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Electrical Activity During the P-R Interval By BRIAN F . HOFFMAN, M.D., PAUL P . CRANEFIELD, P H . D . , JACKSON H. STUCKEY, M.D., AND ALBIN A. BAGDONAS, M.D. With the assistance of Juan Piera, M.D. and left ventricles.0"11 This method, which permits exact localization of the recording electrodes without apparent injury to the tissues under investigation, has been used to record from the His bundle, the bundle branches and the false tendons of the canine heart. The electrical activity of the specialized conducting system has been correlated with the standard electrocardiogram both in the open-chest preparation and in the intact animal after completion of the surgical repair. R Downloaded from http://circres.ahajournals.org/ by guest on May 7, 2017 ECENT studies of the electrical activity of single cardiac fibers suggest that most, if not all, disturbances of rhythm have their origin in specialized cardiac tissues rather than in the muscle fibers of the atria or ventricles.1'2 Similarly, many disorders of conduction result from disordered function of these same structures.2 Unfortunately, the leads employed in clinical electrocardiography fail to show any direct indication of electrical activity of nodal tissue or of the specialized conducting system. Even if electrocardiograms are recorded directly from the epicardial surface of the heart, no obvious deflections occur during P-R interval which are attributable to activity in the atrioventricular node, the His bundle, bundle branches and the Purkinje fibers. In attempting to detect activity in these tissues, only a few records have been obtained from the sinoatrial3 and atrioventricular nodes3'4 and Purkinje system5"7 of closed heai'ts by means of needle electrodes inserted through the epicardium and into these structures. However, this method has the disadvantage that extract localization of the electrodes is difficult and that injury to tissue surrounding the electrode tip is inevitable. Bipolar needle electrodes also have been used to record from the His bundle of isolated perfused dog hearts.s It is possible to record the electrical activity of the specialized ventricular conducting S3'stem during total cardiopulmonary bypass through small electrodes attached to the endocardial surfaces of the right atrium and right Methods Surgical Technics Healthy mongrel dogs weighing 18 to 23 Kg. were anesthetized by intravenous injection of 2.5 per cent thiopental sodium and placed on controlled respiration. The chest was opened transsternally at the level of the fifth interspace and tapes were placed around the superior and the inferior venae cavae. The pericardium was opened widely and the dog was given an intravenous injection of heparin, 2.5 mg./Kg. body weight. One venous drainage catheter of the bypass circuit was introduced into the superior vena eava through the azygos vein and a second was introduced directly into the inferior vena cava. The arterial cannula was placed in the femoral artery. Venous blood flowed by gravity from the superior and inferior venae cavae to the oxygenator where it was oxygenated in an atmosphere of 97 per cent oxygen and 3 per cent carbon dioxide in a rotating disk oxygenator and then returned to the animal by occlusive roller pump through the femoral artery. Cardiopulmonary bypass was achieved by tightening the slings around the catheters in the superior and inferior venae cavae. With the dog on cardiopulmonary bypass, the right atrium and one or both ventricles were opened. In making the right ventriculotomy incision care was taken not to injure the freerunning Purkinje fibers which extend from the base of the anterior papillary muscle to the wall of the right ventricle. Blood was titrated against protamine at 30 minute intervals and a heparin level of SO to 90 gamma per ml. was maintained throughout perfusion. The rectal temperature was maintained From the Departments of Physiology and Surgery, State University of New York Downstate Medical Center, Brooklyn, N. T. Supported in part by grants from the American Heart Association and the TJ. S. Public Health Service (H-3916; H-4801; H-1101). Beceived for publication June 3, 1960. 1200 Circulation Research, Volume VIII. November 1960 1201 ACTIVITY DURING P-R INTERVAL Downloaded from http://circres.ahajournals.org/ by guest on May 7, 2017 at 37 to 38 C. by incorporating a heat exchanger in the perfusion circuit. The mean blood pressure was kept above 100 mm. Hg during the perfusion by flow rates of 80 to 90 ml. of blood per Kg. of body weight. Recording Technics The recording electrodes employed in these experiments consisted of fine silver wires embedded in plastic plaques.