Identification of reproducible ventricular tachycardia in a canine model

Identification of Reproducible Ventricular Tachycardia in a Canine Model GUST H. BARDY, MD, WILLIAM M. SMITH, PhD, ROSS M. UNGERLEIDER, MD, JAMES L. COX, MD, JOHN J. GALLAGHER, MD, and RAYMOND E. IDEKER, MD, PhD

Epicardial mapping was used as a standard to investigate how well the limb leads, both alone and in conjunction with 5 select epicardial electrodes, can verify reproducibility in a common, open-chest canine model of ventricular tachycardia (VT). Reproducible VT was defined as 2 or more episodes of monomorphic VT with similar rates, limb lead tracings and epicardial maps. In this study, 21 dogs underwent P-hour occlusion of the left anterior descending coronary artery followed by reperfusion. Three days later, programmed stimulation was used to induce VT that was analyzed with limb leads I, II and Ill and 27 simultaneously recorded, bipolar epicardial electrodes. Thirteen dogs had VT of which 11 had polymorphic VT (varying QRS morphology). Twelve dogs yielded at least 1 form of monomorphic VT. Eight had 2 or more distinct forms of monomorphic VT (pleomorphism). Four of these 8 dogs had pleomorphic VT that was not apparent from the

limb lead tracings, but was recognized from the epicardial activation maps constructed from the 27 epicardial recordings. To provide a method of distinguishing various VTs without the need of full epicardial mapping, 5 of the 27 epicardial electrodes were selected. These were postitioned over the midanterior and midposterior right and left ventricles, and the left ventricular apex. By analyzing electrogram morphology and activation time, VT reproducibility could be as accurately identified with these 5 electrodes as with epicardial mapping derived from 27 electrodes. In conclusion, multiple VT morphologies are common in this open-chest canine model. Limb lead recordings alone are inadequate for analysis of VT reproducibility. The limb leads in conjunction with 5 select epicardial electrodes can verify VT reproducibility as well as 27-electrode epicardial maps can. (Am J Cardiol 1984;53:819-825)

Many canine models of ventricular tachycardia (VT) have contributed significantly to our understanding of arrhythmogenesis-l8 The identification of reproducible VT is important in any canine model used to study surgical and pharmacologic treatment of arrhythmias. If an arrhythmia is not reproducible, the absence of a particular arrhythmia or the appearance of another arrhythmia after a therapeutic intervention may be due to the vagaries of the animal model rather than to the treatment itself. Reproducible arrhythmias also are valuable for determining mechanisms of arrhythmogenesis; they allow sequential mapping from different

sets of electrodes, and the introduction of interventions to test a proposed mechanism. Using epicardial maps obtained from 27 electrodes as a standard, this study assesses how well the limb leads, both alone and in conjunction with 5 epicardial electrodes, can determine VT reproducibility in an open-chest animal preparation. Methods Twenty-one 1% to Z&kg dogs were studied. Each dog was anesthetized with sodium pentobarbital(30 mg/kg) and was intubated. Ventilation was maintained with a Harvard respiration pump, model 607. Under sterile conditions a left lateral thoracotomy was performed to expose the left anterior descending coronary artery. After the heart was suspended in a pericardial cradle, the left anterior descending coronary artery was isolated beyond the first anterolateral branch and was loosely encircled with a 4-O silk ligature snare occluder. After 2 hours of coronary occlusion, the snare ligature was removed and reperfusion was established. Prophylactic lidoCaine (2 mg/kg) was administered 5 minutes before reperfusion. The pericardium and chest wall were closed, and postoperative care was given.

