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Number 3 Mechanism of irregular parasystole

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Nau GJ, Aldariz AE, Acunzo RS, Halpern MS, Davidenko JM, Elizari MV, Rosenbaum MB. Modulation of parasystolic ac- tivity by nonparasystolic beats. Circulation 1982;66:462-9. Castellanos A, Luceri RM, Moleiro F, Kayden DS, Trohman RG. Zaman L, Myerberg RJ. Annihilation, entrainment and modulation of ventricular parasystolic rhythms. Am d Cardiol 1984;54:317-22. Kinoshita S. Mechanisms of ventricular parasystole. Circula- tion 197858715-22. Kinoshita S. Konishi G. Mizutani M. Tanabe Y. Influence of sinus impulses on the parasystolic cycle length. J Electrocar- diol 1989;22:285-91. ,Jalife J, Moe GK. Effect of electrotonic potentials on pace- maker activity of canine Purkinje fibers in relation to para- systole. Circ Res 1976;39:801-8. Kinoshita S, Konishi G, Kinoshita Y. Intermittent ventricu- lar bigeminy as an expression of two-level Wenckebach peri- odicity in the reentrant pathway of extrasystoles. PACE Pac- ing Clin Electrophysiol 1990;13:119-22. Kinoshita S, Konishi G, Kinoshita Y. Mechanism of ventric- ular extrasystoles with fixed coupling: a theoretical model de- rived from the concept of longitudinal dissociation in the re- entram pathwayofextrasystoles. J Electrocardiol1990;23:249- 54.

20. Kinoshita S. Concealed ventricular extrasystoles due to inter- ference and due to exit block. Circulation 1975;52:230-7.

21. Kinoshita S, Takahashi K, Nakagawa K, Sagawa A. Tanabe Y, Kawasaki T. Mechanisms of concealed ventricular bigeminy: the concept of concealed conduction in the reentrant pathway. J Electrocardiol 1986;19:67-76.

22. Kinoshita S, Fujita K, Kanda K, Tanabe Y, Kawasaki T. A cause of paired ventricular extrasystoles. Circulation 1979;60: 1395-401.

23. Kinoshita S, Kato Y, Kawasaki T, Okimori K. Ventricular ta- chycardia initiated by late-coupled ventricular extrasystoles: the concept of longitudinal dissociation in the microreentry pathway. AM HEART J 1982;103:1090-5.

24. Kinoshita S, Nakagawa K, Kato Y, Yasukouchi T. Second de- gree entrance block with supernormal conduction in intermit- tent ventricular parasystole. J Electrocardiol1984;17:199-204.

25. Kinoshita S. Mechanisms of intermittent ventricular parasys- tole due to type II second degree entrance block. J Electrocar- diol 1983;16:7-14.

26. Kinoshita S. Mechanisms of ventricular arrhythmias: a theo- retical model derived from the concepts of “electrotonic interaction” and “longitudinal dissociation.” Am .I Cardiol 1983:52:1350-4.

lsorhythmic atrioventricular dissociation revisited

Archana Patel, MD, Rick Pumill, MD, Daniel Goldman, MD, and Anthony N. Damato, MD Jersey City, N.J.

Control of the atria and ventricles by independent pacemakers defines atrioventricular (AV) dissocia- tion. The term isorhythmic AV dissociation is used when the rates of the independent pacemakers ap- proximate each other and there occurs rhythmic os- cillations of the P-P interval within a limited range of PR and RP intervals. The pacemaker for the atria is usually the sinus node but may reside anywhere within the atria, while the pacemaker site for the ventricles may be within the AV junction or the ven- tricles. Either slowing of the sinus node discharge rate or the emergence of a slightly faster subsidiary pacemaker controlling the ventricles is the common

From the Division of Cardiology, Department of Medicine, Jersey City Medical Center, and Seton Hall University School of Graduate Medical Education.

Received for publication Feb. 10, 1992; accepted March 20, 1992.