* The diameter of the wire varied from 0.036 to 0.12 mm. depending on the number of contacts and the use of the electrode. Each plaque contained from 3 to 16 contacts separated by distances of 0.3 to 1.0 mm. The plaque containing the silver wires was attached to the endocardium at the desired location by 5-0 silk sutures which were located 1.5 to 3.0 mm. from the actual recording site. Similar electrodes usually were attached to the epicardium of the right atrium and right or left ventricle to record from these chambers and to apply driving and testing stimuli. A plastic probe containing 2 or 4 contacts at the tip was employed as an exploring electrode to locate the optimum site for recording the electrical activity of the bundle of His and the right and left bundle branches. Records from the free-running Purkin je fibers in the false tendons were obtained through electrodes embedded in a small groove in a similar plastic probe; this probe was positioned manually so that the electrodes made only light contact with the false tendons. Bipolar leads were employed for most tracings of the electrical activity of the specialized conducting system; unipolar tracings using the left leg for the indifferent electrode were recorded in some instances. For most records from the specialized conducting system the low frequency components of the electrogram were filtered to increase baseline stability and to facilitate identification of the electrical activity of the specialized fibers. The characteristics of the filters employed are shown in figure 1; filter settings, where pertinent, are specified for each illustration. Records were displayed on an 8-trace switched beam oscilloscope (Electronics for Medicine) and photographed on 7-inch paper moving at a speed of 200 mm./sec. Driving and testing stimuli were provided by American Electronics stimulators and stimulus isolation units. Electrocardiograms were recorded through needle electrodes by means of a standard ECG preamplifier. The temperature of the endoeardial surface of the heart was recorded by means of a miniature thermister which was placed on the *The authors would like to acknowledge the kindness of Professor T>. Durrer of Amsterdam who supplied 2 excellent 10-contact electrodes of extremely small size. Circulation Research, Volume VIII, November 1960 iiooo cps Figure 1 Characteristics of loio-pass and high-pass filters of preamplifiers. (A) Low-pass filter set at 0.1 c.p.s.; high-pass filter settings at 2,000 c.p.s. (o—o), 500 c.p.s. (•—•) and 100 c.p.s. (x—a;). (B) Response plotted as per cent of maximum amplitude with low-pass filter at 0.1 c.p.s. when low- and high-pass filters were at the folloicing settings: (•—•) 4,500; (o—o) 4^00; (x—x) 1.2,500; and (A.—A), 40,500. endocardium next to the electrode sites after each series of recordings. Results Electrical Activity of the Bundle of His Identification of Records Figure 2 shows records of the electrical activity of the His bundle recorded from an intact dog, after closure of the heart and thoracotomy incision, through electrodes attached to atrial muscle overlying the common bundle. Also shown are bipolar electrograms recorded directly from the right atrium and the right and left ventricles and a standard lead II electrocardiogram. The bipolar electrogram recorded through the electrodes located over the common bundle shows 3 discrete complexes: The first set of the deflections (a) appears slightly after the earliest recorded atrial activity and clearly results from depolarization of atrial muscle; the final HOFFMAN, CRANEFIELD, STUCKEY, BAGDONAS 1202 "4 ir i i r J L+M-JU-U-i Downloaded from http://circres.ahajournals.org/ by guest on May 7, 2017 f B c t _ /! a h i 1 i -\ I A^ I H , f V I— Figure 2 Bipolar electrograms recorded from a closed-chest dog through implanted electrodes and a lead II electrocardiogram. (A) Records obtained 2 hours after surgical preparation. Top trace, electrogram from right atrial appendage; second trace, electrograin from bundle of His; third and fourth traces, electrograms from the right and left ventricles; bottom trace, lead II. In the His electrogram, (a) indicates local atrial activity and (h) electrical activity in the common bundle. Low- and high-pass filter settings for His electrogram at 40/1,000 and for other electrograms at 4/200 (B) Lead II electrocardiogram recorded immediately prior to surgery; compare with similar records in (A) and (C). (C) Records obtained from the same animal one day after surgical preparation shoiving the same sequence of leads as in (A). Polarity of His electrogram reversed. Note general similarity of His electrogram and constancy of P-R interval of electrocardiogram. Filter settings at 40/2,000 for His bundle and 4/500 for other electrograms. In this and all subsequent records, time lines indicate intervals of 40 msec. set of deflections occurs during and after the S wave of the electrocardiogram and presumably results from depolarization of the base of the interventricular septum and the crista supraventrieularis.12 The second set of deflections (h), identified as resulting from electrical