTIVATION LAS on photographic paper at recording speeds of 50, 100, and 200 mm/sec. Seven of these studies initially were performed using sterile techniques (1). These dogs were permitted to recover and were then restudied 1-2 weeks later under sodium pentobarbital anesthesia while they were lying on their left side; thus, P-wave polarity and morphology were compared with the chest open and closed in the same dog. During normal and ectopic rhythms, P-wave polarity always was identical, and P-wave morphology, although never completely identical, was quite similar under both conditions, confirming previous observations (1,3,8). STUDIES OF THE SEQUENCE OF ATRIAL ACTIVATION PLA Downloaded from http://circres.ahajournals.org/ by guest on May 4, 2017 LAA FIGURE 1 Sketches of four views of the canine atria. A: View of the free wall of the right atrium. B: View of the right side of the interatrial septum and A V junction visualized after the free wall of the right atrium and part of the right ventricle have been cut away. C: View of Bachmann's bundle and both atrial appendages as well as a portion of the left atrium. D: View of the inferior aspects of both atria. The fixed electrode recording sites include the region of the sinus node (SN), the right atrial appendage (RAA), the low atrial septum in the region of the A V node (LAS), Bachmann's bundle (BB), the left atrial appendage (LAA), the posterior-inferior left atrium (PLA), and the right ventricular epicardium (RV). During the studies of sequence of atrial activation, fixed electrodes were placed only at the SN, PLA, and RV sites. The black dots represent the points at which electrograms were recorded during atrial activation when the atria were paced from the SN, PLA, and RV sites. Pacing sites anterior and posterior to the coronary sinus ostium (CSO) are identified by two small arrows; the A arrow is the posterior site and the B arrow is the anterior site. SVC = superior vena cava, IVC = inferior vena cava, PV = pulmonary veins, RA = right atrium, LA = left atrium, RV = right ventricle, LV = left ventricle, CS = coronary sinus, and TV = tricuspid valve. bundle (BB) overlying the interatrial septum, the right atrial appendage (RAA), the left atrial appendage (LAA), the posterior-inferior left atrium (PLA), the free wall of the right ventricle (RV), and, in 14 studies, the low atrial septum in the region of the AV node (LAS). During spontaneous sinus rhythms and during atrial rhythms produced during bipolar threshold pacing through the SN electrode, the PLA electrode, and the RV electrode, standard bipolar and augmented unipolar ECGs and atrial electrograms from each electrode site were monitored simultaneously on a DR-8 Electronicsfor-Medicine switched-beam oscilloscope and recorded Circulation Research, Vol. 37, August 1975 Preparation of the Study (Perfused) Heart.—Studies were performed on 13 isolated canine hearts perfused with arterial blood from a donor (support) dog. The donor dogs weighed 30-40 kg. The study heart was obtained from dogs which weighed 18-25 kg. After the study dog's heart had been exposed, electrodes were sutured to the SN, PLA, and RV sites. Modifying previously described techniques (15), the study heart was isolated intact, and perfusion with arterial blood from the donor dog was initiated. The isolated heart was then placed in a blood-filled bath. Using standard techniques, the perfused blood and the bath were maintained at 37°C. Using a roller pump, the venous blood, which drained directly into the bath, was returned to the donor dog through a defoaming reservoir. During the periods of data collection, the ventricles remained immersed in the bath, and blood from the bath was gently poured over the atria at appropriate intervals to prevent any drying of the atrial tissue. In three additional experiments, the study heart was exposed through a right thoracotomy, and the heart was then perfused in situ. This in situ study allowed the recording of standard ECGs in the study dog during the experiment. In these studies, electrodes were placed at the same epicardial sites used in the studies of P-wave polarity and morphology. Conduction in the study heart, checked periodically by pacing through each fixed electrode with threshold stimuli and then measuring the conduction time to the other fixed electrodes, remained constant throughout each study. After completion of all epicardial mapping studies, a right atriotomy was performed to permit endocardial mapping. The right atriotomy incision was placed 5 mm from the margin of fat in the AV groove and extended no closer than 1 cm to the crista terminalis. Mapping the Sequence of Atrial Activation.