Effects of unipolar cathodal and bipolar stimulation on vulnerability of ischemic ventricles to fibrillation

Effects of Unipolar Cathodal and Bipolar Stimulation on Vulnerability of lschemic Ventricles to Fibrillation WOLFGANG MERX, MD* JAOK HAN, MD, PhD, FACC MYUNG S. YOON, MD Albany, New York

From the Department of Medicine (Cardioiogy), Albany Medical College of Union University, and the Electrocardiography Laboratory, Albany Medioal Center Hospital, Albany, N.Y. This study was supported by Contract NHLI-72-2974 from the National Institutes of Health, Bethesda, Md. and a grant from the Heart Association of Eastern New York, Albany, NY. Manuscript accepted June 12, 1974. *Dr. Merx is a visiting scientist from the Department of internal Medicine, North RhineWestphalia Technical University, Aachen. West German Federal Republic, and supported by a grant from the German Research Association. Address for reprints: Jaok Han, MD, Department of Medicine, Albany Medical College, Albany, N.Y. 12208.

The effects of unipolar and bipolar stimulation on ventricular fibrillation threshold were studied during acute occlusion of the left anterior descending coronary artery in 13 anesthetized dogs. Values for ventricular fibrillation threshold were determined by delivering trains of rapid bipolar or unipolar pulses (lOO/sec) during the vulnerable period. The mean threshold value was found to be 13.0 ma for bipolar, 13.9 ma for unipolar anodai and 21.0 ma for unipolar cathodal stimulation. Ventricular fibrillation threshold was significantly lower (P < 0.01) with both unipolar anodal and bipolar stimulation than with unipolar cathodai stimulation. in these animals, the first premature beats induced by the rapid stimuli occurred significantly earlier with unipolar anodal and bipolar stimulation than with unipolar cathodal stimulation. The effect of competition of unipolar or bipolar pacing stimuli with normally conducted ventricular beats was also studied in a group of 16 dogs. Repeated trials of competitive pacing during coronary occlusion showed that the incidence of ventricular fibrillation was significantly greater (P < 0.05) with bipolar pacing (36 percent) than with unipolar cathodal pacing (15 percent). These results indicate that bipolar pacing is potentially more dangerous than unipolar cathodal pacing and suggest that the tncidence of pacemaker-induced ventricular fibrillation might be further reduced by the use of unipolar cathodal stimulation during acute myocardial infarction.

-Both unipolar cathodal and bipolar electrode systems are used for permanent ventricular pacing with implanted pacemakers, but virtually all temporary ventricular pacing is currently performed with a bipolar pacemaker system. The possibility that ventricular fibrillation will be induced by a pacemaker stimulus falling in the vulnerable period exists when a fixed-rate pacemaker competes with spontaneously occurring beats. 1-6 This risk is even greater in patients whose ventricle is paced during acute myocardial infarction.4-8 The use of demand or standby pacemakers has reduced the possibility of pacemaker-induced ventricular fibrillation,2 but these pacemakers are not totally safe, since they may fail to sense spontaneous beats and continue to function in the fixed-rate mode.9 A recent report’0 suggests that the elimination of bipolar pacing systems may further reduce the frequency of ventricular fibrillation induced by the competitive pacing.‘O The risk of ventricular fibrillation had not been considered to be dependent upon the type of pacing stimuli until PrestonlO reported recently that all documented cases of pacemaker-induced ventricular tachycardia or fibrillation occurred in association with bipolar stimulation. It might be argued whether this single report is sufficient evidence for eliminating the bipolar pacing system since it is possible that cases of ventricular tachyarrhythmias induced by unipolar cathodal stimulation may have been overlooked. In view of the clinical importance of this matter, we examined the effects of unipolar and bipolar stimulation on ventricular vulnerability to fibrillation during acute myocardial ischemia.