activity in the bundle of His, appears midway in the P-R interval of lead I I ; it thus follows the end of atrial activity and precedes the earliest depolarization of ventricular muscle. A similar deflection has been recorded from the His bundle by Alanis.8 Several criteria can be employed in support of the identification of this complex with the electrical activity of the bundle of His. A complex similar to that indicated by h in figure 2 could be recorded only from a sharply circumscribed area which agreed in extent with the anatomic location of the common bundle. The possibility that the h complex resulted from electrical activity in the atrioventricular node was made unlikely by results obtained during stimulation of the cut peripheral end of either vagus nerve. As shown in figure 3, when the atrium was driven electrically at a constant rate, vagal stimulation caused a progressive increase in the separation between the atrial (a) and His bundle (h) complexes (fig. 3B) indicating that the activity identified as depolarization of the His bundle originated distal to the site of increased A-V delay and thus distal to the atrioventricular node.13'14 Also, during the period of complete A-V dissociation caused by vagal activity (fig. 3B) the atrial component of the electrocardiogram (a) recorded from the vicinity of the common bundle can be identified with ease. In many experiments, identification of the His electrogram was facilitated by studying records obtained during spontaneous or induced ventricular extrasystoles or after "vagal escape." Results varied depending on the site of origin of the extrasystole and the rapidity with which activity entered the specialized conducting system ; in some instances, the His electrogram was buried in the complex resulting from ventricular depolarization, but often a clearly identifiable electrogram recorded from the bundle of His preCirculation Research, Volume Vlll, November 1960 1203 ACTIVITY DURING P-R INTERVAL Downloaded from http://circres.ahajournals.org/ by guest on May 7, 2017 ceded the local ventricular electrogram while the component due to atrial depolarization followed ventricular activity after an appropriate V-A (vcntriculo-atrial) delay (see figs. 4 and 6). The records shown in figure 4 are of interest, not only with respect to the question of identification of the electrogram recorded from the bundle of His, but also in relation to the site of the ventricular pacemaker during the A-V dissociation caused by vagal activity. In this experiment, records were obtained during cardiopulmonary bypass. Electrodes were attached to the right atrial appendage, over the common bundle, over the anterior portion of the left bundle branch at its site of emergence from the left septal surface, and at a point close to the junction of the anterior false tendon with the anterior papillary muscle of the left ventricle. The sequence of discrete electrograms recorded from the bundle of His (h)and from the 2 ends of the false tendon is the same before (A) and during (B) vagal stimulation. However, the shift in the atrial electrogram indicates that during vagal activity the pacemaker site shifted to some location in the His bundle. The absence of an appreciable change in the time interval between activity in the His bundle and other sites in the specialized conducting system, taken in conjunction with the long delay between the His complex and the atrial electrogram, strongly supports the conclusion that the pacemaker site is distal to the atrioventricular node. This observation is in agreement with results obtained from records of the transmembrane potentials of single fibers in the His bundle and atrioventricular node of isolated preparations of rabbit and dog hearts.14 These records, in conjunction with those in figure 3, also show that vagal activity sufficient to cause complete atrioventricular dissociation has no measurable effect on conduction velocity in the bundle of His, the bundle branches or the Purkinje fibers of the ventricular conducting system. This result would be expected from the results of studies of transmembrane potentials of isolated preparations.2-15 Circulation Research, Volume VIII, November I960 A L V a b 1 1 •! i \ /I ft -s B[ 1 V a I f ft A 1/ Figure 3 Electrocardiogram and electrogranns recorded from the same animal as for figure 2, showing the effects of stimulation of the vagus nerve. (A) Control conditions; electrograms from above down show activity of right atrial appendage, bundle of His (filter settings 40/1,000), bundle of Sis (filter settings 4/200), and left ventricle. Bottom trace is a> lead II electrocardiogram. Note effect of amplifier frequency response on relative amplitude of His bundle electrogram. (B) Vagal stimulation. Note prolongation of delay betiveen atrial (a) and His bundle (h) activity and unchanged interval between activity in His bundle and ventricle. The appearance of