From the Department of Medicine, Division of Cardiology, and the Departments of Surgery and Pathology, Duke University Medical Center, Durham, North Carolina. This study was supported in part by research grants HL-17670 and HL-15190 and by the National Service Award HL-07101 from the National Heart, Lung, and Blood Institute. Manuscript received June 13, 1983; revised manuscript received October 11, 1983; accepted October 14, 1983. Address for reprints: Raymond E. Ideker, MD, PhD, P.O. Box 3140, Duke University Medical Center, Durham, North Carolina 27710. 619

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FIGURE 1. Types of ventricular tachycardia (VT) seen in each dog. Ten of 13 dogs with VT had both monomorphic and polymorphic VT and 8 of 12 dogs with monomorphic VT had 2 or more forms of VT (that is, pleomcrphism). Four dogs with pleomorphic VT manifested similar limb lead recordings, suggesting that VT was reproducible although patterns of epicardial activation were actually different. See text for definitions of types of VT.

Three days later each dog was anesthetized and ventilated as described earlier. An indwelling femoral arterial catheter was inserted percutaneously for monitoring arterial blood pressure from a Gould P23 ID Statham pressure transducer. Through a median sternotomy the heart was suspended in a pericardial cradle. A nylon mesh sock, holding 27 bipolar electrodes with interelectrode distances of 1 mm, was secured to the epicardium.‘9 A bipolar epicardial reference electrode was sutured to the right ventricular epicardium. To monitor cardiac temperature, an Instrumentation Laboratory thermistor (catalog #44910) was inserted into the ventricular septum. Stimuli used to initiate VT were delivered to the ventricles through bipolar hook electrodes constructed from Teflon-coated silver wires that were inserted into the ventricles and withdrawn so that the wires were lodged against the endocardium. The right ventricular outflow tract, the right ventricular apex, the anterolateral left ventricle and 3 sites just outside the grossly visible border of infarcted myocardium were chosen as pacing sites. To stabilize blood pressure and cardiac output during VT, cardiopulmonary bypass was established in 14 of 21 dogs with a bypass pump (Suns, Inc.) and a blood oxygenator (Shiley lOOA). Venous return to the oxygenator was through a Bardic 38-gauge cannula inserted into the right atrium. Oxygenated blood was returned to the right femoral artery through a Is-gauge cannula. Both programmed stimulation and rapid ventricular pacing were used to initiate VT. Programmed stimulation was undertaken with 8 ventricular drive beats with a basic cycle length of 250 ms (Sr). Premature stimuli (Ss) were introduced at progressively shorter Si-Ss coupling intervals until the stimulus failed to capture. If an Si-Sz sequence failed to initiate tachycardia, a second premature ventricular beat (Ss) was introduced. If programmed stimulation from each pacing site failed to initiate VT, then rapid ventricular pacing (8 cycles) was used. Pacing cycle length was progessively shortened from 250 ms by 5-ms decrements until a ventricular

arrhythmia or ventricular refractoriness occurred. Stimulus current was twice diastolic threshold with a pulse width of 4 ms.20 Electrocardiographic limb lead signals I, II and III and 27 bipolar epicardial signals were recorded continuously on an FM analog tape recorder (Ampex PR-2200). Limb lead signals I, II and III were chosen because they could be easily recorded and because of their traditional use in most open-chest animal models of VT. Precordial leads were not used because the chest of the dog was open. The analog data from epicardial electrograms recorded during VT were later digitized and entered in a Digital Equipment Corporation PDP-11/34 computer.21 The digitized epicardial electrograms were filtered using a digital Butterworth low-pass filter with a cutoff frequency of 200 Hz. The limb lead electrograms were passed through a similar filter with a cutoff frequency of 125 Hz as well as a band stop filter to eliminate 60-Hz interference. Local activation times were chosen from these data by the computer and used to construct isochronous maps of epicardial activation during ventricular tachycardia. Details of this analysis have been described.22 Limb leads and epicardial maps were analyzed for uniformity during all runs of VT. Limb leads were analyzed for cycle length and QRS morphology. Epicardial maps were analyzed for the pattern of epicardial activation, including the site of earliest epicardial activation, the total duration of epicardial activation and the extent of epicardium activated in the first 10 ms after epicardial breakthrough.23 VT was defined as a run of 5 or more spontaneous ventricular beats. Polymorphic VT was defined as having varying epicardial activation sequences from cycle to cycle. Monomorphic VT had uniform epicardial activation sequences from cycle to cycle. Reproducible VT is defined as the same monomorphic VT from run to run in the same dog. Pleomorphism is defined as 2 or more distinct forms of monomorphic VT in the same dog. After each run of VT was characterized by epicardial mapping, 5 select bipolar epicardial electrograms were analyzed from the full set of epicardial electrodes to assess their ability to discriminate various forms of VT. These 5 electrodes were located over the left ventricular apex, the midanterior left ventricle, the midanterior right ventricle, the midposterior left ventricle and the midposterior right ventricle. No more than 5 epicardial electrodes were used because this number,