Reprint requests: Anthony N. Damato, MD, Department of Medicine, Jer- sey City Medical Center. Jersey City, NJ 07304. 411139276

initiating event. As the P-to-QRS interval shortens, the P wave appears to be “marching” through the QRS complex and may come to be located to the right of it. A fixed RP interval may occur for a variable pe- riod of time, after which the P-P interval shortens and the P wave again appears to the left of the QRS complex. The term synchronization has been used to describe that period during which the RP interval remains fixed and constant. Fig. 1 is an example of isorhythmic AV dissociation in which all of the fea- tures defined above are present, i.e., AV conduction followed by AV dissociation, oscillation of the P waves within a narrow range of PR and RP intervals, a period of synchronization, acceleration of the P wave frequency, and reestablishment of sinus rhythm.

Isorhythmic AV dissociation is an uncommonly encountered arrhythmia which, as will be discussed below, can vary somewhat in its electrocardiographic presentation. Little appears in many textbooks of cardiology and electrocardiography regarding the proposed mechanisms underlying this rhythm dis-

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Fig. 1. A case of isorhythmic AV dissociation. See text for explanation.

turbance. It is the purpose of this communication to review the limited number of experimental studies on this subject and the interacting mechanisms that have been reported for this cardiac rhythm distur- bance. Earlier observers of this phenomenon ques- tioned whether the discharge of two independent pacemakers at the same or nearly the same rates was a chance phenomenon or was the result of some sort of interaction, especially when the two pacemakers appeared synchronized over relatively long periods of time.lMg

Segers’ demonstrated that hearts or fragments thereof with intrinsically different heart rates tended to synchronize when juxtaposed. Brief periods in which the independent pacemakers maintained the same rate were termed “accrochage” and longer pe- riods were termed “synchronization.” From the re- sults of these studies, the concept of an electronic in- teraction was considered to explain isorhythmic AV dissociation. Other concepts that have been proposed included mechanical or reflex interactions,2 a rela- tionship of the sinus node artery pulse to sinus node rate, and the analogy of coupled relaxation oscilla- tors.3-7 None of these proposed concepts adequately explained all of the electrocardiographic characteris- tics of isorhythmic AV dissociation as observed clin- ically. In 1965, EttingeriO reported a case of synchro- nization that occurred during ventricular pacing in a patient with Adams-Stokes attacks caused by inter- mittent AV conduction.

In 1968, Waldo et al.ll reported on 11 patients un- dergoing cardiac surgery, all of whom had spontane- ous isorhythmic AV dissociation. Using atria1 elec- trograms recorded from the surface of the heart at the time of surgery, they noted that during the period of synchronization (when the RP interval was constant and fixed), the atria were retrogradely activated by

an AV junctional pacemaker. They concluded that isorhythmic AV dissociation occurs when an atria1 rhythm alternates with an AV junctional rhythm caused either by slowing of the dominant atria1 pace- maker or acceleration of a latent pacemaker. They also observed that the retrogradely activated P waves were frequently biphasic (-,+), with the initial neg- ative portion or the entire P wave buried within the QRS complex, thus making the morphology of the P wave on the surface electrocardiogram an inaccurate method of determining whether retrograde activa- tion of the atria is present or not. This study high- lighted the fact that when synchronization is the re- sult of retrograde atria1 capture, AV dissociation is no longer present. Subsequently, a number of investiga- tive groups 12-16 studied isorhythmic AV dissociation in animals and man by pacing the bundle of His or the right ventricle at rates slightly in excess of the spon- taneous atria1 rate. Fig. 2 is an example of one of the methods used in these studies. During studies of pacing-induced isorhythmic AV dissociation, the discharge rate of the artificial pacemaker needs to be finely tuned to the inherent atria1 rate to induce sta- ble periods of this arrhythmia.

Levy and Zieskei2 created complete AV block in dogs and studied isorhythmic AV dissociation by pacing the ventricles at rates approximating the sinus rate. They noted that the P wave rhythmically oscil- lated around the QRS complex. The blood pressure fell when the P wave followed the QRS complex, as opposed to when it preceded it. They attributed the fall in blood pressure to a loss of atria1 contribution to ventricular filling, since the timing of atria1 con- traction relative to ventricular contraction is an im- portant determinant of ventricular filling and stroke volume.17-20 At a less than optimum PR interval stroke volume and arterial blood pressure are de-

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Fig. 2. Continuous rhythm strip showing isorhythmic AV dissociation during right ventricular pacing at 69/min, in a patient with sinus rhythm and complete AV block. Starting with the fifth P wave (upper strip) the P-P interval increases and the P wave begins to appear closer to the QRS complex and thereafter to the right of the QRS complex (left portion of lower strip). Subsequently, the P-P interval decreases and the P wave again appears in front of the QRS complex.

creased; with the reestablishment of an optimum PR interval, these hemodynamic parameters are normal- ized. Levy and Zieske12 noted that rhythmic oscilla- tions of the P wave were always associated with pro- nounced oscillations in the arterial blood pressure. However, when the amplitude of the blood pressure oscillations were attenuated, synchronization ceased, suggesting a cause-and-effect relationship.