complete failure of A-V nodal transmission of the second atrial impulse clearly identifies the atrial component of the His bundle electrogram. Form of the His Bundle Electrogram We have made no systematic attempt to study the confirmation of the electrogram recorded from the bundle of His at different .1204 HOFFMAN, CRANEFIELD, STUCKEY, BAGDONAS J — Jit Downloaded from http://circres.ahajournals.org/ by guest on May 7, 2017 B a ^ ^ 1 t K Figure 4 Biopolar electrograms recorded from 4 different sites during total cardiopulmonary bypass. Heart temperature 37.5 G. Top trace, right atrial appendage; second trace, bundle of His; third trace, septal end of anterior false tendon of left ventricle; bottom trace, peripheral end of same false tendon. (A) Control records: (a), atrial electrogram complex; (h), His bundle electrogram; (s), electrogram from septal end of false tendon; and (p), electrogram from peripheral Purkinje fibers. Filter settings of 12/500 employed for bundle of His and 4/200 for all other traces. (B) Effect of vagal stimulation. Note that earliest recorded electrical activity is the electrogram complex of the His bundle, that conduction time from His to 2)eripheral Purkinje fiber is unchanged and that the conduction time from the bundle of His to the atrium is approximately twice the normal atriumHin interval. The absence of change in the polarity of the biphasic His deflection suggests that the pacemaker site is between the recording electrode and the atrioventricular node. locations; indeed, in most experiments, filters were employed to emphasize this complex in the electrogram and to diminish in amplitude any activity of atrium or ventricle which might distort or mask the activity recorded from the specialized tissue. For the same reason, most records were obtained with contiguous bipolar electrodes. The effect of the filters on the bipolar electrogram can be seen in figure 3. In this tracing, the records on the second and third lines were obtained through the same set of close bipolar leads using a different filter setting for each channel. It is clear from a comparison of the relative amplitudes of His bundle and ventricular electrograms that a poor highfrequency response seriously limits ability to obtain good records from the His bundle. Similarly, if the low-frequency components of the ventricular electrogram are present, the relative amplitude of the h complex is less and its identification is made more difficult. Unipolar electrograms were recorded only infrequently from the His bundle. The third trace of figure 5 shows one such set of records obtained from a closed-chest dog through an electrode containing 5 contacts and located over the common bundle. Also shown in the figure are bipolar electrograms recorded from the right atrium, the bundle of His, the left ventricle and a standard lead II electrocardiogram. The unipolar His bundle electrogram obviously varies in shape depending on the location of the electrode employed; the record obtained through a contact nearer the atrioventricular node (fig. 5A) shows only a small, largely monophasic His deflection arising from the latter part of a large, slow positive wave; somewhat farther from the atrioventricular node the His deflection arises slightly later and shows a more prominent initial positivity (fig. 5B) and at the recording site nearest the septal end of the common bundle of the slow wave has changed in amplitude and configuration and the His bundle electrogram is clearly diphasic (fig. 5C). The possible significance of the slow waves preceding the His bundle electrogram are discussed in a subsequent section. Circulation Research, Volume Vlll, November I960 ACTIVITY DURING P-R INTERVAL Downloaded from http://circres.ahajournals.org/ by guest on May 7, 2017 Perhaps the most significant observation made on the general appearance of the electrogram deflection recorded from the bundle of His is that, during normal atrioventricular transmission, this component of the electrogram always was of short duration (10 msec, or less) and relatively simple in contour. Although polyphasic deflections and notches were frequently recorded from other parts of the heart, unipolar and bipolar records from the bundle of His were of a configuration compatible with almost simultaneous excitation of parallel fibers conducting at more or less uniform velocity. During retrograde excitation, however, the electrogram recorded from the His bundle at times revealed a greater degree of asynchrony than was present during normal activation (fig. 6). This record, obtained through electrodes implanted in a dog with a closed chest, shows several beats originating from some focus distal to the common bundle followed by several driven beats caused by stimuli applied to the right atrium. The polyphasic complex recorded during retrograde activity contracts sharply with.that observed after resumption of normal A-V transmission. 