together with the 3 limb lead tracings, can be monitored on an &channel recorder. Electrogram morphology, polarity, amplitude and timing were analyzed for each run of VT. Results were compared with those of epicardial mapping to assess the validity of using this technique to document reproducibility of VT. Results VT developed in 13 of 21 dogs (Fig. 1). From these 13 dogs, 216 runs of VT were analyzed with epicardial mapping and with the 5 select epicardial bipolar electrodes. One hundred nineteen runs of VT were classified as polymorphic. All runs of polymorphic VT were characterized by cycle-to-cycle variability both in limb lead QRS morphology and in epicardial activation sequence. Ninety-seven runs of monomorphic VT occurred in 12 dogs. Ten of these dogs also manifested runs of polymorphic VT. Only 4 of the 12 dogs had reproducible VT (that is, 2 or more runs of the same stable VT). The other 8 had pleomorphic VT (that is, 22 separate forms of monomorphic VT). Some dogs showed as many as 5 distinct forms of monomorphic VT. In 4 dogs, this lack of reproducibility was apparent in the limb lead re-

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FKWRE 2. Epicardial activation sequences, recordings from limb leads and recordings from 5 select epicardial bipolar electrodes showing considerable differences in all 3 for 2 distinct forms of monomorphic ventricular tachycardia (VT) in the same dog. Limb leads and epicardial activation sequence are shown for 1 form of VT in panel A and for the other form in panel B. In panel C, the columns of epicardial electrode recordings labeled a and b are for the forms of VT shown in panels A and B, respectively. The epicardial activation sequence and the epicardial electrode recordings are for 1 cycle of the tachycardia. In the activation maps, the ventricular epicardium is displayed as if the heart were flattened after an incision was made along the posterior interventricular groove from the crux to the apex. The lfghl dotted Iloes separate the heart into 4 epicardial regions (anterior and posterior di-

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visions of the left and right ventricles). The heavy dashed Ilne denotes the border of the infarct. Aslerlshs overlying the anteroapical left ventricle designate electrode locations where no discrete electrogam was recorded. Numbers refer to local epicardial activation times in milliseconds, referenced to the earliest recorded site of epicardial activation (labeled time 0). Epicardial activation is shown using lO-ms isochrones. Circled numbers designate the position of the 5 select epicardiil bipoles whose tracings are shown in panel C. At the dashed vertical Ilne, the electrogams in panel C are tkne-allgned to the onset of the QRS in the limb leads. A = anterior; LAD = left anterior descending coronary artery; LV = left ventricle; P = posterior; PA = pulmonary artery: RV = right ventricle.

