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Atrial Excitability and Conduction During Rapid Atrial Pacing VANCE J. PLUMB, M.D., ROBERT B. KARP, M.D., THOMAS N. JAMES, M.D., AND ALBERT L. WALDO, M.D. SUMMARY Using temporary atrial wire electrodes placed at selected atrial sites, rapid atrial pacing at rates of up to 368 beats/min was used to study atrial excitability and conduction in seven patients who underwent open heart surgery. The threshold for atrial pacing was found to be an exponential function of pacing rate (r = 0.55, p < 0.01), increasing threefold when the fastest pacing rates were compared with the slowest pacing rates (p < 0.005). Atrial conduction times (measured from pacing to recording sites), prolonged dur- ing rapid atrial pacing both for studies conducted before institution of cardiopulmonary bypass (p < 0.005) and for those done 7 days postoperatively (p < 0.05). However, prolongation of conduction times always depended on achievement of a critically rapid pacing rate. During rapid atrial pacing, we observed a high incidence of alternans of the atrial electrogram (17 of 42 studies). Thus, human atrial excitability, conduction and electrogram morphology are not constant during pacing at rapid rates. Rather, at rapid pacing rates, there is depression of atrial excitability, prolongation of atrial conduction times and alternation in electrogram morphology. These findings have clinical relevance and theoretical implications for the understanding and treatment of rapid atrial rhythms. Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017 bypass and on the seventh postoperative day. At the time of the intraoperative study, two of the patients had been receiving digoxin and two had been receiving propranolol. During induction and/or maintenance of anesthesia, three patients received scopolamine (0.4-0.5 mg) and all patients received diazepam, morphine, nitrous oxide, halothane, fentanyl and pancuronium. At the time of the postoperative study, three patients were receiving digoxin, one in combination with procainamide and one in combination with alpha-methyldopa. Four patients were taking no cardioactive drugs at the time of postoperative study. The subjects gave informed consent for all aspects of the study. Patients who undergo open heart surgery at the University of Alabama in Birmingham routinely have a pair of Teflon-coated, stainless-steel wire electrodes placed on the right atrial epicardium near the sulcus terminalis. These wire electrodes are brought through the anterior chest wall for use in the diagnosis and treatment of postoperative arrhythmias in a manner previously described.7 All patients in this study also had another pair of wire electrodes placed on the Bachmann's bundle (the anterior interatrial myocardial band) and another pair placed on the posteroinferior left atrium near the coronary sinus. The usual technique of electrode placement was modified only in that the electrodes were placed before cardiopulmonary bypass. Using bipolar threshold stimuli, defined as the minimal stimulus (mA) required to obtain and maintain constant atrial capture,8 each electrode site was paced in turn at a constant basic rate just faster than the spontaneous rate to measure a control conduction time to each of the other electrode sites. The pacing rate was then increased up to rates of 368 beats/min (range 237-368 beats/min) in a stepwise fashion in increments of 5-10 beats/min. At each pacing rate, pacing was performed for brief periods (at least 15 beats), the maximum pacing rate in each study being deter- LITTLE is known about atrial excitability and conduction in man or experimental animals during rapid atrial rhythms, particularly at rates greater than 200 beats/min. In our studies of rapid atrial pacing to interrupt atrial flutter in man," 2 unexpectedly high stimulus strengths were often required to obtain atrial capture. Other investigators have observed or suggested that atrial conduction time is prolonged in experimental models of atrial flutter.3`6 It is not clear whether these incomplete observations are peculiar to atrial flutter or are characteristic of any rapid atrial rhythm. Learning more of the nature of atrial excitability and conduction during rapid atrial rhythms should provide better understanding of rhythms such as atrial flutter, atrial fibrillation, and ectopic (nonparoxysmal) atrial tachycardia. Therefore, we designed a study of atrial excitability and conduction in patients using fixed atrial wire electrodes. Methods Atrial pacing thresholds and atrial conduction times were determined 42 times in seven patients. Five patients were studied during open heart surgery and seven after open heart surgery. Six of the seven patients had aortocoronary artery saphenous vein bypass grafting and one had mitral valvuloplasty to correct mitral regurgitation due to mitral valve prolapse. The patients were 52-64 years old. Studies were conducted intraoperatively before cardiopulmonary From the Departments of Medicine and Surgery, University of Alabama Medical Center, Birmingham, Alabama. Supported by NHLBI program project grant HL11,310 and SCOR in Ischemic Heart Disease 5P5OHL7667, a grant-in-aid from the American Heart Association, and the Greater Birmingham Foundation. Address for correspondence: Vance J. Plumb, M.D., Department of Medicine, University of Alabama Medical Center, Birmingham, Alabama 35294. Received April 10, 1980; revision accepted August 20, 1980. Circulation 63, No. 5, 1981. 