The authors postulated that the fall in blood pres- sure initiated baroreceptor reflexes operating through the sympathetic-parasympathetic pathways, causing the P wave frequency to increase and move back to the left of the QRS complex. To test this hypothesis, the investigators performed a series of denervation studies. In all five experiments in which vagotomy was first performed, synchronization could still be achieved. Subsequent stellate ganglionectomy pre- vented synchronization in four of the five experi- ments. Levy and Zieske concluded that blood pres- sure changes have an inverse effect on P wave frequency, acting through the baroreceptor reflex. They acknowledged that other mechanisms for changes in P wave frequency may also be operative.

Levy and Zieske made no comment as to whether retrograde atria1 activation was present during peri- ods of synchronization, although it seems unlikely given the destructive nature of the procedure to pro- duce complete AV block in these animals (i.e., injec- tion of 95 % ethanol into the region of the AV node). Thus it would appear that synchronization could oc- cur in either the presence or the absence of retrograde atria1 activation. In a follow-up clinical study of seven cases (three with spontaneous isorhythmic AV disso-

ciation and four induced by ventricular pacing), Levy and Edelstein13 found that the inverse relationship between P wave frequency and arterial blood pres- sure was similar to that observed in experimental animal studies.

Paulay et a1.14s l5 studied isorhythmic AV dissoci- ation in dogs with intact AV conduction systems by pacing either the bundle of His or the right ventricle at rates approximating the sinus rate. Right atria1 and aortic pressures were recorded along with multi- ple bipolar atria1 electrograms, which allowed the se- quence of atria1 activation to be determined. Syn- chronization with rhythmic oscillations of the P wave before and after the QRS complex occurred in animals with and without intact retrograde conduc- tion. At times, fusion activation of the atria by the two independent pacemakers was also observed. These investigators found hemodynamic changes similar to those observed by Levy and Zieske. The loss of atria1 contribution to ventricular filling during synchronization caused a fall in aortic pressure, a rise in right atria1 pressure, and visible distention of the atria. Following upon these hemodynamic changes, accelerating forces caused the P-P interval to de- crease with resumption of sinus rhythm and normal- ization of pressures. The mean percentage increase in sinus acceleration during ventricular pacing was ap- proximately 11%. The effects of extrinsic cardiac denervation on sinus acceleration were consistent. Acceleration of the sinus node rate could be signifi- cantly attenuated by bilateral stellate ganglionecto- my and thoracic ganglionectomy, but not by bilateral vagotomy alone. It was also noted following bilateral

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RAP

0.w 1000 MSEC

Fig. 3. Phasic oscillations in P-P frequency, brachial artery pressure (BAP), and right atria1 pressure (RAP) in a patient with right ventricular pacing-induced isorhythmic AV dissociation. S, pacemaker stim- ulus interval; IAE, intraatrial electrogram intervals. (From Paulay KL, Damato AN. AM HEART J 1972;83:5-11.)

Fig. 4. A case of isorhythmic AV dissociation showing a limited range of PR intervals. See text for expla- nation.

stellate ganglionectomy and thoracic ganglionectomy that the rise in right atria1 pressure upon repeat pac- ing was minimal. Partial restoration of right atria1 pressure by infusion of de&ran resulted in a 4% to 5 % increase in sinus acceleration in these denervated animals. From these results, the authors conclude that right atria1 stretch may be an additional factor causing sinus acceleration. The positive chronotropic effects of increasing right atria1 pressure and of stretch applied to the region of the sinoatrial node have been demonstrated previously.21, 22

Similar findings were observed by Paulay et a1.15 in a follow-up clinical report of nine patients studied by

right ventricular pacing. Fig. 3 is reproduced from that report and shows the characteristic phasic changes in P-P interval, brachial artery, and right atria1 pressures. The inverse changes in brachial ar- tery and right atria1 pressure occur simultaneously and are followed by sinus acceleration, reestablish- ment of an optimal PR interval, and reversal of the hemodynamic alterations. Eight of nine patients demonstrated sinus node acceleration ranging from 4 % to 41.7 5%. One patient not demonstrating sinus acceleration was suspected of having the sick sinus syndrome.