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Methods Mongrel dogs weighing 10 to 20 kg were anesthetized by intravenous injection of sodium pentobarbitol, 30 to 35 mg/kg body weight. Under artificial respiration, a midline thoracotomy was performed and the heart was cradled in the opened pericardium. The sinoatrial node was inactivated by crushing in order to drive the heart at a constant rate by stimuli applied to the right atrium or ventricle. A femoral artery was cannulated to obtain arterial samples for the determination of blood gas and to monitor arterial pressure. Arterial blood gas and pH levels were frequently checked and corrected as necessary. For reversible occlusion of the anterior descending branch of the left coronary artery, the artery was dissected free 15 to 20 mm from its origin, and a snare was applied around the vessel. The artery was -occluded about 5 minutes before each determination of ventricular fibrillation threshold. The bipolar stimulating and recording electrodes were small steel hooks with an interelectrode distance of about 5 mm. The stimulating electrodes were attached to the anterior septal margin of the right ventricle about 10 mm from the edge of the area of expected ischemia. The recording electrodes were attached to a site close to the stimulating electrodes. For unipolar stimulation, cathodal or anodal stimuli were delivered through one of the pair of stimulating electrodes, and a hypodermic needle inserted subcutaneously in the right front leg served as the indifferent electrode. A lead III electrocardiogram, the local electrogram and the artifact of stimuli delivered to the stimulating electrodes were recorded on an Electronics for Medicine recorder or a Grass polygraph recorder. The stimuli were also displayed on an oscilloscope and calibrated by means of a Tektronix current probe amplifier. The patterns of pacing and test stimuli delivered to the heart were programmed by using a variable interval generator and a series of Tektronix wave form and pulse generators. The output of the pulse generator triggered a Grass stimulator that delivered pulses of 2 msec duration to the ventricular stimulating electrodes. Ventricular fibrillation threshold was determined by delivering trains of rapid unipolar or bipolar pulses during the vulnerable period. The ventricle was paced by basic stimuli at a cycle length of 400 msec, and the train of rapid pulses was delivered after every 12th basic ventricular response. These pulses were 2 msec in *duration and occurred at an interval of 10 msec A

BIPOLAR

B

(lOO/sec). The train was started 60 to 80 msec after the basic response and its duration did not extend beyond the absolute refractory period of the first premature beat evoked by the train. The intensity of the rapid stimuli was gradually increased until fibrillation resulted. The ventricular fibrillation threshold vyas then defined as the minimal current (expressed in milliamperes [ma]) that induced fibrillation. At the onset of fibrillation, the occluding snare on the left anterior descending artery was immediately released, and defibrillation was accomplished by direct-current countershock. A period of 15 to 20 minutes was then allowed before the next observation was made. In some experiments, the competition between pacing stimuli and normally conducted beats was achieved by pacing the right ventricle at a cycle length of 640 msec and the right atrium at 400 msec.

Results Ventricular Fibrillation Threshold Ventricular fibrillation threshold was determined using trains of bipolar, unipolar anodal or unipolar cathodal pulses in 13 dogs during acute coronary occlusion. The left anterior descending artery was occluded about 5 minutes before each threshold determination. Figure 1 illustrates the results obtained from one of these experiments. In panel A, the ventricular fibrillation threshold determined using bipolar stimuli was 13 ma, and fibrillation was initiated by the first premature beat coupled to the basic response at an interval of 182 msec. In panel B, the threshold with unipolar anodal stimulation was 15 ma with a coupling interval of 188 msec, and in C the threshold obtained with unipolar cathodal stimulation was 28 ma with a coupling interval of 198 msec. The results clearly indicate that ventricular fibrillation threshold with bipolar and unipolar anodal stimulation is lower than the threshold obtained by unipolar cathodal stimulation, and the first premature beat can be induced earlier by bipolar or unipolar anodal than by unipolar cathodal stimulation. Figure 2 shows the mean values for ventricular fibrillation threshold obtained using the three differ-

UNIPDLAR ANODAL

c

UNIPDLARCATHODAL

28

’ 500 msec

I

FIGURE 1. Values for ventricular fibrillation threshold determined with trains of bipolar (A), unipolar anodal (B) and unipolar cathodal (C) stimuli applied during the vulnerable period. S = the artifact of stimuli applied to stimulating electrodes attached to the right ventricle; Ill = lead Ill electrocardiogram; V = local electrogram recorded at a site close to stimulating electrodes. Upper numerical values indicate coupling interval of the firstpremature beat in milliseconds, lower values indicate ventricular fibrillation threshold in milliamperes.