1140 ATRIAL EXCITABILITY AND CONDUCTION/Plumb et al. Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017 mined by clinical circumstances. For each increment in pacing rate, both the stimulus threshold and the conduction time from the pacing site to each of the other two recording sites were measured. Between each increment in pacing rate, the control pacing rate was resumed. When the strength of the pacing stimulus had to be increased to achieve capture, the new stimulus strength was maintained upon return to the basic (control) pacing rate, and the conduction times at the basic (control) rate were determined at this new stimulus strength. At the termination of the study, the'threshold stimulus for pacing at the basic (control) rate was determined again to insure'that the initially determined threshold had not changed. Atrial pacing was performed using a Medtronic Model 1 349A battery-powered pacemaker, which delivered a constant current stimulus of 2 msec duration. During atrial pacing, ECG leads I, II and III were recorded simultaneously with the stimulus artifact and with the bipolar atrial electrograms from each of the other two sites using an Electronics for Medicine DR-12 switched-beam oscilloscopic recorder. These data were also simultaneously recorded on magnetic tape (Honeywell model 5600) for later playback'and analysis. ECGs were recorded between a bandpass of 0.1-500 Hz, and electrograms were recorded between a bandpass of 0.1-500 Hz or 12-500 Hz. The bipolar atrial wire electrodes were always electrically isolated from ground and from the recording device. Conduction times were measured from the stimulus artifact to the dominant deflection of the atrial electrogram of each recording site using a vernier measuring device with an accuracy of 1 msec at a paper recording speed of 100 mm/sec or using two Hewlett-Packard Model 5300A Universal interval counters. The latter were connected to two character generators which printed out the measurements in milliseconds on the Electronics for Medicine recorder.' The accuracy of the printed-out measurements was randomly cross-checked using the vernier measuring device. To allow for a relatively constant electrophysiologic state to develop, the first eight paced beats were not included in any measurements. To compare atrial conduction times at the various atrial pacing rates, the time from each stimulus site to each recording site at each of the several pacing rates was expressed as the percent change in conduction time compared with control: conduction time (fast rate) - conduction time (basic rate) X 100 conduction time (basic rate) The significance of conduction time prolongation was analyzed by applying the Fisher-Behrens test of significance for grouped data with unequal variance.9 Regression equations were computed for the mean change in conduction times plotted as a function of pacing rate. The slopes of the regression equations for rates less than the critical pacing rate were then compared to the slopes for rates faster than the critical rate using the Fisher-Behrens test. The mean pacing threshold at the fastest rates was compared to the 1141 RELATIONSHIP OF PACING THRESHOLD TO RATE S_] 0 (I, z LX U1) CC z 0 CD - c OD 120 165 300 255 210 ATRIAL PACING RATE (beats/min) 345 FIGURE 1. Comparison of the increase in threshold (plotted as the natural logarithm) and the atrial pacing rate for all studies. The solid line indicates the regression line and the dotted line the standard error. mean threshold at the basic pacing rate using the t test for paired means of unequal variance, and the natural logarithm of the fractional increase of threshold was plotted as a function of the pacing rate. Results Pacing Threshold In all studies, pacing threshold significantly increased (r = 0.55, p < 0.01) with increasing pacing rates (fig. 1). The threshold rise ranged from 25-925% when compared at the slowest and fastest rates (fig. 2). The average threshold at the fastest rate was three times that at the slowest rate (p < 0.0005). The same magnitude of threshold increase was seen among patients studied before cardiopulmonary bypass as among those studied postoperatively. Figure 3 is an example of pacing threshold determination during atrial pacing at a rate of 330 beats/min. When an increase in pacing