—Grid maps were drawn on Polaroid photographs of several views of the isolated heart, providing accurate identification of mapping sites both during each study and for the permanent record. The grid sites were not always equidistant from one another but were generally separated by 5 mm, i.e., the diameter of the electrode probe (2, 3) utilized to record bipolar electrograms from each of the sites. Figure 1 shows drawings of four views of the canine atria with the grid sites superimposed. The sequence of atrial activation was mapped during threshold pacing from each fixed electrode (SN, PLA, and RV). During bipolar threshold pacing from the PLA site, the SN site, and the RV site, conduction times from each pacing site to each grid site were measured directly from the WALDO. VITIKAINEN, HOFFMAN 158 oscilloscope grid of a Tektronix 502 dual-beam oscilloscope whose sweep was triggered from thejiacing stimulus at a sweep speed of 1 mm/sec. When the RV site was paced, the oscilloscope was triggered after a suitable delay which allowed for retrograde conduction of the impulse through the AV node to the atria, and the electrogram recorded from the SN electrode was used as a time reference. Also, during ventricular pacing, the earliest point of activation of the atria was considered zero time. In the three studies in which the study heart was perfused in situ, utilizing the electrode probe to deliver bipolar threshold stimuli, the atria were also paced from sites just anterior and posterior to the coronary sinus ostium (Fig. 1C); ECGs and electrograms were recorded as described for studies of P-wave polarity and morphology. For all studies, ECGs were recorded at a band pass between 0.1 and 200 Hz and electrograms at a band pass between 12 and 200 Hz. Downloaded from http://circres.ahajournals.org/ by guest on May 4, 2017 Results PACING FROM THE REGION OF THE SINUS NODE This portion of the study largely confirms the results of previous studies in which the sequence of atrial activation during sinus rhythm has been mapped either partially (8, 16-20) or completely (21). The P waves in ECG leads II, III, and aVF were always positive. Figure 2 illustrates the sequence of activation in a representative study in which the atria were paced from the region of the sinus node. For this and other such figures, the sequence of atrial activation is illustrated by isochronous lines drawn at 5-msec intervals. The activation front in the free wall of the right atrium (Fig. 2A) spread inferiorly down the sulcus terminalis and anteriorly along the pectinate muscles. Most of the left atrium was depolarized through a wave front from Bachmann's bundle (Fig. 2C). However, the posterior-inferior region (PLA) consistently was activated relatively late by a wave front which seemed to come from the lower interatrial septum (Fig. 2D). Thus, the direction of spread of activation in the left atrium with the exception of the left atrial appendage was basically directed inferiorly. The wave front in the AV junction consistently D FIGURE 2 Maps of the sequence of atrial activation in a representative study when the atria were paced from the electrode in the region of the sinus node (SN). Isochronous lines are drawn at 5-msec intervals. Abbreviations are the same as they are in Figure 1. Circulation Research, Vol. 37, August 1975 159 SEQUENCE OF ATRIAL ACTIVATION Downloaded from http://circres.ahajournals.org/ by guest on May 4, 2017 FIGURE 3 Maps of the sequence of atrial activation in a representative study when the atria were paced from the posterior-inferior left atrial electrode site (PLA). Isochronous lines are drawn at 5-msec intervals. Abbreviations are the same as they are in Figure I. advanced to the coronary sinus ostium, suggesting that a wave front from the posterior internodal pathway does not contribute to activation of the AV node when the atria are paced from the SN site. This direct observation is consistent with previously published indirect observations in the dog (4) and in man (22) which suggested that normally the main route of conduction between the sinus node and AV node is via the anterior internodal pathway. These data conflict with the observations of Goodman et al. (21), who suggested that activation of the AV node occurs via the posterior internodal pathway, and with the data of Spach et al. (23), who described simultaneous activation of the AV nodal region from an anterior and a posterior wave front. PACING FROM THE POSTERIOR-INFERIOR LEFT ATRIUM As we (3, 4) and others (24-26) have previously described, the P waves in ECG leads II, III, and aVF were always deeply negative when the PLA site was paced. As illustrated in the representative Circulation Research, Vol. 37, August 1975 example shown in Figure 3, when the atria were paced from the PLA site, the interatrial septum, the right atrial free wall, and the left atrium were depolarized by retrograde wave fronts. Therefore, except for the tips of the left and right atrial appendages, the atria were depolarized in a sequence opposite to that which occurred during the paced sinus rhythm. Thus, negative P waves in leads II, III, and aVF can be correlated with true retrograde activation of the atria. The left atrial portion of Bachmann's bundle was depolarized simultaneously throughout its length (Fig. 3C), thereby explaining previous observations (4) in which discrete lesions in Bachmann's bundle did not alter the polarity, morphology, or duration of the P wave when the atria were paced from the PLA site. PACING THROUGH THE