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cordings as well as in the epicardial maps (Fig. 2). In Figure 2A, epicardial activation spreads from the right ventricular side of the infarct to the left ventricular side, and the limb lead complexes are upright. In Figure 2B, epicardial activation spreads from the left ventricular side of the infarct to the right ventricular side, and the limb lead complexes are inverted. In the other 4 dogs, pleomorphic VT could not be easily distinguished by the limb lead tracings alone. In these dogs, the limb lead tracings for 2 episodes of VT appeared similar, while the epicardial maps showed that the 2 tachycardias were different (Fig. 3). Figures 3A and B indicate the range of variation in limb lead tracings and epicardial maps for different episodes considered to be the same form of monomorphic VT. The maps have similar patterns of activation, including similar sites of earliest epicardial activation, total duration of activity and extent of epicardium activated within the first 10 ms after earliest recorded epicardial activation. The epicardial activation sequence shown in Figure 3C is clearly different; it shows earliest recorded activation near the apex rather than over the midanterior wall of the left ventricle as in Figures 3B and C. The limb lead tracings in Figure 3C are similar to those in Figures 3A and B. In all, 4 of the 8 dogs with pleomorphic VT would inappropriately have been considered to have a single reproducible monomorphic VT based upon limb lead morphology alone.

The 5 select bipolar epicardial electrograms provided as accurate information about reproducibility as did epicardial mapping with 27 electrodes. Analysis of epicardial electrogram amplitude, polarity, morphology and timing identified VT as monomorphic or polymorphic and as reproducible or pleomorphic in all instances. For example, recordings from the anterior right ventricle (ARV) electrode shown in Figure 2C yielded electrograms that differed considerably for the 2 runs of VT. The amplitude of the ARV electrogram on the left is almost an order of magnitude smaller than the electrogram that is on the right. The polarity for the ARV electrogram on the left is positive while that on the right is predominantly negative. The morphology of the electrogram on the left is an R wave and on the right is an RSR’ wave. The onset of electrical activity is early in the cardiac cycle for the ARV electrogram on the left but late for the electrogram on the right. Even when the limb lead tracings were similar for episodes of VT with different activation sequences, some of the 5 select epicardial electrode recordings were different. For example, the apex electrode recordings in Figure 3D differ markedly in wave shape and timing. Discussion This study shows that different morphologies of VT cannot always be differentiated by standard limb lead

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FffiURE 3. Epicardiil activation sequences, recordings from limb leads and recordings from 5 select epicardial bipolar electrodes showing inability of limb leads to detect pleomorphism during 3 separate episodes of monomorphic ventricular tachycardia (VT) in the same dog. The limb leads appear similar for all 3 episodes of VT (A, B and C). In panel D, the 3 columns of epicardial electrode recordings labeled a, b and c are for the forms of VT shown in panels A, B and C. respectively. The 2 episodes of VT in panels A and B have similar activation sequences and epicardial electrograms. Epicardial activation first appears in the anterolateral midwall of the left ventricle near the infarct border and traverses the ventricles to terminate over the pulmonary conus. The epicardial activation sequences and the epicardial electrograms labeled APEX for panel C are considarabfy dlfferent frcm U-rose for panels A and B. Epicardial activation in panel C appears near the apex and terminates over the pulmonary conus and the basal portion of the anterior right ventricle. A retative maximum of activation time surrounded by regions of earlier activation is over the center of the infarct. Panel C is an example of pleomcrphic VT that cannot be detected from the limb leads alone but can be detected by 5 select epicardial electrodes. Abbreviations as in Figure 2.

recordings in the open-chest dog. In 4 of 8 dogs, episodes of VT that appeared different by epicardial mapping generated limb lead tracings that could not be differentiated. Many previous studies have judged the reproducibility of VT from standard limb lead recordings. Our results indicate that other techniques should be used to make this judgment. Body surface limb leads other than the limb leads may better assess VT reproducibility, particularly when the chest is closed. Precordial leads and vectorcardiographic leads are almost universally available, and

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would be expected to discriminate some of the morphologies of VT not detected by the limb leads. Even the vectorcardiogram, however, can exhibit similar frontal-plane QRS loops during pacing from different ventricular sites.24 Although less readily available, body surface maps would be expected to differentiate most morphologies of VT based upon differences in the maps during both the QRS and the period of low-level potentials in the early ST segment.25 Although the equipment is not generally available to acquire complete body surface maps with more than 150 electrode re-