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ma

ent types of stimuli in all 13 experiments. The mean fibrillation threshold was 13.0 f 1.6 (standard error) ma for bipolar, 13.9 & 1.8 ma for unipolar anodal and 21.0 f 1.9 ma for unipolar cathodal stimulation. Ventricular fibrillation threshold with both bipolar and unipolar anodal stimulation was significantly lower (P < 0.01) than that obtained with unipolar cathodal stimulation. The difference between fibrillation thresholds obtained with bipolar and unipolar anodal pacing was not statistically significant. In 8 of the 13 experiments, the coupling intervals of the first premature beat induced by the rapid stimuli were measured. The mean coupling interval was 187.5 f 3.4 msec for bipolar, 191.9 f 4.5 msec for unipolar anodal and 202.5 f 3.8 msec for unipolar cathodal stimulation. The coupling intervals for both bipolar and unipolar anodal stimulation were significantly shorter (P < 0.05) than that for unipolar cathodal stimulation.

UNIPOLAR CATHOOAL

UNIPOLAR ANODAL BIPOLAR

-r

Coinpetitive Ventricular Pacing

The effect of competition between unipolar or bipolar pacing stimuli and normally conducted beats was studied during acute myocardial &hernia in 16 dogs. Since unipolar anodal stimulation is not used in the clinical setting, only unipolar cathodal and bipolar stimuli were used to simulate the competitive pacing occurring in clinical situations. The competition was achieved by pacing the right atrium at a cycle length of 400 msec and the right ventricle at 640 msec, so that some ventricular stimuli would fall in the vulnerable period. The ventricular pacing stimuli were of 2 msec duration and delivered at tin intensity of 6 ma. While the ventricle was in competitive rhythm, the left anterior descending artery was occluded. If ventricular fibrillation occurred, the occluding snare was released immediately and defibrillation was accomplished by direct-current countershock. If fibrillation did not occur, the snare was released 5 minutes after the start of occlusion. Repeat occlusion began 15 to 20 minutes after defibrillation or cessation of coronary occlusion. The results of a representative experiment are shown in Figure 3. In panel A, during bipolar stimulation of the ventricle, ventricular fibrillation developed 2 minutes, 30 seconds after the start of coronary /,

FIGURE 2. Comparison of ventricular fibrillation thresholds obtained with bipolar, unipolar anodal and unipolar cathodal stimulation in 13 dogs. The values are expressed as mean f standard error.

occlusion when an early premature beat was induced by one of the bipolar stimuli. In panel B, during unipolar cathodal stimulation, fibrillation did not develop within the 5 minute period of coronary occlusion, although early premature beats were induced by cathodal stimuli. Similar, results were consistently observed on repeat trials of coronary occlusion in the 16 dogs, and the cumulative data are shown in Figure 4. Ventricular fibrillation occurred within 5 minutes after the start of coronary occlusion in 12 of 33 trials (36 percent) during competitive pacing with bipolar stimuli, and in 5 of 33 trials (15 percent) with unipolar cathodal stimuli. This difference in frequency of ventricular fibrillation was statistically significant

(P KO.05). Myocardial and unipolar

Discussion ischemk, ventricular fibrillation vs. bipolar stimulation: Our results

clearly demonstrate that ventricular fibrillation threshold is lower and the ventricle more vulnerable

BIPOLAR STIMULATION: INDUCTION OF VENTRICULAR FIBRILLATION 2 MIN AND 30 SEC AFTER CO

B UNIPOLAR CATHODAL STIMULATION: NO INDUCTION OF VENTRICULAR

FIBRILLATION WITHIN 5 MIN

FIGURE 3. Ventricular arrhythmias resulting from competitive bipolar (A) and unipolar cathodal (B) pacing during acute coronary occlusion (CO). The artifacts of ventricular stimuli occurring at a cycle length of 640 msec are smaller with bipolar stimulation in A. Ill = lead Ill electrocardiogram.