RIGHT VENTRICULAR ELECTRODE WITH RETROGRADE CAPTURE OF THE ATRIA As Moore et al. (1, 8) have previously described, the P waves in ECG leads II, III, and aVF were 160 WALDO. VITIKAINEN, HOFFMAN Downloaded from http://circres.ahajournals.org/ by guest on May 4, 2017 D FIGURE 4 Maps of the sequence of atrial activation in a representative study when the atria were paced from the right ventricular epicardial electrode site (RV). Isochronous lines are drawn at 5-msec intervals. Abbreviations are the same as they are in Figure 1. consistently positive with retrograde atrial capture during ventricular pacing. A representative study of the sequence of atrial activation during retrograde atrial capture with pacing from the right ventricle is illustrated in Figure 4. The depolarization wave front spread quickly up the interatrial septum, consistently emerging superiorly very early (within 15 msec in this example) at Bachmann's bundle (Fig. 4C). Having reached this site, the activation front proceeded along Bachmann's bundle to depolarize a considerable portion of the left atrium in a manner similar to that which occurred during the paced sinus rhythm and clearly opposite to that which occurred during the rhythm produced by pacing at the PLA site. In addition, an activation front proceeded from Bachmann's bundle toward the sinus node and spread to depolarize a significant portion of the upper right atrium (Fig. 4A and C) in a manner similar to that which occurred during paced sinus rhythm. The caudal aspects of both atria consistently were activated by retrograde wavefronts (Fig. 4D), the right atrial wave front being primarily in the region of the posterior internodal pathway (27-29). Also present in some studies and illustrated in Figure 4A was a third contribution to right atrial epicardial activation which corresponded in location to the anatomical locus of the middle internodal pathway (27-29). As can be extrapolated from these data on the sequence of atrial activation during ventricular pacing with retrograde atrial capture, the critical factor in determining P-wave polarity seems to be the relatively rapid spread of the impulse to the region of Bachmann's bundle from which point it can be spread inferiorly over significant portions of both atria. Cancellation of early wave fronts also may be important. PACING FROM SITES IN PROXIMITY TO THE CORONARY SINUS OSTIUM When the atria were paced from site B just anterior to the coronary sinus ostium (Fig. IB) P Circulation Research, Vol. 37, August 1975 SEQUENCE OF ATRIAL ACTIVATION 161 occurred during sinus rhythm. When this group paced the posterior site in proximity to the coronary sinus ostium, the sequence of atrial activation was almost identical to that which occurred when the atria were activated from the PLA site in the present study, i.e., there was complete retrograde activation of the atria without any inferiorly directed wave fronts. Discussion RELATIONSHIP OF THE SEQUENCE OF ATRIAL ACTIVATION TO P-WAVE POLARITY AND MORPHOLOGY FIGURE 5 Downloaded from http://circres.ahajournals.org/ by guest on May 4, 2017 A: P wave recorded in lead II when the atria were paced from the posterior coronary sinus ostial site (see Fig. IB). B: P wave recorded in lead II when the atria were paced from the anterior coronary sinus ostial site (see Fig. IB). The relative times of arrival of the impulse at the various atrial recording sites have been superimposed on each P wave. STIM = stimulus, PLA = posterior-inferior left atrium, LAS = low atrial septum, BB = Bachmann's bundle, SN = sinus node, and LAA = left atrial appendage. waves were positive in ECG leads II, III, and aVF (1) (Fig. 5B). As illustrated by the relative sequence of activation of the atrial sites from which electrograms were recorded (Fig. 5B), the impulse arrived relatively early at the BB site particularly in comparison with its arrival at the PLA site. Data from a previous study (4) in which positive P waves in leads II, III, and aVF were produced when the atria were paced from a LAS site also were associated with relatively early activation of a BB site and significantly later activation of a PLA site. Thus, the positive P waves in leads II, III, and aVF during "retrograde" activation of the atria seem to be consistently associated with early activation of Bachmann's bundle and relatively later activation of the posterior-inferior left atrium. When the atria were paced from site A just posterior to the coronary sinus ostium (Fig. IB), P waves in leads II, III, and aVF were negative (Fig. 5A). These negative P waves were associated with early activation of the PLA site and relatively later activation of the BB site (Fig. 5A). Goodman et al. (21) paced the canine atria from similar sites in proximity to the coronary sinus ostium and studied the sequence of atrial activation, but they did not record any ECGs. When this group paced the site anterior to the coronary sinus ostium, the wave front spread rapidly up the interatrial septum to Bachmann's bundle and from there it spread inferiorly over significant portions of both atria in a manner