rate resulted in incomplete atrial capture (2:1 in this example), complete (1:1) capture could be reestablished by increasing the pacing stimulus strength. The development of 2: 1 atrial capture was the most frequent consequence of the rise in pacing threshold, and was seen in 42 of 50 instances. Seven patients had intermittent, irregular loss of atrial capture ("Mobitz II"). One example of "Mobitz I' loss of atrial capture was seen, manifested as atypical Wenckebach periodicity with the greatest increase in conduction time in the beat just preceding the dropped beat. Conduction Times Significant conduction time prolongation was seen with increasing pacing rate in all patients, but only after a critical pacing rate was achieved. Figure 4 -f1wUyWog7nl-t' 1J VOL 63, No 5, MAY 1981 CIRCULATION 1142 p < 0.0005 * = Prebypass o = Post op Means * = FIGURE 2. Pacing threshold at the slowest pacing rate (range 102-125 beats/min) compared with the pacing threshold at the fastest pacing rate (range 273-345 beats/min) for each study. E c) -J 0 U) Li I cr. I 14 5- Fastest Pacing Rate Slowest Pacing Rate Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017 conduction times prolong (p < 0.01). As the pacing rate increases, so does the pacing threshold, from 8 to shows atrial conduction time determination and illustrates the prolongation of conduction times noted during critically rapid pacing (see also figure 3). Table I is a list of the full range of pacing rates and corresponding conduction times for the entire study from which figure 4 is taken. Figure 5 is from a representative study in which the percent change in conduction time from the pacing site on Bachmann's bundle to the recording site on the posterior left atrium is plotted over the full range of pacing rates. Note that as the pacing rate increases, conduction times are relatively constant until a critical rate is reached, at which point 23 mA. When the pacing threshold increased from 7 to 15 mA at a pacing rate of 300 beats/min, the increased stimulus strength was associated with a decrease in the control conduction times at the basic pacing rate of 103 beats/min (table 1). Because pacing threshold increased as rate increased, conduction times were remeasured at the basic rate for each increase in stimulus strength. As stimulus strength increased, conduction times at the basic rate shortened (fig. 6). 1 sec-. * WS ECG % 1 S AEG ' 4 I ' ., 1 1111 1,1 .,1.1 11 (ST) /1 -i 1.S AEG d 1, _00 -0-01-11'lTr.~.m- W~ 91r 1 ' 'F 1'-1s (BB) 1 12 mA 14mA L 1. .I 7' L 1. n"ul~ A 1 I. v . I 11 ' r . .1.1. .. i I 4 1.1 !I' 1'J* ` - il I. 1.I 1- 1- S-S 182 msec (Rate 330 bpm) FIGURE 3. ECG lead I recorded simultaneously with bipolar atrial electrograms (A EG) recorded from the sulcus terminalis (ST) and Bachmann's bundle (BB) during pacing from the posteroinferior left atrium. At the previous pacing rate of 320 beats/min, the atria were completely captured at a stimulus strength of 12 mA. However, when the pacing rate was abruptly increased from the control rate to 330 beats/min, there was only 2:1 atrial capture. Illustrated are the last several beats of2:1 atrial capture as the stimulus strength was being increased to 14 mA, at which point 1:1 atrial capture was obtained. Paper recording speed is 50 mm/sec. Time lines are at 1-second intervals. S = stimulus artifact. ATRIAL EXCITABILITY AND CONDUCTION/Plumb et al. 1 143 ECG I S-S 210 msec (Rate 285 bpmn) * lsec s~~S * -~ S-S 585 msec (Rate 103 bpm) AEG (BB) 72 74 74 75 75/ 74 68 68 S AEG (PL A') 84 83 83 1 72 73 Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017 FIGURE 4. ECG lead I recorded simultaneously with unfiltered bipolar atrial electrograms (AEG) from Bachmann's bundle (BB) and the posteroinferior left atrium (PLA) during pacing from the sulcus terminalis. Conduction times from the stimulus site to each recording site are shown (in msec) both at a pacing rate of 285 beats/min and at the basic pacing rate of 103 beats/min. Paper recording speed is 100 mm/sec. Time lines are at 1-second intervals. S = stimulus artifact. Maximal suprathreshold pacing (determined by the pacing threshold at the fastest pacing rate) shortened the conduction times during pacing at the basic rate by an average of 6% (range 2-8%) from values observed when pacing at basic rate using threshold stimuli. In the one case where Bachmann's bundle was paced before cardiopulmonary bypass, conduction DEPENDENCE OF ATRIAL CONDUCTION AND EXCITABILITY ON PACED RATE +30 I 2 +20 z 0 U o z I (REPRESENTATIVE STUDY) 11.