1205 I Hi Possible Effects of Injury Whenever electrodes are applied directly to the heart, there probably is some local injury and, as a result, some distortion of the records of electrical activity obtained through such electrodes. Since the bundle of His is located beneath a superficial layer of atrial myocardium, it was thought that attachment of the electrode to endocardium over the His bundle would not injure that structure. The records shown in figure 2C support this impression. These tracings were obtained through the same electrode employed for figure 2A, 20 hours after electrode implantation and 18 hours after closure of the chest. It is clear that there has been no measurable change in either the interval between atrial depolarization and the h complex or between the h complex and depolarization of the ventricular myocardium. The configuration of the electrogram recorded from atrial muscle is changed in figure 2C because driving stimuli were apCirculation Research, Volume VIII, November 1960 Figure 5 'Records of activity in the bimclle of His recorded from a closed-chest dog through unipolar and biopolar leads. (A) From above downward, the records shoiv biopolar electrograins from the right atrium, the bundle of His, a unipolar electrogram from the bundle of His, a bipolar electrogram from the left ventricle and lead II. The filter setting for the bipolar His electrogram was 40/1,000 and for the unipolar electrogram 0.1/500. (B) and (C) The second, third and fourth traces a>re shown. The unipolar recording site is moved progressively farther from the atrioventricular node in (B) and (C). Note the change in configuration of the slow deflection proceeding the His electrogram. See text for discussion. 1206 HOFFMAN, CRANBFIBLD, STUCKBY, BAGDONAS I '••! v v Downloaded from http://circres.ahajournals.org/ by guest on May 7, 2017 \J I\ Figure 6 Records obtained through implanted electrodes 24 hours after surgical preparation. Top trace, right wtrial appendage; second and third traces, bipolar electrograms recorded from the bundle of Sis; fourth trace, bipolar electrogram from the epicardial surface of the left ventricle; bottom trace, lead II. In the His electrogram, (a) represents atrial and, (h) His btmdle activity. In all traces except the fourth, the artifact of the driving stimulus is apparent. Filter settings for the upper and lower His electrograms are 40/1,000 and 4/200, respectively. Arrow indicates the instant at which normal A-V transmission through the His bundle is initiated; note the fusion beat in lead II. Note the change in configuration and synchrony of activity in the bundle of His on resumption of normal A-V transmission. plied to the right atrium; the complex recorded from the His bundle, however, is similar in configuration to that shown in A. Electrical Activity of the Bundle Branches and Peripheral Purkinje Fibers Electrograms were recorded from the right and left bundle branches at the point of their appearance on the right and left septal surfaces. On the left side, the emergence of the left branch was visualized with ease. On the right side, the bundle branch was located with an exploring electrode in an area posterior to the superior papillary muscle and beneath the septal cusp of the tricuspid valve. Electrograms were recorded both through the exploring electrode, which was placed lightly on the septal surface, and through multipolar electrodes sutured to the septal endocardium. Comparison of the records obtained by both means suggested that the method employed to attach the electrode to the endocardium did not injure the fibers of the bundle branch under study. Records were obtained from the free-running false tendons through bipolar electrodes located in a groove in curved probe. The probe was positioned by hand so that the false tendon lay lightly in this groove. The electrical activity of Purkinje fibers at the junction of the false tendons with the papillary muscles was recorded either through the exploring electrode or through multipolar electrodes sutured to the base of the papillary muscle. Up to the present time records from the bundle branches, false tendons and peripheral Purkinje fibers have been obtained only through ventriculotomy incisions during cardiopulmonary bypass. Figure 4 shows bipolar electrograms recorded in one experiment from the His bundle Circulation Research, Volume V1H, November 1960 ACTIVITY DURING P-R INTERVAL Downloaded from http://circres.ahajournals.org/ by guest on May 7, 2017 and the proximal (septal) and distal ends of the anterior false tendon of the left ventricle. Figure 7A, obtained in another experiment, shows records from the His bundle, the upper part of the right bundle branch and the papillary-Purkinje junction on the anterior papillary muscle of the right ventricle. Electrograms from the left bundle branch recorded during normal A-V transmission are shown in figure 