similar to that which Circulation Research, Vol. 37, August 1975 Data from the present study and, by extrapolation, combined data from the present study and the study of Goodman et al. (21) clearly demonstrate that for the canine heart the positive retrograde P waves in ECG leads II, III, and aVF result from rapid spread of the wave of excitation up the interatrial septum to Bachmann's bundle from which point it then spreads inferiorly over a significant portion of both atria in a manner similar to that which occurs during spontaneous sinus rhythm. This finding confirms previous hypotheses (3, 4, 7, 10). Furthermore, the relative time of arrival of the impulse at Bachmann's bundle compared with that at the posterior-inferior left atrium and the direction of spread of the impulse in and from Bachmann's bundle play a critical role in determining P-wave polarity and morphology. Relatively early activation of Bachmann's bundle compared with the posterior-inferior left atrium permits excitation to spread inferiorly from Bachmann's bundle to depolarize significant portions of both atria, thereby producing positive P waves in leads II, III, and aVF. When activation of the posterior-inferior left atrium is relatively early during the sequence of atrial activation and activation of Bachmann's bundle is relatively later during the sequence of atrial activation, excitation from the posterior-inferior left atrium spreads as a retrograde wave front over much if not all of the left atrium, thereby preventing the occurrence of any significant inferiorly directed wave front from Bachmann's bundle. The result is negative P waves in leads II, III, and aVF. There is some evidence in patients that the preceding explanation for the positive retrograde P wave probably holds true for the human heart as well. In studies of the P wave produced by pacing the atria in the region of the AV node in patients with ostium primum atrial septal defects, only negative retrograde P waves in leads II, III, and aVF have been produced (22); however, in patients with ostium secundum or sinus venosus atrial septal defects or with intact atrial septa, positive 162 WALDO. VITIKAIIMEN. HOFFMAN retrograde P waves in the same ECG leads have been produced (3, 22). Thus, it is evident that the critical location of the ostium primum lesion in the atrial septum precludes the possibility of retrograde activation of the atria in the previously described manner; moreover, these data suggest that the sequence of atrial activation during the inscription of the positive retrograde P wave in man is quite similar to that demonstrated for the canine heart. SPECIALIZED ATRIAL CONDUCTION Downloaded from http://circres.ahajournals.org/ by guest on May 4, 2017 Data from the present study are consistent with the considerable body of evidence (30) which demonstrates the presence and supports the functional significance of specialized atrial pathways. However, no discrete, functionally isolated pathways of rapid conduction in the atria equivalent to those which can be demonstrated for the His bundle or the bundle branches were identified in the present study. As conduction in the former pathways normally occurs simultaneously with conduction in working atrial muscle, there is no way to distinguish qualitatively between electrograms recorded from the specialized atrial pathways and those recorded from working atrial muscle. In contradistinction, it is only the fact that conduction in the His bundle and bundle branches normally occurs during the isoelectric portion of the P-R interval (when simultaneous conduction in any other cardiac tissue normally does not occur) which permits electrophysiological identification of the His bundle and the bundle branches when electrograms are recorded from the whole heart. It should be noted that several studies have concluded that there are no functionally significant specialized atrial pathways but rather that there are preferential atrial pathways (16, 21, 23). The major objection seems to be primarily with the term specialized. However, for the data presented in this paper, the semantic difference between specialized and preferential atrial pathways seems relatively unimportant. Acknowledgment The authors would like to express their appreciation to Dr. Thomas N. James for his critical review of this manuscript. References 1. 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Philadelphia, Lea & Febiger, 1974, pp 37-74 The sequence of retrograde atrial activation in the canine heart. Correlation with positive and negative retrograde P waves. A L Waldo, K J Vitikainen and B F Hoffman Downloaded from http://circres.ahajournals.org/ by guest on May 4, 2017 Circ Res. 1975;37:156-163 doi: 10.1161/01.RES.37.2.156 Circulation Research is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1975 American Heart Association, Inc. 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/content/37/2/156 Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation Research can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. 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