~~~~~ +10 0 Ii1 ' z 0 iI I {iil 1 t tt -101 8 9 mA 1114 mA mA mA 1 lOC3 140 180 220 1 260 19 mA 23 mA 1 300 ---v 340 PACED RATE (beats/m FIGURE 5. The percent change (+ SD) in conduction time and the pacing threshold are plotted as a function ofpacing rate for a representative study. Note the constancy of conduction times until the pacing rate reached the critical rate of 286 beats/min, when conduction times prolonged markedly. TABLE 1. Conduction Times-Representative Site Sulcus Terminalis) CT to BB Stimulus Pacing rate (mseC - SD) (mA) (beats/min) 65 0.4 7 103 111 67 - 0.7 7 68 - 0.6 7 120 7 129 68- 0.7 69 0.6 7 141 69 -0.5 7 150 70 0.7 7 160 7 170 700 0.8 69 1.1 180 7 7 69 0.9 192 69 0.8 7 200 69 0.6 7 214 69 1.0 7 225 69 0.6 7 235 70 1.1 240 7 69 1.1 7 252 70 1.2 7 267 74 3.0 7 273 285 7 733 1.7 76 3.3 15 300 60 0.4 103 15 15 72- 1.2 311 Abbreviations: CT = conduction time; mann's bundle; PLA = posteroinferior left Study (Pacing CT to PL (mseC SD) 68 0.7 68 1.0 68 1.1 69 1.8 71 3.0 70 1.8 69 - 0.8 70 -0.8 70 -1.9 69 0.5 70-1.4 71- 1.0 70 1.6 71 1.0 73 1.7 74 1.6 76 2.0 77 1.7 80 1.9 90 1.8 60 0.8 82 1.7 BB = Bachatrium. ClIRCULATION 1144 +8 DEPENDENCE OF ATRIAL CONDUCTION TIME ON STIMULUS STRENGTH +4 TABLE 2. Critical Pacing Rate-Prebypass Studies (REPRESENTATIVE STUDY) Pt 0I z 0 U -4 z 0 -8 z C-, hIC i -12 i -16 10 15 20 PACING STIMULUS STRENtGTH (mA) 25 Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017 FIGURE 6. Comparison of the percent change in conduction time (± SD) at a constant pacing rate as the stimulus strength is increased. Threshold for this pacing rate was 8 mA. times to both distal recording sites decreased by 7-20% at intermediate pacing rates and increased at very rapid pacing rates (fig. 7). This was the only time we saw a significant conduction time decrease. Studies Before Cardiopulmonary Bypass Eleven of 13 studies showed significant conduction time prolongation with increasing pacing rate. Conduction time prolongation in every study depended on achieving a critically rapid pacing rate. The magnitude of this critical pacing rate varied among patients, and in individual patients varied among the various pacing sites (table 2). Figure 8 shows the grouped data on conduction time changes for patients studied before cardiopulmonary bypass (13 studies in five patients) analyzed by the linear regression method for pacing rates less than 240 beats/min and faster than 240 beats/min. There was a clear difference (p < 0.005) in 30 * = * z 0 U 20 = BB BB - VOL 63, No 5, MAY 1981 ST PLA 1 2 2 3 3 6 6 6 7 7 7 Pacing Recording Critical rate site ST ST PLA ST ST ST PLA PLA PLA BB BB site BB PLA BB BB PLA BB ST BB ST ST PLA (beats/min) 251 275 221 216 159 290 275 275 203 312 312 Mean 253.5 Abbreviations: ST = sulcus terminalis; BB = Bachmann's bundle; PLA = posteroinferior left atrium. the slope of the slower vs the faster pacing rates, representing conduction time prolongation at the faster rates. The choice of 240 beats/min as the critical pacing rate for the group is arbitrary, with individual variation in the critical pacing rate. For example, the circled data points show a study in which conduction times began to prolong at a pacing rate of only 159 beats/min (from a patient with coronary artery disease). Postoperative Studies Conduction time prolongation at increasing pacing rates showed greater variability in the postoperative studies than in the studies performed before cardiopulmonary bypass. All patients still showed conduction time prolongation with increasing pacing rates, but not invariably with each combination of pacing and recording site. In only two patients did conduction time prolong regardless of pacing site or recording site. In two cases conduction times prolonged to one distant site but not to the other site being simultaneously recorded. In fact, in individual patients, the incidence of postoperative studies showing conduction time prolongation ranged from 25-100% (mean 77%). Table 3 shows for all post- 10 n z I Ue o 1= '_ * * F---- ,3 TABLE 3. Postoperative Pacing Studies -10 -201 140 180 220 260 300 340 ATRIAL PACING RATE (beats/min) FIGURE 7. Percent change in conduction time (± SD) from the pacing site on Bachmann's bundle (BB) to the sulcus terminalis (ST) and to the posteroinferior left atrium (PLA) in patient 7. Conduction times decreased at pacing rates of 203-261 beats/min and increased at pacing rates over 300 beats/min. % studies with CT prolongation 100 PLA 66.7 ST 80 BB 80 ST 100 Abbreviations: ST = sulcus terminalis; BB = Bachmann's bundle; PLA = posteroinferior left atrium; CT = conduction time. Pacing site ST ST PLA PLA BB Recording site BB 0 ATRIAL EXCITABILITY AND CONDUCTION/Plumb et al. < 240 beats/min Regression Line: y = -1.115 + 0.013(x) r =0.09 1 D 2 Data points 3 Data points a 4 Data points ! 