7B. In each of these tracings, the electrical activity of the specialized conducting system is identified with ease. In every instance, the record from either the right or left bundle branch clearly precedes the earliest ventricular activity; records from the papillary-Purkinje junction, however, at times merge with the deflections resulting from depolarization of adjacent ventricular muscle. In all experiments, the eonfiguration of electrograms from the right bundle branch indicated synchronous activity of the underlying fibers of the specialized conducting system. This was true regardless of the exact location of the electrodes with respect to the bundle branch. On the left side of the heart, in contrast, if the recording electrodes were located high on the septum the electrogram recorded from the left bundle branch was of short duration and similar in configuration to that shown in figure 7B. If the recording electrodes were located somewhat lower on the septum and thus made contact with more than one subdivision of the left bundle, the shape of the electrogram indicated some slight degree of asynchronj' of depolarization in the underlying specialized fibers. Records from the free-running false tendons were biphasic or triphasic; close to the junction of the Purkinje fibers with the papillary muscles the records from the specialized tissues frequently were polyphasic. In all instances, however, electrograms recorded from various parts of the specialized conducting system gave no indication of any important degree of asynchrony in the activation of the various fibers in any one bundle. From records similar to those shown in figures 4, 6 and 7, it is possible to determine the speed of conduction in each part of the Circulation Research, Volume VIII, November 1960 1207 v P ,1 \ i a Figure 7 (A) Bipolar electrograms recorded from the right atrial appendage (a, bottom trace), the bundle of His (h), the right bundle branch (s) and the junction of the Purkinje fibers loith the anterior papillary muscle (p, top trace) during cardiopidmonary bypass. (B) Bipolar electrograms recorded during cavdiopulmonary bypass from another dog. Top trace, His bundle (h); middle trace, left bundle branch (s); and bottom trace, peripheral~Pur~kinje-papillaryjunction (p). See text for discussion. specialized ventricular conducting system and it has been found that velocity is considerably higher in the false tendons than in the bundle of His.10 Also, it is possible to compare the speed of conduction during normal and retrograde transmission. If A'entricular activity originates late enough during diastole, it has been found that conduction velocit}' is the same in both directions in the His bundle and the ventricular Purkinje system.10 The propagation of early ventricular extrasystoles is reported elsewhere.10 1*208 HOFFMAN, CRANBFIELD, STUCKEY, BAGDONAS Downloaded from http://circres.ahajournals.org/ by guest on May 7, 2017 Figure 8 Superimposed tracings of bipolar electrograms recorded in one animal from A, right atrial appendage; H, bundle of His; LBB, left bundle branch; RFT, right ventricular false tendon; LAFT, anterior false tendon of left ventricle. Also sho%vn is the simultaneous lead II electrocardiogram. See discussion. Transmission Through the Atrioventricular Node Electrograms recorded from the region of the His bundle through close bipolar leads give a clear indication of the time of local excitation of atrial muscle and also of the time at which propagated activity passes through the His bundle. Because of the great difference in velocity of propagation in the atrioventricular node and bundle of His,13 it is reasonable to assume that a major part of the delay between the atrial and His bundle components of the local electrogram results from delay in the spread of excitation through the atrioventricular node. If the timing of the h complex is related to the standard lead II electrocardiogram, it is clear that activity in the His bundle is initiated about midway in the P-R interval; also, if the local atrial deflection is compared to the P wave in the limb leads, it is apparent that the termination of the P wave is an inappropriate reference point for timing the beginning of A-V nodal delay. In most experiments, atrial activity recorded through electrodes located over the His bundle appears rather early in the P wave, as would be expected from the results of earlier studies.17 This timing sequence is the same whether atrial activity originates from the normal sinus area (fig. 2A) or from driving electrodes located on the right atrial appendage (fig. 2C). Finally, it is apparent that the extent to which the V-A delay exceeds the A-V delay is extremely variable. This question is considered in detail elsewhere ;10 however, records of retrograde transmission obtained from hearts with essentially normal specialized conducting systems suggest that conduction time in the