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cordings, recent work indicates that fewer electrodes can be used. Body surface maps obtained from 24 or 32 select electrode locations have been shown to vary only slightly from maps obtained from a full component of electrodes.26,27 When the chest is open, electrodes can be placed directly on the heart to assess VT reproducibility. As for body surface maps, the equipment for obtaining epicardial maps from many electrodes is not generally available. Our study shows that 5 select epicardial electrodes, in conjunction with the limb leads, provide essentially the same discriminatory ability in judging VT reproducibility as does epicardial mapping with 27 electrodes. Monitoring the 5 epicardial electrodes and the limb leads on an s-channel recorder allows rapid assessment of whether VT occurring after a surgical or pharmacologic intervention has the same morphology as that o&urring before the intervention. Although the 5 epicardial electrodes provide some information about the sequence of right and left ventricular activation, they cannot take the place of more complete mapping to identify the site of origin or the mechanism of VT. If more complete mapping is accomplished by recording sequentially from different sets of many electrodes, the 5 select electrodes can still be useful. During sequential mapping, the activation sequence detected by 1 set of electrodes is determined rapidly during the study to guide the placement of the next set of electrodes to map a key arrhythmogenic region in more detai1.21y22The 5 select electrodes can be monitored on line during different episodes of VT to determine if the episodes are the same or different, before taking the time to analyze the full set of electrode recordings. The use of epicardial maps as a standard to document reproducibility of VT is open to question. The site of earliest epicardial activation does not always directly overlie the region giving rise to the arrhythmia.7T28 In addition to the site of earliest epicardial activation, analysis of all of the information in an epicardial map, which includes the ,activation time at each electrode site and the spread of activation over the entire epicardium, should considerably lessen the chance that epicardial mapping incorrectly shows 2 different arrhythmias as being the same. Distinct arrhythmias can still have identical epicardial maps, however, if the endocardial or intramyocardial activation sequence is slightly different or if localized differences in epicardial activation occur between epicardial electrodes. Thus, epicardial maps may incorrectly classify pleomorphic arrhythmias as reproducible. Nevertheless, epicardial mapping can still be used as a discriminating tool to test the limb leads because the reverse error does not occur, that is, 2 arrhythmias classified as different by epicardial mapping when they are the same. In no cases did arrhythmias appear different by limb leads but similar by epicardial mapping. Thus, the findings that the limb leads may falsely classify pleomorphic VT as reproducible and that 5 select epicardial recordings in conjunction with the limb leads classify VT as well as all 27 electrograms are still valid, even though the epicardial maps may rarely misclassify some pleomorphic arrhythmias as reproducible.

This study shows that more than 1 morphology of VT can occur in a commonly studied canine model. Episodes of some morphologies of VT lasted only a few seconds. If only episodes of sustained VT lasting at least 30 seconds were considered, fewer dogs would have been classified as exhibiting pleomorphism. Arrhythmias occurring acutely or 1 day after coronary occlusion are pleomorphic in morphology and mechanism.2g~30 If pleomorphism decreases with time after coronary occlusion, an animal studied 10 days or 3 weeks after occlusion may show less pleomorphism than dogs we studied 3 days after occlusion. Pleomorphic VT may not decrease with time; in patients with old infarcts, pleomorphic VT may be the rule.31 The concepts of reproducibility and mechanism are not identical. Two episodes of reproducible VT should always arise by the same mechanism, but 2 episodes of VT arising by the same mechanism do not always have to be reproducible. For example, the 2 episodes of VT illustrated in Figure 3 may be arising by the same reentrant mechanism. As discussed by El-Sherif et a1,32 the reentrant pathway may form a figure-of-8 pattern, with the crux of the 8 over the infarct in the region designated by asterisks in Figure 2. In Figure 2A, activation over the crux of the 8 may proceed from the left ventricle to the right ventricle, while in Figure 2B the direction of activation may be reversed. Thus, the 2 arrhythmias in Figure 2 could occur by the same basic mechanism despite different limb lead tracings and epicardial maps. Acknowledgment: We express appreciation for technical assistance provided by Jimmy Manley and for secretarial skills provided by Nancy Cheek. Illustrations were prepared by Francine Muehler and David Hugett from University Photography and Illustration, Inc. Finally, we thank Joseph C. Greenfield, MD, for advice and support.