20 0J 10 0O 0 * 0 -10- Rum~ 120 150 y = -32.651 + 0.1i 30(x) r = 0.45 i~~~~~~~ * * 0 z 0 L0 in z 0 240 beats/min Regression Line: p < 0.005 * 1 Data point z 0 > 1145 180 210 240 .S 270 300 330 Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017 ATRIAL PACING RATE (beats/min) FIGURE 8. Rate dependence ofconduction time for allprecardiopulmonary bypass studies. Rates less than and equal to 240 beats/min are compared with rates greater than 240 beats/min. the fastest rates that occurred in 22 of the 29 postoperative studies. The circled data points show a study where conduction time prolongation began at a pacing rate of only 140 beats/min (from the patient with mitral valve prolapse), illustrating the individual variability of this phenomenon and the somewhat arbitrary nature of the choice of 240 beats/min as the critical pacing rate for the group. Table 4 shows the critical pacing rate for each postoperative study. operative studies the incidence of conduction time prolongation to each of the other two sites when each site was paced. The grouped data on conduction time changes for all postoperative studies (29 studies in seven patients) are shown in figure 9. Again, the linear regression equation slopes are significantly different for the fast pacing rates compared with the slow pacing rates (p < 0.05), indicating conduction time prolongation at LUJ z 0 0 0 z 0 t 240 beats/min Regression Line: y = -0.203 ± 0.020 (x) r = 0.13 501 p 0.05 1 Data point 40 D 2 Data points 1 3 Data points & ' 4 Data points 30 * 20 ^ 0 CJ) 0 0 z 10- 0 0' m 0 0 0 ...... ... 0; > 240 beats/min Regression Line: y = -12.307 + 0.058 (x) r = 0.15 00 ............. ...... 120 150 180 210 240 270 300 330 ATRIAL PACING RATE (beats/min) FIGURE 9. Rate dependence of conduction time for all postoperative studies. 240 beats/min are compared with rates greater than 240 beats/min. Rates less than and equal to CIRCULATION 1146 VOL 63, No 5, MAY 1981 Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017 immediately below the stimulating electrodes.'0"12 A TABLE 4. Critical Pacing Rate-Postoperative Studies ~ ~, Critical Recordiantge~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ similar explanation seems reasonable for our studies. Critical rate Pacing Recording of our study did not permit us to detect design The (beats/min) site site Pt any supernormal phase of excitability such as has been 200 BB 1 ST reported for canine atrium,'3 for the canine 140 BB 2 ST Bachmann's bundle,'4 and for isolated specialized 162 atrial fibers.1" In one of our experiments, conduction ST 2 PLA times decreased by 7-20% while pacing Bachmann's 194 BB 2 PLA bundle at intermediate rates (fig. 7), a finding that may 2a5 BB 3 ST indicate a supernormal phase of conduction.'4 16 214 PLA ST 3 The increase in atrial pacing threshold as the pacing 286 ST BB 3 rate is increased has clear clinical implications and 222 may help explain certain problems in the clinical use PLA 3 BB of rapid atrial pacing to interrupt type I atrial flutter. 280 BB 4 ST The pacing threshold may be quite high at pacing rates 280 PLA 4 ST and exceeding the atrial rate during type approaching 280 ST 4 PLA I atrial flutter (240-340 beats/min).2 The successful 330 ST 4 BB interruption of type I atrial flutter by rapid atrial pac330 ing typically requires pacing rates substantially in ex4 PLA BB cess of the flutter rate,1 so further increases in 296 BB ST 5 should be anticipated. In fact, the pacing threshold 204 BB ST at very rapid pacing rates may sometimes threshold 6 240 PLA 6 ST exceed 20 mA,'7 the maximal current output of most 180 ST 6 PLA commercially available pacemakers. It is reasonable 242 to suspect that some reported failures of pacing to inBB 6 PLA 6 7 7 7 ST BB BB ST ST PLA 188 240 2233 290 PLA.k ST 240.3 Mean Abbreviations: ST = sulcus terminal[is; BB bundle; PLA = posteroinferior left atriium. = Bachmann's Electrical Alternans of the Atrial Electrogram During rapid atrial pacing, electrical alternans appeared in the atrial electrogram in 17 of 42 studies (fig. 10). Electrical alternans is also present in figure 4 in the atrial electrogram recorded from the posterior left atrium. Figure 10 represents an example of alternation of the conduction time intervals that accompanied the electrical alternans in six of 17 studies. When the slower basic pacing rate was resumed, the alternans was abolished (fig. 10). Eight times, the electrical alternans occurred in only one of the two simultaneous atrial electrograms recorded from different atrial sites (figs. 4 and 10). Discussion Atrial Excitability The demonstration by our study that atrial excitability becomes depressed as the atrial pacing rate is increased has not, to our knowledge, been described in man. However, stimulus thresholds are known to increase with increasing pacing rate in isolated guinea pig ventricles'0 and isolated rat atria.1" 12 It has been assumed that the rise in threshold is due to the stimuli falling in the relative refractory period of the muscle terrupt classic (type I) atrial flutter may have been caused by using subthreshold stimuli. Conduction Time Prolongation We found that as the atrial pacing rate is increased, atrial conduction time almost always prolongs, but only after a critical rate is reached. Others have shown that atrial conduction might prolong at rapid atrial