retrograde direction is not necessarily much greater than in a normal direction. If, on the other hand, there is some disturbance of normal A-V nodal transmission or if retrograde transmission reaches the node before complete recovery of its excitability, the usual prolongation of V-A conduction time is observed. Electrograms recorded through unipolar leads on the upper end of the bundle of His occasionally show a slow wave somewhat similar to that obtained from the atrioventricular node by Scher.4 This wave is seen only in records obtained with a long time-constant on the preamplifiers, and thus has been eliminated from most tracings shown in this paper. To what extent this deflection represents nodal depolarization and to what extent it results from repolarization of atrial muscle is difficult to decide. Additional studies in progress are designed to record more successfully from the atrioventricular node itself. Electrical Activity During the P-R Interval We have not yet obtained records through chronically implanted electrodes from numerous sites in the specialized ventricular conducting system. For this reason, it is perhaps premature to assign any specific timing to the depolarization of various parts of this system. On the other hand, simultaneous Circulation Research, Volume VIII, November 1960 ACTIVITY DURING P-R INTERVAL Downloaded from http://circres.ahajournals.org/ by guest on May 7, 2017 electrograms from the His bundle, the bundle branches and the peripheral Purkinje fibers recorded during total cardiopulmonary bypass probably do give a reasonable indication of the sequence of electrical activity in the specialized conducting system in relation to the standard electrocardiogram recorded under the same conditions. One such set of records is reproduced in figure 8 and emphasizes several points. First, as mentioned before, the bundle of His is activated early in the P-R interval. Since conduction through the atrioventricular node is known to be slow13 the conduction time between atrial muscle near the sinoatrial node and the atrioventricular node nmst be quite short. Second, although the distance from the His bundle to the emergence of the bundle branches on the interventricular septum is short in comparison to the distance from the bundle branches to the periphery, a major part of the delay between activity in the His bundle and depolarization of ventricular muscle is due to conduction in the His bundle and bundle branches. This finding would be expected from the observation that conduction velocity in the free-running Purkinje fibers is considerably higher than in the bundle of His. 8 ' 10 Finally, it is apparent that, there is electrical activity somewhere in the conducting system during the entire P-R interval even though that activity is not detected in the electrocardiogram. Discussion The electrical activity of the specialized conducting system was first recorded from excised, perfused dog hearts in 1930 by Maeno.18 Subsequently Burchell et al.,5 Scher7 and others recorded from either the bundle branches or subendocardial Purkinje fiber network through needle electrodes plunged into the myocardium. More recently a number of investigators have employed needle electrodes inserted into various parts of the heart to record from the atrioventricular node,4 the bundle of His 8 ' 19 and the specialized ventricular conducting system. As a result of these and other studies attempts have been made to characterize the electroCirculation Research, Volume VIII, November I960 1209 gram deflections typical of electrical activity in each part of the specialized conducting system and to determine the electrophysiologic properties of the specialized tissues. Also, it has been possible to indicate the sequence of activation of the specialized conducting system with respect to the standard electrocardiogram. The results reported in this paper have been obtained by a teehnic somewhat different from that employed by others. It is thought that this teehnic offers several advantages. In the first place, by use of total cardiopulmonary bypass, direct observation, and an exploring electrode it is possible to locate any part of the specialized conducting system with certainty. Also, comparison of records obtained through the exploring electrode and through the electrodes attached to the endocardium permits evaluation of local injury resulting from the method of attachment. Records obtained from more than 50 dogs during the past 2 years suggest that surface electrodes can be used for long periods of time without producing appreciable injury to the tissues under consideration. In contrast, studies of single cardiac fibers made with intracelhilar mieroelectrodes have clearly demonstrated that an electrode tip of as little as 2 microns in diameter will cause an important degree of injury to cardiac muscle. Records similar to those shown in figure 2, which demonstrate