Using ventricular pacing, Diedrich and Djonlagic”

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Fig. 5. Isorhythmic AV dissociation with a relatively long period of synchronization terminated by an an- tegrade atria1 capture beat. See text for explanation.

studied isorhythmic AV dissociation in cats with in- tact AV conduction systems. They observed P wave oscillations and concomitant hemodynamic changes similar to those reported by Levy and Zieske and by Paulay et a1.i4,r5 However, unlike Levy and Zieske, Diedrich and Djonlagic found no inhibition of accel- erating forces acting on the P-P interval when aortic pressure oscillations were attenuated. They also noted that synchronization persisted when right atria1 pressure was held constant. In their studies, neither vagotomy nor pharmacologic blockage of the parasympathetic and adrenergic nervous systems abolished synchronization. The authors conceded that variations in aortic and right atria1 pressure play an important role in the biologic control system. This leads to synchronization by baroreceptors operating through the parasympathetic and adrenergic nervous system or by a direct influence upon pressure in the sinus node artery. They felt, however, that the dom- inant mechanism responsible for synchronization was stretching of the sinus node fibers during con- traction of the atria against a closed tricuspid valve.

From the limited number of experimental studies

on this subject, it would appear that the development of isorhythmic AV dissociation and the particular electrocardiographic patterns resulting therefrom are dependent upon several interacting factors, which include: (1) the relative discharge rates of the dom- inant atria1 and subsidiary pacemakers; (2) the pres- ence or absence of retrograde conduction; (3) the hemodynamic consequences of the timing of atria1 contraction; (4) the chronotropic response to atria1 stretch; (5) the magnitude of accelerating forces act- ing to increase P wave frequency (baroreceptor-me- diated autonomic nervous system output and atria1 stretch); and (6) responsiveness of the sinus node it- self to these accelerating forces.

The presence or absence of accelerating forces, their magnitude, and time of onset can cause varia- tions in the oscillations of P waves both to the left and right of the QRS complex. Fig. 4 illustrates a short period of isorhythmic AV dissociation in which the P wave always remains visible to the left of the QRS complex. This is probably the result of the early on- set of accelerating forces that limits the range of P wave oscillations. The reports by Levy and Zieskei2

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ture.

and by Paulay et al. l5 both illustrate some periods during isorhythmic AV dissociation in which phasic variations in acceleration of P wave frequency some- times resulted in limited migration of the P wave to the left of the QRS complex and failure to reestablish AV conduction.

Fig, 5 of this report illustrates an example of iso- rhythmic AV dissociation with synchronization and without retrograde atria1 capture in which accelera- tion of the sinus rate does not occur and AV conduc- tion is reestablished following an antegrade atria1 capture beat. In such cases, failure of sinus acceler- ation could be the result of an absence of significant hemodynamic changes despite a suboptimal PR interval, absence of significant atria1 stretch, inade- quate sensing or output from the baroreceptor reflex arc, or sinus node unresponsiveness. In a strict sense, the term isorhythmic AV dissociation should only be applied to those cases in which retrograde conduction to the atria is not present and the atria and ventricles remain dissociated throughout the entire spectrum of PR and RP intervals, except when AV conduction is reestablished. The presence of retrograde conduction with retrograde activation of the atria interposes a period in which the atria and ventricles are not dis- sociated. The major problem with a strict application of the term lies in the difficulty in determining from electrocardiographic tracings whether the P wave morphology represents antegrade or retrograde acti- vation of the atria. This is made more difficult by the fact that at times only a portion of the P wave can be seen. A change from a totally positive P wave (leads 2, 3, and AVF) to a totally negative P wave suggests retrograde activation (Fig. 6). A change from a pos-

itive P wave to a biphasic (-,+) P wave suggests par- tial or total retrograde activation, while a totally un- changed upright P wave suggests the absence of ret- rograde activation.