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fibrillation when the anodal electrode is involved unipolarly or bipolarly in ventricular stimulation during acute myocardial ischemia. They also showed that ventricular fibrillation is induced more frequently by bipolar stimuli than by unipolar cathodal stimuli during the competition between pacing stimuli and conducted ventricular beats. Our data further support the view that the risk of life-threatening ventricular arrhythmias is greater with bipolar than with unipolar cathodal pacing in the presence of acute myocardial infarction. lo These observations are not surprising when the results of earlier. experimental studies11-13‘ are taken into consideration. Moe et al. 12v13demonstrated that ventricular fibrillation occurred much more frequently with anodal stimuli than with cathodal stimuli applied to the vulnerable period. They also found that fibrillation originated from the anodal site when a bipolar stimulus was applied to the vulnerable period. In our study, the coupling interval between the basic response and the first premature beat induced by the train of rapid stimuli was significantly shortened when the anodal electrode was involved unipolarly or bipolarly. This is also an expected finding in light of the results of earlier studies by Hoffmani and Cranefield15 and their associates, who studied the strength-interval curves obtained with bipolar, unipolar anodal and unipolar cathodal stimulation. They found (Fig. 5) that during diastole the threshold for excitation is higher with anodal stimulation than with cathodal stimulation, but during the dip in the relative refractory period the reverse is true. The vulnerable period coincides with the dip, and the ventricle is most prone to fibrillation during this period. The strength-interval curve obtained with bipolar stimulation would then be a composite of the lowest portions of the anodal and cathodal curves. Thus, during the vulnerable period excitation should originate from the anodal electrode, but during diastole the cathode should be more effective in initiating excitation. These observations suggest that the shortened coupling intervals and lower ventricular fibrillation thresholds with unipolar anodal and bipolar stimulation may be due to the lower anodal threshold for excitation during the vulnerable period. Ventricular premature beats and ventricular fibrillation: Ventricular premature beats, whether generated spontaneously or induced by pacemaker stimuli, have the potential to initiate ventricular tachycardia and fibrillation. The risk of ventricular fibrillation is particularly great when the premature beats are closely coupled to the previous beat and fall in the vulnerable period. 7p8The ventricle is vulnerable during this period because excitability and conductivity are irregularly depressed as a result of nonuniform recovery of excitability in different segments of the myocardium. The premature impulse may travel rapidly through relatively more excitable tissues, propagate slowly through poorly excitable areas and fail to excite those still refractory. These conditions may further increase the nonuniformity of excitability and conductivity, leading to the developto

)IPOLAR

UN IPOLAR CATHO[

12 33

FIGURE 4. The incidence of ventricular fibrillation induced by competitive bipolar and unipolar cathodal pacing during acute coronary occlusion (CO). The data are from 33 paired trials of competitive pacing in 16 dogs.

ma

STIMULATION .........‘..UNI POLAR

ANODAL

-UNIPOLAR

CATHODAL

-BIPOLAR

FIGURE 5. Strength-interval curves for unipolar anodal. unipolar cathodal and bipolar stimulation. Stimulus strengths required to evoke excitation are plotted on the ordinate in milliamperes and various intervals after the preceding excitation on the abscissa in milliseconds.

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ment of reentrant circuits and fractionation of the excitation wave front into many irregular wavelets, that is, fibrillation. The ventricle with an ischemic area should be more vulnerable to fibrillation, since reentrant activity and disorganization of the wave front are more likely to occur because of marked depression of excitability and conductivity in the ischemit area.7,8 Our study showed that ventricular premature beats can be induced significantly earlier with unipolar anodal and bipolar stimulation than with cathodal stimulation. This earlier onset may have facilitated the induction of ventricular fibrillation since the chance of reentrant activity and subsequent disorganization of the excitation wave front is expected to be enhanced with an increase in the prematurity of ventricular excitation.7T8 Clinical implications: There are several possible reasons why, even with bipolar pacing, ventricular fibrillation occurs rather infrequently in clinical situations. When bipolar electrodes are inserted in the right ventricle the distal electrode may be in better contact with the endocardium than is the proximal electrode. Since the distal electrode is routinely connected to the cathode of a pulse generator, bipolar pacing may be more like unipolar cathodal stimulation in many cases. Cases in which the proximal electrode is in good contact with the endocardium, and hence true bipolar stimulation is possible, may be fewer than one might anticipate. Demand or standby pacemakers are now generally used for temporary ventricular pacing, and the possibility of pacemaker competition has been reduced significantly.2 How-