the constancy of the P-R interval and timing of the His electrogram after recovery from cardiopulmonary bypass, support the belief that neither the surgical procedure itself nor the presence of the electrode causes an appreciable distortion of the normal sequence of activation. Another advantage of the methods described is the possibility of obtaining simultaneous records from a number of different parts of specialized conducting system. Even when electrical activity is recorded simultaneously from the His bundle and a peripheral Purkinje fiber, estimates of conduction velocity give a wide range of variation (2.6 to 4.4 M./sec.).11' This variation results from local differences in conduction velocity in the His bundle, bundle branches, free-running HOFFMAN, CRANEFIELD, STUCKEY, BAGDONAS 1210 Downloaded from http://circres.ahajournals.org/ by guest on May 7, 2017 Purkinje fibers and subendocardial Purkinje network;10 measurements of conduction velocity require records of local activity at either end of each part of the specialized conducting system. Similarly, since it has beeu demonstrated that the transmembrane action potentials of the atrioventricular node, the His bundle, the false tendons and the subendocardial Purkinje fibers differ with respect to magnitude, voltage-time course and duration, simultaneous records from several of these tissues are essential in a stud}' of the electrophysiology of the intact specialized conducting system. Identification of various unusual waveforms observed in records from parts of the specialized conducting system is greatly facilitated if simultaneous electrograms indicate the time of activation of other parts of the His bundle or bundle branches. This is true particularly in the ease of records from the region of the atrioventricular node. The low rate of depolarization of nodal fibers and the extremely low conduction velocity in the atrial end of the node13 strongly suggest that records of electrical activity made with surface electrodes will fail to show rapid transients. On the other hand, since activity in the bundle of His is initiated early in the P-R interval and often shortly after the end of the P wave, it is unlikely that slow deflections which have their origin late in the P-R interval and which last well into the QRS complex are indeed nodal potentials.19 In particular, if records from the nodal region are obtained through needle electrodes, local injury must be considered as a possible cause of slowly rising monophasic deflections of long duration. For positive identification of surface records of nodal activity other criteria such as the effects of rate or of vagal stimulation are essential. Summary Electrical activity of the specialized conducting system (His bundle, bundle branches, false tendons and peripheral Purkinje fibers) of canine hearts has been recorded in situ through electrodes attached to the endocardium during total cardiopulmonary bypass. Simultaneous records from multiple sites have been correlated with electrocardiograms to indicate the sequence of activation of the specialized conducting system during normal and retrograde activation and during vagal stimulation. The results obtained indicate that the method employed has several advantages among which are an absence of injury at the recording site and an applicability to chronic studies. Summario in Interlingua Le activitate electric del specialisate systema de conduction del corde canin—fasce de His, brancas, tendines false, fibras peripheric de Purkinje—cssova rogistrate in sito per electrodos attachate al endocardio durante circumconduction cardiopulmonar total. Le registrationes in multiple sitos, obtenito simultanccmente, esseva correlationate con le electrocardiogramma pro indicar le sequentia del activation in le specialisate systema de conduction durante le activation normal o retrograde e durante stimulation vagal. Le resultatos obtenite indica quo le metliodo empleate lia pluro avantages, incluse le facto que nulle trauma, occurre al sito del registration e que illo es applicable a studios chronic. References 1. HOFFMAN, B. F.: Physiologic basis of disturbances of cardiac rhythm and conduction. Progr. in Cardiovas. Bis. 2: 319, I960. 2. —, AND CRANEFIELD, P. F . : Eloctrophysiology of the Heart. New York, McGraw-Hill Book Co., Inc., 1960. 3. VAN DER KOOI, M. W., DURRER, D., VAN DAM, R. T., AND VAN DER TWEEL, L. H.: Electrical activity in the sinus node .and atrioventricular node. Am. Heart J. 51: 684, 1956. 4. SCHER, A. M., RODRIGUEZ, M. I., LIIKANE, J., AND YOUNG, A. C.: Mechanism of atrioventrieular conduction. Circulation Research 7: 54, 1959. 5. BURCHELL, H. B., ESSEX, H. E., AND LAMBERT, E. H.: Action potentials supporting the presence of specialized conduction pathways in the dog's ventricle. Circulation Research 1: 186, 1953. (5. DURRER, D., AND VAN DER TWEEL, L. 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