Conclusions. Isorhythmic AV dissociation, an un- commonly encountered arrhythmia, involves various physiologic mechanisms that determine the different electrocardiographic patterns observed during this rhythm disturbance. From a small number of exper- imental and human studies done since 1965, it appears that these factors include (1) the relative discharge rates of the dominant and subsidiary pacemakers; (2) the presence or absence of retrograde conduction; (3) the hemodynamic consequences of the timing of atria1 contraction; (4) the magnitude of accelerating forces occurring through baroreceptor reflex mechanisms acting to increase P wave fre- quency; (5) the chronotropic response to sinoatrial stretch; and (6) responsiveness of the sinus node to accelerating forces. The absence, presence, or mag- nitude of the above-mentioned interacting factors are responsible for the varied electrocardiographic manifestations of this rhythm disturbance.

REFERENCES

1. Segers M. Les phenomenes de synchronization au niveau du co&r. Arch Intern Physiol 1946;54:87-106.

2. Rosenbaum MB. Leneschkin E. Effect of ventricular svstole _ on auricular rhythm In auriculoventricular block. Circulation 1955;11:240-61.

3. James TN. Pulse and impulse in the sinus node. Henry Ford Hosp Med J 1957;15:275-99.

4. Grant RP. The mechanism of AV arrhythmias. Am J Med 1956;20:334-44.

5. Nadeau RA, James TN. Behavior of atrioventricular nodal rhythm following direct perfusion of the sinus node. Can J Physiol Pharmacol 1966;44:317-24.

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6.

7.

8.

9.

10.

11.

12.

13.

Roberge FA, Nadeau RA. Simulation of sinus node activity by an electronic relaxation oscillator. Can J Physiol Pharmacol 1966;44:301-15. Roberge FA, Nadeau RA, James TN. Nature of the PR inter- val. Cardiovasc Res 1968;2:19-30. Marriott HJL. Atrioventricular synchronization and accro- chage. Circulation 1957;14:38-43. Schubart AF, Marriott HJL, Gorten RJ. Isorhythmic dissoci- ation. Atrioventricular dissociation with synchronization. Am J Med 1958;24:209-14. Ettinger P. Synchronization during electrical pacing. AM HEART J 1965;70:110-4. Waldo AL, Vitkainen KJ, Harris PD, Malm JR, Hoffman BF. The mechanism of synchronization in isorhythmic AV disso- ciation. Some observations on the morphology and polarity of the P wave during retrograde capture of the atria. Circulation 1968;38:880-98. Levy MN, Zieske H. Mechanism of synchronization in iso- rhythmic dissociation. I. Experiments on dogs. Circ Res 1970;27:429-43. Levy MN, Edelstein J. Mechanisms of synchronization in iso- rhythmic AV dissociation. II. Clinical studies. Circulation 1970;72:689-99.

14.

15.

16.

17.

18.

19.

20.

21.

22.

Paulay KL, Damato AN. Atrioventricular interaction in iso- rhythmic dissociation. AM HEART J 19'71;82:647-53. Paulay KL, Damato AN. Atrioventricular interaction in man during pacing-induced isorhythmic AV dissociation. AM HEART J 1972;83:5-11. Diedrich KW, Djonlagic H. Mechanism of synchronization in isorhythmic dissociation. Cardiology 1973;58:129-38. Brockman SK. Dynamic function of atria1 contraction in reg- ulation of cardiac performance. Am J Physiol 1963;204:597- 603. Brunwald E, Frahm CJ. Studies on Starling’s law of the heart. Circulation 1961;24:633-42. Skinner SN Jr, Mitchell JH, Wallace AG, Sarnoff SJ. Hemo- dynamic timing of atria1 systole. Am J Physiol 1963;205:499- 503. Mitchell JH, Gupta DN, Payne RM. Influence of atria1 systole on effective ventricular stroke volume. Circ Res 1965;17:11-8. Brooks C McC, Lu HH, Lange G, Mangi R, Shaw R, Geoly K. Effects of localized stretch on the sinoatrial region of the dog heart. Am J Physiol 1966;211:1197-202. Lange G, Lu HH, Chang A, Brooks C McC. Effect of Stretch on the isolated cat sinoatrial node. Am J Physiol 1966; 211:1192-6.