rates. Atrial conduction time has been reported to increase in dogs as the rate of atrial stimulation was increased beyond a critical rate.'8 Parallel decreases in conduction velocity and the rate of rise of the action potential have been reported during rapid stimulation above a critical rate in isolated rabbit atria.'9 Similar findings have been reported without changes in resting (diastolic) transmembrane potential.20 In isolated rabbit atria, the conduction velocity during induced circus movement tachycardia was shown to be much slower than conduction in the same tissue paced at slower rates.2" 22 Slow atrial conduction has been demonstrated in a variety of models of canine atrial flutter.3-5 Our experiments measured the conduction time between two atrial sites, which is a function not only of conduction velocity, but also of the length of the pathway of conduction, the stimulus strength and stimulus latency. Stimulus latency would be expected to show approximately equal degrees of conduction prolongation to all recording sites during stimulation at a fixed site and would not be expected to be a function of rate. The four studies in which conduction times prolonged to one distant site but not to another simultaneously recorded site provide indirect evidence against stimulus latency as an explanation of our results. We presume that the decrease in conduction times 1147 ATRIAL EXCITABILITY AND CONDUCTION/Plumb et al. 1 sec-b ECG 1 ,AS I S AEG (ST) AEG (B B) I I. I. 109 7 11 111 ll109 1 11 - 12 108 105 106 108 .,111.2.1,1 ,1 .d ,~~~~~~~~~~V1 X L10 108S13 L1n 1. I.1 I iJW ,-J-- L - 1~-VJJJ '- I 1 76 68 77 69 76 70 776 77 Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017 S-S 212 msec (Rate 283bpn) 77 6977 -I. 1 -I Sf I. rnrnLrninLii. ,1 1 1 79 79 79 S-S 480msec (Rate 125 bpnm FIGURE 10. ECG lead I recorded simultaneously with bipolar atrial electrograms (AEG) recordedfrom the sulcus terminalis (ST) and Bachmann's bundle (BB) during pacing from the posteroinferior left atrium. Conduction times from the pacing stimulus (S) to each recording site are shown (in msec) during rapid pacing at 283 beats/min and at the basic pacing rate of 125 beats/min, illustrating the alternation of conduction times and atrial electrogram morphology noted during rapid atrial pacing. Paper recording speed is 50 mm/sec. Time lines are at 1-second intervals. at the basic pacing rate as the stimulus strength was increased represents the activation of an increasingly large area of atrial mass at the site of stimulation.23 The nonuniform decrease in conduction time at the basic rate as suprathreshold pacing stimuli were used may be related to variation in the absolute magnitude of the increase in stimulus strength, to variation in bipolar interelectrode distance, and to variation in the nature of the myocardial tissues24 in contact with the epicardial wires. A lengthening of the pathway of impulse conduction would also be manifest as conduction time prolongation. Since atrial refractoriness is known to be inhomogenous,3' 56 25, 26 an increase in rate might render parts of the prior shortest path refractory, so that conduction via a new pathway would be longer. The bipolar atrial electrogram morphology changes we observed, however, were largely a change in the amplitude of the atrial electrogram with preservation of the form recorded simultaneously at two widely spaced atrial sites, suggesting almost identical directions of atrial depolarization. As the pacing rate increases, the stimulus may encroach upon phase 3 of the action potential, decreasing the takeoff potential of the propagated impulse compared with pacing at slower rates and resulting in a slowing of conduction velocity.27 28 Unfortunately, in vivo atrial refractoriness has not been defined in man for rates in excess of 150 beats/min.29 At even faster rates the action potential duration and atrial refractoriness may continue to shorten.26 However, the tail of atrial refractoriness after 70% of repolarization may be very important in considering the relationship of pacing rate and atrial conduction to atrial refractoriness, and encroachment of the stimulus on repolarization may be a cause for slowing of conduction velocity and prolongation of conduction times. Rapid atrial pacing at a critically rapid rate might be associated with a relative depolarization of transmembrane resting potential apart from repolarization (phase 3) considerations. In fact, rate-dependent rises in extracellular potassium concentration, which decrease the resting transmembrane potential of human atrium,30 have been reported during rapid stimulation of isolated rabbit atria,31 and would be expected to decrease conduction velocity at rapid pacing rates, but do not explain why prolongation of conduction time depended on achievement of a critical pacing rate. Whatever the mechanism of prolongation of atrial conduction times with faster