References 1. Michelson Eh, Spear JF, Moore EN. Description of chronic canine myocardial infarcbon models suitable for the electropharmacologic evaluation of new antiarrhythmic drugs. In: Morganroth J, Moore EN, Dreifus LS, Michelson EL, eds. The Evaluation of New Ant&rhythmic Drugs. The Hague: Martinus Nijhoff, 1981:33-46. 2. Michelson EL. Canine models for ventricular tachycardia arrhythmia. Ann Intern Med 1981;95:648-649. 3. Harris AS. Delayed development of ventricular ectopic rhythms following experimental coronary occlusion. Circulation 1950;1:1318-1328. 4. Waldo AL, Kaiser GA. A study of ventricular arrhythmias associated with acute myocardial infarction in the canine heart. Circulation 1973;47: 1222-1228. 5. Boineau JP, Cox JL. Slow ventricular activation in acute myocardial infarction: a sovce of reentrant premature ventricular contraction. Circulation 1973;48:702-713. BJ, El-Sherlf N, Nope R, Lazzara R. Characterization and local6. SCherlaQ ization of ventricular arrhythmias resulting from myocardial ischemia and infarction. Circ Res 1974;35:372-383. 7. Horowitz LN, Spear JF, Moore EN. Subendocardial origin of ventricular arrhythmias in 24 hour old experimental myocardial infarction. Circulation 1976;53:56-63. 6. Nafto M, Mkhefeon EL, Kapllnsky E, Dreffus LS, David D, Blenko TM. Role of early cycle ventricular extrasystoles in initiation of ventricular tachycardia and fibrillation: evaluation of the R on T phenomenon during acute ischemia in a canine model. Am J Cardiol 1981;49:317-322. 9. Kaplinsky E, Ogawa S, Michelson EL, Dreifus LS. Instantaneous and delayed ventricular arrhythmias after reperfusion of acutely ischemic myocardium: evidence for multiple mechanisms. Circulation 1981;63:333340. 10. Hamamoto H, Peter T, Mandel WJ. Characteristics of conduction of premature impulses during acute myocardial ischemia and reperfusion: a comparison of epicardial and endocardial activation. Circulation 1981; 64190-198. 11. Karagueuzlan HS, Fenoglio JJ, Welee MB, Wit AL. Protracted ventricular tachycardia induced by premature stimulation of the canine heart after coronary artery occlusion and reperfusion. Circ Res 1979;44:833-846. 12. Klein GJ, ldeker RE, Smith WM, Harrfson LA, Kasell J, Wallace AG, Gallagher JJ. Epicardiil mapping of the onset of ventricular tachycardia initiated by programmed stimulation in the canine heart with chronic infarction.