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ever, it is possible that these pacemakers may still function in the fixed-rate mode and that competitive pacing may result when the ventricular potentials registered by the bipolar electrodes are too small to be sensed by the demand pacemaker.g The failure of such a sensing function is less likely to occur with unipolar cathodal pacing because the amplitude of ventricular potentials recorded by the unipolar electrode is much greater.9 In most cases of competitive bipolar pacing the intensity of bipolar stimuli falling in the vulnerable period may not be strong enough to induce ventricular fibrillation, but fibrillation will occur when the threshold is abnormally lowered during acute myocardial infarction.79s Our results indicate that unipolar cathodal pacing is potentially safer than bipolar pacing when ventricular vulnerability to fibrillation is increased, and they suggest that the incidence of pacemaker-induced ventricular fibrillation can be further reduced by the use of unipolar cathodal stimulation for temporary ventricular pacing during acute myocardial infarction. Virtually all temporary ventricular pacing is currently performed using bipolar electrodes and bipolar pulse generators. Such pacemaker systems can be easily unipolarized by connecting the distal electrode to the cathode and a remote indifferent electrode to the anode of pulse generators. Acknowledgment We are grateful to Rosalyn Rogers and Marilee Jones for technical assistance and to Andrea Kross for preparation of the manuscript.

References 1. Sowton, E: Artificial pacemaking and sinus rhythm. Br Heart J 27:31 l-318, 1965 2. Bilitch M: Ventricular fibrillation and pacing. Ann NY Acad Sci 167:934-940, 1969 3. Sowton E, Flares J: Natural history of pacemaker patients. Bull NY Acad Med 47:999-1010, 1971 4. Chardack WM, lshikawa H, Fochler FJ, et al: Pacing and ventricular fibrillation, Ann NY Acad Sci 167:919-933, 1969 5. Bllitch M, Cosby RS, Cafferky EA: Ventricular fibrillation and competitive pacing, N Engl J Med 276598604, 1967 6. Escher DJW: The present status of clinical cardiac pacing. Am Heart J 74:126-132, 1967 7. Han J: Mechanisms of ventricular arrhythmias associated with myocardial infarction. Am J Cardiol 24:800-813, 1969 8. Han J: Ventricular vulnerability durlhg acute coronary occlusion. Am J Cardiol 24:857-864, 1989 9. Barold SS, Gaidula JJ: Evaluation of normal and abnormal sensing functions of demand pacemakers. Am J Cardiol 28:

201-210.1971 10. Preston TA: Anodal stimulation as a cause of pacemaker-induced ventricular fibrillation. Am Heart J 86:366-372, 1973 11. Han J: Ventricular vulnerability to fibrillation. In, Cardiac Arrhythmias (Dreifus L, Likoff WL, ed). New York, Grune & Stratton, 1973, p 87-95 12. Moe GK, HarrisAS, Wlggers CJ: Analysis of the initiation of fibrillation by electrographic studies. Am J Physiol 134:473-492, 1941 13. Harris AS, Moe GK: ldioventricular rhythms and fibrillation induced at the anode or the cathode by direct currents of long duration. Am J Physiol 136:318-331, 1942 14. Hoffman BF, Govin EF, Wax FS, et al: Vulnerability to fibrillation and the ventricular excitability curve. Am J Physiol 167:88-94, 1951 15. Cranefield PF, Hoffman BF, Siebens AA: Anodal excitation of cardiac muscle. Am J Physiol 190:383-390, 1957

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