rates, our studies suggest a fundamental difference from the mechanism of the rise in atrial pacing threshold with increasing rate. First, the rate dependence of threshold was seen in each study, in contrast to the conduction time prolongation during rapid pacing which, while noted in the majority of studies, was not always seen. Second, the rises of threshold and increases in conduction times did not occur concurrently (fig. 5). Third, CIRCULATION 1148 the increase in threshold did not appear to depend on achievement of a critical pacing rate, whereas prolongation of conduction did. Electrical Alternans Atrial electrical alternans demonstrated in our study during pacing at very rapid rates has also been demonstrated during rapid atrial pacing in the dog,"' induced by prior during canine atrial arrhythmias atrial electrical stimulation, 32-5 during aconitineinduced atrial arrhythmias,36 during spontaneous canine atrial flutter,5 and in spontaneous human atrial flutter." 2, Its mechanism has been attributed to local change in conduction32 and to the stimulation rates approaching the maximum frequency permitted by the limiting refractory period of the tissue involved.35 These observations suggest that the presence of electrical alternans is a function of rapid rate and is independent of the underlying mechanism of the rhythm. as 17 Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017 Theoretical Implications Although the mechanism of rapid atrial arrhythmias such as ectopic atrial tachycardia, atrial flutter and atrial fibrillation is uncertain, it has been proposed that conditions of slowed conduction and diminished excitability are necessary for their perpetuation.37 The present study suggests that since slowed conduction and diminished excitability are an intrinsic property of rapid atrial rates, rapid atrial rhythms of whatever mechanism might tend to be selfsustaining. Acknowledgment We gratefully acknowledge the statistical assistance provided by Roy Swatzell and Dr. Malcom Turner. We also thank Al Germann for invaluable aid and BeaJudson for patient secretarial assistance. References 1. Waldo AL, MacLean WAH, Karp RB, Kouchoukos NT, flutter with James TN: Entrainment and interruption of atrialsurgery. Ciratrial pacing. Studies in man following open heart culation 56: 737, 1977 James TN, Waldo AL: 2. Wells JL Jr, MacLean WAH, Characterization of atrial flutter. Studies in man after open heart surgery using fixed atrial electrodes. Circulation 60: 665, 1979 3. Lewis T, Feil HS, Stroud WD: Observations upon flutter and fibrillation. Part II. The nature of auricularflutter. Heart 7: 191, 1920 M, Corday E, Brill IC, Sellers AL, Oblath RW, Flieg WA, Kruger HE: Mechanism of the auricular arrhythmias. Circulation 1: 241, 1950 Boineau JP, Mooney CR, Hudson RD, Hughes DG, Erdin RA Wylds AC: Observations on reentrant excitation pathways Jr, and refractory period. Distributions in spontaneous and experimental atrial flutter in the dog. In Reentrant Arrhythmias, edited by Kulbertus HE. Baltimore, University Park Press, 4. Prinzmetal 5. 1977, pp 72-98 RT, Durrer D: Epicardial HJ, Janse MJ, van Dam with atrial flutter. Br Heart J citation of the atria in a 6. Wellens 33: 233, 1971 ex- patient 7. Waldo AL, MacLean WAH, Cooper TB, Kouchoukos NT, Karp RB: Use of temporarily placed epicardial atrial wire electrodes for the diagnosis and treatment of cardiac arrhythmias 14CCAOVOL 63, No 5, MAY 1981 following open heart surgery. J Thorac Cardiovasc Surg 76: 500, 1978 8. Preston TA, Barold SS: Problems in measuring threshold for cardiac pacing. Am J Cardiol 40: 658, 1977 9. Fischer RA, Yates F: Statistical Tables for Biological, Agricultural and Medical Research, 3rd ed. London, Oliver and Boyd, 1949 10. Johnson EA, McKinnon MG: The differential effect of quinidine and pyrilamine on the myocardial action potential at various rates of stimulation. i Pharmacol Exp Ther 120: 460, 1957 11. Landmark K: The action of promazine and thioridazine in isolated rat atria. 3. Effects of varying concentrations of calcium in different frequencies and strengths of stimulation on contractile force and excitability. Eur J Pharmacol 17: 365, 1972 12. Refsum H, Landmark K: The effect of nifedipine on the effective refractory period and excitability of the isolated rat atrium at different calcium levels and frequencies of stimulation. Acta Pharmacol Toxicol 39: 353, 1976 13. Brooks CM, Orias 0, Gilbert JL, Siebens AA, Hoffman B, Suckling EE: Excitability cycle of mammalian auricle. Am J Physiol 163: 469, 1950 14. Childers RW, Merideth J, Moe GK: Supernormality in Bachmann's bundle. Circ Res 22: 363, 1968 15. 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Circ Res 20: 496, 1967 35. Pastelin G, Mendez R, Moe GK: Participation of atrial specialized conduction pathways in atrial flutter. Circ Res 42: 1149 386, 1978 36. Lanari A, Lambertini A, Ravin A: Mechanism of experimental atrial flutter. Circ Res 4: 282, 1956 37. Allessie MA, Bonke FIM, Schopman FJG: Circus movement in rabbit atrial muscle as a mechanism for tachycardia. 