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Circulation 1979;60:1375-1384. 13. Michelson EL, Spear JF, Moore EN. Electrophysiologic and anatomic correlates of sustained ventricular tachyarrhythmias in a model of chronic myocardial infarction. Am J Cardiol 1980;45:583-590. 14. Garan H, Fallon JT, Ruskln JN. Sustained tachycardia in recent canine myocardial infarction. Circulation 1980;62:980-987 15. Garan H, Fallon JT, Ruskln JN. Nonsustained polymorphic ventricular tachycardia induced by electrical stimulation in 3 week old canine myocardia. Am J Cardiol 1981;48:280-286. 16. Michelson EL, Spear JF, Moore EN. Initiation of sustained ventrrcular tachyarrhythmias in a canine model of chronic myocardial infarction: importance of the site of stimulation. Circulation 1981;63:776-784. 17. Wit AL, Allessle MA, Bonke FIM, Lammers W, Smeets J, Fenoglio JJ Jr. Electrophysiologic mapping to determine the mechanism of experimental ventricular tachycardia initiated by premature impulses, Experimental approach and initial results demonstrating reentrant excitation. Am J Cardiol 1982:49:16X-185. 18. Myerburg RJ, Epstein K, Gaide MS, Wong SS, Castellanos A, Gelband H, Bassett AL. Electrophysiologic consequences of experimental acute ischemia superimposed on healed myocardial infarction in cats. Am J Cardiol 1982;49:323-330. 19. Harrison L, ldeker RE, Smith WM, Klein GJ, Kasell J, Wallace AG, Gallagher JJ. The sock electrode array: a tool for determining global epicardial activation during unstable arrhythmias. PACE 1980;3:531-540. 20. Moore EN, Spear JF, Michelson EL, Euler DE. What is an optimal pulse duration for programmed electrical stimulation? (abstr). Circulation 1980;62:lll-172. 21. ldeker RE, Smith WM, Wallace AG, Kasell J, Harrison L, Klein GJ, Kinicki RE, Gallagher JJ. A computerized method for tha rapid display of ventricular activation during the intraoperative study of arrhythmias, Circulation 1979;59:449-458. 22. Smith WM, kfeker RE, Harrison L. A computer system for the intraoperatrve mapprng of ventricular arrhythmias. Comput Biomed Res 1980;13.6172.

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23. Smith WM, ldeker RE, Smith WM, Kasell J, Harrison L, Bardy GH, Gallagher JJ, Wallace AG. Localization of septal pacing sates in the dog heart by epicardial mapping. J Am Coll Cardiol 1983;1:1423-1434. 24. Boineau JP, Spach MS, Harris JS. Study of premature systoles of the canine heart by means of the spabal vectorcardiogram. Am Heart J 1960;60: 924-935. 25. Benson DW Jr, Sterba R, Gallagher JJ, Walston A II, Spach MS. Localrzation of the site of ventricular preexcrtation wrth body surface maps in patients with Wolff-Parkinson-White syndrome Circulation 1982:65: 1259-1268. 26. Barr RC, Spach MS, Herman-Giddens GS. Selection of the number and positron of measuring locations for electrocardiography. IEEE Trans Biomed Eno 1971:18:125-138 27. Lux RL, Burgess MJ, Wyatt RF, Evans AK, Vincent GM, Abildskov JA. Clinically practical lead systems for Improved electrocardiography: comparison with precardial grids and conventional lead systems. Circulation 1979;59:356-363 26. Horowitz LN, Josephson ME, Harken AH. Eprcardtal and endocardial actrvatron during sustained ventricular tachycardia in man Circulation 1980;61:1227-1238. 29. El-Sherff N, Mehra R, Gough WB, Zeiler RH. Ventricular activation patterns of spontaneous and induced ventricular rhythms in canine one-day-old myocardial infarction: evidence for focal and reentrant mechanisms. Circ Res 1982;51.152-166. 30. Janse MJ, Van Capelle FJL, Yorsink H, Kleber AG, Wilms-Schopman F, Cardinal R. D’Alnooncourt N. Durrer D. Flow of iniurv current and oatterns of excitation during early ventricular arrhythmias’ in’ acute regional myocardral rschemia in isolated porcine and canine hearts: evidence for two different arrhythmogenic mechanisms. Crrc Res 1980;47:151-165. 31. Josephson ME, Horowitz LN, Farshidi A, Spielman SR, Michelson EL, Greenspan AM. Recurrent sustained ventricular tachycardia. 4. Pleomorphtsm. Circulatton 1979;59:459-468. 32. El-Sherif N. Smith RA. Evans K. Canine ventricular arrhvthmras rn the late myocardial infarction period. 8. Epicardral mapping of reentrant circuits. Circ Res 1981;49.255-265.