111. The "leading circle" concept: a new model of circus movement in cardiac tissue without the involvement of an anatomical obstacle. Circ Res 41: 9, 1977 The Nature of Atriosinus Conduction During Rapid Atrial Pacing in the Rabbit Heart CHARLES R. KERR, M.D., AND HAROLD C. STRAUSS, M.D., C.M. Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017 SUMMARY During clinical electrophysiologic investigations, the sinus node recovery time (SNRT) lengthens as the atrial pacing rate increases; after reaching a maximum value, SNRT shortens with further increases in pacing rate. This phenomenon has been ascribed to the onset of atriosinus entrance block. In this study we investigated the nature of atriosinus conduction during rapid atrial pacing and related changes in SNRT to changes in conduction. In eight rabbit sinus node preparations, the crista terminalis was paced for 1 minute at cycle lengths ranging from 400 to 100 msec, while crista terminalis electrograms were recorded by surface electrode and sinus node transmembrane action potentials were recorded by microelectrode. In all experiments SNRT prolonged progressively as the cycle length shortened until 2: 1 atriosinus block occurred; at that point SNRT shortened. After correction for spontaneous cycle length, SNRT was inversely related to the cycle length of action potentials recorded from the pacemaker site in the sinus node (r = -0.84), indicating that SNRT depends on the number of impulses reaching the pacemaker site. In four experiments, the microelectrode was moved toward the crista terminalis in intervals of 50-100 ju, repeating the pacing sequence at each site. The site of atriosinus block could be identified as the point at which action potential amplitude fell rapidly. With progressively shorter cycle lengths, the site of block moved progressively farther from the pacemaker site in the sinus node. Therefore, the shortening of SNRT with rapid pacing may be explained by the presence of atriosinus block and by a reduction in the number of impulses that reach the pacemaker site in the sinus node. RAPID ATRIAL PACING is frequently used to sinus node automaticity in patients suspected of having sinus node dysfunction. The duration of the recovery cycle after a train of rapid atrial pacing is called the sinus node recovery time (SNRT), and its prolongation has been widely accepted as evidence of sinus node dysfunction.'-' In general, as the rate of atrial pacing is increased, the duration of the recovery cycle increases until a maximum degree of suppresassess From the Division of Cardiology, Department of Medicine, and the Department of Pharmacology, Duke University Medical Center, Durham, North Carolina. Supported in part by USPHS grant HL19216, HL 07101 and RR30, General Clinical Research Centers Program of the Division of Research Resources, NIH. Dr. Strauss is recipient of Research Career Development Award 1-K04-HL-00268, NIH. Dr. Kerr is a Fellow of the Medical Research Council of Canada. Address for correspondence: Charles R. Kerr, M.D., Division of Cardiology, Vancouver General Hospital, 2775 Heather Street, Vancouver, B.C. VSZ, 3J5. Received May 20, 1980; revision accepted September 3, 1980. Circulation 63, No. 5, 1981. sion occurs; beyond this point the recovery cycle shortens as the atrial pacing rate continues to be increased. In man, maximum suppression normally occurs at 118-130 beats/min.2 5, '6 The decrease in SNRT at faster rates may be the result of block of impulses before they can reach and depolarize the sinus node. Such a reduction in the rate of sinus node discharge would cause a reduction in sinus node suppression."7 10 In cases of sinus node dysfunction, atriosinus entrance block may occur at lower pacing rates, so maximum sinus node recovery time may occur at pacing rates lower than 1 18 beats/min.4' 6 9, 11, 12 Although the shortening of the SNRT at fast pacing rates has been well documented and the presence of atriosinus block has been postulated to explain this phenomenon, in vitro studies are required to corroborate these findings. In this study we used an isolated sinus node preparation from the rabbit to characterize atriosinus conduction during rapid atrial pacing. In particular, we examined the nature and site of block of retrogradely conducted impulses and the relationship between the rate of pacing and SNRT. Atrial excitability and conduction during rapid atrial pacing. V J Plumb, R B Karp, T N James and A L Waldo Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017 Circulation. 1981;63:1140-1149 doi: 10.1161/01.CIR.63.5.1140 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1981 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. 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